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1
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Wan X, Wang D. Curcumin: Epigenetic Modulation and Tumor Immunity in Antitumor Therapy. PLANTA MEDICA 2025; 91:320-337. [PMID: 39689889 DOI: 10.1055/a-2499-1140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
Curcumin (turmeric) is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of the antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and a novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.
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Affiliation(s)
- Xin Wan
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Dong Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
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2
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Roointan A, Xu R, Corrie S, Hagemeyer CE, Alt K. Nanotherapeutics in Kidney Disease: Innovations, Challenges, and Future Directions. J Am Soc Nephrol 2025; 36:500-518. [PMID: 39705082 PMCID: PMC11888965 DOI: 10.1681/asn.0000000608] [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: 08/28/2024] [Accepted: 12/17/2024] [Indexed: 12/22/2024] Open
Abstract
The treatment and management of kidney diseases present a significant global challenge, affecting over 800 million individuals and necessitating innovative therapeutic strategies that transcend symptomatic relief. The application of nanotechnology to therapies for kidney diseases, while still in its early stages, holds transformative potential for improving treatment outcomes. Recent advancements in nanoparticle-based drug delivery leverage the unique physicochemical properties of nanoparticles for targeted and controlled therapeutic delivery to the kidneys. Current research is focused on understanding the functional and phenotypic changes in kidney cells during both acute and chronic conditions, allowing for the identification of optimal target cells. In addition, the development of tailored nanomedicines enhances their retention and binding to key renal membranes and cell populations, ultimately improving localization, tolerability, and efficacy. However, significant barriers remain, including inconsistent nanoparticle synthesis and the complexity of kidney-specific targeting. To overcome these challenges, the field requires advanced synthesis techniques, refined targeting strategies, and the establishment of animal models that accurately reflect human kidney diseases. These efforts are critical for the clinical application of nanotherapeutics, which promise novel solutions for kidney disease management. This review evaluates a substantial body of in vivo research, highlighting the prospects, challenges, and opportunities presented by nanotechnology-mediated therapies and their potential to transform kidney disease treatment.
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Affiliation(s)
- Amir Roointan
- NanoBiotechnology Laboratory, Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- NanoTheranostics Laboratory, Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Rong Xu
- NanoBiotechnology Laboratory, Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Simon Corrie
- Department of Chemical and Biological Engineering, Monash University, Melbourne, Victoria, Australia
| | - Christoph E. Hagemeyer
- NanoBiotechnology Laboratory, Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Karen Alt
- NanoTheranostics Laboratory, Australian Centre for Blood Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
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Lv M, Sun Q, Yu Y, Bao J. Nanocurcumin in myocardial infarction therapy: emerging trends and future directions. Front Bioeng Biotechnol 2025; 12:1511331. [PMID: 39845374 PMCID: PMC11750836 DOI: 10.3389/fbioe.2024.1511331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/19/2024] [Indexed: 01/24/2025] Open
Abstract
Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Curcumin has been observed to significantly reduce pathological processes associated with MI. Its clinical application is limited due to its low bioavailability, rapid degradation, and poor solubility. Advancements in nanotechnology can be used to enhance its therapeutic potentials in MI. Curcumin nano-formulation enhances its solubility, stability, and bioavailability, allowing more precise delivery to ischemic cardiac tissue. Curcumin nanoparticles have been observed to successfully reduce infarct size, maintain heart function by modulating essential molecular pathways in MI. Its liposomal formulations provide sustained release and higher tissue penetration with improved pharmacokinetics and enhanced therapeutic efficacy. Preclinical studies revealed that nanocurcumin drastically lower oxidative stress indicators, inflammatory cytokines, and cardiac damage. Micelles composed of polymers have demonstrated high biocompatibility and targeting capabilities with increased cardio-protective effects. Research and clinical trials are essential for comprehensive analysis and efficacy of curcumin-based nano-therapeutics in cardiovascular condition and lowering risk of MI.
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Affiliation(s)
- Mei Lv
- General Medicine Department, Yantaishan Hospital, Yantai, Shandong, China
| | - Qing Sun
- Department of Cardiology, Yantaishan Hospital, Yantai, Shandong, China
| | - Yilin Yu
- Preventive medicine, Shandong University, Jinan, Shandong, China
| | - Jinwei Bao
- Department of Cardiology, Yantaishan Hospital, Yantai, Shandong, China
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Roquito T, Colaço M, Costa JP, Borges O. Curcumin-encapsulated glucan nanoparticles as an oxidative stress modulator against human hepatic cancer cells. Colloids Surf B Biointerfaces 2024; 245:114326. [PMID: 39442411 DOI: 10.1016/j.colsurfb.2024.114326] [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: 06/28/2024] [Revised: 10/10/2024] [Accepted: 10/15/2024] [Indexed: 10/25/2024]
Abstract
In Hepatitis B patients, the virus targets liver cells, leading to inflammation and liver damage, which can result in severe complications such as liver failure, cirrhosis, and liver cancer. Therapeutic options for liver disease are currently limited. Curcumin, a polyphenol with potential protective effects against chronic diseases like cancer, suffers from poor water solubility, restricting its pharmacological applications. This study explores the encapsulation of curcumin in glucan nanoparticles (NPs) and its impact on oxidative stress in liver cancer cells. Two sizes of curcumin-loaded glucan NPs, GC111 (111 nm) and GC398 (398 nm), were produced with nearly 100 % encapsulation efficiency. Cytotoxicity studies revealed that particle size influences the extent of observed effects, with GC111 NPs causing a greater reduction in cell viability. Additionally, the smaller GC111 NPs demonstrated a higher capacity to induce oxidative stress in cancer cells by stimulating the production of ROS, NO, and the chemokine RANTES in a concentration-dependent manner. These findings suggest that the smaller GC111 NPs are promising candidates for future studies aimed at evaluating oxidative stress-induced tumor cell death mechanisms.
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Affiliation(s)
- Tiago Roquito
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal
| | - Mariana Colaço
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal
| | - João Panão Costa
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal
| | - Olga Borges
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Portugal; CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Portugal.
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Mad Azli AA, Salamt N, Aminuddin A, Roos NAC, Mokhtar MH, Kumar J, Hamid AA, Ugusman A. The Role of Curcumin in Modulating Vascular Function and Structure during Menopause: A Systematic Review. Biomedicines 2024; 12:2281. [PMID: 39457594 PMCID: PMC11504472 DOI: 10.3390/biomedicines12102281] [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: 09/17/2024] [Revised: 10/04/2024] [Accepted: 10/06/2024] [Indexed: 10/28/2024] Open
Abstract
The risk of developing cardiovascular disease (CVD) escalates in women during menopause, which is associated with increased vascular endothelial dysfunction, arterial stiffness, and vascular remodeling. Meanwhile, curcumin has been demonstrated to enhance vascular function and structure in various studies. Therefore, this study systematically reviewed the recent literature regarding the potential role of curcumin in modulating vascular function and structure during menopause. The Ovid MEDLINE, PubMed, Scopus, and Web of Science electronic databases were searched to identify relevant articles. Clinical and preclinical studies involving menopausal women and postmenopausal animal models with outcomes related to vascular function or structure were included. After thorough screening, seven articles were selected for data extraction, comprising three animal studies and four clinical trials. The findings from this review suggested that curcumin has beneficial effects on vascular function and structure during menopause by addressing endothelial function, arterial compliance, hemodynamic parameters, and the formation of atherosclerotic lesions. Therefore, curcumin has the potential to be utilized as a supplement to enhance vascular health in menopausal women. However, larger-scale clinical trials employing gold-standard techniques to evaluate vascular health in menopausal women are necessary to validate the preliminary results obtained from small-scale randomized clinical trials involving curcumin supplementation (INPLASY, INPLASY202430043).
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Affiliation(s)
- Amanina Athirah Mad Azli
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
| | - Norizam Salamt
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
| | - Amilia Aminuddin
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
- Cardiovascular and Pulmonary Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
| | - Nur Aishah Che Roos
- Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur 57000, Malaysia;
| | - Mohd Helmy Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
| | - Jaya Kumar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
| | - Adila A. Hamid
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
- Cardiovascular and Pulmonary Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
| | - Azizah Ugusman
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (A.A.M.A.); (N.S.); (A.A.); (M.H.M.); (J.K.)
- Cardiovascular and Pulmonary Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
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Perales-Salinas V, Purushotham SS, Buskila Y. Curcumin as a potential therapeutic agent for treating neurodegenerative diseases. Neurochem Int 2024; 178:105790. [PMID: 38852825 DOI: 10.1016/j.neuint.2024.105790] [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: 05/07/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/11/2024]
Abstract
Neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function, posing a tremendous burden on health systems worldwide. Although the underlying pathological mechanisms for various neurodegenerative diseases are still unclear, a common pathological hallmark is the abundance of neuroinflammatory processes, which affect both disease onset and progression. In this review, we explore the pathways and role of neuroinflammation in various neurodegenerative diseases and further assess the potential use of curcumin, a natural spice with antioxidant and anti-inflammatory properties that has been extensively used worldwide as a traditional medicine and potential therapeutic agent. Following the examination of preclinical and clinical studies that assessed curcumin as a potential therapeutic agent, we highlight the bioavailability of curcumin in the body and discuss both the challenges and benefits of using curcumin as a therapeutic compound for treating neurodegeneration. Although elucidating the involvement of curcumin in aging and neurodegeneration has great potential for developing future CNS-related therapeutic targets, further research is required to elucidate the mechanisms by which Curcumin affects brain physiology, especially BBB integrity, under both physiological and disease conditions.
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Affiliation(s)
| | | | - Yossi Buskila
- School of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia; The MARCS Institute, Western Sydney University, Penrith, NSW, 2751, Australia.
