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Wei S, Li Y, Zhou J, Xia Y. Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance. Hereditas 2025; 162:15. [PMID: 39901302 PMCID: PMC11789369 DOI: 10.1186/s41065-025-00364-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/06/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) presents a significant global health burden, necessitating a deeper understanding of its molecular underpinnings for improved diagnostics and therapeutics. METHODS In this study, we investigated the expression profiles and clinical implications of MAP3K genes in GC using in silico and in vitro experiments. RESULTS Utilizing RT-qPCR analysis, we observed significant up-regulation of MAP3K1, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 in GC cell lines, while MAP3K2, MAP3K3, MAP3K11, MAP3K12, MAP3K13, MAP3K14, and MAP3K15 exhibited down-regulation. Prognostic evaluation revealed that elevated expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 was associated with shorter overall survival (OS), emphasizing their clinical significance. Furthermore, the diagnostic potential was demonstrated through robust Receiver operating characteristics (ROC) curve analysis, indicating the strong discriminatory power of these genes in distinguishing GC patients. Proteomic analysis further confirmed the higher expression of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes in GC. Methylation profiling further supported the idea that promoter hypomethylation of MAP3K1, MAP3K4, MAP3K7, MAP3K8, MAP3K9, and MAP3K10 genes was associated with their up-regulation. Single-cell functional analysis elucidated the involvement of MAP3K genes in shaping the tumor microenvironment. miRNA-mRNA network analysis revealed intricate regulatory mechanisms, with hsa-mir-200b-3p emerging as a key regulator. Finally, the MAP3K1 knockdown has shown significant impacts on the cellular behavior of the BGC823 cells. CONCLUSION This comprehensive assessment provides valuable insights into the role of MAP3K genes in GC, offering avenues for further research and therapeutic exploration.
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Affiliation(s)
- Senhui Wei
- Department of Gastroenterolog, Shenzhen Guangming District People's Hospital, Shenzhen City, 518107, P.R. China
| | - Ying Li
- Department of Gastroenterolog, Shenzhen Guangming District People's Hospital, Shenzhen City, 518107, P.R. China
| | - Jing Zhou
- Department of Gastroenterolog, Shenzhen Guangming District People's Hospital, Shenzhen City, 518107, P.R. China
| | - Yongming Xia
- Department of Hepatobiliary Gastrointestinal Surgery, Shenzhen Guangming District People's Hospital, Shenzhen City, 518107, P. R. China.
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Shadnoush M, Momenan M, Seidel V, Tierling S, Fatemi N, Nazemalhosseini-Mojarad E, Norooz MT, Cheraghpour M. A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer. Pharmacol Rep 2025; 77:103-123. [PMID: 39304638 DOI: 10.1007/s43440-024-00652-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 09/07/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related mortality worldwide. The efficacy of chemotherapy agents in CRC treatment is often limited due to toxic side effects, heterogeneity of cancer cells, and the possibility of chemoresistance which promotes cancer cell survival through several mechanisms. Combining chemotherapy agents with natural compounds like curcumin, a polyphenol compound from the Curcuma longa plant, has been reported to overcome chemoresistance and increase the sensitivity of cancer cells to chemotherapeutics. Curcumin, alone or in combination with chemotherapy agents, has been demonstrated to prevent chemoresistance by modulating various signaling pathways, reducing the expression of drug resistance-related genes. The purpose of this article is to provide a comprehensive update on studies that have investigated the ability of curcumin to enhance the efficacy of chemotherapy agents used in CRC. It is hoped that it can serve as a template for future research on the efficacy of curcumin, or other natural compounds, combined with chemotherapy agents to maximize the effectiveness of therapy and reduce the side effects that occur in CRC or other cancers.
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Affiliation(s)
- Mahdi Shadnoush
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehrnaz Momenan
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Sascha Tierling
- Department of Genetics/Epigenetics, Faculty NT, Life Sciences, Saarland University, Saarbrücken, Germany
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Tayefeh Norooz
- General Surgery Department, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran.
