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Zhang ZL, Xu HN, Gong CM, Li YZ, Song XM, Li YM, Zhang DD, Wang R. Microorganism-Derived Bisindole Alkaloids With Anticancer Potential and Their Mechanisms: A Comprehensive Review. Chem Biodivers 2025; 22:e202402398. [PMID: 39714457 DOI: 10.1002/cbdv.202402398] [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: 09/23/2024] [Revised: 12/12/2024] [Accepted: 12/20/2024] [Indexed: 12/24/2024]
Abstract
Bisindole alkaloids constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the last six decades, researchers have isolated 425 microorganism-derived bisindole alkaloids (MDBAs). Among them, 187 MDBAs have demonstrated anticancer properties against various in vitro cancer cell lines, primarily by impeding the cell cycle, restraining cell proliferation, and inducing apoptosis and autophagy. These effects are mediated by regulating key targets and signaling pathways such as hypoxia-inducible factor (HIF)-1, MAPK, and phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR. This review provides a comprehensive examination of the sources, chemical diversity, and anticancer properties of these compounds. Furthermore, it summarizes the structure-activity relationship (SAR), druggability, and the mechanisms underlying MDBAs' anticancer effects. Ultimately, this article aims to furnish a thorough overview of the advancements in the investigation of microorganism-derived bisindole alkaloids for their continued development and utilization.
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Affiliation(s)
- Zi-Long Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Hao-Nan Xu
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Chuan-Ming Gong
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Yu-Ze Li
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Xiao-Mei Song
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Yi-Ming Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Dong-Dong Zhang
- School of Pharmacy, Shaanxi Key Laboratory of Research and Application of "Taibai Qi Yao", Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, P. R. China
| | - Rui Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
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Lotfi MS, Rassouli FB. Natural Flavonoid Apigenin, an Effective Agent Against Nervous System Cancers. Mol Neurobiol 2024; 61:5572-5583. [PMID: 38206472 DOI: 10.1007/s12035-024-03917-y] [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: 07/27/2023] [Accepted: 12/31/2023] [Indexed: 01/12/2024]
Abstract
Cancer is a serious public health concern worldwide, and nervous system (NS) cancers are among the most life-threatening malignancies. Efforts have been devoted to introduce natural anticancer agents with minimal side effects. Apigenin is an edible flavonoid that is abundantly found in many vegetables and fruits. Various pharmaceutical activities, including anti-inflammatory, antioxidative, antimicrobial, and anticancer effects have been reported for apigenin. This review provides insights into the therapeutic effects of apigenin and flavonoids with similar structure on glioblastoma and neuroblastoma. Current evidence indicates that apigenin has the unique ability to cross the blood-brain barrier, and its antioxidative, anti-inflammatory, neurogenic, and neuroprotective effects have made this flavonoid a great option for the treatment of neurodegenerative disorders. Meanwhile, apigenin has low toxicity on normal neuronal cells, while induces cytotoxicity on NS cancer cells via triggering several signal pathways and molecular targets. Anticancer effects of apigenin have been contributed to various mechanisms such as induction of cell cycle arrest and apoptosis, and inhibition of migration, invasion, and angiogenesis. Although apigenin is a promising pharmaceutical agent, its low bioavailability is an important issue that must be solved before introducing to clinic. Recently, nano-delivery of apigenin by liposomes and poly lactic-co-glycolide nanoparticles has greatly improved functionality of this agent. Hence, investigating pharmaceutical effects of apigenin-loaded nanocarriers on NS cancer cell lines and animal models is recommended for future studies.
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Affiliation(s)
- Mohammad-Sadegh Lotfi
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Fatemeh B Rassouli
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
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Jian H, Zhang J, Liu Z, Zhang Z, Zeng P. Amentoflavone reverses epithelial-mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis. J Cell Mol Med 2024; 28:e18442. [PMID: 38842135 PMCID: PMC11154840 DOI: 10.1111/jcmm.18442] [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: 02/02/2024] [Revised: 05/08/2024] [Accepted: 05/11/2024] [Indexed: 06/07/2024] Open
Abstract
Epithelial-mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone-regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK-8 kit, wound healing assay, Transwell assay and annexin V-FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V-FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.
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Affiliation(s)
| | | | - Zhuo Liu
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese MedicineHunan Academy of Chinese MedicineHunanChina
| | - Zhen Zhang
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese MedicineHunan Academy of Chinese MedicineHunanChina
| | - Pu‐Hua Zeng
- Hunan Provincial Hospital of Integrated Traditional Chinese and Western, Cancer Research Institute of Hunan Academy of Traditional Chinese MedicineHunan Academy of Chinese MedicineHunanChina
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Negm WA, Elekhnawy E, Mahgoub S, Ibrahim HA, Ibrahim Elberri A, Abo Mansour HE, Mosalam EM, Moglad E, Alzahraa Mokhtar F. Dioon rzedowskii: An antioxidant, antibacterial and anticancer plant extract with multi-faceted effects on cell growth and molecular signaling. Int Immunopharmacol 2024; 132:111957. [PMID: 38554441 DOI: 10.1016/j.intimp.2024.111957] [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: 01/17/2024] [Revised: 03/18/2024] [Accepted: 03/26/2024] [Indexed: 04/01/2024]
Abstract
This study investigated the antioxidant, anticancer, antibacterial properties of Dioon rzedowskii extract, which had not been previously explored. We aimed to determine the extract's effect on liver and breast cancer cell lines and on solid Ehrlich carcinoma (SEC) mouse model to investigate the underlying molecular mechanisms. Three female albino mice groups were established: a tumor control group, a group treated with 100 mg/kg of the extract (D100), and a group treated with 200 mg/kg of the extract (D200) for 16 days after tumor development. Results showed that the D. rzedowskii extract inhibited cell growth in both MCF-7 and HepG2 cells in a concentration-dependent manner. This was achieved by suppressing the cell proliferation and inducing apoptosis. The extract also improved liver, heart, and kidney functions compared to the tumor control. Furthermore, oral administration of the extract reduced tumor volume and alleviated oxidative stress in tumor tissue. The anticancer effects were associated with overexpression of p53 and Bax and downregulation of cyclin D1 expression, which was attributed to decreased phosphorylated MAPK kinases. Additionally, D. rzedowskii exhibited antibacterial activity against K. pneumoniae isolated from cancer patients. The extract inhibited bacterial growth and reduced the membrane integrity. The study suggests that D. rzedowskii has promising potential as an adjunctive therapy for cancer treatment. Further investigations are needed to explore its combined anticancer efficacy. These results emphasize the value of natural products in developing compounds with potential anticancer activity and support a paradigm shift in cancer management to improve patients' quality of life.