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Zhao Y, Xu X, Dai A, Jia Y, Wang W. Enhanced Dissolution and Bioavailability of Curcumin Nanocrystals Prepared by Hot Melt Extrusion Technology. Int J Nanomedicine 2024; 19:5721-5737. [PMID: 38895153 PMCID: PMC11182756 DOI: 10.2147/ijn.s463918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Purpose Curcumin nanocrystals (Cur-NCs) were prepared by hot melt extrusion (HME) technology to improve the dissolution and bioavailability of curcumin (Cur). Methods Cur-NCs with different drug-carrier ratios were prepared by one-step extrusion process with Eudragit® EPO (EEP) as the carrier. The dispersed size and solid state of Cur in extruded samples were characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The thermal stability of Cur was analyzed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC). Dissolution and pharmacokinetics were studied to evaluate the improvement of dissolution and absorption of Cur by nano-preparation. Results Cur-NCs with particle sizes in the range of 50~150 nm were successfully prepared by using drug-carrier ratios of 1:1, 2:1 and 4:1, and the crystal form of Cur was Form 1 both before and after HME. The extrudate powders showed very efficient dissolution with the cumulative dissolution percentage of 80% in less than 2 min, and the intrinsic dissolution rates of them were 13.68 ± 1.20 mg/min/cm2, 11.78 ± 0.57 mg/min/cm2 and 4.35 ± 0.20 mg/min/cm2, respectively, whereas that of pure Cur was only 0.04 ± 0.00 mg/min/cm2. The TGA data demonstrated that the degradation temperature of Cur was about 250 °C, while the HPLC results showed Cur was degraded when extruded at the temperature over 150 °C. Pharmacokinetic experiment showed a significant improvement in the absorption of Cur. The Cmax of Cur in the Cur-NC group was 1.68 times that of pure Cur group, and the Cmax and area under the curve (AUC0-∞) of metabolites were 2.79 and 4.07 times compared with pure Cur group. Conclusion Cur-NCs can be prepared by HME technology in one step, which significantly improves the dissolution and bioavailability of Cur. Such a novel method for preparing insoluble drug nanocrystals has broad application prospects.
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Affiliation(s)
- Yujie Zhao
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, People’s Republic of China
| | - Xiaoyin Xu
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, People’s Republic of China
| | - Anyin Dai
- Department of Pharmacy, The 903rd Hospital of People’s Liberation Army, Hangzhou, People’s Republic of China
| | - Yunxiang Jia
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, People’s Republic of China
| | - Wenxi Wang
- College of Pharmacy, Zhejiang University of Technology, Hangzhou, People’s Republic of China
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Izadi M, Sadri N, Abdi A, Zadeh MMR, Jalaei D, Ghazimoradi MM, Shouri S, Tahmasebi S. Longevity and anti-aging effects of curcumin supplementation. GeroScience 2024; 46:2933-2950. [PMID: 38409646 PMCID: PMC11009219 DOI: 10.1007/s11357-024-01092-5] [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: 10/09/2023] [Accepted: 02/03/2024] [Indexed: 02/28/2024] Open
Abstract
Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.
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Affiliation(s)
- Mehran Izadi
- Department of Infectious and Tropical Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
| | - Nariman Sadri
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirhossein Abdi
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahdi Raeis Zadeh
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Dorsa Jalaei
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad Mahdi Ghazimoradi
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Shouri
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran
- School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Safa Tahmasebi
- Synapse Laboratory Diagnostic Technologies Accelerator, Tehran, Iran.
- Department of Research & Technology, Zeenome Longevity Research Institute, Tehran, Iran.
- Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Han Y, Zhang H, Zhao H, Fu S, Li R, Wang Z, Wang Y, Lu W, Yang X. Nanoparticle encapsulation using self-assembly abietic acid to improve oral bioavailability of curcumin. Food Chem 2024; 436:137676. [PMID: 37832417 DOI: 10.1016/j.foodchem.2023.137676] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/13/2023] [Accepted: 10/04/2023] [Indexed: 10/15/2023]
Abstract
This research constructed composite nanoparticles (NPs) using abietic acid (AA) as a carrier for significantly enhancing the bioavailability of curcumin (CCM). CCM-loaded AA NPs were synthesized using a low-energy microemulsification method, and the obtained nanoparticles had a spherical morphology with an average diameter of 458.66 nm, a narrow size distribution and a negative surface charge of -19.13 mV. The encapsulation efficiency of CCM was 17.98 %, while its solubility was 20-fold that of free curcumin. FITR, UV, and MD revealed hydrogen bonds and hydrophobic forces between AA and CCM. Thein-vitrorelease profile showed sustainable release of CCM in simulated gastric and intestinal fluids up to 2 h at 37 °C. In cellular studies, CCM-loaded AA NPs with the same CCM concentration exhibited greater bioaccessibility and bioavailability than free CCM. These data suggested a possible utilization of AA NPs in improving water solubility, bioavailability and activity of lipophilic bioactive food factors.
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Affiliation(s)
- Ying Han
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China
| | - Hua Zhang
- School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China
| | - Haitian Zhao
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China; Chongqing Research Institute, Harbin Institute of Technology, Chongqing 401135, China
| | - Shiyao Fu
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China
| | - Ruiling Li
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China
| | - Zhili Wang
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China
| | - Yangxin Wang
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China
| | - Weihong Lu
- School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China
| | - Xin Yang
- School of Medicine and Health, Harbin Institute of Technology, Harbin 150001, China; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China; Chongqing Research Institute, Harbin Institute of Technology, Chongqing 401135, China.
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Ross SA, Emenaker NJ, Kumar A, Riscuta G, Biswas K, Gupta S, Mohammed A, Shoemaker RH. Green Cancer Prevention and Beyond. Cancer Prev Res (Phila) 2024; 17:107-118. [PMID: 38251904 PMCID: PMC10911807 DOI: 10.1158/1940-6207.capr-23-0308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/13/2023] [Accepted: 01/18/2024] [Indexed: 01/23/2024]
Abstract
The concept of green chemoprevention was introduced in 2012 by Drs. Jed Fahey and Thomas Kensler as whole-plant foods and/or extract-based interventions demonstrating cancer prevention activity. Refining concepts and research demonstrating proof-of-principle approaches are highlighted within this review. Early approaches included extensively investigated whole foods, including broccoli sprouts and black raspberries showing dose-responsive effects across a range of activities in both animals and humans with minimal or no apparent toxicity. A recent randomized crossover trial evaluating the detoxification of tobacco carcinogens by a broccoli seed and sprout extract in the high-risk cohort of current smokers highlights the use of a dietary supplement as a potential next-generation green chemoprevention or green cancer prevention approach. Challenges are addressed, including the selection of dose, duration and mode of delivery, choice of control group, and standardization of the plant food or extract. Identification and characterization of molecular targets and careful selection of high-risk cohorts for study are additional important considerations when designing studies. Goals for precision green cancer prevention include acquiring robust evidence from carefully controlled human studies linking plant foods, extracts, and compounds to modulation of targets for cancer risk reduction in individual cancer types.
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Affiliation(s)
- Sharon A. Ross
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Nancy J. Emenaker
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Amit Kumar
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Gabriela Riscuta
- Division of Cancer Prevention, Nutritional Sciences Research Group, National Cancer Institute, Rockville, Maryland
| | - Kajal Biswas
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Shanker Gupta
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Altaf Mohammed
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
| | - Robert H. Shoemaker
- Division of Cancer Prevention, Chemopreventive Agent Development Research Group, National Cancer Institute, Rockville, Maryland
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Zare'i M, Rabieepour M, Ghareaghaji R, Zarrin R, Faghfouri AH. Nanocurcumin supplementation improves pulmonary function in severe COPD patients: A randomized, double blind, and placebo-controlled clinical trial. Phytother Res 2024; 38:1224-1234. [PMID: 38178561 DOI: 10.1002/ptr.8114] [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: 07/08/2023] [Revised: 10/30/2023] [Accepted: 12/17/2023] [Indexed: 01/06/2024]
Abstract
Considering the anti-inflammatory properties of curcumin, the present study was designed to investigate the effect of nano-curcumin on respiratory indices and interleukin-6 (IL-6) levels in severe chronic obstructive pulmonary disease (COPD) patients as a common pulmonary disease causing restricted airflow and breathing problems. In the current double-blind placebo-controlled randomized clinical trial study, 60 patients with stages 3 and 4 COPD were randomly assigned into 80 mg nano-curcumin (n = 30) and placebo groups (n = 30) for 3 months. The effect of nano-curcumin on pulmonary function was evaluated by the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC) ratio. IL-6 serum level, blood pressure, and anthropometric indices were also measured. Nano-curcumin supplementation led to a significant decrease in IL-6 level (p < 0.001) and an increase in FEV1 (p < 0.001), FVC (p = 0.003), and FEV1/FVC (p < 0.001) compared to placebo at the endpoint. Nano-curcumin had a significantly increasing effect on weight and body mass index compared to the placebo group (PANCOVA adjusted for baseline values = 0.042). There was a meaningful improvement in systolic blood pressure in the nano-curcumin group compared to the placebo group (PANCOVA adjusted for baseline values = 0.026). There was no significant difference between the two groups in terms of waist circumference, waist-to-hip ratio, and diastolic blood pressure (PANCOVA adjusted for baseline values >0.05). Nano-curcumin supplement seems to have favorable effects on inflammation status and respiratory indices of patients with severe COPD.
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Affiliation(s)
- Mahdieh Zare'i
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Masoumeh Rabieepour
- Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Rasoul Ghareaghaji
- Department of Epidemiology and Biostatistics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Rasoul Zarrin
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Amir Hossein Faghfouri
- Maternal and Childhood Obesity Research Center, Urmia University of Medical Sciences, Urmia, Iran
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Noor A, Shafi S, Sehar N, Qadir I, Bilquees, Rashid S, Arafah A, Rasool S, Dar NJ, Masoodi MH, Rehman MU. Curcuminoids as Cell Signaling Pathway Modulators: A Potential Strategy for Cancer Prevention. Curr Med Chem 2024; 31:3093-3117. [PMID: 37559247 DOI: 10.2174/0929867331666230809100335] [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: 09/13/2022] [Revised: 02/23/2023] [Accepted: 03/03/2023] [Indexed: 08/11/2023]
Abstract
Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidence reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoid, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/β-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoid also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoid against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKβ, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology- based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.