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Gabe HB, Queiroga FR, Taruhn KA, Trevisan R. Mitigating oxidative stress in oyster larvae: Curcumin promotes enhanced redox balance, antioxidant capacity, development, and resistance to antifouling compounds. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2025; 279:107231. [PMID: 39756171 DOI: 10.1016/j.aquatox.2024.107231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/27/2024] [Accepted: 12/27/2024] [Indexed: 01/07/2025]
Abstract
Curcumin (CUR) is a natural compound recognized for stimulating the expression of antioxidant genes. This characteristic has been used to promote animal health and production in aquaculture settings. We hypothesized that supplementing embryos of Crassostrea gigas oysters with CUR would improve their antioxidant capacity, development, and resilience to stress. Embryos were exposed to CUR ranging from 0.03 to 30 µM for 24 h. Their development was assessed, along with measurements of glutathione levels, glutathione S-transferase activity, antioxidant capacity, production of reactive oxygen species (ROS), metabolic activity, and resistance to organic hydroperoxide and the antifouling compound dichlorooctylisothiazolinone (DCOIT). Low curcumin concentrations (up to 1 μM) activated the d-larvae antioxidant system, with a significant threefold increase in glutathione levels and a 50 % decrease in ROS production. This enhancement in antioxidant defense improved the ability of larvae to detoxify organic hydroperoxide. It also resulted in larger larval size and increased survival rates, whether under normal conditions or exposure to peroxide or DCOIT. CUR shows great promise in supporting larval development, but high concentrations were toxic (EC50 = 2.90 μM), probably due to excessive antioxidant activation. Our results indicate that the antioxidant system may play a role in controlling bivalve early development. Understanding how antioxidants influence redox balance and gene expression during early life can enhance our knowledge of stress response mechanisms in marine organisms, offering insights into how they cope with pollutants and environmental challenges. Integrating CUR and antioxidant defense pathway approaches into aquaculture practices could boost productivity and sustainability in oyster aquaculture.
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Affiliation(s)
- Heloísa Bárbara Gabe
- Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, Brazil; Univ Brest, Ifremer, CNRS, IRD, LEMAR, IUEM, F-29280 Plouzané, France
| | | | - Karine Amabile Taruhn
- Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, Brazil
| | - Rafael Trevisan
- Univ Brest, Ifremer, CNRS, IRD, LEMAR, IUEM, F-29280 Plouzané, France.
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Su J, Liu X, Zhao X, Ma H, Jiang Y, Wang X, Wang P, Zhao M, Hu X. Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling. Recent Pat Anticancer Drug Discov 2025; 20:145-157. [PMID: 38243928 DOI: 10.2174/0115748928261490231124055059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/07/2023] [Accepted: 09/14/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known. OBJECTIVES To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article. METHODS The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells. RESULTS Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC. CONCLUSION Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.
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Affiliation(s)
- Jiaqi Su
- Department of Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Xianbing Liu
- Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Xiaoyue Zhao
- Department of Clinical Psychology, Yantai Affiliated Hospital of Binzhou Medial University, Yantai, 264100, Shandong, China
| | - Hongjie Ma
- Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Yuzhu Jiang
- Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Xu Wang
- Department of Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Peiyuan Wang
- Department of Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Mingdong Zhao
- Department of Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China
| | - Xuemei Hu
- Department of Immunology, Binzhou Medical University, Yantai, 264003, Shandong, China
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Veselá K, Kejík Z, Masařík M, Babula P, Dytrych P, Martásek P, Jakubek M. Curcumin: A Potential Weapon in the Prevention and Treatment of Head and Neck Cancer. ACS Pharmacol Transl Sci 2024; 7:3394-3418. [PMID: 39539276 PMCID: PMC11555516 DOI: 10.1021/acsptsci.4c00518] [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: 08/27/2024] [Revised: 09/27/2024] [Accepted: 10/03/2024] [Indexed: 11/16/2024]
Abstract
Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent. Numerous studies have shown that curcumin and its derivatives have the potential to affect signaling pathways (NF-κB, JAK/STAT, and EGFR) and molecular mechanisms that are crucial for the growth and migration of head and neck tumors. Furthermore, its ability to interact with the tumor microenvironment and trigger the immune system may significantly influence the organism's immune response to the tumor. Combining curcumin with conventional therapies such as chemotherapy or radiotherapy may improve the efficacy of treatment and reduce the side effects of treatment, thereby increasing its therapeutic potential. This review is a comprehensive overview that discusses both the benefits and limitations of curcumin and its therapeutic effects in the context of tumor biology, with an emphasis on molecular mechanisms in the context of HNC. This review also includes possibilities to improve the limiting properties of curcumin both in terms of the development of new derivatives, formulations, or combinations with conventional therapies that have potential as a new type of therapy for the treatment of HNC and subsequent use in clinical practice.
