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Barman P, Hazarika S, Roy K, Rawal RK, Konwar R. Phytochemical analysis of leaf extract of Piper nigrum and investigation of its biological activities. Inflammopharmacology 2025:10.1007/s10787-025-01701-5. [PMID: 40251438 DOI: 10.1007/s10787-025-01701-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/31/2025] [Indexed: 04/20/2025]
Abstract
BACKGROUND This study investigates the phytoconstituents of the less explored leaf of Piper nigrum, a common ethnomedicinal plant as an alternate source for multiple bioactivities. METHODS Hydro-ethanolic (1:4) extract of Piper nigrum leaves (PNLE) prepared and profiled using liquid chromatography and mass spectrometry for identification of phytomolecules. Anti-oxidant activity, intracellular reactive oxygen species (ROS) expression, phagocytosis activity, and cytokine expression were estimated using cell-free and cell-based assays. Anti-cancer activity was determined with cancer cell viability, migration inhibition and colony-formation assay. Apoptosis and membrane depolarization assay were done using fluorescent microscopic staining methods while network pharmacology, and molecular docking analysis were done using open source and online tools. RESULTS Major phytomolecules identified in PNLE were pentanamide N,N-didecyl, piperettine, curcumin, myristicin, pipernonaline, sesamin, and lupenone. PNLE exhibited anti-bacterial activity with higher activity against Gram-positive bacteria, Staphylococcus aureus. PNLE also showed anti-oxidant and anti-inflammatory activity through neutralization of free radicals; inhibition of intracellular ROS generation; inhibition of phagocytosis and reduction of cytokine (IL-6 and TNF-α) levels. PNLE showed anti-proliferative activity against human breast cancer cells (MDA-MB-231), rat mammary tumor cells (LA7), and mouse melanoma cells (B16-F10) with highest activity against MDA-MB-231 cells. The extract did not inhibit human kidney cells (HEK-293). Further, PNLE treatment significantly inhibited cell migration and colony formation of MDA-MB-231 cells. Fluorescent staining techniques confirmed induction of apoptosis in cancer cells by PNLE. Further, network pharmacology and molecular docking studies revealed that the identified PNLE phytomolecules share 97 targets of out of potential breast cancer and inflammation-related target genes with four best common target proteins among the top hub genes and sesamin showed the highest binding affinity with these important cellular targets. CONCLUSIONS Overall, the phytochemical profile of PNLE showed clear presence of important phytomolecules and their association with critical human cellular mechanistic pathways responsible for exhibited bioactivities. This study further establishes the leaf of P. nigrum as an additional anatomical plant part with potent medicinal properties and as a potential renewable source for bioactive phyomolecules.
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Affiliation(s)
- Pankaj Barman
- Centre for Preclinical Studies (CPS), Biological Science and Technology Division (BSTD), CSIR-North East Institute of Science and Technology (NEIST), Jorhat, Assam, 785006, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Srija Hazarika
- Natural Product Chemistry Group, Chemical Science and Technology Division (CSTD), CSIR-North East Institute of Science and Technology, Jorhat, 785006, India
| | - Kallol Roy
- Centre for Preclinical Studies (CPS), Biological Science and Technology Division (BSTD), CSIR-North East Institute of Science and Technology (NEIST), Jorhat, Assam, 785006, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Ravindra K Rawal
- Natural Product Chemistry Group, Chemical Science and Technology Division (CSTD), CSIR-North East Institute of Science and Technology, Jorhat, 785006, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Rituraj Konwar
- Centre for Preclinical Studies (CPS), Biological Science and Technology Division (BSTD), CSIR-North East Institute of Science and Technology (NEIST), Jorhat, Assam, 785006, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
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Zhang C, Huang DL, Zhou K, Cai JT, Liu D, Tan MH, Zhu GY, Wu XH. Human blood metabolites and gastric cancer: a Mendelian randomization analysis. BMC Gastroenterol 2024; 24:478. [PMID: 39736510 DOI: 10.1186/s12876-024-03576-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 12/22/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) remains one of the predominant malignant tumors within the digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective of this study is to delineate the causal relationship between circulating metabolites and GC. METHOD The primary Mendelian randomization (MR) analysis was based on three large GWAS datasets. While the inverse variance weighted served as the primary analysis technique for investigating causal relationships, additional sensitivity analyses were facilitated through methods such as MR-PRESSO, the weighted median, and MR-Egger. Subsequently, replication, meta-analysis, and multivariable MR were executed using another GC GWAS. RESULTS The results of this study indicated significant associations between three metabolites 3-methyl-2-oxovalerate (OR 5.8, 95%CI: 1.53-22.05, p = 0.0099), piperine (OR 2.05, 95%CI: 1.13-3.7, p = 0.0175), Phe-Phe dipeptide (OR 0.16, 95%CI: 0.03-0.93, p = 0.0409) and GC. CONCLUSION The present study provides evidence supporting a causal relationship between these three circulating metabolites and GC risk. Elevated levels of 3-methyl-2-oxovalerate and piperine may increase the risk of GC, while Phe-Phe dipeptide may have a protective effect. By integrating genomics and metabolomics, we offer a novel perspective on the biological mechanisms underlying GC. Such insights have the potential to enhance strategies for the screening, prevention, and treatment of GC.
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Affiliation(s)
- Chao Zhang
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Dao Lai Huang
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Kun Zhou
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Jin Tao Cai
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Dang Liu
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Ming Hao Tan
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Guan Yu Zhu
- Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China
| | - Xiang Hua Wu
- Guangxi Medical University, Nanning, 530021, Guangxi, China.
- Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, Guangxi, China.
- Department of Gastrointestinal Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Qingxiu District Nanning, 22 Shuangyong Road, Guangxi, 530021, China.
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Liu Y, Yu X, Shen H, Hong Y, Hu G, Niu W, Ge J, Xuan J, Qin JJ, Li Q. Mechanisms of traditional Chinese medicine in the treatment and prevention of gastric cancer. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156003. [PMID: 39305742 DOI: 10.1016/j.phymed.2024.156003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/21/2024] [Accepted: 06/07/2024] [Indexed: 12/01/2024]
Abstract
BACKGROUND Gastric cancer (GC) ranks as the fifth most prevalent malignancy worldwide. Conventional treatments, including radiotherapy and chemotherapy, often induce severe side effects and significant adverse reactions, and they may also result in drug resistance. Consequently, there is a critical need for the development of new therapeutic agents. Traditional Chinese Medicine (TCM) and natural products are being extensively researched due to their low toxicity, multi-targeted approaches, and diverse pathways. Scholars are increasingly focusing on identifying active anticancer components within TCM. PURPOSE This review aims to summarise research conducted over the past 14 years on the treatment of GC using TCM. The focus is on therapeutic targets, mechanisms, and efficacy of Chinese medicine and natural products, including monomer compounds, extracts or analogues, and active ingredients. METHODS Relevant articles on TCM and GC were retrieved from PubMed using appropriate keywords. The collected articles were screened and classified according to the types of TCM, with an emphasis on the molecular mechanisms underlying the treatment of GC. RESULTS The research on TCM indicates that TCM and natural products can effectively inhibit the metastasis, proliferation, and invasion of tumour cells. They can also induce apoptosis, autophagy and improve the chemosensitivity of drug-resistant cells. Additionally, injections derived from Chinese herbal medicine, when used as an adjunct to conventional chemotherapy, can significantly improve the prognosis of GC patients by reducing chemotherapy toxicity. CONCLUSION This review summarises the progress of TCM treatment of GC over the past 14 years, and discusses its therapeutic application of GC, which proves that TCM is a promising treatment strategy for GC in the future.
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Affiliation(s)
- Yanyang Liu
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuefei Yu
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China
| | - Huize Shen
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yangjian Hong
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Gaofeng Hu
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wenyuan Niu
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jiaming Ge
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jie Xuan
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jiang-Jiang Qin
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
| | - Qinglin Li
- Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, No. 1, Banshan east road, Gongshu district, Hangzhou, Zhejiang, China.
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Demir K, Turgut R, Şentürk S, Işıklar H, Günalan E. The Therapeutic Effects of Bioactive Compounds on Colorectal Cancer via PI3K/Akt/mTOR Signaling Pathway: A Critical Review. Food Sci Nutr 2024; 12:9951-9973. [PMID: 39723045 PMCID: PMC11666977 DOI: 10.1002/fsn3.4534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/25/2024] [Accepted: 09/28/2024] [Indexed: 12/28/2024] Open
Abstract
Understanding the molecular signaling pathways of colorectal cancer (CRC) can be accepted as the first step in treatment strategy. Permanent mTOR signaling activation stimulates the CRC process via various biological processes. It supplies the survival of CRC stem cells, tumorigenesis, morbidity, and decreased response to drugs in CRC pathogenesis. Therefore, inhibition of the mTOR signaling by numerous bioactive components may be effective against CRC. The study aims to discuss the therapeutic capacity of various polyphenols, terpenoids, and alkaloids on CRC via the PI3K/Akt/mTOR pathway. The potential molecular effects of bioactive compounds on the mTOR pathway's upstream and downstream targets are examined. Each bioactive component causes various physiological processes, such as triggering free radical production, disruption of mitochondrial membrane potential, cell cycle arrest, inhibition of CRC stem cell migration, and suppression of glycolysis through mTOR signaling inhibition. As a result, carcinogenesis is inhibited by inducing apoptosis and autophagy. However, it should be noted that studies are primarily in vitro dose-dependent treatment researchers. This study raises awareness about the role of phenolic compounds in treating CRC, contributing to their future use as anticancer agents. These bioactive compounds have the potential to be developed into food supplementation to prevent and treat various cancer types including CRC. This review has the potential to lead to further development of clinical studies. In the future, mTOR inhibition by applying several bioactive agents using advanced drug delivery systems may contribute to CRC treatment with 3D cell culture and in vivo clinical studies.
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Affiliation(s)
- Kübra Demir
- Institute of Graduate EducationIstanbul Health and Technology UniversityIstanbulTürkiye
- Faculty of Health Science, Department of Nutrition and DieteticsSabahattin Zaim UniversityIstanbulTürkiye
| | - Rana Turgut
- Institute of Graduate EducationIstanbul Health and Technology UniversityIstanbulTürkiye
| | - Selcen Şentürk
- Institute of Graduate EducationIstanbul Health and Technology UniversityIstanbulTürkiye
| | - Handan Işıklar
- Faculty of Medicine, Department of Internal MedicineYalova UniversityYalovaTürkiye
| | - Elif Günalan
- Faculty of Health Science, Department of Nutrition and DieteticsIstanbul Health and Technology UniversityIstanbulTürkiye
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Kumari H, Ganjoo A, Shafeeq H, Ayoub N, Babu V, Ahmed Z. Microbial transformation of some phytochemicals into value-added products: A review. Fitoterapia 2024; 178:106149. [PMID: 39089598 DOI: 10.1016/j.fitote.2024.106149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/26/2024] [Accepted: 07/28/2024] [Indexed: 08/04/2024]
Abstract
Phytochemicals, plant-derived compounds, are the major components of traditional medicinal plants. Some phytochemicals have restricted applications, due to low bioavailability and less efficacy. However, their medicinal properties can be enhanced by converting them into value-added products for different bioactivities like anti-oxidant, neuroprotective, anti-obesity, anti-neuroinflammatory, anti-microbial, anti-cancer and anti-inflammatory. Microbial transformation is one such process that is generally more specific and makes it possible to modify a compound without making any unwanted alterations in the molecule. This has led to the efficient production of value-added products with important pharmacological properties and the discovery of new active compounds. The present review assimilates the existing knowledge of the microbial transformation of some phytochemicals like eugenol, curcumin, ursolic acid, cinnamaldehyde, piperine, β-carotene, β-sitosterol, and quercetin to value-added products for their application in food, fragrances, and pharmaceutical industries.