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Affiliation(s)
- Aneeza Noor
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Saimeena Shafi
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Nouroz Sehar
- Centre for Translational and Clinical Research, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi 110062, India
| | - Insha Qadir
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Bilquees
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al Kharj, 11942, Saudi Arabia
| | - Azher Arafah
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Saiema Rasool
- Department of School Education, Govt. of Jammu & Kashmir, Srinagar, J&K 190001, India
| | - Nawab John Dar
- Cellular Neurobiology Laboratory (CNB-P), Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA92037, USA
| | - Mubashir Hussain Masoodi
- Natural Products Research Laboratory, Department of Pharmaceutical Sciences, School of Applied Sciences & Technology, University of Kashmir, Hazratbal Srinagar, J&K, India
| | - Muneeb U Rehman
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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13
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Kroon MAGM, Berbee JK, Majait S, Swart EL, van Tellingen O, van Laarhoven HWM, Kemper EM. Non-therapeutic plasma levels in individuals utilizing curcumin supplements in daily life. Front Nutr 2023; 10:1267035. [PMID: 38099182 PMCID: PMC10720437 DOI: 10.3389/fnut.2023.1267035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
Introduction The spice curcumin and its metabolites are widely used by cancer patients but have not shown proven health benefits in clinical studies, likely due to low plasma concentrations after oral intake. However, public interest in curcumin continues to grow, and companies claim enhanced absorption in their formulations. This study aims to determine if daily oral intake of curcumin leads to sufficient plasma concentrations for health effects. The study was registered in the Dutch Clinical Trial Register with ID NL5931. Methods We used a validated HPLC-MS/MS method to measure curcumin and its metabolites in 47 individuals using their own curcumin formulations. Questionnaires assessed other supplement and medication use. Plasma samples were collected before and 1.5 h after intake, analyzing curcumin and metabolite levels with and without β-glucuronidase pretreatment to measure conjugated and unconjugated forms. Results Plasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin, ranged between 1.0 and 18.6 ng/mL. Adding β-glucuronidase resulted in an increase of unconjugated curcumin plasma levels to 25.4 ng/mL; however still significantly below (1000-fold) a plasma concentration that is expected to have a beneficial health effect. The use of adjuvants like piperine did not result in higher curcumin plasma concentrations. Discussion Our study shows that using oral curcumin supplements still does not result in therapeutic plasma levels. Health care practitioners need to be critical toward the claimed beneficial systemic health effects of current curcumin supplement use by their patients. Clinical Trial Registration https://onderzoekmetmensen.nl/en/trial/25480, NL5931.
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Affiliation(s)
- Maurice A. G. M. Kroon
- Department of Pharmacy and Pharmacology, Amsterdam UMC location AMC, Amsterdam, Netherlands
| | - Jacqueline K. Berbee
- Department of Pharmacy and Pharmacology, Amsterdam UMC location AMC, Amsterdam, Netherlands
| | - Soumia Majait
- Department of Pharmacy and Pharmacology, Amsterdam UMC location AMC, Amsterdam, Netherlands
| | - Eleonora L. Swart
- Department of Pharmacy and Pharmacology, Amsterdam UMC location AMC, Amsterdam, Netherlands
| | - Olaf van Tellingen
- Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
| | - Hanneke W. M. van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - E. Marleen Kemper
- Department of Pharmacy and Pharmacology, Amsterdam UMC location AMC, Amsterdam, Netherlands
- Department of Experimental Vascular Medicine, Amsterdam UMC location AMC, Amsterdam, Netherlands
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14
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Yıldırım M, Sessevmez M, Poyraz S, Düzgüneş N. Recent Strategies for Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals and Their Cellular Targets. Pharmaceutics 2023; 15:2566. [PMID: 38004545 PMCID: PMC10675520 DOI: 10.3390/pharmaceutics15112566] [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: 09/07/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/26/2023] Open
Abstract
Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In comparison to the free compounds, phytochemicals loaded into nanoparticles have greater activity and bioavailability against many cancer types. In this review, we describe the preparation and characterization of natural phytochemical-loaded polymer NP formulations with significant antioxidant and anti-inflammatory effects, their in vitro and in vivo anticancer activities, as well as their possible cellular targets.
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Affiliation(s)
- Metin Yıldırım
- Department of Biochemistry, Faculty of Pharmacy, Harran University, Sanliurfa 63050, Turkey;
| | - Melike Sessevmez
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey;
| | - Samet Poyraz
- Department of Analytical Chemistry, Faculty of Pharmacy, Harran University, Sanliurfa 63050, Turkey;
| | - Nejat Düzgüneş
- Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94103, USA
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15
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Wang Y, Lu L, Ling C, Zhang P, Han R. Potential of Dietary HDAC2i in Breast Cancer Patients Receiving PD-1/PD-L1 Inhibitors. Nutrients 2023; 15:3984. [PMID: 37764768 PMCID: PMC10537481 DOI: 10.3390/nu15183984] [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: 08/02/2023] [Revised: 09/09/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Breast cancer (BC) is a lethal malignancy with high morbidity and mortality but lacks effective treatments thus far. Despite the introduction of immune checkpoint inhibitors (ICIs) (including PD-1/PD-L1 inhibitors), durable and optimal clinical benefits still remain elusive for a considerable number of BC patients. To break through such a dilemma, novel ICI-based combination therapy has been explored for enhancing the therapeutic effect. Recent evidence has just pointed out that the HDAC2 inhibitor (HDAC2i), which has been proven to exhibit an anti-cancer effect, can act as a sensitizer for ICIs therapy. Simultaneously, dietary intervention, as a crucial supportive therapy, has been reported to provide ingredients containing HDAC2 inhibitory activity. Thus, the novel integration of dietary intervention with ICIs therapy may offer promising possibilities for improving treatment outcomes. In this study, we first conducted the differential expression and prognostic analyses of HDAC2 and BC patients using the GENT2 and Kaplan-Meier plotter platform. Then, we summarized the potential diet candidates for such an integrated therapeutic strategy. This article not only provides a whole new therapeutic strategy for an HDAC2i-containing diet combined with PD-1/PD-L1 inhibitors for BC treatment, but also aims to ignite enthusiasm for exploring this field.
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Affiliation(s)
- Yuqian Wang
- Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- Department of Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Lingeng Lu
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA
- School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, New Haven, CT 06520, USA
- Yale Cancer Center, Yale University, 60 College Street, New Haven, CT 06520, USA
| | - Changquan Ling
- Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- Department of Chinese Medicine, Naval Medical University, Shanghai 200433, China
| | - Ping Zhang
- Center for Integrative Conservation, Yunnan Key Laboratory for the Conservation of Tropical Rainforests and Asian Elephants, Xishuangbanna Tropical Botanical Garden, Xishuangbanna 666303, China
| | - Rui Han
- Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
- Department of Chinese Medicine, Naval Medical University, Shanghai 200433, China
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA
- School of Medicine, Center for Biomedical Data Science, Yale University, 60 College Street, New Haven, CT 06520, USA
- Yale Cancer Center, Yale University, 60 College Street, New Haven, CT 06520, USA
- Department of Oncology, The First Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou 510405, China
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16
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Kroon M, van Laarhoven H, Swart E, Kemper E, van Tellingen O. A validated HPLC-MS/MS method for simultaneously analyzing curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetra-hydrocurcumin and piperine in human plasma, urine or feces. Heliyon 2023; 9:e15540. [PMID: 37131436 PMCID: PMC10149208 DOI: 10.1016/j.heliyon.2023.e15540] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 04/05/2023] [Accepted: 04/13/2023] [Indexed: 05/04/2023] Open
Abstract
Background The spice curcumin is supposed to have many different beneficial health effects. To understand the complete pharmacokinetics of curcumin we need an analytical method to determine curcumin and its metabolites in human plasma, urine or feces. We have developed an HPLC-MS/MS method for the simultaneous analysis of curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine in human plasma, urine or feces. Methods Sample pretreatment involved a simple liquid-liquid extraction with tert-butyl methyl ether. Conjugated curcumin and analogs can be measured after enzymatic hydrolysis. Reversed-phase chromatography with a linear gradient of 50-95% methanol in 0.1% formic acid was used. Total run time is 15 min. The method was validated with regards to stability, specificity, sensitivity, linearity, accuracy, repeatability and reproducibility. The applicability of the method was tested using actual patients samples. Results The LLOQ in plasma, urine and feces for curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine ranged from 1 to 5 nM. Whereas all compounds could be quantified on a linear range between 2 and 400 nM. Plasma and feces recovery of curcumin was 97.1 ± 3.7% and 99.4 ± 16.2%, whereas urine showed a recovery of 57.1 ± 9.3%. All compounds had acceptable in-between day or between day variability in the different matrixes. Conclusion A HPLC-MS/MS method was developed and validated for the simultaneous quantification of curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and piperine in human plasma, urine or feces. This method will aid in critically verifying the pharmacokinetics of curcumin made by supplement manufacturers and help us to provide insight in the claimed bioavailability of curcumin supplements.