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Affiliation(s)
- Kateřina Veselá
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Zdeněk Kejík
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Michal Masařík
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
- Department
of Physiology, Faculty of Medicine, Masaryk
University, Kamenice 5, 625 00 Brno, Czech Republic
- Department
of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Petr Babula
- Department
of Physiology, Faculty of Medicine, Masaryk
University, Kamenice 5, 625 00 Brno, Czech Republic
| | - Petr Dytrych
- First
Department of Surgery-Department of Abdominal, Thoracic Surgery and
Traumatology, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 2, 121
08 Prague, Czech
Republic
| | - Pavel Martásek
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
| | - Milan Jakubek
- BIOCEV,
First Faculty of Medicine, Charles University, 252 50 Vestec, Czech Republic
- Department
of Paediatrics and Inherited Metabolic Disorders, First Faculty of
Medicine, Charles University and General
University Hospital in Prague, Ke Karlovu 455/2, 128 08 Prague 2, Czech Republic
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Mahjoubin-Tehran M, Hasan A, Eid AH, Almahmeed W, Kesharwani P, Butler AE, Jamialahmadi T, Sahebkar A. Effects of dietary curcumin on gene expression: An analysis of transcriptomic data in mice. Pathol Res Pract 2024; 263:155653. [PMID: 39426142 DOI: 10.1016/j.prp.2024.155653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 10/03/2024] [Accepted: 10/11/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Curcumin, a ubiquitous polyphenol in turmeric, possesses many anti-cancer and anti-inflammatory properties. These therapeutic effects are largely resultant of curcumin's ability to modulate global gene expression. Bioinformatics-based approaches for analyzing differential gene expression are effective tools in gaining a more profound understanding of the underlying mechanisms of action. AIM In this study, we aimed to identify key genes that were differentially regulated by curcumin treatment of mice. METHODS We downloaded GSE10684 and GSE13705 microarray profiles from the GEO database. Differentially expressed genes were identified and compared in both data sets. Twenty-seven genes that are significantly differentially regulated in both datasets were considered as key genes. RESULTS Gene ontology (GO) enrichment indicates these key genes were mostly enriched in GO Process of regulation of immune response and immune system process. The KEGG pathways of Cytokine-cytokine receptor interaction and TISSUES of Immune system were the top enriched terms of key genes base on strength and false discovery rate. The protein-protein interactions were analyzed by the STRING. PPI clustering showed that cluster 1 with Csf1, Cxcl16, Cxcr3, Fas, Il7r, Rassf2, and Rp2h was the most significant cluster. GO enrichment analysis for this cluster also showed the roles of these genes in immune system regulation. CONCLUSIONS Overall, the microarray datasets to identify the key genes and the related pathways which were affected by curcumin treatments show that curcumin has a significant impact on immune system regulation through the modulation of gene expression.