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Affiliation(s)
- Hema Kumari
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Ananta Ganjoo
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Haseena Shafeeq
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Nargis Ayoub
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Vikash Babu
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
| | - Zabeer Ahmed
- CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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Kačániová M, Čmiková N, Ban Z, Garzoli S, Elizondo-Luevano JH, Ben Hsouna A, Ben Saad R, Bianchi A, Venturi F, Kluz MI, Haščík P. Enhancing the Shelf Life of Sous-Vide Red Deer Meat with Piper nigrum Essential Oil: A Study on Antimicrobial Efficacy against Listeria monocytogenes. Molecules 2024; 29:4179. [PMID: 39275027 PMCID: PMC11396834 DOI: 10.3390/molecules29174179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 08/27/2024] [Accepted: 09/02/2024] [Indexed: 09/16/2024] Open
Abstract
Using sous-vide technology in combination with essential oils offers the potential to extend the preservation of food items while preserving their original quality. This method aligns with the growing consumer demand for safer and healthier food production practices. This study aimed to assess the suitability of minimal processing of game meat and the effectiveness of vacuum packaging in combination with Piper nigrum essential oil (PNEO) treatment to preserve red deer meat samples inoculated with Listeria monocytogenes. Microbial analyses, including total viable count (TVC) for 48 h at 30 °C, coliform bacteria (CB) for 24 h at 37 °C, and L. monocytogenes count for 24 h at 37 °C, were conducted. The cooking temperature of the sous-vide was from 50 to 65 °C and the cooking time from 5 to 20 min. Additionally, the study monitored the representation of microorganism species identified through mass spectrometry. The microbiological quality of red deer meat processed using the sous-vide method was monitored over 14 days of storage at 4 °C. The results indicated that the TVC, CB, and L. monocytogenes counts decreased with the temperature and processing time of the sous-vide method. The lowest counts of individual microorganism groups were observed in samples treated with 1% PNEO. The analysis revealed that PNEO, in combination with the sous-vide method, effectively reduced L. monocytogenes counts and extended the shelf life of red deer meat. Kocuria salsicia, Pseudomonas taetrolens, and Pseudomonas fragi were the most frequently isolated microorganism species during the 14-day period of red deer meat storage prepared using the sous-vide method.
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Affiliation(s)
- Miroslava Kačániová
- Institute of Horticulture, Faculty of Horticulture and Landscape Engineering, Slovak University of Agriculture, Trieda Andreja Hlinku 2, 94976 Nitra, Slovakia
- School of Medical & Health Sciences, University of Economics and Human Sciences in Warsaw, Okopowa 59, 01043 Warszawa, Poland
| | - Natália Čmiková
- Institute of Horticulture, Faculty of Horticulture and Landscape Engineering, Slovak University of Agriculture, Trieda Andreja Hlinku 2, 94976 Nitra, Slovakia
| | - Zhaojun Ban
- Zhejiang Provincial Key Laboratory of Chemical and Biological Processing Technology of Farm Products, Zhejiang Provincial Collaborative Innovation Center of Agricultural Biological Resources Biochemical Manufacturing, School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China
| | - Stefania Garzoli
- Department of Chemistry and Technologies of Drug, Sapienza University, P. le Aldo Moro, 5, 00185 Rome, Italy
| | - Joel Horacio Elizondo-Luevano
- Faculty of Agronomy, Universidad Autónoma de Nuevo León (UANL), Av. Francisco Villa S/N, Col. Ex Hacienda el Canadá, General Escobedo, Nuevo León 66050, Mexico
| | - Anis Ben Hsouna
- Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, B.P "1177", Sfax 3018, Tunisia
- Department of Environmental Sciences and Nutrition, Higher Institute of Applied Sciences and Technology of Mahdia, University of Monastir, Monastir 5000, Tunisia
| | - Rania Ben Saad
- Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, B.P "1177", Sfax 3018, Tunisia
| | - Alessandro Bianchi
- Department of Agriculture, Food and Environment, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
| | - Francesca Venturi
- Department of Agriculture, Food and Environment, University of Pisa, Via del Borghetto 80, 56124 Pisa, Italy
| | - Maciej Ireneusz Kluz
- School of Medical & Health Sciences, University of Economics and Human Sciences in Warsaw, Okopowa 59, 01043 Warszawa, Poland
| | - Peter Haščík
- Institute of Food Technology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture, Trieda Andreja Hlinku 2, 94976 Nitra, Slovakia
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Talib WH, Abed I, Raad D, Alomari RK, Jamal A, Jabbar R, Alhasan EOA, Alshaeri HK, Alasmari MM, Law D. Targeting Cancer Hallmarks Using Selected Food Bioactive Compounds: Potentials for Preventive and Therapeutic Strategies. Foods 2024; 13:2687. [PMID: 39272454 PMCID: PMC11395675 DOI: 10.3390/foods13172687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 08/23/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.
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Affiliation(s)
- Wamidh H Talib
- Faculty of Allied Medical Sciences, Applied Science Private University, Amman 11931, Jordan
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
| | - Ilia Abed
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Daniah Raad
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Raghad K Alomari
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Ayah Jamal
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Rand Jabbar
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Eman Omar Amin Alhasan
- Faculty of Allied Medical Sciences, Applied Science Private University, Amman 11931, Jordan
| | - Heba K Alshaeri
- Department of Pharmacology, Faculty of Medicine, King Abdul-Aziz University, Rabigh 25724, Saudi Arabia
| | - Moudi M Alasmari
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah 21423, Saudi Arabia
- King Abdullah International Medical Research Centre (KAIMRC), Jeddah 22233, Saudi Arabia
| | - Douglas Law
- Faculty of Health and Life Sciences, Inti International University, Nilai 71800, Negeri Sembilan, Malaysia
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Ren L, Zhang T, Zhang J. Recent advances in dietary androgen receptor inhibitors. Med Res Rev 2024; 44:1446-1500. [PMID: 38279967 DOI: 10.1002/med.22019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/07/2023] [Accepted: 01/10/2024] [Indexed: 01/29/2024]
Abstract
As a nuclear transcription factor, the androgen receptor (AR) plays a crucial role not only in normal male sexual differentiation and growth of the prostate, but also in benign prostatic hyperplasia, prostatitis, and prostate cancer. Multiple population-based epidemiological studies demonstrated that prostate cancer risk was inversely associated with increased dietary intakes of green tea, soy products, tomato, and so forth. Therefore, this review aimed to summarize the structure and function of AR, and further illustrate the structural basis for antagonistic mechanisms of the currently clinically available antiandrogens. Due to the limitations of these antiandrogens, a series of natural AR inhibitors have been identified from edible plants such as fruits and vegetables, as well as folk medicines, health foods, and nutritional supplements. Hence, this review mainly focused on recent experimental, epidemiological, and clinical studies about natural AR inhibitors, particularly the association between dietary intake of natural antiandrogens and reduced risk of prostatic diseases. Since natural products offer multiple advantages over synthetic antiandrogens, this review may provide a comprehensive and updated overview of dietary-derived AR inhibitors, as well as their potential for the nutritional intervention against prostatic disorders.
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Affiliation(s)
- Li Ren
- College of Food Science and Engineering, Jilin University, Changchun, China
| | - Tiehua Zhang
- College of Food Science and Engineering, Jilin University, Changchun, China
| | - Jie Zhang
- College of Food Science and Engineering, Jilin University, Changchun, China
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Zhang L, Kuang G, Gong X, Huang R, Zhao Z, Li Y, Wan J, Wang B. Piperine attenuates hepatic ischemia/reperfusion injury via suppressing the TLR4 signaling cascade in mice. Transpl Immunol 2024; 84:102033. [PMID: 38484898 DOI: 10.1016/j.trim.2024.102033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 03/09/2024] [Accepted: 03/11/2024] [Indexed: 03/19/2024]
Abstract
Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed. The infiltration of inflammatory cells and production of inflammatory mediators in the liver tissue were determined by immunofluorescence and immunohistochemical staining. The protein levels of toll-like receptor 4 (TLR4) and related proteins such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), p65, and p38 were detected by western blotting. The results showed that plasma aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte apoptosis, oxidative stress, and inflammatory cell infiltration significantly increased in HIRI mice. Piperine pretreatment notably repaired liver function, improved the histopathology and apoptosis of liver cells, alleviated oxidative stress injury, and reduced inflammatory cell infiltration. Further analysis showed that piperine attenuated tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-κB in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-κB signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.
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Affiliation(s)
- Lidan Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ge Kuang
- Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China
| | - Xia Gong
- Department of Anatomy, Chongqing Medical University, Chongqing 400016, China
| | - Rui Huang
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang 310058, China
| | - Zizuo Zhao
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yan Li
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jingyuan Wan
- Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
| | - Bin Wang
- Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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10
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Asoka AS, Kolikkandy A, Nair B, Kamath AJ, Sethi G, Nath LR. Role of Culinary Indian Spices in the Regulation of TGF-β Signaling Pathway in Inflammation-Induced Liver Cancer. Mol Nutr Food Res 2024; 68:e2300793. [PMID: 38766929 DOI: 10.1002/mnfr.202300793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/29/2023] [Indexed: 05/22/2024]
Abstract
SCOPE Hepatocellular carcinoma (HCC) results from various etiologies, such as Hepatitis B and C, Alcoholic and Non-alcoholic fatty liver disorders, fibrosis, and cirrhosis. About 80 to 90% of HCC cases possess cirrhosis, which is brought on by persistent liver inflammation. TGF-β is a multifunctional polypeptide molecule that acts as a pro-fibrogenic marker, inflammatory cytokine, immunosuppressive agent, and pro-carcinogenic growth factor during the progression of HCC. The preclinical and clinical evidence illustrates that TGF-β can induce epithelial-to-mesenchymal transition, promoting progression and hepatocyte immune evasion. Therefore, targeting the TGF-β pathway can be a promising therapeutic option against HCC. METHODS AND RESULTS We carry out a systemic analysis of eight potentially selected culinary Indian spices: Turmeric, Black pepper, Ginger, Garlic, Fenugreek, Red pepper, Clove, Cinnamon, and their bioactives in regulation of the TGF-β pathway against liver cancer. CONCLUSION Turmeric and its active constituent, curcumin, possess the highest therapeutic potential in treating inflammation-induced HCC and they also have the maximum number of ongoing in-vivo and in-vitro studies.
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Affiliation(s)
- Ajay Sarija Asoka
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
| | - Anusha Kolikkandy
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
| | - Bhagyalakshmi Nair
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
| | - Adithya J Kamath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Lekshmi R Nath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, P.O., Kochi, Kerala, 682041, India
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11
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Torres Vargas OL, Rodríguez Agredo IA, Galeano Loaiza YV. Effect of incorporating white pepper ( Piper nigrum L.) oleoresin on starch/alginate films. RSC Adv 2024; 14:15293-15301. [PMID: 38741955 PMCID: PMC11089458 DOI: 10.1039/d4ra00821a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 05/07/2024] [Indexed: 05/16/2024] Open
Abstract
The development of films based on natural components has demonstrated their potential for food preservation. In this research, the effect of the inclusion of white pepper oleoresin (WPO) in a film made from cassava starch and sodium alginate (FWPO) on the antimicrobial, physicochemical, mechanical, optical, and structural properties was evaluated. The films were formulated with different concentrations of WPO (0.0, 0.5, 1.0 and 1.5%). The results obtained indicated that the incorporation of WPO in the film increased the antioxidant activity against the 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH), and an inhibitory effect against Escherichia coli and Staphylococcus aureus bacteria was also observed. Elongation at break (EB), water vapor permeability (WVP), moisture content, solubility, and luminosity (L*) decreased significantly (p < 0.05) with the addition of WPO. On the other hand, the tensile strength (TS), the value of b* (tendency toward yellow) and the opacity increased. Scanning electron microscopy (SEM) images showed a smooth, uniform appearance, and continuous dispersion between cassava starch, alginate and WPO. FTIR spectra showed the interactions between the film components. X-ray diffraction (XRD) patterns showed that the addition of WPO did not affect the structural stability of the films. The results obtained indicate the possible use of WPO in the packaging of food products, contributing to the improvement of food quality and safety.
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Affiliation(s)
- Olga Lucía Torres Vargas
- Group of Research on Agro-industrial Sciences, Interdisciplinary Science Institute, Food Engineering Laboratory, Universidad del Quindío Cra. 15# 12 N Armenia Quindío 630004 Colombia
| | - Iván Andrés Rodríguez Agredo
- Group of Research on Agro-industrial Sciences, Interdisciplinary Science Institute, Food Engineering Laboratory, Universidad del Quindío Cra. 15# 12 N Armenia Quindío 630004 Colombia
| | - Yessica Viviana Galeano Loaiza
- Group of Research on Agro-industrial Sciences, Interdisciplinary Science Institute, Food Engineering Laboratory, Universidad del Quindío Cra. 15# 12 N Armenia Quindío 630004 Colombia
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12
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Xu ZY, Du NN, La CS, Huang XX, Song SJ. Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2024:1-10. [PMID: 38594843 DOI: 10.1080/10286020.2024.2335279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 03/19/2024] [Indexed: 04/11/2024]
Abstract
Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.