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Affiliation(s)
- M.A.G.M. Kroon
- Department of Pharmacy and Pharmacology, Amsterdam UMC Location AMC, the Netherlands
- Corresponding author. Amsterdam UMC, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
| | - H.W.M. van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - E.L. Swart
- Department of Pharmacy and Pharmacology, Amsterdam UMC Location AMC, the Netherlands
| | - E.M. Kemper
- Department of Pharmacy and Pharmacology, Amsterdam UMC Location AMC, the Netherlands
| | - O. van Tellingen
- Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
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17
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de Waure C, Bertola C, Baccarini G, Chiavarini M, Mancuso C. Exploring the Contribution of Curcumin to Cancer Therapy: A Systematic Review of Randomized Controlled Trials. Pharmaceutics 2023; 15:pharmaceutics15041275. [PMID: 37111761 PMCID: PMC10144810 DOI: 10.3390/pharmaceutics15041275] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/13/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
Although the anticancer role of curcumin has been extensively addressed in preclinical research, only a few studies were carried out in humans, with conflicting results. The aim of this systematic review is to collate together the results of the therapeutic effect of curcumin in cancer patients. A literature search was carried out in Pubmed, Scopus, and the Cochrane Central Register of Controlled Trials up to 29 January 2023. Only randomized controlled trials (RCTs) designed to evaluate the effects of curcumin on cancer progression, patient survival, or surgical/histological response were included. Seven out of 114 articles, published between 2016 and 2022, were analyzed. They evaluated patients with locally advanced and/or metastatic prostate, colorectal, and breast cancers, as well as multiple myeloma and oral leucoplakia. Curcumin was given as an add-on therapy in five studies. Cancer response was the most investigated primary endpoint and curcumin issued some positive results. On the contrary, curcumin was ineffective in improving overall or progression-free survival. The curcumin safety profile was favorable. In conclusion, available clinical evidence is not strong enough to support the therapeutic use of curcumin in cancer. New RCTs exploring the effects of different curcumin formulations in early-stage cancers would be welcome.
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Affiliation(s)
- Chiara de Waure
- Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy
| | - Carlotta Bertola
- Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy
| | - Gaia Baccarini
- Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy
| | - Manuela Chiavarini
- Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy
| | - Cesare Mancuso
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito 1, 00168 Rome, Italy
- Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
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18
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Kunnumakkara AB, Hegde M, Parama D, Girisa S, Kumar A, Daimary UD, Garodia P, Yenisetti SC, Oommen OV, Aggarwal BB. Role of Turmeric and Curcumin in Prevention and Treatment of Chronic Diseases: Lessons Learned from Clinical Trials. ACS Pharmacol Transl Sci 2023; 6:447-518. [PMID: 37082752 PMCID: PMC10111629 DOI: 10.1021/acsptsci.2c00012] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Indexed: 03/08/2023]
Abstract
Turmeric (Curcuma longa) has been used for thousands of years for the prevention and treatment of various chronic diseases. Curcumin is just one of >200 ingredients in turmeric. Almost 7000 scientific papers on turmeric and almost 20,000 on curcumin have been published in PubMed. Scientific reports based on cell culture or animal studies are often not reproducible in humans. Therefore, human clinical trials are the best indicators for the prevention and treatment of a disease using a given agent/drug. Herein, we conducted an extensive literature survey on PubMed and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The keywords "turmeric and clinical trials" and "curcumin and clinical trials" were considered for data mining. A total of 148 references were found to be relevant for the key term "turmeric and clinical trials", of which 70 were common in both PubMed and Scopus, 44 were unique to PubMed, and 34 were unique to Scopus. Similarly, for the search term "curcumin and clinical trials", 440 references were found to be relevant, of which 70 were unique to PubMed, 110 were unique to Scopus, and 260 were common to both databases. These studies show that the golden spice has enormous health and medicinal benefits for humans. This Review will extract and summarize the lessons learned about turmeric and curcumin in the prevention and treatment of chronic diseases based on clinical trials.
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Affiliation(s)
- Ajaikumar B. Kunnumakkara
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Mangala Hegde
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Dey Parama
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Sosmitha Girisa
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Aviral Kumar
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Uzini Devi Daimary
- Department
of Biosciences and Bioengineering, Indian
Institute of Technology Guwahati, Assam-781039, India
| | - Prachi Garodia
- Integrative
Research Center, Miami, Florida 33125, United States
| | - Sarat Chandra Yenisetti
- Department
of Zoology, Drosophila Neurobiology Laboratory, Nagaland University (Central), Lumami, Nagaland-798627, India
| | - Oommen V. Oommen
- Department
of Computational Biology and Bioinformatics, University of Kerala, Kariavattom, Thiruvananthapuram, Kerala-695581, India
| | - Bharat B. Aggarwal
- Inflammation
Research Center, San Diego, California 92109, United States
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19
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Hegde M, Girisa S, BharathwajChetty B, Vishwa R, Kunnumakkara AB. Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far? ACS OMEGA 2023; 8:10713-10746. [PMID: 37008131 PMCID: PMC10061533 DOI: 10.1021/acsomega.2c07326] [Citation(s) in RCA: 81] [Impact Index Per Article: 40.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 01/18/2023] [Indexed: 05/30/2023]
Abstract
Curcumin has been credited with a wide spectrum of pharmacological properties for the prevention and treatment of several chronic diseases such as arthritis, autoimmune diseases, cancer, cardiovascular diseases, diabetes, hemoglobinopathies, hypertension, infectious diseases, inflammation, metabolic syndrome, neurological diseases, obesity, and skin diseases. However, due to its weak solubility and bioavailability, it has limited potential as an oral medication. Numerous factors including low water solubility, poor intestinal permeability, instability at alkaline pH, and fast metabolism contribute to curcumin's limited oral bioavailability. In order to improve its oral bioavailability, different formulation techniques such as coadministration with piperine, incorporation into micelles, micro/nanoemulsions, nanoparticles, liposomes, solid dispersions, spray drying, and noncovalent complex formation with galactomannosides have been investigated with in vitro cell culture models, in vivo animal models, and humans. In the current study, we extensively reviewed clinical trials on various generations of curcumin formulations and their safety and efficacy in the treatment of many diseases. We also summarized the dose, duration, and mechanism of action of these formulations. We have also critically reviewed the advantages and limitations of each of these formulations compared to various placebo and/or available standard care therapies for these ailments. The highlighted integrative concept embodied in the development of next-generation formulations helps to minimize bioavailability and safety issues with least or no adverse side effects and the provisional new dimensions presented in this direction may add value in the prevention and cure of complex chronic diseases.
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20
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Seyed Hosseini E, Alizadeh Zarei M, Tarrahimofrad H, Zamani J, Haddad Kashani H, Ahmad E, Nikzad H. Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs. Biol Res 2023; 56:3. [PMID: 36658640 PMCID: PMC9854214 DOI: 10.1186/s40659-023-00412-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 01/09/2023] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS AND MATERIALS In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.
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Affiliation(s)
- Elahe Seyed Hosseini
- grid.444768.d0000 0004 0612 1049Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Science, Kashan, Iran ,grid.444768.d0000 0004 0612 1049Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Marziyeh Alizadeh Zarei
- grid.444768.d0000 0004 0612 1049Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Science, Kashan, Iran
| | - Hossein Tarrahimofrad
- grid.419420.a0000 0000 8676 7464Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Javad Zamani
- grid.419420.a0000 0000 8676 7464Department of Plant Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Hamed Haddad Kashani
- grid.444768.d0000 0004 0612 1049Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Ejaz Ahmad
- grid.214458.e0000000086837370Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109 USA
| | - Hossein Nikzad
- grid.444768.d0000 0004 0612 1049Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Science, Kashan, Iran ,grid.444768.d0000 0004 0612 1049Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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21
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Talpan D, Salla S, Seidelmann N, Walter P, Fuest M. Antifibrotic Effects of Caffeine, Curcumin and Pirfenidone in Primary Human Keratocytes. Int J Mol Sci 2023; 24:ijms24021461. [PMID: 36674976 PMCID: PMC9862324 DOI: 10.3390/ijms24021461] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/14/2023] Open
Abstract
We evaluated the small molecules (AFM) caffeine, curcumin and pirfenidone to find non-toxic concentrations reducing the transformation of activated human corneal stromal keratocytes (aCSK) to scar-inducing myofibroblasts (MYO-SF). CSK were isolated from 16 human corneas unsuitable for transplantation and expanded for three passages in control medium (0.5% FBS). Then, aCSK were exposed to concentrations of caffeine of 0−500 μM, curcumin of 0−200 μM, pirfenidone of 0−2.2 nM and the profibrotic cytokine TGF-β1 (10 ng/mL) for 48 h. Alterations in viability and gene expression were evaluated by cell viability staining (FDA/PI), real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. We found that all AFMs reduced cell counts at high concentrations. The highest concentrations with no toxic effect were 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone. The addition of TGF-β1 to the control medium effectively transformed aCSK into myofibroblasts (MYO-SF), indicated by a 10-fold increase in α-smooth muscle actin (SMA) expression, a 39% decrease in lumican (LUM) expression and a 98% decrease in ALDH3A1 expression (p < 0.001). The concentrations of 100 µM of caffeine, 20/50 µM of curcumin and 1.1 nM of pirfenidone each significantly reduced SMA expression under TGF-β1 stimulation (p ≤ 0.024). LUM and ALDH3A1 expression remained low under TGF-β1 stimulation, independently of AFM supplementation. Immunocytochemistry showed that 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone reduce the conversion rate of aCSK to SMA+ MYO-SF. In conclusion, in aCSK, 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone significantly reduced SMA expression and MYO-SF conversion under TGF-β1 stimulation, with no influence on cell counts. However, the AFMs were unable to protect aCSK from characteristic marker loss.