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Affiliation(s)
- Maryam Mahjoubin-Tehran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ammar Hasan
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
| | - Alexandra E Butler
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Tannaz Jamialahmadi
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Center for Global health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Roy D, Ghosh R, Ghosh R, Khokhar M, Naing MYY, Benito-León J. Decoding visceral adipose tissue molecular signatures in obesity and insulin resistance: a multi-omics approach. Obesity (Silver Spring) 2024; 32:2149-2160. [PMID: 39400526 DOI: 10.1002/oby.24146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/23/2024] [Accepted: 08/04/2024] [Indexed: 10/15/2024]
Abstract
OBJECTIVE Obesity-associated insulin resistance (IR) is responsible for considerable morbidity and mortality globally. Despite vast genomic data, many areas, from pathogenesis to management, still have significant knowledge gaps. We aimed to characterize visceral adipose tissue (VAT) in obesity and IR through a multi-omics approach. METHODS We procured data on VAT samples from the Gene Expression Omnibus (GEO) for the following two groups: 1) populations with obesity (n = 34) versus those without (n = 26); and 2) populations with obesity and IR (n = 15) versus those with obesity but without IR (n = 15). Gene set enrichment, protein-protein interaction network construction, hub gene identification, and drug-gene interactions were performed, followed by regulatory network prediction involving transcription factors (TFs) and microRNAs (miRNAs). RESULTS Interleukin signaling pathways, cellular differentiation, and regulation of immune response revealed a significant cross talk between VAT and the immune system. Other findings include cancer pathways, neurotrophin signaling, and aging. A total of 10 hub genes, i.e., STAT1, KLF4, DUSP1, EGR1, FOS, JUN, IL2, IL6, MMP9, and FGF9, 24 TFs, and approved hub gene-targeting drugs were obtained. A total of 10 targeting miRNAs (e.g., hsa-miR-155-5p, hsa-miR-34a-5p) were associated with obesity and IR-related pathways. CONCLUSIONS Our multi-omics integration method revealed hub genes, TFs, and miRNAs that can be potential targets for investigation in VAT-related inflammatory processes and IR, therapeutic management, and risk stratifications.
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Affiliation(s)
- Dipayan Roy
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Patna, India
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, India
| | - Raghumoy Ghosh
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, India
- Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Singapore
| | - Ritwik Ghosh
- Department of General Medicine, Burdwan Medical College & Hospital, Burdwan, India
| | - Manoj Khokhar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, India
| | - Ma Yin Yin Naing
- Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Singapore
| | - Julián Benito-León
- Department of Neurology, University Hospital "12 de Octubre", Madrid, Spain
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
- Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain
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Farzaneh S, Salehipour M, Tafvizi F, Naseh V. The Effect of Curcumin on the Activity of MMP-17 and MMP-24 in Hepatocytes of Mice Exposed to Thioacetamide. Rep Biochem Mol Biol 2024; 13:329-340. [PMID: 40330566 PMCID: PMC12050055 DOI: 10.61186/rbmb.13.3.329] [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: 06/05/2024] [Accepted: 01/09/2025] [Indexed: 05/08/2025]
Abstract
Background Hepatocellular carcinoma is the most primitive form of liver cancer, which is related to chemo carcinogens such as thioacetamide (TAA) and tissue remodeling molecules such as Matrix metalloproteinases (MMPs). Antioxidants, like curcumin (Cur), can inhibit these factors. In this research, the effect of curcumin on the expression and activity of two MMP enzymes, MMP-14 and MMP-17, which are involved in the carcinogenesis of mice after chronic exposure to thioacetamide, is investigated. Methods In this study, 30 mice were divided into six groups and studied for 4 months. The first group, control; the second group, curcumin; the third group, TAA; the fourth group, TAA and curcumin simultaneously; the fifth group, first treated with TAA for 2 months and then curcumin; and finally, the sixth group, first treated with curcumin for 2 months and then TAA. Afterward, the mice were euthanized, and their liver tissues were transferred to the laboratory for analysis of gene and protein expression. Results The averages of gene expression were calculated using SigmaPlot software and showed that the expression of MMP-17 and MMP-24 genes and the levels of their proteins were significantly increased by thioacetamide (****p < 0001) compared to the control group. Pathological observations indicated necrosis and dysplastic foci in the TAA group. Conclusions Considering the crucial roles of MMPs in various diseases, including hepatocellular carcinoma, the regulation of their gene expression and enzymatic activity is significant in preventing tumor progression. Compounds such as thioacetamide and polyphenols like curcumin can modulate the activity of MMP-17 and MMP-24.