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Affiliation(s)
- Zhi-Yong Xu
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Liaoning 110016, China
| | - Ning-Ning Du
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Liaoning 110016, China
| | - Chang-Sheng La
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Liaoning 110016, China
| | - Xiao-Xiao Huang
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Liaoning 110016, China
| | - Shao-Jiang Song
- Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Engineering Research Center of Natural Medicine Active Molecule Research & Development, Key Laboratory of Natural Bioactive Compounds Discovery & Modification, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Liaoning 110016, China
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13
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Lim ES, Lee SE, Park MJ, Han DH, Lee HB, Ryu B, Kim EY, Park SP. Piperine improves the quality of porcine oocytes by reducing oxidative stress. Free Radic Biol Med 2024; 213:1-10. [PMID: 38159890 DOI: 10.1016/j.freeradbiomed.2023.12.042] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 12/08/2023] [Accepted: 12/27/2023] [Indexed: 01/03/2024]
Abstract
Oxidative stress caused by light and high temperature arises during in vitro maturation (IVM), resulting in low-quality embryos compared with those obtained in vivo. To overcome this problem, we investigated the influence of piperine (PIP) treatment during maturation of porcine oocytes on subsequent embryo development in vitro. Porcine oocytes were cultured in IVM medium supplemented with 0, 50, 100, 200, or 400 μM PIP. After parthenogenetic activation, the blastocyst (BL) formation was significantly higher and the apoptosis rate was significantly lower using 200 μM PIP-treated oocytes (200 PIP). In the 200 PIP group, the level of reactive oxygen species at the metaphase II stage was decreased, accompanied by an increased level of glutathione and increased expression of antioxidant processes (Nrf2, CAT, HO-1, SOD1, and SOD2). Consistently, chromosome misalignment and aberrant spindle organization were alleviated and phosphorylated p44/42 mitogen-activated protein kinase activity was increased in the 200 PIP group. Expression of development-related (CDX2, NANOG, POU5F1, and SOX2), anti-apoptotic (BCL2L1 and BIRC5), and pro-apoptotic (BAK, FAS, and CASP3) processes was altered in the 200 PIP group. Ultimately, embryo development was improved in the 200 PIP group following somatic cell nuclear transfer. These findings suggest that PIP improves the quality of porcine oocytes by reducing oxidative stress, which inevitably arises via IVM. In-depth mechanistic studies of porcine oocytes will improve the efficiencies of assisted reproductive technologies.
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Affiliation(s)
- Eun-Seo Lim
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Seung-Eun Lee
- Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Cronex Co., 110 Hwangtalli-gil, Gangnae-myeon, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28174, South Korea
| | - Min-Jee Park
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Dong-Hun Han
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Han-Bi Lee
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Bokyeong Ryu
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea
| | - Eun-Young Kim
- Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Mirae Cell Bio, 1502 isbiz-tower 147, Seongsui-ro, Seongdong-gu, Seoul, 04795, South Korea
| | - Se-Pill Park
- Stem Cell Research Center, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Department of Bio Medical Informatics, College of Applied Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, Jeju Special Self-Governing Province, 63243, South Korea; Mirae Cell Bio, 1502 isbiz-tower 147, Seongsui-ro, Seongdong-gu, Seoul, 04795, South Korea.
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14
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Afroz M, Bhuia MS, Rahman MA, Hasan R, Islam T, Islam MR, Chowdhury R, Khan MA, Antas E Silva D, Melo Coutinho HD, Islam MT. Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies. Eur J Pharmacol 2024; 965:176289. [PMID: 38158111 DOI: 10.1016/j.ejphar.2023.176289] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 12/02/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024]
Abstract
Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.
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Affiliation(s)
- Meher Afroz
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Md Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Md Anisur Rahman
- Department of Pharmacy, Islamic University, Kushtia, 7003, Bangladesh.
| | - Rubel Hasan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Tawhida Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Md Rakibul Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Raihan Chowdhury
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | - Md Ali Khan
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
| | | | | | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
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15
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Fayad MA, Charles S, Shelvy S, Sheeja TE, Sangeetha K, Angadi UB, Tandon G, Iquebal MA, Jaiswal S, Kumar D. Whole genome based identification of BAHD acyltransferase gene involved in piperine biosynthetic pathway in black pepper. J Biomol Struct Dyn 2024:1-13. [PMID: 38344997 DOI: 10.1080/07391102.2024.2313164] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 01/25/2024] [Indexed: 03/08/2025]
Abstract
Black pepper (Piper nigrum L.), a crop of the genus Piper, is an important spice that has both economic and ecological significance. It is widely regarded as the "King of Spices" because of its pungency, attributed to the presence of piperine. BAHD acyl transferase, the crucial enzyme involved in the final step in piperine biosynthesis was the focus of our study and the aim was to identify the candidate isoform involved in biosynthesis of piperine. Reference genome-based analysis of black pepper identified six BAHD-AT isoforms and mapping of these sequences revealed that the isoforms were situated on six distinct chromosomes. By using specific primers for each of these transcripts, qPCR analysis was done in different tissues as well as berry stages to obtain detectable amplification products. Expression profiles of isoforms from chromosome 6 correlated well with piperine content compared to other five isoforms, across tissues and was therefore assumed to be involved in biosynthesis of piperine. In addition to this, we could also identify the binding sites of MYB transcription factor in the cis-regulatory regions of the isoforms. We also used in-silico docking and molecular dynamics simulation to calculate the binding free energy of the ligand and confirmed that among all the isoforms, BAHD-AT from chromosome 6 had the lowest free binding energy and highest affinity towards the ligand. Our findings are expected to aid the identification of new genes connecting enzymes involved in the biosynthetic pathway of piperine, which will have major implications for future research in metabolic engineering.
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Affiliation(s)
- M A Fayad
- ICAR - Indian Institute of Spices Research, Kozhikode, Kerala, India
| | - Sona Charles
- ICAR - Indian Institute of Spices Research, Kozhikode, Kerala, India
| | - S Shelvy
- ICAR - Indian Institute of Spices Research, Kozhikode, Kerala, India
| | - T E Sheeja
- ICAR - Indian Institute of Spices Research, Kozhikode, Kerala, India
| | - K Sangeetha
- ICAR - Indian Institute of Spices Research, Kozhikode, Kerala, India
| | - U B Angadi
- ICAR - Indian Agricultural Statistics Research Institute, New Delhi, India
| | - Gitanjali Tandon
- ICAR - Indian Agricultural Statistics Research Institute, New Delhi, India
| | - Mir Asif Iquebal
- ICAR - Indian Agricultural Statistics Research Institute, New Delhi, India
| | - Sarika Jaiswal
- ICAR - Indian Agricultural Statistics Research Institute, New Delhi, India
| | - Dinesh Kumar
- ICAR - Indian Agricultural Statistics Research Institute, New Delhi, India
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16
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Huang X, Lowrie DB, Fan XY, Hu Z. Natural products in anti-tuberculosis host-directed therapy. Biomed Pharmacother 2024; 171:116087. [PMID: 38171242 DOI: 10.1016/j.biopha.2023.116087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/17/2023] [Accepted: 12/26/2023] [Indexed: 01/05/2024] Open
Abstract
Given that the disease progression of tuberculosis (TB) is primarily related to the host's immune status, it has been gradually realized that chemotherapy that targets the bacteria may never, on its own, wholly eradicate Mycobacterium tuberculosis, the causative agent of TB. The concept of host-directed therapy (HDT) with immune adjuvants has emerged. HDT could potentially interfere with infection and colonization by the pathogens, enhance the protective immune responses of hosts, suppress the overwhelming inflammatory responses, and help to attain a state of homeostasis that favors treatment efficacy. However, the HDT drugs currently being assessed in combination with anti-TB chemotherapy still face the dilemmas arising from side effects and high costs. Natural products are well suited to compensate for these shortcomings by having gentle modulatory effects on the host immune responses with less immunopathological damage at a lower cost. In this review, we first summarize the profiles of anti-TB immunology and the characteristics of HDT. Then, we focus on the rationale and challenges of developing and implementing natural products-based HDT. A succinct report of the medications currently being evaluated in clinical trials and preclinical studies is provided. This review aims to promote target-based screening and accelerate novel TB drug discovery.
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Affiliation(s)
- Xuejiao Huang
- Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 201508, China
| | - Douglas B Lowrie
- Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 201508, China
| | - Xiao-Yong Fan
- Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 201508, China.
| | - Zhidong Hu
- Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai 201508, China.
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17
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Ferreira FM, Gomes SV, Carvalho LCF, de Alcantara AC, da Cruz Castro ML, Perucci LO, Pio S, Talvani A, de Abreu Vieira PM, Calsavara AJC, Costa DC. Potential of piperine for neuroprotection in sepsis-associated encephalopathy. Life Sci 2024; 337:122353. [PMID: 38104862 DOI: 10.1016/j.lfs.2023.122353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 12/11/2023] [Accepted: 12/12/2023] [Indexed: 12/19/2023]
Abstract
AIMS Sepsis-associated encephalopathy (SAE) is a common complication that increases mortality and leads to long-term cognitive impairment in sepsis survivors. However, no specific or effective therapy has been identified for this complication. Piperine is an alkaloid known for its anti-inflammatory, antioxidant, and neuroprotective properties, which are important characteristics for treatment of SAE. The objective of this study was to evaluate the neuroprotective effect of piperine on SAE in C57BL/6 mice that underwent cecum ligation and perforation surgery (CLP). MAIN METHODS C57BL/6 male mice were randomly assigned to groups that underwent SHAM surgery or CLP. Mice in the CLP group were treated with piperine at doses of 20 or 40 mg/kg for short- (5 days) or long-term (10 days) periods after CLP. KEY FINDINGS Our results revealed that untreated septic animals exhibited increased concentrations of IL-6, TNF, VEGF, MMP-9, TBARS, and NLRP3, and decreased levels of BDNF, sulfhydryl groups, and catalase in the short term. Additionally, the levels of carbonylated proteins and degenerated neuronal cells were increased at both time points. Furthermore, short-term and visuospatial memories were impaired. Piperine treatment reduced MMP-9 activity in the short term and decreased the levels of carbonylated proteins and degenerated neuronal cells in the long term. It also lowered IL-6 and TBARS levels at both time points evaluated. Moreover, piperine increased short-term catalase and long-term BDNF factor levels and improved memory at both time points. SIGNIFICANCE In conclusion, our data demonstrate that piperine exerts a neuroprotective effect on SAE in animals that have undergone CLP.
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Affiliation(s)
- Flavia Monteiro Ferreira
- Laboratory of Metabolic Biochemistry (LBM), Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Sttefany Viana Gomes
- Laboratory of Metabolic Biochemistry (LBM), Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Luana Cristina Faria Carvalho
- Laboratory of Metabolic Biochemistry (LBM), Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Ana Carolina de Alcantara
- Laboratory of Cognition and Health (LACOS), School of Medicine, Department of Pediatric and Adult Clinics (DECPA), Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Maria Laura da Cruz Castro
- Laboratory of Metabolic Biochemistry (LBM), Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Luiza Oliveira Perucci
- Laboratory of Immunobiology of Inflammation, Department of Biological Sciences (DECBI), Graduate Program in Health and Nutrition, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Sirlaine Pio
- Laboratory of Immunobiology of Inflammation, Department of Biological Sciences (DECBI), Graduate Program in Health and Nutrition, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - André Talvani
- Laboratory of Immunobiology of Inflammation, Department of Biological Sciences (DECBI), Graduate Program in Health and Nutrition, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Paula Melo de Abreu Vieira
- Morphopathology Laboratory, Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Allan Jefferson Cruz Calsavara
- Laboratory of Cognition and Health (LACOS), School of Medicine, Department of Pediatric and Adult Clinics (DECPA), Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil
| | - Daniela Caldeira Costa
- Laboratory of Metabolic Biochemistry (LBM), Department of Biological Sciences (DECBI), Graduate Program in Biological Sciences, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil.
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Warerkar OD, Mudliar NH, Momin MM, Singh PK. Targeting Amyloids with Coated Nanoparticles: A Review on Potential Combinations of Nanoparticles and Bio-Compatible Coatings. Crit Rev Ther Drug Carrier Syst 2024; 41:85-119. [PMID: 37938191 DOI: 10.1615/critrevtherdrugcarriersyst.2023046209] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023]
Abstract
Amyloidosis is the major cause of many neurodegenerative diseases, such as, Alzheimer's and Parkinson's where the misfolding and deposition of a previously functional protein make it inept for carrying out its function. The genesis of amyloid fibril formation and the strategies to inhibit it have been studied extensively, although some parts of this puzzle still remain unfathomable to date. Many classes of molecules have been explored as potential drugs in vitro, but their inability to work in vivo by crossing the blood-brain-barrier has made them an inadequate treatment option. In this regard, nanoparticles (NPs) have turned out to be an exciting alternative because they could overcome many drawbacks of previously studied molecules and provide advantages, such as, greater bioavailability of molecules and target-specific delivery of drugs. In this paper, we present an overview on several coated NPs which have shown promising efficiency in inhibiting fibril formation. A hundred and thirty papers published in the past two decades have been comprehensively reviewed, which majorly encompass NPs comprising different materials like gold, silver, iron-oxide, poly(lactic-co-glycolic acid), polymeric NP, etc., which are coated with various molecules of predominantly natural origin, such as different types of amino acids, peptides, curcumin, drugs, catechin, etc. We hope that this review will shed light on the advancement of symbiotic amalgamation of NPs with molecules from natural sources and will inspire further research on the tremendous therapeutic potential of these combinations for many amyloid-related diseases.