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Affiliation(s)
- Delia Talpan
- Department of Ophthalmology, RWTH Aachen University, 52074 Aachen, Germany
| | - Sabine Salla
- Department of Ophthalmology, RWTH Aachen University, 52074 Aachen, Germany
- Cornea Bank Aachen, RWTH Aachen University, 52074 Aachen, Germany
| | - Nina Seidelmann
- Department of Ophthalmology, RWTH Aachen University, 52074 Aachen, Germany
| | - Peter Walter
- Department of Ophthalmology, RWTH Aachen University, 52074 Aachen, Germany
- Cornea Bank Aachen, RWTH Aachen University, 52074 Aachen, Germany
| | - Matthias Fuest
- Department of Ophthalmology, RWTH Aachen University, 52074 Aachen, Germany
- Cornea Bank Aachen, RWTH Aachen University, 52074 Aachen, Germany
- Correspondence:
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22
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Sedighiyan M, Jafari E, Athar SS, Yekaninejad MS, Alvandi E, Abdolahi M, Djalali M. The Effects of Nano-curcumin Supplementation on Leptin and Adiponectin in Migraine Patients: A Double-blind Clinical Trial Study from Gene Expression to Clinical Symptoms. Endocr Metab Immune Disord Drug Targets 2023; 23:711-720. [PMID: 35786344 DOI: 10.2174/1871530322666220701100817] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/31/2022] [Accepted: 04/06/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Migraine is a disabling neurogenic disorder characterized by recurrent headache attacks. Adipokines act as inflammatory and pain mediators that contribute to migraine pathogenesis. Leptin and adiponectin levels change in migraine patients and are associated with headache attacks. Curcumin can exert modulatory and analgesic effects on adipokines through several mechanisms, from gene expression to suppressing pain. The aim of the present study was to evaluate the effects of nano-curcumin supplementation on leptin and adiponectin gene expression, their serum levels and migraine symptoms in patients with migraine. METHODS Forty-four episodic migraine patients enrolled in this trial were divided into two groups as nano-curcumin (80 mg/day) and placebo group, over a two-month period. At the beginning and the end of the study, the mRNA expression of leptin and adiponectin from isolated PBMCs and their serum levels were measured using real-time PCR and ELISA method, respectively. The headache frequencies, severity and duration of pain were also recorded. RESULTS The results of the present research showed that nano-curcumin can up-regulate adiponectin mRNA and increase its serum level significantly (P < 0.05). In the case of leptin, a reduction in gene expression and concentration was found in the nano-curcumin group but it was not statistically significant (P > 0.05). Nano-curcumin also significantly reduced the frequency, severity and duration of headaches (P < 0.05). CONCLUSION These findings indicate that nano-curcumin supplement can be considered as a promising approach to migraine management and clinical symptoms improvement.
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Affiliation(s)
- Mohsen Sedighiyan
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
| | - Elham Jafari
- Headache Research Center, Sina Hospital, Tehran University of Medical Sciences, Imam Khomeini Street, Tehran, Iran
| | - Sara Sohrabi Athar
- Department of Human Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Resalat Street, Urmia, Iran
| | - Mir-Saeed Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ehsan Alvandi
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
| | - Mina Abdolahi
- Amir Alam Hospital Complexes, Tehran University of Medical Sciences, Sa'adi Street, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
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Sadeghian M, Rahmani S, Jafarieh A, Jamialahmadi T, Sahebkar A. The effect of curcumin supplementation on renal function: A systematic and meta-analysis of randomized controlled trials. J Funct Foods 2023. [DOI: 10.1016/j.jff.2022.105396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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24
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de Oliveira GV, Alvares TS. Effect of curcumin on endothelial function in humans and their proposed physiological mechanism: Insights in formulating curcumin products supplementation. PHARMANUTRITION 2022. [DOI: 10.1016/j.phanu.2022.100313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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25
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Abe T, Horisawa Y, Kikuchi O, Ozawa-Umeta H, Kishimoto A, Katsuura Y, Imaizumi A, Hashimoto T, Shirakawa K, Takaori-Kondo A, Yusa K, Asakura T, Kakeya H, Kanai M. Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin. Eur J Pharmacol 2022; 935:175321. [PMID: 36228744 DOI: 10.1016/j.ejphar.2022.175321] [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: 04/25/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/16/2022]
Abstract
Curcumin (aglycone curcumin) has antitumor properties in a variety of malignancies via the alteration of multiple cancer-related biological pathways; however, its clinical application has been hampered due to its poor bioavailability. To overcome this limitation, we have developed a synthesized curcumin β-D-glucuronide sodium salt (TBP1901), a prodrug form of aglycone curcumin. In this study, we aimed to clarify the pharmacologic characteristics of TBP1901. In β-glucuronidase (GUSB)-proficient mice, both curcumin β-D-glucuronide and its active metabolite, aglycone curcumin, were detected in the blood after TBP1901 injection, whereas only curcumin β-D-glucuronide was detected in GUSB-impaired mice, suggesting that GUSB plays a pivotal role in the conversion of TBP1901 into aglycone curcumin in vivo. TBP1901 itself had minimal antitumor effects in vitro, whereas it demonstrated significant antitumor effects in vivo. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen disclosed the genes associated with NF-κB signaling pathway and mitochondria were among the highest hit. In vitro, aglycone curcumin inhibited NF-kappa B signaling pathways whereas it caused production of reactive oxygen species (ROS). ROS scavenger, N-acetyl-L-cysteine, partially reversed antitumor effects of aglycone curcumin. In summary, TBP1901 can exert antitumor effects as a prodrug of aglycone curcumin through GUSB-dependent activation.
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Affiliation(s)
| | - Yoshihito Horisawa
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Osamu Kikuchi
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | | | | | | | | | - Kotaro Shirakawa
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kosuke Yusa
- Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Tadashi Asakura
- Radioisotope Research Facilities, Jikei University School of Medicine, Tokyo, Japan
| | - Hideaki Kakeya
- Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
| | - Masashi Kanai
- Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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26
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Formulation development and in vitro–in vivo anticancer potential of novel nanoliposomal fluorinated curcuminoids. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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27
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Sedighiyan M, Abdolahi M, Jafari E, Vahabi Z, Sohrabi Athar S, Hadavi S, Narimani Zamanabadi M, Yekaninejad MS, Djalali M. The effects of nano-curcumin supplementation on adipokines levels in obese and overweight patients with migraine: a double blind clinical trial study. BMC Res Notes 2022; 15:189. [PMID: 35606882 PMCID: PMC9125853 DOI: 10.1186/s13104-022-06074-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 05/11/2022] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine. RESULTS Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings. TRIAL REGISTRATION This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.
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Affiliation(s)
- Mohsen Sedighiyan
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
| | - Mina Abdolahi
- Amir Alam Hospital Complexes, Tehran University of Medical Sciences, Sa’adi Street, Tehran, Iran
| | - Elham Jafari
- Headache Research Center, Sina Hospital, Tehran University of Medical Sciences, Imam Khomeini Street, Tehran, Iran
| | - Zahra Vahabi
- Department of Geriatric Medicine, Ziaeian Hospital, Tehran University of Medical Sciences, Ghazvin street, Tehran, Iran
- Memory and Behavioral Neurology Division, Roozbeh Hospital, Tehran University of Medical Sciences, Kargar Street, Tehran, Iran
| | - Sara Sohrabi Athar
- Department of Human Nutrition, Faculty of Medicine, Urmia University of Medical Sciences, Resalat Street, Urmia, Iran
| | - Shima Hadavi
- Treatment Department, Tehran University of Medical Sciences, Hafez Street, Tehran, Iran
| | - Mahnaz Narimani Zamanabadi
- Department of Anesthesiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mir-Saeed Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
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Shaikh S, Shaikh J, Naba YS, Doke K, Ahmed K, Yusufi M. Curcumin: reclaiming the lost ground against cancer resistance. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2022; 4:298-320. [PMID: 35582033 PMCID: PMC9019276 DOI: 10.20517/cdr.2020.92] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 12/15/2020] [Accepted: 01/06/2021] [Indexed: 12/11/2022]
Abstract
Curcumin, a polyphenol, has a wide range of biological properties such as anticancer, antibacterial, antitubercular, cardioprotective and neuroprotective. Moreover, the anti-proliferative activities of Curcumin have been widely studied against several types of cancers due to its ability to target multiple pathways in cancer. Although Curcumin exhibited potent anticancer activity, its clinical use is limited due to its poor water solubility and faster metabolism. Hence, there is an immense interest among researchers to develop potent, water-soluble, and metabolically stable Curcumin analogs for cancer treatment. While drug resistance remains a major problem in cancer therapy that renders current chemotherapy ineffective, curcumin has shown promise to overcome the resistance and re-sensitize cancer to chemotherapeutic drugs in many studies. In the present review, we are summarizing the role of curcumin in controlling the proliferation of drug-resistant cancers and development of curcumin-based therapeutic applications from cell culture studies up to clinical trials.
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Affiliation(s)
- Siraj Shaikh
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India.,Advanced Scientific Research Laboratory, Azam Campus, Pune 411001, India
| | - Javed Shaikh
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India.,Advanced Scientific Research Laboratory, Azam Campus, Pune 411001, India
| | - Yusufi Sadia Naba
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India
| | - Kailas Doke
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India.,Advanced Scientific Research Laboratory, Azam Campus, Pune 411001, India
| | - Khursheed Ahmed
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India.,Advanced Scientific Research Laboratory, Azam Campus, Pune 411001, India
| | - Mujahid Yusufi
- Post-Graduate Department of Chemistry and Research Center, Abeda Inamdar Senior College of Arts, Science and Commerce (Affiliated to SPPU), Pune 411001, India.,Advanced Scientific Research Laboratory, Azam Campus, Pune 411001, India
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29
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Zhou ZW, Long HZ, Xu SG, Li FJ, Cheng Y, Luo HY, Gao LC. Therapeutic Effects of Natural Products on Cervical Cancer: Based on Inflammatory Pathways. Front Pharmacol 2022; 13:899208. [PMID: 35645817 PMCID: PMC9136176 DOI: 10.3389/fphar.2022.899208] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/26/2022] [Indexed: 12/09/2022] Open
Abstract
Inflammation is a protective response of the body to an irritant. When an inflammatory response occurs, immune cells are recruited to the injury, eliminating the irritation. The excessive inflammatory response can cause harm to the organism. Inflammation has been found to contribute to cervical cancer if there is a problem with the regulation of inflammatory response. Cervical cancer is one of the most common malignant tumors globally, and the incidence tends to be younger. The harm of cervical cancer cannot be ignored. The standard treatments for cervical cancer include surgery, radiotherapy and chemotherapy. However, the prognosis for this treatment is poor, so it is urgent to find a safer and more effective treatment. Natural products are considered excellent candidates for the treatment of cervical cancer. In this review, we first describe the mechanisms by which inflammation induces cervical cancer. Subsequently, we highlight natural products that can treat cervical cancer through inflammatory pathways. We also introduce natural products for the treatment of cervical cancer in clinical trials. Finally, methods to improve the anticancer properties of natural products were added, and the development status of natural products was discussed.