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Affiliation(s)
- Walaa A Negm
- Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Engy Elekhnawy
- Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Sebaey Mahgoub
- Food Analysis Laboratory, Ministry of Health, Zagazig, Egypt
| | - Hanaa A Ibrahim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Aya Ibrahim Elberri
- Genetic Engineering and Molecular Biology Division, Department of Zoology, Faculty of Science, Menoufia University, 32511 Shebin El-Kom, Menoufia, Egypt.
| | - Hend E Abo Mansour
- Biochemistry Department, Faculty of Pharmacy, Menoufia University, 32511 Shebin EL-Kom, Menoufia, Egypt.
| | - Esraa M Mosalam
- Biochemistry Department, Faculty of Pharmacy, Menoufia University, 32511 Shebin EL-Kom, Menoufia, Egypt; Department of Pharmacy, Faculty of Pharmacy, Jadara University, Irbid, Jordan.
| | - Ehssan Moglad
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, P.O. Box 173, Alkharj 11942, Saudi Arabia.
| | - Fatma Alzahraa Mokhtar
- Department of Pharmacognosy, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida 44813, Sharkia, Egypt; Fujairah Research Centre, Sakamkam Road, Fujairah, United Arab Emirates
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Guo Y, Jia X, Du P, Wang J, Du Y, Li B, Xue Y, Jiang J, Cai Y, Yang Q. Mechanistic insights into the ameliorative effects of Xianglianhuazhuo formula on chronic atrophic gastritis through ferroptosis mediated by YY1/miR-320a/TFRC signal pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117608. [PMID: 38158098 DOI: 10.1016/j.jep.2023.117608] [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: 10/10/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. AIM OF THE STUDY To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. METHODS A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. RESULTS In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. CONCLUSION XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.
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Affiliation(s)
- Yuxi Guo
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Xuemei Jia
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Pengli Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Jie Wang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China
| | - Yao Du
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Bolin Li
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China
| | - Yucong Xue
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Jianming Jiang
- College of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050200, China
| | - Yanru Cai
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
| | - Qian Yang
- Department of Spleen and Stomach Diseases, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Heibei, 050011, China; Hebei Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China; Hebei Key Laboratory of Turbidity Toxin Syndrome, First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050011, China.
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Al-Shuhaib MBS, Al-Shuhaib JMB. Phytochemistry, pharmacology, and medical uses of Oldenlandia (family Rubaceae): a review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2021-2053. [PMID: 37837473 DOI: 10.1007/s00210-023-02756-3] [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: 08/24/2023] [Accepted: 09/27/2023] [Indexed: 10/16/2023]
Abstract
The Oldenlandia genus comprises approximately 240 species of plants, yet only a limited number of these have been investigated for their chemical composition and medicinal properties. These species contain a wide range of compounds such as iridoids, anthraquinones, triterpenes, phytosterols, flavonoids, anthocyanidins, vitamins, essential oils, phenolic acids, and coumarins. These diverse phytochemical profiles underscore the pharmacological potential of Oldenlandia plants for various medical purposes. Among other chemical constituents, ursolic acid stands out as the most important active compound in Oldenlandia, owing to its proven anticancer, anti-inflammatory, antimicrobial, and hepatoprotective properties. The evaluation of Oldenlandia's pharmacological prospects indicates that the holistic utilization of the entire plant yields the most significant effects. Oldenlandia diffusa showcases anticancer and anti-inflammatory capabilities attributed to its varying constituents. Across a broad spectrum of pharmacological capacities, anticancer research predominates, constituting the majority of medical uses. Oldenlandia diffusa emerges as a standout for its remarkable anticancer effects against diverse malignancies. Antioxidant applications follow, with O. corymbosa demonstrating potent antioxidant properties alongside O. umbellata and O. diffusa. Subsequent priority lies in anti-inflammatory studies, wherein O. diffusa exhibits noteworthy efficacy, trailed by O. corymbosa also takes the lead in antimicrobial activity, with O. umbellata as a strong contender. Additional investigation is essential to ascertain the relative significance of these species in various pharmacological applications. This comprehensive assessment underscores the multifaceted potential of Oldenlandia as a versatile herbal resource, offering diverse pharmacological capacities. The call for sustained exploration and research remains essential to unlock the full extent of Oldenlandia's medicinal benefits.
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Affiliation(s)
- Mohammed Baqur S Al-Shuhaib
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, Al-Qasim 8, Babil, 51001, Iraq.
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Gao HH, Qin LF, Zhang X, Yuan X, Feng ZM, Jiang JS, Zhang PC, Yang YN. Six new iridoid glycosides from the whole plants of Hedyotis diffusa. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2024; 26:112-119. [PMID: 38185895 DOI: 10.1080/10286020.2023.2293068] [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: 09/19/2023] [Accepted: 12/01/2023] [Indexed: 01/09/2024]
Abstract
Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (1), Z-6-O-p-methoxycinnamoyl-10-O-acetyl scandoside acid methyl ester (2), E-6-O-caffeoyl scandoside methyl ester (3), E-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (4), Z-6-O-p-coumaroyl-6'-O-acetyl scandoside methyl ester (5), and E-6-O-p-coumaroyl-4'-O-acetyl scandoside methyl ester (6). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.