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Affiliation(s)
- Oshin D Warerkar
- SVKM's Shri C.B. Patel Research Centre, Vile Parle, Mumbai, Maharashtra 400056, India
| | - Niyati H Mudliar
- SVKM's Shri C.B. Patel Research Centre, Vile Parle, Mumbai, Maharashtra 400056, India
| | - Munira M Momin
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, Maharashtra, India; SVKM's Shri C.B. Patel Research Centre for Chemistry and Biological Sciences, Vile Parle (West), Mumbai, Maharashtra, 400056, India
| | - Prabhat K Singh
- Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India
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Lv Y, Zhu J, Huang S, Xing X, Zhou S, Yao H, Yang Z, Liu L, Huang S, Miao Y, Liu X, Fernie AR, Ding Y, Luo J. Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L. THE PLANT JOURNAL : FOR CELL AND MOLECULAR BIOLOGY 2024; 117:107-120. [PMID: 37753665 DOI: 10.1111/tpj.16476] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 09/01/2023] [Accepted: 09/11/2023] [Indexed: 09/28/2023]
Abstract
Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.
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Affiliation(s)
- Yuanyuan Lv
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
- Yazhouwan National Laboratory (YNL), Sanya, 572025, China
| | - Jinjin Zhu
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Sihui Huang
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Xiaoli Xing
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Shen Zhou
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Hui Yao
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Zhuang Yang
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Ling Liu
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Sishu Huang
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Yuanyuan Miao
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Xianqing Liu
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Alisdair R Fernie
- Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, 14476, Germany
| | - Yuanhao Ding
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
| | - Jie Luo
- School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China
- Yazhouwan National Laboratory (YNL), Sanya, 572025, China
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Rezaei S, Meftah HS, Ebtehajpour Y, Rahimi HR, Chamani J. Investigation on the Effect of Fluorescence Quenching of Calf Thymus DNA by Piperine: Caspase Activation in the Human Breast Cancer Cell Line Studies. DNA Cell Biol 2024; 43:26-38. [PMID: 38079271 DOI: 10.1089/dna.2023.0269] [Citation(s) in RCA: 35] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024] Open
Abstract
In this study, we determined the interaction of piperine and calf thymus DNA (ct DNA) in Tris-HCl buffer solution at pH = 6.8 and also evaluated the binding mechanism through the data of multi-spectroscopic techniques along with thermal melting and viscosity measurements. The outcomes of fluorescence quenching confirmed the occurrence of interactions between piperine and ctDNA and pointed out the role of piperine as the quencher. In addition, the KSV values were measured at three different temperatures of 298, 303, and 308 K to be 4.5 × 107 M-1, 5.65 × 107 M-1, and 9.36 × 107 M-1, respectively, which suggested the dominance of dynamic mechanism as the fluorescence quenching of piperine-ctDNA. The thermodynamic parameters revealed the predominance of hydrophobic forces in the interaction of ctDNA with piperine. According to the resonance light scattering data, the formation of a complex between piperine and ctDNA led to the creation of a larger particle. Ethidium bromide (EB) and acridine orange (AO) displacement studies, along with the ionic effects of NaCl and KI assessments, confirmed the interaction of piperine-ctDNA through a groove binding mode. The melting temperature assay of ctDNA upon the addition of piperine concentration indicated the probable groove binding of piperine to ctDNA, which was affirmed by relative viscosity measurement as well. The lack of detecting any alterations in the circular dichroism (CD) spectrum of CD investigation verified as a characteristic sign of groove binding mechanism and also confirmed all the experimental results with regard to the binding of piperine-ctDNA complex. Next to observing a concentration and time-dependent cytotoxicity in MDA-MB-231 cells, the impact of piperine on increasing lipid peroxidation and decreasing the activity of superoxide dismutase was also noticed. Apparently, piperine is capable of inducing caspase-3 activity as well.
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Affiliation(s)
- Sakineh Rezaei
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Hoda-Sadat Meftah
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Yasamin Ebtehajpour
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Hamid Reza Rahimi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jamshidkhan Chamani
- Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
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García-Gavilán JF, Babio N, Toledo E, Semnani-Azad Z, Razquin C, Dennis C, Deik A, Corella D, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Lapetra J, Lamuela-Raventos R, Clish C, Ruiz-Canela M, Martínez-González MÁ, Hu F, Salas-Salvadó J, Guasch-Ferré M. Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease. Cardiovasc Diabetol 2023; 22:340. [PMID: 38093289 PMCID: PMC10720204 DOI: 10.1186/s12933-023-02066-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/14/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD. METHODS The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models. RESULTS We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence. CONCLUSIONS This study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence. TRIAL REGISTRATION The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).
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Affiliation(s)
- Jesús F García-Gavilán
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
| | - Nancy Babio
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Estefanía Toledo
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain
| | - Zhila Semnani-Azad
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Cristina Razquin
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain
| | | | - Amy Deik
- The Broad Institute of Harvard and MIT, Boston, MA, USA
| | - Dolores Corella
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Ramón Estruch
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
- Institut de Nutrició I Seguretat Alimentària (INSA-UB), Universitat de Barcelona, Barcelona, Spain
| | - Emilio Ros
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Lipid Clinic, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Montserrat Fitó
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain
| | - Fernando Arós
- Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, 01009, Vitoria-Gasteiz, Spain
| | - Miquel Fiol
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Plataforma de Ensayos Clínicos, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, 07120, Palma, Spain
| | - José Lapetra
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Seville, Spain
| | - Rosa Lamuela-Raventos
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Institut de Nutrició I Seguretat Alimentària (INSA-UB), Universitat de Barcelona, Barcelona, Spain
- Polyphenol Research Group, Departament de Nutrició, Ciències de L'Alimentació I Gastronomia, Universitat de Barcelon (UB), Av. de Joan XXII, 27-31, 08028, Barcelona, Spain
| | - Clary Clish
- The Broad Institute of Harvard and MIT, Boston, MA, USA
| | - Miguel Ruiz-Canela
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain
| | - Miguel Ángel Martínez-González
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Frank Hu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jordi Salas-Salvadó
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
| | - Marta Guasch-Ferré
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Øster Farimagsgade 5, 1014, Copenhagen, Denmark.
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Usmani K, Jain SK, Yadav S. Mechanism of action of certain medicinal plants for the treatment of asthma. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116828. [PMID: 37369335 DOI: 10.1016/j.jep.2023.116828] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/06/2023] [Accepted: 06/20/2023] [Indexed: 06/29/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Asthma is often treated and prevented using the pharmacological properties of traditional medicinal plants. These healthcare systems are among the most well-known, conveniently accessible, and economically priced in India and several other Asian countries. Traditional Indian Ayurvedic plants have the potential to be used as phyto-therapeutics, to create novel anti-asthmatic drugs, and as a cost-effective source of pharmaceuticals. Current conventional therapies have drawbacks, including serious side effects and expensive costs that interfere with treatment compliance and affect the patient's quality of life. The primary objective of the article is to comprehensively evaluate the advancement of research on the protective phytochemicals of traditional plants that target immune responses and signaling cascades in inflammatory experimental asthma models. The study would assist in paving the way for the creation of natural phytomedicines that are protective, anti-inflammatory, and immunomodulatory against asthma, which may then be used in individualized asthma therapy. AIM OF THE STUDY The study demonstrates the mechanisms of action of phytochemicals present in traditional medicinal plants, diminish pulmonary disorder in both in vivo and in vitro models of asthma. MATERIALS AND METHODS A comprehensive review of the literature on conventional plant-based asthma therapies was performed from 2006 to 2022. The study uses authoritative scientific sources such as PubMed, PubChem Compound, Wiley Online Library, Science Direct, Springer Link, and Google Scholar to collect information on potential phytochemicals and their mechanisms of action. World Flora Online (http://www.worldfloraonline.org) and Plants of the World Online (https://wcsp.science.kew.org) databases were used for the scientific names of medicinal plants. RESULTS The study outlines the phytochemical mechanisms of some traditional Ayurveda botanicals used to treat asthma. Active phytochemicals including curcumin, withaferin-A, piperine, glabridin, glycyrrhizin, 18β-glycyrrhetinic acid, trans-cinnamaldehyde, α-hederin, thymoquinone, eugenol, [6]-shogoal, and gingerol may treat asthma by controlling inflammation and airway remodeling. The study concluded that certain Ayurvedic plants' phytochemicals have the ability to reduce inflammation and modulate the immune system, that can effectively cure asthma. CONCLUSION Plants used in traditional Ayurvedic medicine have been utilized for millennia, advocating phyto-therapy as a treatment for a variety of illnesses. A theoretical foundation for the use of cutting-edge asthma treatments has been built with the growth of experimental research on traditional phytochemicals. In-depth phytochemical research for the treatment of asthma using Indian Traditional Ayurvedic herbs is compiled in the study. The approach for preventative therapeutics and cutting-edge alternatives to battle the molecular pathways in the pathophysiology of asthma are the key themes of the study. The phytochemical mechanism of action of traditional Ayurvedic herbs is explained to get the attention of the pharmaceutical industry so they can make future anti-asthma drugs for personalized asthma care in the community. The study develops strategies for customized phyto-therapeutics, concentrating on low-cost, side-effect-free approaches that employ bioactive phytochemicals from plants as the major source of effective anti-asthmatic therapy.
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Affiliation(s)
- Kainat Usmani
- Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, 470003, MP, India.
| | - Subodh Kumar Jain
- Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, 470003, MP, India.
| | - Shweta Yadav
- Department of Zoology, School of Biological Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, 470003, MP, India.
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Xu W, Xiao Y, Zheng L, Xu M, Jiang X, Wang L. Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein. Pharmaceutics 2023; 15:2703. [PMID: 38140044 PMCID: PMC10747290 DOI: 10.3390/pharmaceutics15122703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/24/2023] [Accepted: 11/26/2023] [Indexed: 12/24/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP's inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro.
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Affiliation(s)
- Wenwen Xu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Yumeng Xiao
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Liang Zheng
- Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China;
| | - Mingyu Xu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Xuehua Jiang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
| | - Ling Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610064, China; (W.X.); (Y.X.); (M.X.); (X.J.)
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24
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Jian P, Kumano T, Kimura M, Kurisaki M, Hashimoto Y, Kobayashi M. Biodegradation of the methylenedioxyphenyl group in piperine and its derivatives: discovery of a novel methylenetransferase in an actinomycete. Appl Environ Microbiol 2023; 89:e0114523. [PMID: 37874289 PMCID: PMC10686052 DOI: 10.1128/aem.01145-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/12/2023] [Indexed: 10/25/2023] Open
Abstract
IMPORTANCE Pepper is a spice that has been used worldwide since the Age of Discovery. The substance that is responsible for the spiciness in pepper is piperine, a type of alkaloid. It has never been reported how piperine is degraded by microorganisms. In this study, we discovered a bacterium in the soil that is capable of catabolizing piperine as its sole nitrogen source. Furthermore, we discovered the enzyme involved in piperine metabolism. This enzyme decomposed the methylenedioxyphenyl group, which is the common structure in various plant-derived bioactive compounds such as sesamin, piperonal, safrole, and berberin. By utilizing this enzyme, piperine can be converted into a useful antioxidant compound. The findings about previously unknown metabolic pathways in nature can lead to the discovery of new enzymes and provide methods for the enzymatic synthesis of useful compounds.
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Affiliation(s)
- Pu Jian
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Takuto Kumano
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Mio Kimura
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Makoto Kurisaki
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Yoshiteru Hashimoto
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Michihiko Kobayashi
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Microbiology Research Center for Sustainability, University of Tsukuba, Tsukuba, Ibaraki, Japan
- Center for Quantum and Information Life Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
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Qiu C, Zhang JZ, Wu B, Xu CC, Pang HH, Tu QC, Lu YQ, Guo QY, Xia F, Wang JG. Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines. J Nanobiotechnology 2023; 21:456. [PMID: 38017573 PMCID: PMC10685519 DOI: 10.1186/s12951-023-02165-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/16/2023] [Indexed: 11/30/2023] Open
Abstract
Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.