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Affiliation(s)
- Zi-Wei Zhou
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Hui-Zhi Long
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Shuo-Guo Xu
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Feng-Jiao Li
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Yan Cheng
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Hong-Yu Luo
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
| | - Li-Chen Gao
- School of Pharmacy, University of South China, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China
- Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Changsha, China
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30
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Rashwan AK, Karim N, Xu Y, Hanafy NAN, Li B, Mehanni AHE, Taha EM, Chen W. An updated and comprehensive review on the potential health effects of curcumin-encapsulated micro/nanoparticles. Crit Rev Food Sci Nutr 2022; 63:9731-9751. [PMID: 35522080 DOI: 10.1080/10408398.2022.2070906] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Curcumin (CUR) is a natural hydrophobic compound, which is available in turmeric rhizome. It has several bioactivities including antioxidant, anti-obesity, anti-diabetic, cardioprotective, anti-inflammatory, antimicrobial, anticancer, and other activities. Despite its medical and biological benefits, it is using in limitations because of its hydrophobicity and sensitivity. These unfavorable conditions further reduced the bioavailability (BA) and biological efficacy of CUR. This review summarizes the stability and BA of free- and encapsulated-CUR, as well as comprehensively discusses the potential biological activity of CUR-loaded various micro-/nano-encapsulation systems. The stability and BA of CUR can be improved via loading in different encapsulation systems, including nanoemulsions, liposomes, niosomes, biopolymer-based nanoparticles, nano-hydrogel, and others. Biopolymer-based nanoparticles (especially poly lactic-co-glycolic acid (PLGA), zein, and chitosan) and nano-gels are the best carriers for encapsulating and delivering CUR. Both delivery systems are suitable because of their excellent functional properties such as high encapsulation efficiency, well-stability against unfavorable conditions, and can be coated using other encapsulation systems. Based on available evidences, encapsulated-CUR exerted greater biological activities especially anticancer (breast cancer), antioxidant, antidiabetic, and neuroprotective effects.
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Affiliation(s)
- Ahmed K Rashwan
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
- Department of Food and Dairy Sciences, Faculty of Agriculture, South Valley University, Qena, Egypt
| | - Naymul Karim
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Yang Xu
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Nemany A N Hanafy
- Nanomedicine Group, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Bin Li
- College of Food Science, Shenyang Agricultural University, Shenyang, China
| | - Abul-Hamd E Mehanni
- Department of Food Science and Nutrition, Faculty of Agriculture, Sohag University, Sohag, Egypt
| | - Eman M Taha
- Department of Food and Dairy Sciences, Faculty of Agriculture, South Valley University, Qena, Egypt
| | - Wei Chen
- Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
- Ningbo Research Institute, Zhejiang University, Ningbo, China
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31
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Ou X, Karmakar B, Awwad NS, Ibrahium HA, Osman HEH, El-kott AF, Abdel-Daim MM. Au nanoparticles adorned chitosan-modified magnetic nanocomposite: An investigation towards its antioxidant and anti-hepatocarcinoma activity in vitro. INORG CHEM COMMUN 2022. [DOI: 10.1016/j.inoche.2022.109221] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Safety Evaluation in Healthy Colombian Volunteers of P2Et Extract Obtained from Caesalpinia spinosa: Design 3+3 Phase I Clinical Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7943001. [PMID: 35251213 PMCID: PMC8890855 DOI: 10.1155/2022/7943001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 01/21/2022] [Accepted: 01/25/2022] [Indexed: 11/17/2022]
Abstract
The polyphenol-enriched extract called P2Et derived from Caesalpinia spinosa (C. spinosa) had antitumor and immunomodulatory activities reported in breast cancer, leukemia, and melanoma. The aim of this study was to evaluate the safety and maximum tolerated dose of P2Et extract in Colombian healthy volunteers in a phase 1 clinical trial, open labelled, single-arm, dose-escalation design 3 + 3. Seven healthy volunteers were included; P2Et was administrated in capsules of 600 mg/d for 28 days. Analysis by intention to treat was performed. 4 volunteers showed adverse events and discontinued the intervention. 94.6% of AE were grade 1, and most of AE had a reasonable possibility of a relationship with the P2Et (83.8%). We found that the oral administration of P2Et is safe in healthy humans with a maximum tolerated dose of 600 mg/d. There was no severe toxicity; most of the adverse events were mild, without significant changes in the safety parameters evaluated.
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Noor NA, Hosny EN, Khadrawy YA, Mourad IM, Othman AI, Aboul Ezz HS, Mohammed HS. Effect of curcumin nanoparticles on streptozotocin-induced male Wistar rat model of Alzheimer's disease. Metab Brain Dis 2022; 37:343-357. [PMID: 35048324 DOI: 10.1007/s11011-021-00897-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 12/13/2021] [Indexed: 12/14/2022]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-ɑ) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD.
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Affiliation(s)
- Neveen A Noor
- Zoology department, Faculty of Science, Cairo University, Giza, Egypt
| | - Eman N Hosny
- Department of Medical Physiology, Medical Division, National Research Center, El-Behouth St., Giza, Egypt
| | - Yasser A Khadrawy
- Department of Medical Physiology, Medical Division, National Research Center, El-Behouth St., Giza, Egypt.
| | - Iman M Mourad
- Zoology department, Faculty of Science, Cairo University, Giza, Egypt
| | - Amel I Othman
- Zoology department, Faculty of Science, Cairo University, Giza, Egypt
| | - Heba S Aboul Ezz
- Zoology department, Faculty of Science, Cairo University, Giza, Egypt
| | - Haitham S Mohammed
- Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
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Pluta R, Furmaga-Jabłońska W, Januszewski S, Czuczwar SJ. Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer's Disease Proteinopathy: Possible Therapeutic Role of Curcumin. Nutrients 2022; 14:nu14020248. [PMID: 35057429 PMCID: PMC8779038 DOI: 10.3390/nu14020248] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 02/01/2023] Open
Abstract
For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer’s disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.
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Affiliation(s)
- Ryszard Pluta
- Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;
- Correspondence: ; Tel.: +48-22-6086-540
| | - Wanda Furmaga-Jabłońska
- Department of Neonate and Infant Pathology, Medical University of Lublin, 20-093 Lublin, Poland;
| | - Sławomir Januszewski
- Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland;
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Amekyeh H, Alkhader E, Sabra R, Billa N. Prospects of Curcumin Nanoformulations in Cancer Management. Molecules 2022; 27:361. [PMID: 35056675 PMCID: PMC8777756 DOI: 10.3390/molecules27020361] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
There is increasing interest in the use of natural compounds with beneficial pharmacological effects for managing diseases. Curcumin (CUR) is a phytochemical that is reportedly effective against some cancers through its ability to regulate signaling pathways and protein expression in cancer development and progression. Unfortunately, its use is limited due to its hydrophobicity, low bioavailability, chemical instability, photodegradation, and fast metabolism. Nanoparticles (NPs) are drug delivery systems that can increase the bioavailability of hydrophobic drugs and improve drug targeting to cancer cells via different mechanisms and formulation techniques. In this review, we have discussed various CUR-NPs that have been evaluated for their potential use in treating cancers. Formulations reviewed include lipid, gold, zinc oxide, magnetic, polymeric, and silica NPs, as well as micelles, dendrimers, nanogels, cyclodextrin complexes, and liposomes, with an emphasis on their formulation and characteristics. CUR incorporation into the NPs enhanced its pharmaceutical and therapeutic significance with respect to solubility, absorption, bioavailability, stability, plasma half-life, targeted delivery, and anticancer effect. Our review shows that several CUR-NPs have promising anticancer activity; however, clinical reports on them are limited. We believe that clinical trials must be conducted on CUR-NPs to ensure their effective translation into clinical applications.
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Affiliation(s)
- Hilda Amekyeh
- Department of Pharmaceutics, School of Pharmacy, University of Health and Allied Sciences, Ho PMB 31, Ghana;
| | - Enas Alkhader
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan;
| | - Rayan Sabra
- Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA;
| | - Nashiru Billa
- Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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The Effects of Modified Curcumin Preparations on Glial Morphology in Aging and Neuroinflammation. Neurochem Res 2022; 47:813-824. [PMID: 34988899 DOI: 10.1007/s11064-021-03499-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 11/26/2021] [Accepted: 11/27/2021] [Indexed: 12/14/2022]
Abstract
Neuroinflammation is characterized by reactive microglia and astrocytes (collectively called gliosis) in the central nervous system and is considered as one of the main pathological hallmarks in different neurodegenerative diseases such as Alzheimer's disease, age-related dementia, and multiple sclerosis. Upon activation, glia undergoes structural and morphological changes such as the microglial cells swell in size and astrocytes become bushy, which play both beneficial and detrimental roles. Hence, they are unable to perform the normal physiological role in brain immunity. Curcumin, a cytokine suppressive anti-inflammatory drug, has a high proven pre-clinical potency and efficacy to reverse chronic neuroinflammation by attenuating the activation and morphological changes that occur in the microglia and astrocytes. This review will highlight the recent findings on the tree structure changes of microglia and astrocytes in neuroinflammation and the effects of curcumin against the activation and morphology of glial cells.
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Lunz Macedo AC, Santisteban Lores LE, Albuquerque JAT, Duarte NJC, Romano P, Ebner PAR, Rezende VM, Silva CA, Andrade LEC, Vasconcelos DM, Isaac L. A rare association between factor H deficiency and lupus: Case report and experimental treatment with curcumin. Front Pediatr 2022; 10:1039291. [PMID: 36405845 PMCID: PMC9673011 DOI: 10.3389/fped.2022.1039291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/04/2022] [Indexed: 11/06/2022] Open
Abstract
Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. FH deficiency is a rare condition that causes unregulated C3 consumption, leading to an increased susceptibility to infections and glomerulopathies. Our previous studies have demonstrated a FH deficient patient carrying a c.452G > A, p.R127H FH mutation which leads to a misfolded protein and its retention in the endoplasmic reticulum. In his cultured fibroblasts, FH-delayed secretion was partially rescued when treated with curcumin, and once secreted, exhibited normal regulatory function. Here, we report a childhood-onset systemic lupus erythematosus (cSLE) in this FH deficient patient and the results of experimental treatment with curcumin aiming to rescue FH secretion and regulatory activity.