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Affiliation(s)
- Huan-Huan Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Ling-Feng Qin
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Xu Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Xiang Yuan
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Zi-Ming Feng
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Jian-Shuang Jiang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Pei-Cheng Zhang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
| | - Ya-Nan Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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Fikry E, Orfali R, El-Sayed SS, Perveen S, Ghafar S, El-Shafae AM, El-Domiaty MM, Tawfeek N. Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation. Antioxidants (Basel) 2023; 12:2118. [PMID: 38136237 PMCID: PMC10740566 DOI: 10.3390/antiox12122118] [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: 10/28/2023] [Revised: 12/04/2023] [Accepted: 12/05/2023] [Indexed: 12/24/2023] Open
Abstract
Methotrexate (MTX) therapy encounters significant limitations due to the significant concern of drug-induced liver injury (DILI), which poses a significant challenge to its usage. To mitigate the deleterious effects of MTX on hepatic function, researchers have explored plant sources to discover potential hepatoprotective agents. This study investigated the hepatoprotective effects of the ethanolic extract derived from the aerial parts of Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing on MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used to identify 61 compounds in CLAE, with 31 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 potential DILI targets for the bioactive compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted on rats with acute MTX-hepatotoxicity revealed that administering CLAE orally at 200 and 400 mg/kg/day for ten days dose-dependently improved liver function, attenuated hepatic oxidative stress, inflammation, and apoptosis, and reversed the disarrayed hepatic histological features induced by MTX. In general, the findings of the present study provide evidence in favor of the hepatoprotective capabilities of CLAE in DILI, thereby justifying the need for additional preclinical and clinical investigations.
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Affiliation(s)
- Eman Fikry
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; (E.F.); (A.M.E.-S.); (N.T.)
| | - Raha Orfali
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;
| | - Shaimaa S. El-Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt;
| | - Shagufta Perveen
- Department of Chemistry, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA;
| | - Safina Ghafar
- Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia;
| | - Azza M. El-Shafae
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; (E.F.); (A.M.E.-S.); (N.T.)
| | - Maher M. El-Domiaty
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; (E.F.); (A.M.E.-S.); (N.T.)
| | - Nora Tawfeek
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt; (E.F.); (A.M.E.-S.); (N.T.)
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Li F, Cheng Z, Sun J, Cheng X, Li C, Wu Z, Qi F, Zhao Y, Nie G. The Combination of Sinusoidal Perfusion Enhancement and Apoptosis Inhibition by Riociguat Plus a Galactose-PEGylated Bilirubin Multiplexing Nanomedicine Ameliorates Liver Fibrosis Progression. NANO LETTERS 2023; 23:4126-4135. [PMID: 37155569 DOI: 10.1021/acs.nanolett.2c04726] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Chronic liver injury and continuous wound healing lead to extracellular matrix (ECM) deposition and liver fibrosis. The elevated production of reactive oxygen species (ROS) in the liver leads to the apoptosis of hepatocytes and the activation of hepatic stellate cells (HSCs). In the current study, we describe a combination strategy of sinusoidal perfusion enhancement and apoptosis inhibition enabled by riociguat together with a tailor-designed galactose-PEGylated bilirubin nanomedicine (Sel@GBRNPs). Riociguat enhanced sinusoidal perfusion and decreased the associated ROS accumulation and inflammatory state of the fibrotic liver. Concurrently, hepatocyte-targeting galactose-PEGylated bilirubin scavenged excessive ROS and released encapsulated selonsertib. The released selonsertib inhibited apoptosis signal-regulating kinase 1 (ASK1) phosphorylation to alleviate apoptosis in hepatocytes. The combined effects on ROS and hepatocyte apoptosis attenuated the stimulation of HSC activation and ECM deposition in a mouse model of liver fibrosis. This work provides a novel strategy for liver fibrosis treatment based on sinusoidal perfusion enhancement and apoptosis inhibition.
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Affiliation(s)
- Fenfen Li
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Zhaoxia Cheng
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
| | - Jingyi Sun
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaoyu Cheng
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chen Li
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhouliang Wu
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Feilong Qi
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ying Zhao
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guangjun Nie
- CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
- GBA Research Innovation Institute for Nanotechnology, Guangzhou 510530, China
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Tuli HS, Joshi H, Vashishth K, Ramniwas S, Varol M, Kumar M, Rani I, Rani V, Sak K. Chemopreventive mechanisms of amentoflavone: recent trends and advancements. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:865-876. [PMID: 36773053 DOI: 10.1007/s00210-023-02416-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 02/01/2023] [Indexed: 02/12/2023]
Abstract
In parallel to the continuous rise of new cancer cases all over the world, the interest of scientific community in natural anticancer agents has steadily been increased. In the past decades, numerous phytochemicals have been shown to possess a strong anticancer potential in preclinical conditions. One of such interesting compounds, derived from different plants such as ginkgo, hinoki, and St. John`s wort, is amentoflavone. In this review article, a wide range of anticancer properties of this natural biflavone are described, revealing its ability to suppress the malignant growth and lead tumor cells to apoptotic death, besides impeding also angiogenic and metastatic processes. Therefore, amentoflavone can be considered a potential lead compound for the development of novel anticancer drug candidates, definitely deserving further in vivo studies and also initiation of clinical trials. It is expected that this plant biflavone might be important, either alone or in combination with the current standard chemotherapeutics, in providing some alleviation for the continuous rise of global cancer burden.
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Affiliation(s)
- Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Ambala, Mullana, 133207, India
| | - Hemant Joshi
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Kanupriya Vashishth
- Advance Cardiac Centre Department of Cardiology, Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh, Chandigarh, 160012, India
| | - Seema Ramniwas
- University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Mohali, 140413, India
| | - Mehmet Varol
- Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey
| | - Manoj Kumar
- Department of Chemistry, Maharishi Markandeshwar University Sadopur, Ambala, 134007, India
| | - Isha Rani
- Department of Biochemistry, Maharishi Markandeshwar College of Medical Sciences and Research (MMCMSR), Sadopur, 134007, Ambala, India
| | - Vibha Rani
- Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, 201307, Uttar Pradesh, India
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11
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Kakouri E, Trigas P, Daferera D, Skotti E, Tarantilis PA, Kanakis C. Chemical Characterization and Antioxidant Activity of Nine Hypericum Species from Greece. Antioxidants (Basel) 2023; 12:antiox12040899. [PMID: 37107274 PMCID: PMC10135362 DOI: 10.3390/antiox12040899] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/31/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
Hypericum L. comprises about 500 species distributed almost worldwide. Research has mainly focused on H. perforatum with confirmed biological activity on the alleviation of depression symptoms, among others. The compounds responsible for such activity are considered naphthodianthrones and acylphloroglucinols. Other Hypericum species are less studied or not studied, and further research is needed to complete the characterization of the genus. In this study we evaluated the qualitative and quantitative phytochemical profile of nine Hypericum species native to Greece, namely H. perforatum, H. tetrapterum, H. perfoliatum, H. rumeliacum subsp. apollinis, H. vesiculosum, H. cycladicum, H. fragile, H. olympicum and H. delphicum. Qualitative analysis was performed using the LC/Q-TOF/HRMS technique, while quantitative data were calculated with the single point external standard method. Additionally, we estimated the antioxidant activity of the extracts using DPPH and ABTS assays. Three species endemic to Greece (H. cycladicum, H. fragile, H. delphicum) were studied for the first time. Our results indicated that all studied species are rich in secondary metabolites, mainly of the flavonoids family, with strong antioxidant activity.