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Affiliation(s)
- Chong Qiu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jun Zhe Zhang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Bo Wu
- Department of Traditional Chinese Medical Science, Sixth Medical Center of the Chinese PLA General Hospital, Beijing, 100037, China
| | - Cheng Chao Xu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Huan Huan Pang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Qing Chao Tu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Yu Qian Lu
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Qiu Yan Guo
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Fei Xia
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
| | - Ji Gang Wang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore.
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Wu R, Zhao J, Wei P, Tang M, Ma Z, Zhao Y, Du L, Wan L. Piper nigrum Extract Inhibits the Growth of Human Colorectal Cancer HT-29 Cells by Inducing p53-Mediated Apoptosis. Pharmaceuticals (Basel) 2023; 16:1325. [PMID: 37765133 PMCID: PMC10537627 DOI: 10.3390/ph16091325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/14/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract with the second highest mortality rate globally. Piper nigrum is a widely used traditional medicinal plant, exhibiting antitumor activity against various tumor cells. At present, research on the effect of Piper nigrum on CRC is limited to in vitro cytotoxicity, lacking comprehensive mechanism investigations. This study aimed to explore the inhibitory effect and mechanism of Piper nigrum extract (PNE) on HT-29 cells. Firstly, we identified the chemical components of PNE. Then, MTT assay, colony formation assay, JC-1 staining, and flow cytometry were used to analyze the effect of PNE on HT-29 cells in vitro. A xenograft model, histopathological examination, immunohistochemistry, and western blot were used to evaluate the tumor growth inhibitory activity and mechanism of PNE in vivo. The results indicated that PNE could inhibit cell proliferation and colony formation, reduce mitochondrial membrane potential, induce cell apoptosis in vitro, and inhibit tumor growth in vivo. Furthermore, PNE could regulate p53 and its downstream proteins, and subsequently activate the caspase-3 pathway. In summary, PNE probably induced apoptosis of HT-29 cells through the mitochondrial pathway mediated by p53. All these results suggested that PNE might be a potential natural-origin anti-CRC drug candidate.
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Affiliation(s)
- Rui Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
| | - Jiajia Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
| | - Panhong Wei
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
| | - Minghai Tang
- State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China; (M.T.); (Z.M.)
| | - Ziyan Ma
- State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China; (M.T.); (Z.M.)
| | - Yunyan Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
| | - Leilei Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
| | - Li Wan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (R.W.); (J.Z.); (P.W.); (Y.Z.); (L.D.)
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Kotb RR, Afifi AM, El-Houseini ME, Ezz-Elarab M, Basalious EB, Omran MM, Abdellateif MS. The potential immuno-stimulating effect of curcumin, piperine, and taurine combination in hepatocellular carcinoma; a pilot study. Discov Oncol 2023; 14:169. [PMID: 37704828 PMCID: PMC10499730 DOI: 10.1007/s12672-023-00785-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/04/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND This is a phase II clinical trial to investigate the immunotherapeutic effect of Curcumin, Piperine, and Taurine (CPT) combination in hepatocellular carcinoma (HCC). METHODS Twenty-six HCC patients aged (50-80 years) were recruited for administration of a daily dose of 5 g of curcumin, 50 mg of piperine, and 500 mg of taurine divided into three doses for successive 3 months. The three components (CPT) were prepared in one capsule. Patients were assessed after each month (cycle) for the plasma levels of CD4, CD8, CD25, Interleukins-2 (IL-2), IL-6, IL-12, Interferon-gamma (IFN- γ), Lactate dehydrogenase (LDH), and Vascular endothelial growth factor (VEGF), FOXP3 mRNA, and miRNA 21. RESULTS There was a significant increase in the plasma levels of CD4 and CD8, while a significant decrease in the CD25 level after the second and third cycles compared to the baseline level [P < 0.001 for both]. Also, there was a significant increase in the plasma levels of IL-2, IL-12, and IFN-γ [ P = 0.001, P = 0.006, and P = 0.029; respectively], while there was a significant decrease in IL-6, VEGF-α, LDH, and Alpha-fetoprotein (AFP) after CPT administration compared to the baseline levels [P < 0.001, P < 0.001, P = 0.020, and P = 0.004; respectively]. The expression level of miRNA-21 was significantly decreased after CPT administration compared to the baseline level [5.5±0.88, 4.1±0.78, 3±0.75, and 2.5±0.76; respectively, P<0.001]. Though there was a noticeable decrease in the FOXP3 expression after each cycle, however, it didn't reach a significant level [5.3±0.8, 4.2±0.76, 3.2±0.67, and 2.5±0.79; respectively, P=0.184]. CONCLUSION CPT could exhibit a potential immune-stimulating effect in HCC patients. The current trial had been registered at the National Hepatology and Tropical Medicine Research Institute (NHTMRI), with a registration number of NHTMRI-IRB 2-21 on 5th January 2021.
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Affiliation(s)
- Raghda R Kotb
- Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt
| | - Ahmed M Afifi
- Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt
| | - Motawa E El-Houseini
- Medical Biochemistry and molecular biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mohamed Ezz-Elarab
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad B Basalious
- Pharmaceutics and Industrial Pharmacy department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt
| | - Mervat M Omran
- Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt
- Biological science division, University of Chicago, Chicago, IL, USA
| | - Mona S Abdellateif
- Medical Biochemistry and molecular biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
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Kiranmayee M, Rajesh N, Vidya Vani M, Khadri H, Mohammed A, Chinni SV, Ramachawolran G, Riazunnisa K, Moussa AY. Green synthesis of Piper nigrum copper-based nanoparticles: in silico study and ADMET analysis to assess their antioxidant, antibacterial, and cytotoxic effects. Front Chem 2023; 11:1218588. [PMID: 37736256 PMCID: PMC10509375 DOI: 10.3389/fchem.2023.1218588] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 08/14/2023] [Indexed: 09/23/2023] Open
Abstract
Nanobiotechnology is a popular branch of science that is gaining interest among scientists and researchers as it allows for the green manufacturing of nanoparticles by employing plants as reducing agents. This method is safe, cheap, reproducible, and eco-friendly. In this study, the therapeutic property of Piper nigrum fruit was mixed with the antibacterial activity of metallic copper to produce copper nanoparticles. The synthesis of copper nanoparticles was indicated by a color change from brown to blue. Physical characterization of Piper nigrum copper nanoparticles (PN-CuNPs) was performed using UV-vis spectroscopy, FT-IR, SEM, EDX, XRD, and Zeta analyzer. PN-CuNPs exhibited potential antioxidant, antibacterial, and cytotoxic activities. PN-CuNPs have shown concentration-dependent, enhanced free radical scavenging activity, reaching maximum values of 92%, 90%, and 86% with DPPH, H2O2, and PMA tests, respectively. The antibacterial zone of inhibition of PN-CuNPs was the highest against Staphylococcus aureus (23 mm) and the lowest against Escherichia coli (10 mm). PN-CuNPs showed 80% in vitro cytotoxicity against MCF-7 breast cancer cell lines. Furthermore, more than 50 components of Piper nigrum extract were selected and subjected to in silico molecular docking using the C-Docker protocol in the binding pockets of glutathione reductase, E. coli DNA gyrase topoisomerase II, and epidermal growth factor receptor (EGFR) tyrosine to discover their druggability. Pipercyclobutanamide A (26), pipernigramide F (32), and pipernigramide G (33) scored the highest Gibbs free energy at 50.489, 51.9306, and 58.615 kcal/mol, respectively. The ADMET/TOPKAT analysis confirmed the favorable pharmacokinetics, pharmacodynamics, and toxicity profiles of the three promising compounds. The present in silico analysis helps us to understand the possible mechanisms behind the antioxidant, antibacterial, and cytotoxic activities of CuNPs and recommends them as implicit inhibitors of selected proteins.
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Affiliation(s)
- Modumudi Kiranmayee
- Department Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, India
| | - Nambi Rajesh
- Department Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, India
| | - M. Vidya Vani
- Department Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, India
| | - Habeeb Khadri
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia
| | - Arifullah Mohammed
- Department of Agriculture Science, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli, Malaysia
| | - Suresh V. Chinni
- Department of Biochemistry, Faculty of Medicine, Bioscience, and Nursing, MAHSA University, Jenjarom, Malaysia
- Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, India
| | | | - Khateef Riazunnisa
- Department Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, India
| | - Ashaimaa Y. Moussa
- Department of Pharmacognosy, Faculty of Pharmacy, Ain shams University, Cairo, Egypt
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Panchakul C, Thongdeeying P, Itharat A, Pipatrattanaseree W, Kongkwamcharoen C, Davies NM. Analytical determination, antioxidant and anti-inflammatory activities of Bhamrung-Lohit a traditional Thai medicine. Res Pharm Sci 2023; 18:449-467. [PMID: 37614616 PMCID: PMC10443669 DOI: 10.4103/1735-5362.378091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 01/25/2023] [Accepted: 02/28/2023] [Indexed: 08/25/2023] Open
Abstract
Background and purpose Bhamrung-Lohit (BRL) remedy is a traditional Thai medicine (TTM). There are few reports of biological activity, the activity of its constituent plants, or quantitative analytical methods for the content of phytochemicals. In this study, we investigated antioxidant, anti-inflammatory activity, and total phenolic and flavonoid content and validated a new analytical method for BRL. Experimental approach Antioxidant activity was evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging. The cellular antioxidant activity was evaluated by inhibition of the superoxide anion (O2●-) production from HL-60 cells and anti-inflammatory activity by inhibition of nitric oxide production in RAW264.7 cells. The total phenolic and flavonoid contents were analyzed using the Folin-Ciocalteu method and an aluminum chloride colorimetric assay, respectively. Validated analytical procedures were conducted according to International Conference on Harmonization (ICH) guidelines. Findings/Results An ethanolic extract of BRL exerted potent DPPH radical scavenging activity and moderate antioxidant and anti-inflammatory activity. Caesalpinia sappan exerted the greatest effect and the highest content of total phenolics and flavonoids. The HPLC method validated parameters that complied with ICH requirements. Each peak showed selectivity with a baseline resolution of 2.0 and precision was less than 2.0% CV. The linearity of all compounds was > 0.999 and the recovery % was within 98.0%-102.0%. The validated results demonstrated specificity/selectivity, linearity, precision, and accuracy with appropriate LOD and LOQ. Conclusion and implication BRL remedy, a TTM demonstrated antioxidant and anti-inflammatory properties. This study is the first report on the biological activity and the validation of an HPLC method for BRL remedy.
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Affiliation(s)
- Chitralada Panchakul
- Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand
| | - Pakakrong Thongdeeying
- Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120 Thailand
- Center of Excellence in Applied Thai Traditional Medicine Research, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand
| | - Arunporn Itharat
- Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120 Thailand
- Center of Excellence in Applied Thai Traditional Medicine Research, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand
| | - Weerachai Pipatrattanaseree
- Regional Medical Science Center 12 Songkhla, Department of Medical Sciences, Ministry of Public Health, Songkhla, 90100, Thailand
| | - Chonthicha Kongkwamcharoen
- Graduate School of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand
| | - Neal M. Davies
- Faculty of Pharmacy and Pharmaceutical Sciences, Katz Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta T6G2E1, Canada
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Balakrishnan R, Azam S, Kim IS, Choi DK. Neuroprotective Effects of Black Pepper and Its Bioactive Compounds in Age-Related Neurological Disorders. Aging Dis 2023; 14:750-777. [PMID: 37191428 PMCID: PMC10187688 DOI: 10.14336/ad.2022.1022] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 10/22/2022] [Indexed: 11/18/2022] Open
Abstract
Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders whose risk increases with age. The main pathological hallmarks of ANDs include behavioral changes, excessive oxidative stress, progressive functional declines, impaired mitochondrial function, protein misfolding, neuroinflammation, and neuronal cell death. Recently, efforts have been made to overcome ANDs because of their increased age-dependent prevalence. Black pepper, the fruit of Piper nigrum L. in the family Piperaceae, is an important food spice that has long been used in traditional medicine to treat various human diseases. Consumption of black pepper and black pepper-enriched products is associated with numerous health benefits due to its antioxidant, antidiabetic, anti-obesity, antihypertensive, anti-inflammatory, anticancer, hepatoprotective, and neuroprotective properties. This review shows that black pepper's major bioactive neuroprotective compounds, such as piperine, effectively prevent AND symptoms and pathological conditions by modulating cell survival signaling and death. Relevant molecular mechanisms are also discussed. In addition, we highlight how recently developed novel nanodelivery systems are vital for improving the efficacy, solubility, bioavailability, and neuroprotective properties of black pepper (and thus piperine) in different experimental AND models, including clinical trials. This extensive review shows that black pepper and its active ingredients have therapeutic potential for ANDs.