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Affiliation(s)
- Ana Catarina Lunz Macedo
- Pediatric Nephrology Unit, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil.,Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Nilo José Coelho Duarte
- Laboratory of Medical Investigation - LIM 03- Central Laboratory Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Paschoalina Romano
- Laboratory of Medical Investigation - LIM 03- Central Laboratory Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Persio Almeida Rezende Ebner
- Laboratory of Medical Investigation - LIM 03- Central Laboratory Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Vinicius Marcondes Rezende
- Laboratory of Medical Investigation - LIM 03- Central Laboratory Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Clovis A Silva
- Pediatric Rheumatology Unit, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | | | - Dewton Moraes Vasconcelos
- Laboratory of Medical Investigation in Dermatology and Immunodeficiencies - LIM 56, Institto de Medicina Tropical, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Lourdes Isaac
- Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil
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Kumar A, Hegde M, Parama D, Kunnumakkara AB. Curcumin: The Golden Nutraceutical on the Road to Cancer Prevention and Therapeutics. A Clinical Perspective. Crit Rev Oncog 2022; 27:33-63. [PMID: 37183937 DOI: 10.1615/critrevoncog.2023045587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Cancer is considered as the major public health scourge of the 21st century. Although remarkable strides were made for developing targeted therapeutics, these therapies suffer from lack of efficacy, high cost, and debilitating side effects. Therefore, the search for safe, highly efficacious, and affordable therapies is paramount for establishing a treatment regimen for this deadly disease. Curcumin, a known natural, bioactive, polyphenol compound from the spice turmeric (Curcuma longa), has been well documented for its wide range of pharmacological and biological activities. A plethora of literature indicates its potency as an anti-inflammatory and anti-cancer agent. Curcumin exhibits anti-neoplastic attributes via regulating a wide array of biological cascades involved in mutagenesis, proliferation, apoptosis, oncogene expression, tumorigenesis, and metastasis. Curcumin has shown a wide range of pleiotropic anti-proliferative effect in multiple cancers and is a known inhibitor of varied oncogenic elements, including nuclear factor kappa B (NF-κB), c-myc, cyclin D1, Bcl-2, VEGF, COX-2, NOS, tumor necrosis factor alpha (TNF-α), interleukins, and MMP-9. Further, curcumin targets different growth factor receptors and cell adhesion molecules involved in tumor growth and progression, making it a most promising nutraceutical for cancer therapy. To date, curcumin-based therapeutics have completed more than 50 clinical trials for cancer. Although creative experimentation is still elucidating the immense potential of curcumin, systematic validation by proper randomized clinical trials warrant its transition from lab to bedside. Therefore, this review summarizes the outcome of diverse clinical trials of curcumin in various cancer types.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
| | - Mangala Hegde
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
| | - Dey Parama
- Cancer Biology Laboratory, DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Assam-781039, India
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Guwahati, Guwahati, Assam-781039, India
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Grilc NK, Sova M, Kristl J. Drug Delivery Strategies for Curcumin and Other Natural Nrf2 Modulators of Oxidative Stress-Related Diseases. Pharmaceutics 2021; 13:2137. [PMID: 34959418 PMCID: PMC8708625 DOI: 10.3390/pharmaceutics13122137] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/07/2021] [Accepted: 12/09/2021] [Indexed: 12/21/2022] Open
Abstract
Oxidative stress is associated with a wide range of diseases characterised by oxidant-mediated disturbances of various signalling pathways and cellular damage. The only effective strategy for the prevention of cellular damage is to limit the production of oxidants and support their efficient removal. The implication of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cellular redox status has spurred new interest in the use of its natural modulators (e.g., curcumin, resveratrol). Unfortunately, most natural Nrf2 modulators are poorly soluble and show extensive pre-systemic metabolism, low oral bioavailability, and rapid elimination, which necessitates formulation strategies to circumvent these limitations. This paper provides a brief introduction on the cellular and molecular mechanisms involved in Nrf2 modulation and an overview of commonly studied formulations for the improvement of oral bioavailability and in vivo pharmacokinetics of Nrf2 modulators. Some formulations that have also been studied in vivo are discussed, including solid dispersions, self-microemulsifying drug delivery systems, and nanotechnology approaches, such as polymeric and solid lipid nanoparticles, nanocrystals, and micelles. Lastly, brief considerations of nano drug delivery systems for the delivery of Nrf2 modulators to the brain, are provided. The literature reviewed shows that the formulations discussed can provide various improvements to the bioavailability and pharmacokinetics of natural Nrf2 modulators. This has been demonstrated in animal models and clinical studies, thereby increasing the potential for the translation of natural Nrf2 modulators into clinical practice.
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Affiliation(s)
- Nina Katarina Grilc
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia;
| | - Matej Sova
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia;
| | - Julijana Kristl
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia;
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Bioactive Compounds and Nanodelivery Perspectives for Treatment of Cardiovascular Diseases. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app112211031] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Bioactive compounds are comprised of small quantities of extra nutritional constituents providing both health benefits and enhanced nutritional value, based on their ability to modulate one or more metabolic processes. Plant-based diets are being thoroughly researched for their cardiovascular properties and effectiveness against cancer. Flavonoids, phytoestrogens, phenolic compounds, and carotenoids are some of the bioactive compounds that aim to work in prevention and treating the cardiovascular disease in a systemic manner, including hypertension, atherosclerosis, and heart failure. Their antioxidant and anti-inflammatory properties are the most important characteristics that make them favorable candidates for CVDs treatment. However, their low water solubility and stability results in low bioavailability, limited accessibility, and poor absorption. The oral delivery of bioactive compounds is constrained due to physiological barriers such as the pH, mucus layer, gastrointestinal enzymes, epithelium, etc. The present review aims to revise the main bioactive compounds with a significant role in CVDs in terms of preventive, diagnostic, and treatment measures. The advantages of nanoformulations and novel multifunctional nanomaterials development are described in order to overcome multiple obstacles, including the physiological ones, by summarizing the most recent preclinical data and clinical trials reported in the literature. Nanotechnologies will open a new window in the area of CVDs with the opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues.
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The Inhibitory Activity of Curcumin on P-Glycoprotein and Its Uptake by and Efflux from LS180 Cells Is Not Affected by Its Galenic Formulation. Antioxidants (Basel) 2021; 10:antiox10111826. [PMID: 34829695 PMCID: PMC8615263 DOI: 10.3390/antiox10111826] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 11/15/2021] [Accepted: 11/15/2021] [Indexed: 12/14/2022] Open
Abstract
The biological activities of curcumin in humans, including its antioxidative and anti-inflammatory functions, are limited by its naturally low bioavailability. Different formulation strategies have been developed, but the uptake of curcumin from these galenic formulations into and efflux from intestinal cells, which may be critical processes limiting bioavailability, have not been directly compared. Furthermore, little is known about their effect on P-glycoprotein activity, an important determinant of the pharmacokinetics of potentially co-administered drugs. P-glycoprotein activity was determined in LS180 cells, incubated with 30 or 60 µmol/L of curcumin in the form of seven different formulations or native curcuma extract for 1 h. All formulations inhibited P-glycoprotein activity at both concentrations. Curcumin uptake, after 1 h incubation of LS180 cells with the formulations (60 µmol/L), showed significant variability but no consistent effects. After 1 h pre-treatment with the formulations and further 8 h with curcumin-free medium, curcumin in cell culture supernatants, reflecting the efflux, differed between individual formulations, again without a clear effect. In conclusion, curcumin inhibits P-glycoprotein activity independently of its formulation. Its uptake by and efflux from intestinal cells was not significantly different between formulations, indicating that these processes are not important regulatory points for its bioavailability.
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Curcumin and Radiotherapy Exert Synergistic Anti-Glioma Effect In Vitro. Biomedicines 2021; 9:biomedicines9111562. [PMID: 34829791 PMCID: PMC8615260 DOI: 10.3390/biomedicines9111562] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 11/17/2022] Open
Abstract
Curcumin, a bioactive polyphenol, is known to have anticancer properties. In this study, the effectiveness of curcumin pretreatment as a strategy for radio-sensitizing glioblastoma cell lines was explored. For this, U87 and T98 cells were treated with curcumin, exposed to 2 Gy or 4 Gy of irradiation, and the combined effect was compared to the antiproliferative effect of each agent when given individually. Cell viability and proliferation were evaluated with the trypan blue exclusion assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic effects of the combination treatment were analyzed with CompuSyn software. To examine how the co-treatment affected different phases of cell-cycle progression, a cell-cycle analysis via flow cytometry was performed. Treatment with curcumin and radiation significantly reduced cell viability in both U87 and T98 cell lines. The combination treatment arrested both cell lines at the G2/M phase to a higher extent than radiation or curcumin treatment alone. The synergistic effect of curcumin when combined with temozolomide resulted in increased tumor cell death. Our results demonstrate for the first time that low doses of curcumin and irradiation exhibit a strong synergistic anti-proliferative effect on glioblastoma cells in vitro. Therefore, this combination may represent an innovative and promising strategy for the treatment of glioblastoma, and further studies are needed to fully understand the molecular mechanism underlying this effect.