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Affiliation(s)
- Sahar Farzaneh
- Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
| | - Masoud Salehipour
- Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
| | - Farzaneh Tafvizi
- Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
| | - Vahid Naseh
- Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
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9
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Ding Y, Zhu Z, Zhang X, Wang J. Novel Functional Dressing Materials for Intraoral Wound Care. Adv Healthc Mater 2024; 13:e2400912. [PMID: 38716872 DOI: 10.1002/adhm.202400912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/05/2024] [Indexed: 05/22/2024]
Abstract
Intraoral wounds represent a particularly challenging category of mucosal and hard tissue injuries, characterized by the unique structures, complex environment, and distinctive healing processes within the oral cavity. They have a common occurrence yet frequently inflict significant inconvenience and pain on patients, causing a serious decline in the quality of life. A variety of novel functional dressings specifically designed for the moist and dynamic oral environment have been developed and realized accelerated and improved wound healing. Thoroughly analyzing and summarizing these materials is of paramount importance in enhancing the understanding and proficiently managing intraoral wounds. In this review, the particular processes and unique characteristics of intraoral wound healing are firstly described. Up-to-date knowledge of various forms, properties, and applications of existing products are then intensively discussed, which are categorized into animal products, plant extracts, natural polymers, and synthetic products. To conclude, this review presents a comprehensive framework of currently available functional intraoral wound dressings, with an aim to provoke inspiration of future studies to design more convenient and versatile materials.
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Affiliation(s)
- Yutang Ding
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Zhou Zhu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Xin Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Jian Wang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
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10
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de Freitas Silva M, Juliet Cristancho Ortiz C, Ferreira Coelho L, Pruccoli L, Pagliarani B, Pisani L, Catto M, Poli G, Tuccinardi T, Cardoso Vilela F, Giusti-Paiva A, Amaral Alves M, Ribeiro de Souza HM, Tarozzi A, Silva Gontijo V, Viegas C. Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson's disease. Bioorg Chem 2024; 150:107587. [PMID: 38941700 DOI: 10.1016/j.bioorg.2024.107587] [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: 04/03/2024] [Revised: 06/14/2024] [Accepted: 06/21/2024] [Indexed: 06/30/2024]
Abstract
Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson's disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells. The mechanism of action was determined as a result of Keap1/Nrf2 pathway activation by both compounds and confirmed by different experiments. Furthermore, compound 3e (PQM-164) exhibited a significant effect on the accumulation of α-synuclein and anti-inflammatory activity, leading to an expressive decrease in gene expression of iNOS, IL-1β, and TNF-α. Overall, these results highlighted compound 3e as a promising and innovative multifunctional drug prototype candidate for PD treatment.
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Affiliation(s)
- Matheus de Freitas Silva
- PeQuiM - Laboratory of Research in Medicinal Chemistry, Federal University of Alfenas, Jovino Fernandes Sales Avenue 2600, 37133-840 Alfenas, Brazil; Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy
| | - Cindy Juliet Cristancho Ortiz
- PeQuiM - Laboratory of Research in Medicinal Chemistry, Federal University of Alfenas, Jovino Fernandes Sales Avenue 2600, 37133-840 Alfenas, Brazil
| | - Letícia Ferreira Coelho
- PeQuiM - Laboratory of Research in Medicinal Chemistry, Federal University of Alfenas, Jovino Fernandes Sales Avenue 2600, 37133-840 Alfenas, Brazil
| | - Letizia Pruccoli
- Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy
| | - Barbara Pagliarani
- Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy
| | - Leonardo Pisani
- Department of Pharmacy-Pharmaceutical Sciences, University Aldo Moro of Bari, Via E. Orabona 4, 70125 Bari, Italy
| | - Marco Catto
- Department of Pharmacy-Pharmaceutical Sciences, University Aldo Moro of Bari, Via E. Orabona 4, 70125 Bari, Italy
| | - Giulio Poli
- Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy
| | - Tiziano Tuccinardi
- Department of Pharmacy, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy
| | | | - Alexandre Giusti-Paiva
- Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900 Florianopolis, Brazil
| | - Marina Amaral Alves
- LabMeta, Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, 21941-598 Rio de Janeiro, Brazil
| | - Hygor M Ribeiro de Souza
- LabMeta, Metabolomics Laboratory, Institute of Chemistry, Federal University of Rio de Janeiro, 21941-598 Rio de Janeiro, Brazil
| | - Andrea Tarozzi
- Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy
| | - Vanessa Silva Gontijo
- PeQuiM - Laboratory of Research in Medicinal Chemistry, Federal University of Alfenas, Jovino Fernandes Sales Avenue 2600, 37133-840 Alfenas, Brazil
| | - Claudio Viegas
- PeQuiM - Laboratory of Research in Medicinal Chemistry, Federal University of Alfenas, Jovino Fernandes Sales Avenue 2600, 37133-840 Alfenas, Brazil.