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Affiliation(s)
- Rengasamy Balakrishnan
- Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.
- Department of Biotechnology, College of Biomedical and Health Science, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea.
| | - Shofiul Azam
- Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.
| | - In-Su Kim
- Department of Biotechnology, College of Biomedical and Health Science, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea.
| | - Dong-Kug Choi
- Department of Applied Life Science, Graduate School, BK21 Program, Konkuk University, Chungju 27478, Korea.
- Department of Biotechnology, College of Biomedical and Health Science, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea.
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Perić A, Sotirović J, Jovančević L, Medić SP. Occupational rhinitis caused by hypersensitivity to black pepper. Occup Med (Lond) 2023; 73:167-169. [PMID: 36255261 DOI: 10.1093/occmed/kqac106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Black pepper (Piper nigrum) rarely leads to allergic inflammation of the nasal mucosa. This is a presentation of a 52-year-old female worker exposed to black pepper dust for 10 years suffering from allergic rhinitis and chronic rhinosinusitis. She complained of nasal obstruction, rhinorrhoea, and a weakened sense of smell. Clinical examination showed the bilateral presence of polypoid lesions arising from the middle turbinate. After surgery, histopathological examination confirmed the diagnosis of inflammatory nasal polyps. Duration of exposure to black pepper and serum concentration of specific immunoglobulin E antibodies indicating work-related exposure would support a causal link between exposure to these factors and the development of chronic inflammation in the nasal mucosa. Inflammatory nasal polyps may be noted in the nasal cavity in workers exposed to black pepper dust. The absence of exposure to black pepper resulted in no detectable circulating antibodies one year after the change of workplace.
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Affiliation(s)
- Aleksandar Perić
- Department of Otorhinolaryngology, Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia
| | - Jelena Sotirović
- Department of Otorhinolaryngology, Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia
| | - Ljiljana Jovančević
- Clinic of Otorhinolaryngology and Head and Neck Surgery, University Clinical Centre of Vojvodina, Novi Sad, Serbia
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
| | - Sonja Peričević Medić
- Department of Occupational Medicine, Institute of Occupational Health of Novi Sad, Novi Sad, Serbia
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
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Castillo E, González-Rosende ME, Martínez-Solís I. The Use of Herbal Medicine in the Treatment of Vitiligo: An Updated Review. PLANTA MEDICA 2023; 89:468-483. [PMID: 36379447 DOI: 10.1055/a-1855-1839] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Vitiligo is a chronic disease of unknown etiology that causes progressive cutaneous depigmentation. Current pharmacological treatments have limited success and present significant risks. Many efforts have been made in recent years to explore new anti-vitiligo therapeutic strategies, including herbal-based therapies. The objective of the present review is to provide an updated overview on the most frequently used medicinal plants in the treatment of vitiligo. A bibliographical search was carried out in scientific databases Pubmed, Scifinder, Scopus, Google Scholar, and Medline up to October 2021 using the descriptors vitiligo, herbal, medicinal plants, and alternative therapies. In our search, the highest number of published studies comprise plants commonly used in traditional herbal medicine, highlighting the usefulness of ethnopharmacology in the discovery of new therapeutic agents. The review outlines current understanding and provides an insight into the role of psoralens and khellin (photosensitizing agents obtained from plants such as Cullen corylifolium or Ammi visnaga). The paper also describes other traditional herbs such as Ginkgo biloba, Phlebodium aureum, Piper nigrum, Picrorhiza kurroa, and Baccharoides anthelmintica that can likewise act as potential therapeutical agents. Based on our findings, photosensitizing agents in combination with phototherapy, the association of oral Phebodium aureum with phototherapies as well as oral G. biloba in monotherapy showed greater scientific evidence as therapeutic options. The research results emphasize that further investigation in this area is merited. More long-term follow up clinical trials and higher quality randomized trials are needed.
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Affiliation(s)
- Encarna Castillo
- Department of Pharmacy, Faculty of Health Sciences, University CEU-Cardenal Herrera, CEU Universities, Alfara del Patriarca, Valencia (Spain)
| | - María Eugenia González-Rosende
- Department of Pharmacy, Faculty of Health Sciences, University CEU-Cardenal Herrera, CEU Universities, Alfara del Patriarca, Valencia (Spain)
| | - Isabel Martínez-Solís
- Department of Pharmacy, Faculty of Health Sciences, University CEU-Cardenal Herrera, CEU Universities, Alfara del Patriarca, Valencia (Spain)
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33
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Shanmugam M, Subramanian S, Ramachandran S. Method development and validation for quantification of six bioactive compounds (andrographolide, columbin, piperine, gallic, paracoumaric and oleanolic acids) by HPTLC. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2023; 20:137-145. [PMID: 36384045 DOI: 10.1515/jcim-2022-0135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 11/02/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVES During the spread of pandemic diseases, immunity boosting herbal drugs are taken as a preventive medicine. Kapacurak Kuṭinīr Cūraṇam is a Siddha drug used for flu like viral infections, cold and fever. Developing an analytical method to estimate the content of active phytoconstituents in such antiviral immune boosting drug will be useful in the phyto pharmaceutical industry. METHODS A precise, reliable and sensitive ordinary phase high performance thin layer chromatography (HPTLC) method has been developed and validated for identification and simultaneous estimation of six bioactive components namely like andrographolide, columbin, gallic acid, ρ-coumaric acid, piperine and oleanolic acid from any Indian traditional medicine, medicinal plant, drugs and food materials etc. The separation was achieved on silica gel 60F254 TLC plates using toluene: ethyl acetate: formic acid (7:3:0.5, v/v) as mobile phase. The gallic acid, ρ-coumaric acid, piperine markers were estimated using the densitometric scanning in absorption mode at 254 nm. The densitometric scanning was done after derivatization (vanillin-sulphuric acid reagent) at λ=520 nm for andrographolide, columbin and oleanolic acid. RESULTS The linear regression analysis data for the calibration plots showed a correlation coefficient in the concentration range 1-5 μg per band for the bioactive markers with respect to area. The method was validated for accuracy, precision, limit of detection (LOD), and quantitation of limit (LOQ). CONCLUSIONS Developed method was accurate, precise and fast to ensure the quality of Kapacurak Kuṭinīr Cūraṇam.
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Affiliation(s)
- Murugammal Shanmugam
- Department of Chemistry, Siddha Central Research Institute (Central Council for Research in Siddha, Ministry of AYUSH, Government of India), Chennai, Tamil Nadu, India
| | - Subashini Subramanian
- Department of Chemistry, Siddha Central Research Institute (Central Council for Research in Siddha, Ministry of AYUSH, Government of India), Chennai, Tamil Nadu, India
| | - Shakila Ramachandran
- Department of Chemistry, Siddha Central Research Institute (Central Council for Research in Siddha, Ministry of AYUSH, Government of India), Chennai, Tamil Nadu, India
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Heidari H, Bagherniya M, Majeed M, Sathyapalan T, Jamialahmadi T, Sahebkar A. Curcumin-piperine co-supplementation and human health: A comprehensive review of preclinical and clinical studies. Phytother Res 2023; 37:1462-1487. [PMID: 36720711 DOI: 10.1002/ptr.7737] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 01/08/2023] [Accepted: 01/09/2023] [Indexed: 02/02/2023]
Abstract
Curcumin is extracted from the rhizomes Curcuma longa L. It is known for its anti-inflammatory and anti-oxidant activities. Despite its safety and potential for use against various diseases, curcumin's utility is restricted due to its low oral bioavailability. Co-administration of curcumin along with piperine could potentially improve the bioavailability of curcumin. The present review aimed to provide an overview of the efficacy and safety of curcumin-piperine co-supplementation in human health. The findings of this comprehensive review show the beneficial effects of curcumin-piperine in improving glycemic indices, lipid profile and antioxidant status in diabetes, improving the inflammatory status caused by obesity and metabolic syndrome, reducing oxidative stress and depression in chronic stress and neurological disorders, also improving chronic respiratory diseases, asthma and COVID-19. Further high-quality clinical trial studies are needed to firmly establish the clinical efficacy of the curcumin-piperine supplement.
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Affiliation(s)
- Hajar Heidari
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Thozhukat Sathyapalan
- Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom
| | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.,Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Impact of Dietary Supplementation of Spice Extracts on Growth Performance, Nutrient Digestibility and Antioxidant Response in Broiler Chickens. Animals (Basel) 2023; 13:ani13020250. [PMID: 36670790 PMCID: PMC9854518 DOI: 10.3390/ani13020250] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 12/30/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
This study aimed to investigate the effects of supplementing broiler chicken diets with an encapsulated product based on capsicum and other spice (black pepper and ginger) extracts on growth performance, nutrient digestibility, digestive enzyme activity and antioxidant response. To this end, 480 1-day-old male chicks were randomly assigned to two experimental treatments (12 pens/treatment; 20 birds/pen). Dietary treatments included a basal diet with no additives (CONTROL) and a basal diet supplemented with 250 ppm of the spice additive (SPICY; Lucta S.A., Spain). Supplementation of SPICY increased body weight (p < 0.05) compared with CONTROL at 7 d of age and improved (p < 0.01) ADG from 0 to 7 d of age. The apparent ileal digestibility of dry matter, gross energy and crude protein was higher (p < 0.05) in birds fed the SPICY diet compared with the CONTROL diet. Birds fed SPICY showed lower (p < 0.05) plasma catalase (CAT) activity, and the hepatic gene expression of CAT and Nrf2 was down-regulated (p < 0.05) compared with the CONTROL. In conclusion, the inclusion of 250 ppm of SPICY in broiler diets improved growth performance at 7 d of age and positively affected nutrient digestibility and antioxidant response.
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Haffner JJ, Katemauswa M, Kagone TS, Hossain E, Jacobson D, Flores K, Parab AR, Obregon-Tito AJ, Tito RY, Reyes LM, Troncoso-Corzo L, Guija-Poma E, Meda N, Carabin H, Honap TP, Sankaranarayanan K, Lewis CM, McCall LI. Untargeted Fecal Metabolomic Analyses across an Industrialization Gradient Reveal Shared Metabolites and Impact of Industrialization on Fecal Microbiome-Metabolome Interactions. mSystems 2022; 7:e0071022. [PMID: 36416540 PMCID: PMC9765122 DOI: 10.1128/msystems.00710-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/01/2022] [Indexed: 11/24/2022] Open
Abstract
The metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas-the birthplace and the last continental expansion of our species, respectively-we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features such as amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, coanalyses with over 5,000 publicly available human fecal samples and cooccurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient. IMPORTANCE As the world becomes increasingly industrialized, understanding the biological consequences of these lifestyle shifts and what it means for past, present, and future human health is critical. Indeed, industrialization is associated with rises in allergic and autoimmune health conditions and reduced microbial diversity. Exploring these health effects on a chemical level requires consideration of human lifestyle diversity, but understanding the significance of any differences also requires knowledge of what molecular components are shared between human groups. Our study reveals the key chemistry of the human gut as defined by varied industrialization-based differences and ubiquitous shared features. Ultimately, these novel findings extend our knowledge of human molecular biology, especially as it is influenced by lifestyle and behavior, and provide steps toward understanding how human biology has changed over our species' history.