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Affiliation(s)
- Eleni Kakouri
- Laboratory of Chemistry, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece
| | - Panayiotis Trigas
- Laboratory of Systematic Botany, Department of Crop Science, School of Plant Sciences, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece
| | - Dimitra Daferera
- Laboratory of Chemistry, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece
| | - Efstathia Skotti
- Department of Food Science and Technology, Ionian University, Terma Leoforou Vergoti, 281 00 Argostoli, Cephalonia, Greece
| | - Petros A Tarantilis
- Laboratory of Chemistry, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece
| | - Charalabos Kanakis
- Laboratory of Chemistry, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, Iera Odos 75, 118 55 Athens, Greece
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12
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Tang HZ, Yang ZP, Lu S, Wang B, Wang YY, Sun XB, Qu JX, Rao BQ. Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer. World J Gastrointest Oncol 2023; 15:90-101. [PMID: 36684054 PMCID: PMC9850754 DOI: 10.4251/wjgo.v15.i1.90] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/28/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer (CRC). Given the complicated features of Traditional Chinese medicine formulas, network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases.
AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724.
METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database. In addition, the CRC targets were obtained from Drugbank, TTD, DisGeNET and GeneCards databases. We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724. Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets. Core targets were selected by protein-protein interaction network and herb ingredient-target-disease network analysis. The functional and pathway of core targets were analysed by enrichment analysis.
RESULTS We found 174 active ingredients and 283 compound targets from JC724. 940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis. We constructed the network and found that the five core ingredients were quercetin, β Beta sitosterol, wogonin, kaempferol and baicalein. The core JC724-CRC targets were CYP1A1, HMOX1, CXCL8, NQO1 and FOSL1. JC724 acts on multiple signaling pathways associated with CRC, including the Nrf2 signaling pathway, oxidative stress, and the IL-17 signaling pathway.
CONCLUSION In this study, we systematically analyzed the active ingredients, core targets and main mechanisms of JC724 in the treatment of CRC. This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.
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Affiliation(s)
- Hua-Zhen Tang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Zhen-Peng Yang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Shuai Lu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Bing Wang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Yu-Ying Wang
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Xi-Bo Sun
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian 271000, Shandong Province, China
| | - Jin-Xiu Qu
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
| | - Ben-Qiang Rao
- Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
- Department of Gastrointestinal Surgery, Key Laboratory of Cancer FSMP for State Market Regulation, Beijing 100038, China
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13
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Chen H, Shang X, Yuan H, Niu Q, Chen J, Luo S, Li W, Li X. Total flavonoids of Oldenlandia diffusa (Willd.) Roxb. suppresses the growth of hepatocellular carcinoma through endoplasmic reticulum stress-mediated autophagy and apoptosis. Front Pharmacol 2022; 13:1019670. [PMID: 36523497 PMCID: PMC9745173 DOI: 10.3389/fphar.2022.1019670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/14/2022] [Indexed: 09/21/2023] Open
Abstract
Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world. Although the current treatment methods for HCC are gradually increasing, its efficacy still cannot meet the medical needs of patients with liver cancer, and new and effective treatment strategies are urgently needed. The total flavonoids of Oldenlandia diffusa (FOD) are the main active components in Oldenlandia diffusa, which have anti-inflammatory, antioxidant and anti-tumor effects, but their mechanism of action in liver cancer is unclear. In this study, we examined the effect of FOD on HCC. Using both in vitro and in vivo models, we confirmed that FOD inhibited HCC proliferation and induced apoptosis and autophagy. Mechanistic studies have shown that FOD induces apoptosis and activates autophagy in HCC cells by inducing endoplasmic reticulum stress (ER stress) and activating the PERK-eIF2α-ATF4 signaling pathway. Taken together, our results suggest that FOD is a potential anticancer drug targeting ER stress for the treatment of HCC.
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Affiliation(s)
- Huan Chen
- Integrated Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaofei Shang
- Integrated Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Huixin Yuan
- Integrated Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Qianqian Niu
- Integrated Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jing Chen
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Shumin Luo
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Weihua Li
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiuhui Li
- Integrated Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
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14
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Alherz FA, El-Masry TA, Negm WA, El-Kadem AH. Potential cardioprotective effects of Amentoflavone in doxorubicin-induced cardiotoxicity in mice. Biomed Pharmacother 2022; 154:113643. [PMID: 36942597 DOI: 10.1016/j.biopha.2022.113643] [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: 07/15/2022] [Revised: 08/22/2022] [Accepted: 08/31/2022] [Indexed: 11/21/2022] Open
Abstract
Doxorubicin (DOX) is an available chemotherapeutic drug for treating various tumors. However, its effectiveness is limited by cardiotoxicity. Amentoflavone (AMF), a natural biflavonoid separated from Cycas thouarsii ethyl acetate fraction, displays promising anticancer, anti-inflammatory, and antioxidant effects. Thus, our research aims to explore whether AMF could boost cardioprotective effects against DOX cardiotoxicity and reveal the potential underlying mechanisms of cardioprotection. Mice were classified into four groups; Normal control, Untreated DOX group, and DOX groups treated with AMF (40 and 80 mg/kg, respectively) intraperitoneal injection daily for four days before doxorubicin administration and for additional three days following DOX administration to assess cardiotoxicity. Echocardiography showed that AMF 80 treated group was protected from DOX cardiotoxicity. Additionally, it alleviated histopathological structural alterations and effectively restored heart weight and body weight ratio. These effects were confirmed biochemically by a substantially reduced serum creatine kinase-MB (CK-MB) and aspartate aminotransferase (AST) levels. AMF effectively restored nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM), and normalized heat shock protein - 27(HSP-27) expression levels compared to the DOX group. Moreover, AMF mitigated oxidative stress conditions and significantly suppressed NADPH oxidase (NOX) expression levels. It also showed significant anti-inflammatory effects via suppressing interleukin-6 (IL-6) expression and decreasing nuclear factor Kabba B (NF-κb) immune-staining. In addition, AMF markedly reduced FAS ligand (FASL) expression and p53 immune staining in cardiac tissue. This study is the first for the in vivo potential beneficial effects of AMF against acute DOX cardiotoxicity, possibly via exerting antioxidant, anti-inflammatory, and anti-apoptotic effects and restoring mitochondrial function.