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Flory S, Sus N, Haas K, Jehle S, Kienhöfer E, Waehler R, Adler G, Venturelli S, Frank J. Increasing Post-Digestive Solubility of Curcumin Is the Most Successful Strategy to Improve its Oral Bioavailability: A Randomized Cross-Over Trial in Healthy Adults and In Vitro Bioaccessibility Experiments. Mol Nutr Food Res 2021; 65:e2100613. [PMID: 34665507 DOI: 10.1002/mnfr.202100613] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 08/26/2021] [Indexed: 12/17/2022]
Abstract
SCOPE Different mechanistic approaches to improve the low oral bioavailability of curcumin have been developed, but not yet directly compared in humans. METHODS AND RESULTS In a randomized, double-blind, cross-over trial with 12 healthy adults, the 24 h pharmacokinetics of a single dose of 207 mg curcumin is compared from the following formulations: native, liposomes, with turmeric oils, with adjuvants (including piperine), submicron-particles, phytosomes, γ-cyclodextrin complexes, and micelles. No free, but only conjugated curcumin is detected in all subjects. Compared to native curcumin, a significant increase in the area under the plasma concentration-time curve is observed for micellar curcumin (57-fold) and the curcumin-γ-cyclodextrin complex (30-fold) only. In vitro digestive stability, solubility, and micellization efficiency of micellar curcumin (100%, 80%, and 55%) and curcumin-γ-cyclodextrin complex (73%, 33%, and 23%) are higher compared to all other formulations (<72%, <8%, and <4%). The transport efficiencies through Caco-2 cell monolayers of curcumin from the digested mixed-micellar fractions did not differ significantly. CONCLUSION The improved oral bioavailability of micellar curcumin, and to a lesser extent of γ-cyclodextrin curcumin complexes, appears to be facilitated by increased post-digestive stability and solubility, whereas strategies targeting post-absorptive processes, including inhibition of biotransformation, appear ineffective.
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Affiliation(s)
- Sandra Flory
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Nadine Sus
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Kathrin Haas
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Sina Jehle
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Eva Kienhöfer
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | | | - Günther Adler
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Sascha Venturelli
- Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
| | - Jan Frank
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
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Serum Cytokine Profile, Beta-Hexosaminidase A Enzymatic Activity and GM 2 Ganglioside Levels in the Plasma of a Tay-Sachs Disease Patient after Cord Blood Cell Transplantation and Curcumin Administration: A Case Report. Life (Basel) 2021; 11:life11101007. [PMID: 34685379 PMCID: PMC8539434 DOI: 10.3390/life11101007] [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: 08/09/2021] [Revised: 09/17/2021] [Accepted: 09/20/2021] [Indexed: 11/17/2022] Open
Abstract
Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder that occurs due to a deficiency of a β hexosaminidase A (HexA) enzyme, resulting in the accumulation of GM2 gangliosides. In this work, we analyzed the effect of umbilical cord blood cell transplantation (UCBCT) and curcumin administration on the course of the disease in a patient with adult TSD. The patient’s serum cytokine profile was determined using multiplex analysis. The level of GM2 gangliosides in plasma was determined using mass spectrometry. The enzymatic activity of HexA in the plasma of the patient was assessed using a fluorescent substrate assay. The HexA α-subunit (HexA) concentration was determined using ELISA. It was shown that both UCBCT and curcumin administration led to a change in the patient’s cytokine profile. The UCBCT resulted in an increase in the concentration of HexA in the patient’s serum and in an improvement in the patient’s neurological status. However, neither UCBCT nor curcumin were able to alter HexA activity and the level of GM2 in patient’s plasma. The data obtained indicate that UCBCT and curcumin administration can alter the immunity of a patient with TSD, reduce the level of inflammatory cytokines and thereby improve the patient’s condition.
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Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review. Nutrients 2021; 13:nu13093126. [PMID: 34579002 PMCID: PMC8471428 DOI: 10.3390/nu13093126] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 09/03/2021] [Accepted: 09/04/2021] [Indexed: 12/11/2022] Open
Abstract
Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.
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Mahjoob M, Stochaj U. Curcumin nanoformulations to combat aging-related diseases. Ageing Res Rev 2021; 69:101364. [PMID: 34000462 DOI: 10.1016/j.arr.2021.101364] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 05/11/2021] [Accepted: 05/12/2021] [Indexed: 02/07/2023]
Abstract
Aging increases the susceptibility to a diverse set of diseases and disorders, including neurodegeneration, cancer, diabetes, and arthritis. Natural compounds are currently being explored as alternative or complementary agents to treat or prevent aging-related malfunctions. Curcumin, a phytochemical isolated from the spice turmeric, has garnered great interest in recent years. With anti-oxidant, anti-inflammatory, anti-microbial, and other physiological activities, curcumin has great potential for health applications. However, the benefits of curcumin are restricted by its low bioavailability and stability in biological systems. Curcumin nanoformulations, or nano-curcumin, may overcome these limitations. This review discusses different forms of nano-curcumin that have been evaluated in vitro and in vivo to treat or prevent aging-associated health impairments. We describe current barriers for the routine use of curcumin nanoformulations in the clinic. Our review highlights outstanding questions and future work that is needed to ensure nano-curcumin is efficient and safe to lessen the burden of aging-related health problems.
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Affiliation(s)
- Maryam Mahjoob
- Department of Physiology & Quantitative Life Sciences Program, McGill University, Montreal, QC, H3G 1Y6, Canada
| | - Ursula Stochaj
- Department of Physiology & Quantitative Life Sciences Program, McGill University, Montreal, QC, H3G 1Y6, Canada.
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Abdolahi M, Karimi E, Sarraf P, Tafakhori A, Siri G, Salehinia F, Sedighiyan M, Asanjarani B, Badeli M, Abdollahi H, Yoosefi N, Yousefi A, Rad AS, Djalali M. The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial. BMC Res Notes 2021; 14:283. [PMID: 34301320 PMCID: PMC8305494 DOI: 10.1186/s13104-021-05700-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 07/14/2021] [Indexed: 02/07/2023] Open
Abstract
Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023. Supplementary Information The online version contains supplementary material available at 10.1186/s13104-021-05700-x.
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Affiliation(s)
- Mina Abdolahi
- Amir Alam Hospital Complexes, Tehran University of Medical Sciences, Sa'adi Street, Tehran, Iran
| | - Elmira Karimi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
| | - Payam Sarraf
- Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.,Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Tafakhori
- Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.,Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Goli Siri
- Department of Internal Medicine, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Farahnaz Salehinia
- Department of Internal Medicine, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Sedighiyan
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, PO Box: 14155-6446, Tehran, Iran
| | - Behzad Asanjarani
- Department of Internal Medicine, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Badeli
- Department of Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, Tehran, Iran
| | - Hamed Abdollahi
- Department of Anesthesiology, Amir Alam Hospital Complexes, Tehran University of Medical Sciences, Sa'adi Street, Tehran, Iran
| | - Niyoosha Yoosefi
- Honours Cellular Anatomical Physiology, University of British Columbia, Vancouver, BC, Canada
| | - Abolghasem Yousefi
- Department of Anesthesiology, Amir Alam Hospital Complexes, Tehran University of Medical Sciences, Sa'adi Street, Tehran, Iran
| | - Amir Shayegan Rad
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, PO Box: 14155-6446, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Poursina Street, PO Box: 14155-6446, Tehran, Iran.
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Khezri K, Saeedi M, Mohammadamini H, Zakaryaei AS. A comprehensive review of the therapeutic potential of curcumin nanoformulations. Phytother Res 2021; 35:5527-5563. [PMID: 34131980 DOI: 10.1002/ptr.7190] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 05/19/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022]
Abstract
Today, due to the prevalence of various diseases such as the novel coronavirus (SARS-CoV-2), diabetes, central nervous system diseases, cancer, cardiovascular disorders, and so on, extensive studies have been conducted on therapeutic properties of natural and synthetic agents. A literature review on herbal medicine and commercial products in the global market showed that curcumin (Cur) has many therapeutic benefits compared to other natural ingredients. Despite the unique properties of Cur, its use in clinical trials is very limited. The poor biopharmaceutical properties of Cur such as short half-life in plasma, low bioavailability, poor absorption, rapid metabolism, very low solubility (at acidic and physiological pH), and the chemical instability in body fluids are major concerns associated with the clinical applications of Cur. Recently, nanoformulations are emerging as approaches to develop and improve the therapeutic efficacy of various drugs. Many studies have shown that Cur nanoformulations have tremendous therapeutic potential against various diseases such as SARS-CoV-2, cancer, inflammatory, osteoporosis, and so on. These nanoformulations can inhibit many diseases through several cellular and molecular mechanisms. However, successful long-term clinical results are required to confirm their safety and clinical efficacy. The present review aims to update and explain the therapeutic potential of Cur nanoformulations.
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Affiliation(s)
- Khadijeh Khezri
- Deputy of Food and Drug Administration, Urmia University of Medical Sciences, Urmia, Iran
| | - Majid Saeedi
- Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.,Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
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Oliveira G, Volino-Souza M, Conte-Júnior CA, Alvares TS. Food-derived polyphenol compounds and cardiovascular health: A nano-technological perspective. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101033] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Lai X, Geng X, Li M, Tang M, Liu Q, Yang M, Shen L, Zhu Y, Wang S. Glutathione-responsive PLGA nanocomplex for dual delivery of doxorubicin and curcumin to overcome tumor multidrug resistance. Nanomedicine (Lond) 2021; 16:1411-1427. [PMID: 34047204 DOI: 10.2217/nnm-2021-0100] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Aim: This work aims to develop an injectable nano-drug delivery system to overcome tumor multidrug resistance (MDR). Methods: A drug delivery nanoplatform based on PEGylated PLGA with glutathione (GSH) responsivity was constructed for dual delivery of doxorubicin and curcumin (termed DCNP), and its MDR reversal efficiency was studied in vitro and in vivo. Results: The DCNPs exhibited a rapid drug release profile under high GSH concentration and could enhance the cellular uptake and cytotoxicity of doxorubicin to MDR cancer cells. Moreover, the DCNPs showed better biocompatibility, longer blood circulation and enhanced antitumor efficiency compared with free drugs. Conclusion: The GSH-responsive nanocarrier is believed to be a promising candidate for overcoming tumor MDR.
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Affiliation(s)
- Xuandi Lai
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
| | - Xinran Geng
- Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen 518055, PR China
| | - Mengqing Li
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
| | - Mengxiong Tang
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
| | - Qiong Liu
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
| | - Mengsu Yang
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, PR China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, PR China
| | - Yu Zhu
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
| | - Shubin Wang
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science & Technology Medical Center, Shenzhen 518036, PR China
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