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Affiliation(s)
- Jacob J. Haffner
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | - Mitchelle Katemauswa
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
| | - Thérèse S. Kagone
- Burkina Faso Ministry of Health, Ouagadougou, Kadiogo, Burkina Faso
- Centre MURAZ Research Institute, Bobo-Dioulasso, Burkina Faso
| | - Ekram Hossain
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
| | - David Jacobson
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | - Karina Flores
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Biology, University of Oklahoma, Norman, Oklahoma, USA
| | - Adwaita R. Parab
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma, USA
| | - Alexandra J. Obregon-Tito
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | - Raul Y. Tito
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | | | | | - Emilio Guija-Poma
- Centro de Investigación de Bioquímica y Nutrición, Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Perú
| | - Nicolas Meda
- Burkina Faso Ministry of Health, Ouagadougou, Kadiogo, Burkina Faso
| | - Hélène Carabin
- Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
- Département de Pathologie et Microbiologie, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Quebec, Canada
- Département de Médecine Sociale et Préventive, École de Santé Publique de l’Université de Montréal, Montréal, Quebec, Canada
- Centre de Recherche en Santé Publique (CReSP) de l’Université de Montréal et du CIUSS du Centre Sud de Montréal, Montréal, Quebec, Canada
| | - Tanvi P. Honap
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | - Krithivasan Sankaranarayanan
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma, USA
| | - Cecil M. Lewis
- Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
| | - Laura-Isobel McCall
- Laboratories of Molecular Anthropology and Microbiome Research (LMAMR), University of Oklahoma, Norman, Oklahoma, USA
- Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, USA
- Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma, USA
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Ahmed MB, Islam SU, Alghamdi AAA, Kamran M, Ahsan H, Lee YS. Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation. Int J Mol Sci 2022; 23:15765. [PMID: 36555406 PMCID: PMC9779495 DOI: 10.3390/ijms232415765] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/02/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthetic and natural chemicals are effective for cancer chemoprevention, i.e., the use of exogenous medicine to inhibit or impede tumor development. They help regulate molecular pathways linked to the development and spread of cancer. They can enhance antioxidant status, inactivating carcinogens, suppressing proliferation, inducing cell cycle arrest and death, and regulating the immune system. While focusing on four main categories of plant-based anticancer agents, i.e., epipodophyllotoxin, camptothecin derivatives, taxane diterpenoids, and vinca alkaloids and their mode of action, we review the anticancer effects of phytochemicals, like quercetin, curcumin, piperine, epigallocatechin gallate (EGCG), and gingerol. We examine the different signaling pathways associated with cancer and how inflammation as a key mechanism is linked to cancer growth.
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Affiliation(s)
- Muhammad Bilal Ahmed
- BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Salman Ul Islam
- Department of Pharmacy, Cecos University, Peshawar, Street 1, Sector F 5 Phase 6 Hayatabad, Peshawar 25000, Pakistan
| | | | - Muhammad Kamran
- School of Molecular Sciences, The University of Western Australia, M310, 35 Stirling Hwy, Perth, WA 6009, Australia
| | - Haseeb Ahsan
- Department of Pharmacy, Faculty of Life and Environmental Sciences, University of Peshawar, Peshawar 25120, Pakistan
| | - Young Sup Lee
- BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
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Piperine attenuates hepatic steatosis and insulin resistance in high-fat diet-induced obesity in Sprague-Dawley rats. Nutr Res 2022; 108:9-21. [PMID: 36375392 DOI: 10.1016/j.nutres.2022.10.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 10/10/2022] [Accepted: 10/12/2022] [Indexed: 11/05/2022]
Abstract
Substantial evidence suggests that pepper consumption is associated with a reduced risk of obesity-related complications. However, whether piperine, the main component of pepper, improves obesity-induced hepatic lipid accumulation and insulin resistance and the action mechanism of piperine still remain unclear. We hypothesized that piperine attenuates high-fat diet (HFD)-induced obesity and improves the related metabolic complications in HFD-induced obese rats. Adult Sprague-Dawley (SD) male rats were fed a control diet (CON) or an HFD for 16 weeks. Obese rats were divided into 4 groups: HFD and HFD with daily gavage of piperine 2.7 mg/kg body weight (PIP-Low), 13.5 mg/kg body weight (PIP-Medium), and 27 mg/kg body weight (PIP-High) for another 8 weeks. Rats were euthanized after an 8-hour fast, and the liver, heart, kidney, and white adipose tissue were collected and stored at -80 °C. Piperine administration significantly reduced weight gain, plasma insulin, and glucose concentration. For oral piperine at a dose of 27 mg/kg body weight, body weight significantly decreased by 5.7% compared with that in the HFD group. Additionally, oral piperine administration considerably reduced serum triglyceride concentration. Furthermore, piperine administration reversed the HFD-induced downregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling molecules and increased the plasma levels of adiponectin and the messenger RNA expression of the adiponectin receptor; additionally, it increased the phosphorylation of phosphatidylinositol-3 kinase (PI3K) and protein kinase B. Overall, oral piperine administration reversed HFD-induced liver lipid accumulation and insulin resistance, possibly via the inactivation of adiponectin-AMPK and PI3K-Akt signaling. These findings imply that piperine could serve as an effective agent for healthy weight loss.
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Endah E, Wulandari F, Putri Y, Jenie RI, Meiyanto E. Piperine Increases Pentagamavunon-1 Anti-cancer Activity on 4T1 Breast Cancer Through Mitotic Catastrophe Mechanism and Senescence with Sharing Targeting on Mitotic Regulatory Proteins. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2022; 21:e123820. [PMID: 35765510 PMCID: PMC9191230 DOI: 10.5812/ijpr.123820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/11/2021] [Accepted: 09/12/2021] [Indexed: 06/15/2023]
Abstract
Pentagamavunon-1 performs more potent anti-cancer effects than curcumin against various cancer cells, but it remains to be optimized. Piperine shows the activity as an enhancer of a therapeutic agent. This study expects to achieve higher effectiveness of PGV-1 on 4T1 breast cancer cells through co-treatment with piperine with exploring the effect of cytotoxicity, mitotic catastrophe, cellular senescence, and target proteins of PGV-1 and piperine on the regulation of mitosis in TNBC cells (4T1). The assays emphasize MTT assay, May Grünwald-Giemsa staining, SA-β-galactosidase assay, and bioinformatics analysis, respectively, to elicit the respected activities. The results revealed that PGV-1 performed a cytotoxic effect with an IC50 value of 9 µM while piperine showed a lower cytotoxic effect with an IC50 value of 800 µM on 4T1 cells 24 h treatment. However, the combination treatment of both showed a synergistic cytotoxic enhancement effect with an average CI value < 1. Furthermore, the combination of PGV-1 and piperine induced mitotic catastrophe and senescence better than the single treatment. Treatment of 1 µM of PGV-1 and 400 µM of piperine increased the percentage of senescent cells by 33%. Bioinformatics analysis revealed that PGV-1 and piperine target proteins play a role in mitotic regulation, namely CDK1, KIF11, AURKA, AURKB, and PLK1, to contribute to mitotic catastrophe. Therefore, piperine increases the effectiveness of PGV-1 to suppress 4T1 cells growth synergistically that may occur through mitotic catastrophe and senescence targeting on mitotic regulatory proteins.
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Affiliation(s)
- Endah Endah
- Department of Biotechnology, Graduate School, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Febri Wulandari
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Yurananda Putri
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Riris Istighfari Jenie
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Edy Meiyanto
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, and Epithelial-Mesenchymal Transition by Modulating the SIRT1/Nrf2 Axis. Int J Mol Sci 2022; 23:ijms232314722. [PMID: 36499047 PMCID: PMC9740588 DOI: 10.3390/ijms232314722] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022] Open
Abstract
Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, i.n) were used to assess cytotoxicity, oxidative stress, epithelial−mesenchymal transition (EMT), Sirtuin1 (SIRT1), inflammation-related cellular signaling, and lung function. PIP treatment protects cells from CSE-induced lung epithelial cell death. PIP treatment restores the epithelial marker (p < 0.05) and decreases the mesenchymal, inflammatory markers (p < 0.05) in both in vitro and in vivo models. The PIP treatment improves the altered lung function (p < 0.05) in mice induced by CS exposure. Mechanistically, PIP treatment modulates SIRT1 thereby reducing the inflammatory markers such as IL-1β, IL-6 and TNF-α (p < 0.05) and enhancing the epigenetic marker HDAC2 (p < 0.05) and antioxidant marker Nrf2 (p < 0.05) expressions. Thus, PIP alleviates pulmonary inflammation by modulating the SIRT1-mediated inflammatory cascade, inhibits EMT, and activates Nrf2 signaling.
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Qasem AMA, Rowan MG, Blagbrough IS. Poisonous Piperidine Plants and the Biodiversity of Norditerpenoid Alkaloids for Leads in Drug Discovery: Experimental Aspects. Int J Mol Sci 2022; 23:12128. [PMID: 36292987 PMCID: PMC9603787 DOI: 10.3390/ijms232012128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/04/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022] Open
Abstract
There are famous examples of simple (e.g., hemlock, Conium maculatum L.) and complex (e.g., opium poppy, Papaver somniferum L., Papaveraceae) piperidine-alkaloid-containing plants. Many of these are highly poisonous, whilst pepper is well-known gastronomically, and several substituted piperidine alkaloids are therapeutically beneficial as a function of dose and mode of action. This review covers the taxonomy of the genera Aconitum, Delphinium, and the controversial Consolida. As part of studying the biodiversity of norditerpenoid alkaloids (NDAS), the majority of which possess an N-ethyl group, we also quantified the fragment occurrence count in the SciFinder database for NDA skeletons. The wide range of NDA biodiversity is also captured in a review of over 100 recently reported isolated alkaloids. Ring A substitution at position 1 is important to determine the NDA skeleton conformation. In this overview of naturally occurring highly oxygenated NDAs from traditional Aconitum and Delphinium plants, consideration is given to functional effect and to real functional evidence. Their high potential biological activity makes them useful candidate molecules for further investigation as lead compounds in the development of selective drugs.
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Piperine Enhances the Antimalarial Activity of Curcumin in Plasmodium berghei ANKA-Infected Mice: A Novel Approach for Malaria Prophylaxis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7897163. [PMID: 36106028 PMCID: PMC9467801 DOI: 10.1155/2022/7897163] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 08/04/2022] [Indexed: 11/18/2022]
Abstract
Malaria is a prevalent vector-borne infectious disease in tropical regions, particularly in the absence of effective vaccines and because of the emergence resistance of Plasmodium to available antimalarial drugs. An alternative strategy for malaria eradication could be the combination of existing compounds that possess antimalarial activity to target multiple stages of the parasite. This study evaluated the antimalarial activity of a combination of curcumin and piperine in mice. A total of 42 mice were assigned to six groups depending on the treatment administered: group I (normal group) with aquadest; group II (negative control) with 0.2 ml DMSO; group III received a standard malarial drug (artesunate 5 mg/kg BW); groups IV, V, and VI with curcumin 300 mg/kg BW, curcumin 300 mg/kg BW and piperine 20 mg/kg BW, and piperine 20 mg/kg BW, respectively. The antimalarial activity was evaluated using prophylactic assays in Plasmodium berghei ANKA-infected mice, including the percentage parasitemia, clinical signs, survival rate, serum biochemical analysis, parasitic load in the liver, and liver histopathology. All treatments showed significant (p < 0.05) antiplasmodial activity, with considerable parasite inhibition (>50%), curcumin 300 mg/kg BW (60.22%), curcumin 300 mg/kg BW, and piperine 20 mg/kg BW (77.94%) except for piperine 20 mg/kg BW (47.20%), eliciting greater inhibition relative to that of artesunate (51.18%). The delayed onset of clinical symptoms and prolonged survival rate were also significant (p < 0.05) in the combination of curcumin and piperine treated group. In addition, the low parasitic load in the liver and mild histopathological changes in the liver suggest that the combination of curcumin and piperine had synergistic or additive effects. These findings demonstrate the promising use of these combined compounds as a malarial prophylactic. Further studies were recommended to assess their clinical usefulness.
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Zhang C, Gu F, Hu W, Wu G, Chen W, Dong C, Niu Z. Effect of extraction technique on chemical compositions and antioxidant activities of freeze-dried green pepper. Front Nutr 2022; 9:998840. [PMID: 36118756 PMCID: PMC9479182 DOI: 10.3389/fnut.2022.998840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
In this study, the yield, content of piperine, and antioxidant activity of pepper oleoresin obtained with the methods of maceration, ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and ultrasound-MAE (UMAE) were analyzed, and the microstructure of pepper residue was observed. For the yield and piperine content, the UMAE method had the best extraction capacity among the four methods. While, the oleoresin obtained with maceration had the highest total phenolic content, and the antioxidant activity of the oleoresin obtained by maceration was higher than that of the extracts acquired by UAE, MAE, and UMAE, and a high positive correlation was observed between the antioxidant activity and total phenolic content of the oleoresin obtained by these extraction methods. The ideal parameters for UMAE were an 80-mesh particle size and a 1 g/10 mL solid–liquid ratio. The kinetic parameters and models of the UMAE extraction process were also compared using first- and second-order models. The second-order kinetic equation with the lowest root mean square deviation and highest adjusted correlation coefficient proved to be more suitable for describing the extraction kinetics of pepper oleoresin. This study showed that UMAE is a fast, efficient, and cost-effective technique for the extraction of green pepper oleoresin.