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Affiliation(s)
- Fatemah A Alherz
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
| | - Thanaa A El-Masry
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Walaa A Negm
- Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
| | - Aya H El-Kadem
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
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15
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Characterization, solubility and stability of amentoflavone polymorphs. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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16
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Wu Z, Yin B, You F. Molecular Mechanism of Anti-Colorectal Cancer Effect of Hedyotis diffusa Willd and Its Extracts. Front Pharmacol 2022; 13:820474. [PMID: 35721163 PMCID: PMC9201484 DOI: 10.3389/fphar.2022.820474] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 04/06/2022] [Indexed: 11/13/2022] Open
Abstract
With the sharp change in our diet and lifestyle, the incidence of colorectal cancer (CRC) is increasing among young people and has become the second most common malignant tumor worldwide. Although the current treatment of CRC is getting updated rapidly, recurrence and metastasis are still inevitable. Therefore, new anticancer drugs are needed to break existing limitations. In recent years, Hedyotis diffusa Willd (HDW) extracts have been proved to demonstrate excellent anti-colorectal cancer effects and have been widely used in clinical practices. In this review, we aim to explore the advantages, potential signaling pathways, and representative active ingredients of HDW in the treatment of CRC from the perspective of molecular mechanism, in order to provide new ideas for the future treatment of CRC.
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Affiliation(s)
- Zihong Wu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Bei Yin
- School of Second Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fengming You
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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17
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Qin Y, Zhao B, Deng H, Zhang M, Qiao Y, Liu Q, Shi C, Li Y. Isolation and Quantification of the Hepatoprotective Flavonoids From Scleromitron diffusum (Willd.) R. J. Wang With Bio-Enzymatic Method Against NAFLD by UPLC-MS/MS. Front Pharmacol 2022; 13:890148. [PMID: 35770080 PMCID: PMC9234865 DOI: 10.3389/fphar.2022.890148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 04/25/2022] [Indexed: 12/02/2022] Open
Abstract
Flavonoids were the major phytochemicals against hepatic peroxidative injury in Scleromitron diffusum (Willd.) R. J. Wang with an inventive bio-enzymatic method by our group (LU500041). Firstly, the total flavonoids from Scleromitron diffusum (Willd.) R. J. Wang were extracted by reflux, ultrasonic, ultrasound-assisted enzymatic methods (TFH), and the bio-enzymatic method (Ey-TFH). Then 24 flavonoid compounds were isolated and quantified in the extracts by UPLC-MS/MS. Next, six representative differential compounds in Ey-TFH were further screened out by multivariate statistical analysis compared with those in TFH. In a further step, Ey-TFH presented a higher protective rate (59.30 ± 0.81%) against H2O2-damaged HL-02 hepatocytes than TFH. And six representative differential compounds at 8 and 16 μmol/L all exerted significant hepatoprotective effects (p < 0.05 or p < 0.01). Finally, the therapeutic action of Ey-TFH for nonalcoholic fatty liver disease (NAFLD) was processed by a rat's model induced with a high-fat diet. Ey-TFH (90, 120 mg/kg) significantly ameliorated the lipid accumulation in the rat model (p < 0.05). Meanwhile, Ey-TFH relieved liver damage. The levels of ALT, ALP, AST, LDH, and γ-GT in rats' serum were also significantly reduced (p < 0.05 or p < 0.01). In addition to this, the body's antioxidant capacity was improved with elevated SOD and GSH levels (p < 0.05) and down-regulated MDA content (p < 0.01) after Ey-TFH administration. Histopathological observations of staining confirmed the hepatic-protective effect of Ey-TFH.
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Affiliation(s)
- Yuxi Qin
- School of Public Health, Shaanxi University of Chinese medicine, Xi’an, China
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
| | - Baojin Zhao
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
| | - Huifang Deng
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
| | - Mengjiao Zhang
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
| | - Yanan Qiao
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
| | - Qiling Liu
- School of Public Health, Shaanxi University of Chinese medicine, Xi’an, China
| | - Chuandao Shi
- School of Public Health, Shaanxi University of Chinese medicine, Xi’an, China
| | - Yunlan Li
- School of Public Health, Shaanxi University of Chinese medicine, Xi’an, China
- School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
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18
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Wang X, Zhao J, Zhang R, Liu X, Ma C, Cao G, Wei Y, Yang P. Protective Effect of Hedyotis diffusa Willd. Ethanol Extract on Isoniazid-Induced Liver Injury in the Zebrafish Model. Drug Des Devel Ther 2022; 16:1995-2015. [PMID: 35783199 PMCID: PMC9249440 DOI: 10.2147/dddt.s358498] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 06/10/2022] [Indexed: 11/23/2022] Open
Abstract
Objective Methods Results Conclusion
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Affiliation(s)
- Xin Wang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
| | - Jie Zhao
- School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
| | - Rui Zhang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China
| | - Xinlu Liu
- School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China
| | - Chuanjiang Ma
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
| | - Guangshang Cao
- School of Pharmacy, Shandong University of Traditional Chinese Medicine (TCM), Jinan, 250355, People’s Republic of China
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
| | - Yongli Wei
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
| | - Peimin Yang
- Grade Three Laboratory of TCM Preparation of National Administration of TCM, Affiliated Hospital of Shandong University of TCM, Jinan, 250014, People’s Republic of China
- Correspondence: Peimin Yang, Tel +86-0531-68616607, Email
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19
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Šamec D, Karalija E, Dahija S, Hassan STS. Biflavonoids: Important Contributions to the Health Benefits of Ginkgo ( Ginkgo biloba L.). PLANTS (BASEL, SWITZERLAND) 2022; 11:1381. [PMID: 35631806 PMCID: PMC9143338 DOI: 10.3390/plants11101381] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 05/03/2023]
Abstract
Ginkgo (Ginkgo biloba L.) is one of the most distinctive plants, characterized by excellent resistance to various environmental conditions. It is used as an ornamental plant and is recognized as a medicinal plant in both traditional and Western medicine. Its bioactive potential is associated with the presence of flavonoids and terpene trilactones, but many other compounds may also have synergistic effects. Flavonoid dimers-biflavonoids-are important constituents of ginkgophytopharmaceuticals. Currently, the presence of 13 biflavonoids has been reported in ginkgo, of which amentoflavone, bilobetin, sciadopitysin, ginkgetin and isoginkgetin are the most common. Their role in plants remains unknown, but their bioactivity and potential role in the management of human health are better investigated. In this review, we have provided an overview of the chemistry, diversity and biological factors that influence the presence of biflavonoids in ginkgo, as well as their bioactive and health-related properties. We have focused on their antioxidant, anticancer, antiviral, antibacterial, antifungal and anti-inflammatory activities as well as their potential role in the treatment of cardiovascular, metabolic and neurodegenerative diseases. We also highlighted their potential toxicity and pointed out further research directions.
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Affiliation(s)
- Dunja Šamec
- Department of Food Technology, University North, Trga Dr. Žarka Dolinara 1, 48000 Koprivnica, Croatia
| | - Erna Karalija
- Department for Biology, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71000 Sarajevo, Bosnia and Herzegovina; (E.K.); (S.D.)
| | - Sabina Dahija
- Department for Biology, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33-35, 71000 Sarajevo, Bosnia and Herzegovina; (E.K.); (S.D.)
| | - Sherif T. S. Hassan
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00 Prague, Czech Republic;
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Optimization of Ultrasound-Assisted Cellulase Extraction from Nymphaea hybrid Flower and Biological Activities: Antioxidant Activity, Protective Effect against ROS Oxidative Damage in HaCaT Cells and Inhibition of Melanin Production in B16 Cells. Molecules 2022; 27:molecules27061914. [PMID: 35335279 PMCID: PMC8949894 DOI: 10.3390/molecules27061914] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 01/27/2023] Open
Abstract
In this study, ultrasonic-assisted cellulase extraction (UCE) was applied to extract flavonoids and polyphenols from the Nymphaea hybrid flower. The extraction conditions were optimized using the response surface method (RSM) coupled with a Box-Behnken design. The crude extract of Nymphaea hybrid (NHE) was further purified using AB-8 macroporous resins, and the purified extract (NHEP) was characterized by FTIR and HPLC. In vitro activity determination by chemical method showed that NHEP displayed strong free radical scavenging abilities against the DPPH and ABTS radicals, good reduction power, and hyaluronidase inhibition. The cell viability by CCK-8 assays showed that NHEP had no significant cytotoxicity for B16 and HaCaT cells when the concentration was below 100 μg/mL and 120 μg/mL, respectively. NHEP with a concentration of 20–160 μg/mL can more effectively reduce the ROS level in H2O2 damaged HaCaT cells compared with 10 μg/mL of VC. The 40 μg/mL of NHEP had similar activity against intracellular melanin production in the B16 melanoma cells compared with 20 μg/mL Kojic acid. Good activities of antioxidation, whitening and protective effect against H2O2-induced oxidative damage promote the potential for NHEP as a functional raw material in the field of cosmetics and medicine.
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21
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Xiong X, Tang N, Lai X, Zhang J, Wen W, Li X, Li A, Wu Y, Liu Z. Insights Into Amentoflavone: A Natural Multifunctional Biflavonoid. Front Pharmacol 2022; 12:768708. [PMID: 35002708 PMCID: PMC8727548 DOI: 10.3389/fphar.2021.768708] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 12/02/2021] [Indexed: 12/12/2022] Open
Abstract
Amentoflavone is an active phenolic compound isolated from Selaginella tamariscina over 40 years. Amentoflavone has been extensively recorded as a molecule which displays multifunctional biological activities. Especially, amentoflavone involves in anti-cancer activity by mediating various signaling pathways such as extracellular signal-regulated kinase (ERK), nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and emerges anti-SARS-CoV-2 effect via binding towards the main protease (Mpro/3CLpro), spike protein receptor binding domain (RBD) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Therefore, amentoflavone is considered to be a promising therapeutic agent for clinical research. Considering the multifunction of amentoflavone, the current review comprehensively discuss the chemistry, the progress in its diverse biological activities, including anti-inflammatory, anti-oxidation, anti-microorganism, metabolism regulation, neuroprotection, radioprotection, musculoskeletal protection and antidepressant, specially the fascinating role against various types of cancers. In addition, the bioavailability and drug delivery of amentoflavone, the molecular mechanisms underlying the activities of amentoflavone, the molecular docking simulation of amentoflavone through in silico approach and anti-SARS-CoV-2 effect of amentoflavone are discussed.