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Affiliation(s)
- Chaohua Zhang
- College of Food Science and Engineering, Hainan University, Haikou, China
- Sanya Research Institute of Chinese Academy of Tropical Agricultural Sciences, San Ya, China
- Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning, China
| | - Fenglin Gu
- Sanya Research Institute of Chinese Academy of Tropical Agricultural Sciences, San Ya, China
- Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning, China
- Hainan Key Laboratory for Biosafety Monitoring and Molecular Breeding in Off-Season Reproduction Regions, San Ya, China
- Key Laboratory of Processing Suitability and Quality Control of the Special Tropical Crops of Hainan Province, Wanning, China
- *Correspondence: Fenglin Gu
| | - Weicheng Hu
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, China
- Weicheng Hu
| | - Guiping Wu
- Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning, China
- Key Laboratory of Processing Suitability and Quality Control of the Special Tropical Crops of Hainan Province, Wanning, China
| | - Weijun Chen
- College of Food Science and Engineering, Hainan University, Haikou, China
| | - Conghui Dong
- Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning, China
| | - Zhiqiang Niu
- Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, China
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Jäckel L, Schnabel A, Stellmach H, Klauß U, Matschi S, Hause G, Vogt T. The terminal enzymatic step in piperine biosynthesis is co-localized with the product piperine in specialized cells of black pepper (Piper nigrum L.). THE PLANT JOURNAL : FOR CELL AND MOLECULAR BIOLOGY 2022; 111:731-747. [PMID: 35634755 DOI: 10.1111/tpj.15847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/18/2022] [Accepted: 05/26/2022] [Indexed: 06/15/2023]
Abstract
Piperine (1-piperoyl piperidine) is responsible for the pungent perception of dried black pepper (Piper nigrum) fruits and essentially contributes to the aromatic properties of this spice in combination with a blend of terpenoids. The final step in piperine biosynthesis involves piperine synthase (PS), which catalyzes the reaction of piperoyl CoA and piperidine to the biologically active and pungent amide. Nevertheless, experimental data on the cellular localization of piperine and the complete biosynthetic pathway are missing. Not only co-localization of enzymes and products, but also potential transport of piperamides to the sink organs is a possible alternative. This work, which includes purification of the native enzyme, immunolocalization, laser microdissection, fluorescence microscopy, and electron microscopy combined with liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), provides experimental evidence that piperine and PS are co-localized in specialized cells of the black pepper fruit perisperm. PS accumulates during early stages of fruit development and its level declines before the fruits are fully mature. The product piperine is co-localized to PS and can be monitored at the cellular level by its strong bluish fluorescence. Rising piperine levels during fruit maturation are consistent with the increasing numbers of fluorescent cells within the perisperm. Signal intensities of individual laser-dissected cells when monitored by LC-ESI-MS/MS indicate molar concentrations of this alkaloid. Significant levels of piperine and additional piperamides were also detected in cells distributed in the cortex of black pepper roots. In summary, the data provide comprehensive experimental evidence of and insights into cell-specific biosynthesis and storage of piperidine alkaloids, specific and characteristic for the Piperaceae. By a combination of fluorescence microscopy and LC-MS/MS analysis we localized the major piperidine alkaloids to specific cells of the fruit perisperm and the root cortex. Immunolocalization of native piperine and piperamide synthases shows that enzymes are co-localized with high concentrations of products in these idioblasts.
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Affiliation(s)
- Luise Jäckel
- Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
| | - Arianne Schnabel
- Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
| | - Hagen Stellmach
- Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
| | - Ulrike Klauß
- Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
| | - Susanne Matschi
- Department of Biochemistry of Plant Interactions, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
| | - Gerd Hause
- Electron Microscopy Lab, Biocenter, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, D-06120, Halle (Saale), Germany
| | - Thomas Vogt
- Department of Cell and Metabolic Biology, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120, Halle (Saale), Germany
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Povinelli APR, Zazeri G, Jones AM, Cornélio ML. A Computational–Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction. Int J Mol Sci 2022; 23:ijms23147994. [PMID: 35887341 PMCID: PMC9323498 DOI: 10.3390/ijms23147994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/14/2022] [Accepted: 07/18/2022] [Indexed: 11/16/2022] Open
Abstract
Herein, we elucidate the biophysical aspects of the interaction of an important protein, Interleukin-6 (IL6), which is involved in cytokine storm syndrome, with a natural product with anti-inflammatory activity, piperine. Despite the role of piperine in the inhibition of the transcriptional protein NF-κB pathway responsible for activation of IL6 gene expression, there are no studies to the best of our knowledge regarding the characterisation of the molecular interaction of the IL6-piperine complex. In this context, the characterisation was performed with spectroscopic experiments aided by molecular modelling. Fluorescence spectroscopy alongside van’t Hoff analyses showed that the complexation event is a spontaneous process driven by non-specific interactions. Circular dichroism aided by molecular dynamics revealed that piperine caused local α-helix reduction. Molecular docking and molecular dynamics disclosed the microenvironment of interaction as non-polar amino acid residues. Although piperine has three available hydrogen bond acceptors, only one hydrogen-bond was formed during our simulation experiments, reinforcing the major role of non-specific interactions that we observed experimentally. Root mean square deviation (RMSD) and hydrodynamic radii revealed that the IL6-piperine complex was stable during 800 ns of simulation. Taken together, these results can support ongoing IL6 drug discovery efforts.
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Affiliation(s)
- Ana Paula Ribeiro Povinelli
- Federal Institute of Education, Science and Technology of Mato Grosso, Campo Novo do Parecis 78360-000, Brazil;
| | - Gabriel Zazeri
- Federal Institute of Education, Science and Technology of Mato Grosso, Campo Novo do Parecis 78360-000, Brazil;
- Correspondence: (G.Z.); (M.L.C.)
| | - Alan M. Jones
- School of Pharmacy, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK;
| | - Marinônio Lopes Cornélio
- Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), UNESP, Rua Cristovão Colombo 2265, São José do Rio Preto 15054-000, Brazil
- Correspondence: (G.Z.); (M.L.C.)
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Piperine Derivatives Enhance Fusion and Axonal Transport of Mitochondria by Activating Mitofusins. CHEMISTRY 2022. [DOI: 10.3390/chemistry4030047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Piperine (1-piperoylpiperidine) is the major pungent component of black pepper (Piper nigrum) and exhibits a spectrum of pharmacological activities. The molecular bases for many of piperine’s biological effects are incompletely defined. We noted that the chemical structure of piperine generally conforms to a pharmacophore model for small bioactive molecules that activate mitofusin (MFN)-mediated mitochondrial fusion. Piperine, but not its isomer chavicine, stimulated mitochondrial fusion in MFN-deficient cells with EC50 of ~8 nM. We synthesized piperine analogs having structural features predicted to optimize mitofusin activation and defined structure-activity relationships (SAR) in live-cell mitochondrial elongation assays. When optimal spacing was maintained between amide and aromatic groups the derivatives were potent mitofusin activators. Compared to the prototype phenylhexanamide mitofusin activator, 2, novel molecules containing the piperidine structure of piperine exhibited markedly enhanced passive membrane permeability with no loss of fusogenic potency. Lead compounds 5 and 8 enhanced mitochondrial motility in cultured murine Charcot-Marie-Tooth disease type 2A (CMT2A) neurons, but only 8 improved mitochondrial transport in sciatic nerve axons of CMT2A mice. Piperine analogs represent a new chemical class of mitofusin activators with potential pharmaceutical advantages.
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Evaluation of In Vitro Antiprotease Activity of Selected Traditional Medicinal Herbs in Dentistry and Its In Silico PASS Prediction. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5870443. [PMID: 35707383 PMCID: PMC9192215 DOI: 10.1155/2022/5870443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/06/2022] [Accepted: 05/24/2022] [Indexed: 11/17/2022]
Abstract
Background Dental/oral diseases are one of the significant public health problems globally. Herbal medicines for managing oral diseases are considered an effective alternative to synthetic compounds due to their lower side effect. Azadirachta indica, Terminalia chebula, Camellia sinensis, and Piper nigrum are used to control and prevent oral inflammations in dentistry. In this study, we have evaluated the protease inhibition activity of these plant extracts, and further, the binding mode of the active ingredient of these plants with trypsin was studied using molecular docking. Methods In this study, protease inhibition activity was carried out using aqueous extracts of the plant parts such as Azadirachta indica (neem) twig, Terminalia chebula (Haritaki) fruit, Camellia sinensis (green tea) powder, and Piper nigrum (kali miri) seed. Next, to explore the binding mode of active ingredients azadirachtin, chebuligenic acid, catechin, and piperine with trypsin, we employed a molecular docking study using AutoDock4.2. Results The results revealed that the Azadirachta indica plant extract showed an IC50 value of 96.19 μg mL−1, Camellia sinensis IC50 value of 188.50 μg mL−1, Piper nigrum IC50 value of 371.20 μg mL−1, and Terminalia chebula IC50 value of 639.48 μg mL−1, when compared with standard drug diclofenac sodium, had IC50 value 93.00 μg mL−1. Further, the docking result reveals that all the main active ingredients of these plants have significant binding affinity and prefer the same binding pocket of trypsin. Conclusion Hence, our results show the importance of traditional plants Azadirachta indica, Terminalia chebula, green tea, and Piper nigrum to control oral disease conditions. As they show significant protease inhibition activity, hence, the active ingredient could act as a potential anti-inflammatory agent and further help to prevent or control oral disease conditions such as gingivitis and periodontitis.
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Dewi C, Fristiohady A, Amalia R, Khairul Ikram NK, Ibrahim S, Muchtaridi M. Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27123661. [PMID: 35744786 PMCID: PMC9227697 DOI: 10.3390/molecules27123661] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/25/2022] [Accepted: 05/30/2022] [Indexed: 11/16/2022]
Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, having a poor prognosis and rapid metastases. TNBC is characterized by the absence of estrogen, progesterone, and human epidermal growth receptor-2 (HER2) expressions and has a five-year survival rate. Compared to other breast cancer subtypes, TNBC patients only respond to conventional chemotherapies, and even then, with limited success. Shortages of chemotherapeutic medication can lead to resistance, pressured index therapy, non-selectivity, and severe adverse effects. Finding targeted treatments for TNBC is difficult owing to the various features of cancer. Hence, identifying the most effective molecular targets in TNBC pathogenesis is essential for predicting response to targeted therapies and preventing TNBC cell metastases. Nowadays, natural compounds have gained attention as TNBC treatments, and have offered new strategies for solving drug resistance. Here, we report a systematic review using the database from Pubmed, Science Direct, MDPI, BioScince, Springer, and Nature for articles screening from 2003 to 2022. This review analyzes relevant signaling pathways and the prospect of utilizing natural compounds as a therapeutic agent to improve TNBC treatments in the future.
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Affiliation(s)
- Citra Dewi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia;
- Pharmacy Department, Faculty of Science and Technology, Mandala Waluya University, Kendari 93561, Indonesia
| | - Adryan Fristiohady
- Faculty of Pharmacy, Halu Oleo University, Kampus Hijau Bumi Tridharma, Kendari 93232, Indonesia;
| | - Riezki Amalia
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia;
| | - Nur Kusaira Khairul Ikram
- Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia;
| | - Sugeng Ibrahim
- Department of Molecular Biology, Faculty of Medicine, Universitas Katolik Soegijapranata, Semarang 50234, Indonesia;
| | - Muchtaridi Muchtaridi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia;
- Correspondence:
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Therapeutic potentials and structure-activity relationship of 1,3-benzodioxole N-carbamothioyl carboxamide derivatives as selective and potent antagonists of P2X4 and P2X7 receptors. Eur J Med Chem 2022; 238:114491. [DOI: 10.1016/j.ejmech.2022.114491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/12/2022] [Accepted: 05/21/2022] [Indexed: 11/19/2022]
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Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities. Molecules 2022; 27:molecules27092841. [PMID: 35566194 PMCID: PMC9100884 DOI: 10.3390/molecules27092841] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 04/25/2022] [Accepted: 04/27/2022] [Indexed: 02/01/2023] Open
Abstract
Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines, Vero and Vero E6, as compared to the other compounds in this series. Its half-maximal inhibitory concentration (IC50) for antitrypanosomal activity against Trypanosoma brucei rhodesiense was 15.46 ± 3.09 μM, and its antimalarial activity against the 3D7 strain of Plasmodium falciparum was 24.55 ± 1.91 μM, which were fourfold and fivefold more potent, respectively, than the activities of piperine. Interestingly, compound 5 inhibited the activity of 3C-like main protease (3CLPro) toward anti-SARS-CoV-2 activity at the IC50 of 106.9 ± 1.2 μM, which was threefold more potent than the activity of rutin. Docking and molecular dynamic simulation indicated that the potential binding of 5 in the 3CLpro active site had the improved binding interaction and stability. Therefore, new aryl amide analogs of piperine 5 should be investigated further as a promising anti-infective agent against human African trypanosomiasis, malaria, and COVID-19.
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