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Affiliation(s)
- Xifeng Xiong
- Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Nan Tang
- Department of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Xudong Lai
- Department of Infectious Disease, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Jinli Zhang
- Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Weilun Wen
- Department of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Xiaojian Li
- Department of Burn and Plastic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Aiguo Li
- Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Yanhua Wu
- Department of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Zhihe Liu
- Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
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22
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Li J, Liu D, Li D, Guo Y, Du H, Cao Y. Phytochemical composition and anti-aging activity of n-butanol extract of Hedyotis diffusa in Caenorhabditis elegans. Chem Biodivers 2021; 19:e202100685. [PMID: 34935259 DOI: 10.1002/cbdv.202100685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/21/2021] [Indexed: 11/08/2022]
Abstract
Hedyotis diffusa Willd. ( H. diffusa ), a kind of traditional Chinese medicine, has been evaluated to potential display antioxidant and anti-aging effects in vitro experiments. In this work, we investigated the effects on lifespan and stress resistance of the N-butanol extract from H. diffusa (NHD) in vivo using a Caenorhabditis elegans ( C. elegans ) model. The phytochemicals of NHD were identified by UPLC-ESI-qTOF-MS/MS method. NHD-treated wild-type N2 worms showed an increase in survival time under both normal and stress conditions. Meanwhile, NHD promoted the healthspan of nematodes by stimulating growth and development, reducing the deposition of age pigment, increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase dismutase (GSH-Px), and decreasing the level of ROS without impairing fertility. Moreover, the upregulating of the expression of daf-16 , gst-4 , sod-3 , hsp12.6 genes and the downregulating of the expression of daf-2 were involved in the NHD-mediated lifespan extension. Finally, the increasing of the expression of GST-4::GFP in CL2166 transgenic nematodes and the life-span-extending activity of NHD was completely abolished in daf-2 and daf-16 mutants further revealed that the potential roles for these genes in NHD-induced longevity in C. elegans . Collectively, our findings suggest that NHD may have an active effect in healthy aging and age-related diseases.
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Affiliation(s)
- Jing Li
- Hubei University of Chinese Medicine, college of pharmcy, Hongshan district, 16# West road Huangjiahu, Wuhan, CHINA
| | - Di Liu
- Hubei University of Chinese Medicine, college of pharmcy, Hongshan district, 16# West road Huangjiahu, Wuhan, CHINA
| | - Danqing Li
- Hubei University of Chinese Medicine, college of pharmcy, Hongshan district, 16# West road Huangjiahu, Wuhan, CHINA
| | - Yujie Guo
- Hubei University of Chinese Medicine, college of pharmcy, Hongshan district, 16# West road Huangjiahu, Wuhan, CHINA
| | - Hongzhi Du
- Hubei University of Chinese Medicine, college of pharmcy, Hongshan district, 16# West road Huangjiahu, Wuhan, CHINA
| | - Yan Cao
- Hubei University of Chinese Medicine, college of pharmacy, Hongshan district, 16# West road Huangjiahu, 430065, Wuhan, CHINA
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23
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Cheng YY, Tuzo ET, Dalley JW, Tsai TH. Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen. Biomed Pharmacother 2021; 145:112466. [PMID: 34839255 DOI: 10.1016/j.biopha.2021.112466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/17/2021] [Accepted: 11/19/2021] [Indexed: 11/26/2022] Open
Abstract
Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmacokinetics of tamoxifen and its metabolites. In the present study, male Sprague-Dawley rats were administered different doses of H. diffusa extract for 5 consecutive days prior to the administration of tamoxifen (10 mg/kg). A validated ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system was developed to monitor tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen in rat plasma. Pharmacokinetic results demonstrated that the area under curves (AUCs) of tamoxifen and the relative bioavailability (%) of tamoxifen were dose-dependently decreased (31-68%) by pre-treatment with H. diffusa extract (3 g/kg and 6 g/kg). In addition, the conversion ratio of 4-hydroxytamoxifen was downregulated (0.5-fold change) and the N-desmethyltamoxifen conversion ratio was upregulated (2-fold change) by high-dose H. diffusa extract. As a result, the relative bioavailability and biotransformation changes affect the clinical efficacy of tamoxifen treatment. These preclinical findings reveal a hitherto unreported interaction between tamoxifen and H. diffusa extract that has implications for their therapeutic efficacy in treating breast cancer.
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Affiliation(s)
- Yung-Yi Cheng
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Elise T Tuzo
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Jeffrey W Dalley
- Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK; Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK.
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Li WW, Li D, Qin Y, Sun CX, Wang YL, Gao L, Ling-Hu L, Zhang F, Cai W, Zhu L, Wang G. Cardioprotective effects of Amentoflavone by suppression of apoptosis and inflammation on an in vitro and vivo model of myocardial ischemia-reperfusion injury. Int Immunopharmacol 2021; 101:108296. [PMID: 34794889 DOI: 10.1016/j.intimp.2021.108296] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/17/2021] [Accepted: 10/19/2021] [Indexed: 01/13/2023]
Abstract
Inflammation modulation is currently considered a promising therapeutic strategy to counteract the burden of cardiovascular disease. Amentoflavone (AME) is a natural biflavone with two apigenin molecules that, possess promising anti-inflammatory, anti-oxidative, and anti-cancer properties. In the present study, we aimed to investigate the effects of AME on myocardial ischemia-reperfusion injury in vivo and in vitro, and to elucidate the underlying mechanism. Our results showed that AME significantly reduced the levels of LDH, CK-MB, IL-6, IL-1β, and TNF-α after hypoxia (H) 12 h/reoxygenation (R) 4 h treatment, and significantly increased the cell survival rate of H9c2 cardiomyocytes induced by H/R and inhibited their apoptosis rate. AME (25, 50, 100 mg·kg-1·d-1, i.g.) or a positive control drug diltiazem (DIZ) (16 mg·kg-1·d-1, i.g.) was used as pretreatment for 7 days; the myocardial ischemia-reperfusion(I/R) model was established. TTC staining results showed that the infarct volume was significantly reduced after AME and DIZ treatment. Oral administration of AME dose-dependently ameliorated I/R injury-induced increase in pro-inflammatory factors (IL-6, IL-1β, and TNF-α) and levels of LDH and CK-MB. Results of TUNEL and HE staining showed that the I/R model had more induced apoptosis, but could be effectively reduced by pretreatment with AME. After surgery, the heart of the rat was examined via western blotting to detect inflammation-related proteins. Compared with the sham group, the p-AKT in the I/R group was significantly reduced and the content of p-NF-κBp65 was significantly increased. However, these changes could be reversed by AME treatment. DIZ treatment exerted similar beneficial effects in I/R rats as the high dose of AME did. This study highlights the excellent therapeutic potential of AME for managing myocardial ischemia-reperfusion injury.
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Affiliation(s)
- Wei-Wei Li
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Dan Li
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Yao Qin
- Department of Cardiovascular Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Cheng-Xin Sun
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Yong-Ling Wang
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Lei Gao
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Lang Ling-Hu
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Feng Zhang
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Wen Cai
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Lei Zhu
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.
| | - Gang Wang
- Department of Pharmaceutical Chemistry, School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.
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El-Sadek HM, Al-Shorbagy MY, Awny MM, Abdallah DM, El-Abhar HS. Pentoxifylline treatment alleviates kidney ischemia/reperfusion injury: Novel involvement of galectin-3 and ASK-1/JNK & ERK1/2/NF-κB/HMGB-1 trajectories. J Pharmacol Sci 2021; 146:136-148. [PMID: 34030796 DOI: 10.1016/j.jphs.2021.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/24/2021] [Accepted: 03/29/2021] [Indexed: 02/07/2023] Open
Abstract
Despite the documented renoprotective effect of pentoxifylline (PTX), a non-selective phosphodiesterase-4 inhibitor, the studies appraised only its anti-inflammatory/-oxidant/-apoptotic capacities without assessment of the possible involved trajectories. Here, we evaluated the potential role of galectin-3 and the ASK-1/NF-κB p65 signaling pathway with its upstream/downstream signals in an attempt to unveil part of the cascades involved in the renotherapeutic effect using a renal bilateral ischemia/reperfusion (I/R) model. Rats were randomized into sham-operated, renal I/R (45 min/72 h) and I/R + PTX (100 mg/kg; p.o). Post-treatment with PTX improved renal function and abated serum levels of cystatin C, creatinine, BUN and renal KIM-1 content, effects that were reflected on an improvement of the I/R-induced renal histological changes. On the molecular level, PTX reduced renal contents of galectin-3, ASK-1 with its downstream molecule JNK and ERK1/2, as well as NF-κB p65 and HMGB1. This inhibitory effect extended also to suppress neutrophil infiltration, evidenced by diminishing ICAM-1 and MPO, as well as inflammatory cytokines (TNF-α/IL-18), oxidative stress (MDA/TAC), and caspase-3. The PTX novel renotherapeutic effect involved in part the inhibition of galectin-3 and ASK-1/JNK and ERK1/2/NF-κB/HMGB-1 trajectories to mitigate renal I/R injury and to provide basis for its anti-inflammatory, antioxidant, and anti-apoptotic impacts.
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Affiliation(s)
- Hagar M El-Sadek
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, Giza, 12585, Egypt
| | - Muhammad Y Al-Shorbagy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, 4184, United Arab Emirates
| | - Magdy M Awny
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, Giza, 12585, Egypt
| | - Dalaal M Abdallah
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
| | - Hanan S El-Abhar
- Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, 84518, Egypt
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26
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Liu HM, Xu PF, Cheng MY, Lei SN, Liu QL, Wang W. Optimization of Fermentation Process of Pomegranate Peel and Schisandra Chinensis and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against H 2O 2-induced Oxidative Damage in HaCaT Cells. Molecules 2021; 26:molecules26113432. [PMID: 34198860 PMCID: PMC8201020 DOI: 10.3390/molecules26113432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/31/2021] [Accepted: 06/01/2021] [Indexed: 12/29/2022] Open
Abstract
In this study, the lactobacillus fermentation process of pomegranate (Punica granatum L.) peel and Schisandra chinensis (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 (w:w) ratio of pomegranate peel to Schisandra chinensis, 1% (v:v) of strains with a 1:1 (v:v) ratio of Lactobacillus Plantarum to Streptococcus Thermophilus, a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid–liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS+, DPPH, OH− and O2− radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% (p < 0.001) compared with 294.49% ± 11.54% of the control group in H2O2-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against H2O2-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.
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Affiliation(s)
- Hui-Min Liu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
| | - Peng-Fei Xu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Ming-Yan Cheng
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Sheng-Nan Lei
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Qing-Lei Liu
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
| | - Wei Wang
- School of Perfume & Aroma and Cosmetics, Shanghai Institute of Technology, Shanghai 201418, China; (H.-M.L.); (P.-F.X.); (M.-Y.C.); (S.-N.L.); (Q.-L.L.)
- Engineering Research Center of Perfume & Aroma and Cosmetics, Ministry of Education, Shanghai 201418, China
- Correspondence: ; Tel.: +86-18918830550
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Zhang R, Ma C, Wei Y, Wang X, Jia J, Li J, Li K, Cao G, Yang P. Isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides: A review. Int J Biol Macromol 2021; 183:119-131. [PMID: 33905802 DOI: 10.1016/j.ijbiomac.2021.04.139] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 03/21/2021] [Accepted: 04/22/2021] [Indexed: 12/18/2022]
Abstract
Hedyotis diffusa polysaccharides, as the main component and an important bioactive substance of Hedyotis diffusa, are effective immunomodulators with various pharmacological activities, including antitumour, anti-inflammatory, antioxidant, anti-fatigue and immunity-enhancing activities. The total polysaccharides extracted from Hedyotis diffusa and Scutellaria barbata have great effects in treating liver cancer, gastric cancer, rectal cancer, glioma and nasopharyngeal carcinoma. Moreover, different materials and extraction methods result in differences in the structure and bioactivity of Hedyotis diffusa polysaccharides. Therefore, this paper summarizes the isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides to provide a reference for further study.
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Affiliation(s)
- Rui Zhang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Chuanjiang Ma
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Yongli Wei
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Xin Wang
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Jing Jia
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Ji Li
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Kunlun Li
- Jinan Hangchen Biotechnology Co., Ltd, Jinan 250014, China
| | - Guangshang Cao
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Peimin Yang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
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Zhang Y, Hu H, Luo J. Diffusosides C and D, two new iridoid glucosides from Oldenlandia diffusa. Nat Prod Res 2020; 36:2300-2305. [DOI: 10.1080/14786419.2020.1830397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Yongyong Zhang
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Huiping Hu
- College of Life Sciences, China Jiliang University, Hangzhou, China
| | - Jiabo Luo
- Key Laboratory of Research of TCM and New Drug, Southern Medical University, Guangzhou, China
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