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Amaroli A, Panfoli I, Bozzo M, Ferrando S, Candiani S, Ravera S. The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management. Cancers (Basel) 2024; 16:2580. [PMID: 39061221 PMCID: PMC11275093 DOI: 10.3390/cancers16142580] [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: 06/18/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant therapeutic potential in cancer management. This review explores curcumin's mechanisms of action, the challenges related to its bioavailability, and its enhancement through modern technology and approaches. Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators. Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers. However, its clinical application is limited by its poor bioavailability due to its rapid metabolism and low absorption. Novel delivery systems, such as curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy. Additionally, photodynamic therapy has emerged as a complementary approach, where light exposure enhances curcumin's anticancer effects by modulating molecular pathways crucial for tumor cell growth and survival. Studies highlight that combining low concentrations of curcumin with visible light irradiation significantly boosts its antitumor efficacy compared to curcumin alone. The interaction of curcumin with cytochromes or drug transporters may play a crucial role in altering the pharmacokinetics of conventional medications, which necessitates careful consideration in clinical settings. Future research should focus on optimizing delivery mechanisms and understanding curcumin's pharmacokinetics to fully harness its therapeutic potential in cancer treatment.
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Affiliation(s)
- Andrea Amaroli
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Isabella Panfoli
- Department of Pharmacy (DIFAR), University of Genoa, 16132 Genoa, Italy;
| | - Matteo Bozzo
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Sara Ferrando
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
| | - Simona Candiani
- BIO-Photonics Overarching Research Laboratory (BIOPHOR), Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, 16132 Genoa, Italy; (M.B.); (S.F.); (S.C.)
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
| | - Silvia Ravera
- IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
- Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genoa, Italy
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12
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Quek YW, Kang YT, Huang HC, Chang HY, Huang IC, Lue KH, Ko JL. PM 2.5 induces lung inflammation through ANGPTL4. Mutat Res 2024; 829:111887. [PMID: 39541651 DOI: 10.1016/j.mrfmmm.2024.111887] [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: 06/17/2024] [Revised: 10/11/2024] [Accepted: 11/10/2024] [Indexed: 11/16/2024]
Abstract
Fine particulate matter (PM2.5) is a common major air pollutant associated with decreased lung function, induced allergic airway inflammation closely correlated with chronic lung diseases. Angiopoietin-like protein 4 (ANGPTL4) is a cytokine with multiple functions, participating in processes such as inflammation, angiogenesis, and metastasis. Curcumin is an active compound found in turmeric plants and possesses various pharmacological effects, including antioxidant, anti-inflammatory, anticancer, and immunomodulatory properties. The aim of this study was twofold: firstly, to investigate the involvement of ANGPTL4 in lung inflammation and carcinogenesis under PM2.5 exposure, and secondly, to explore the impact of curcumin on ANGPTL4 expression and its potential in lung cancer chemoprevention. We used protein array to detect several proinflammatory cytokines and then used qPCR to confirm by increasing the concentration of PM2.5 to enhance the expressions of CXCL1, CXCL5; IL-1α, IL-1β, MIP-3α and inflammation- or fibrosis-associated proteins. Curcumin inhibits PM2.5-induced ANGPTL4 and the IκB-α (inhibitor of NFκB)-dependent inflammatory pathway. Silencing ANGPTL4 by shRNA restore IκB-α and MIP-3α expression. In conclusion, the increased expression of ANGPTL4 after treatment with PM2.5 in lung cells may be one of the mechanisms by which PM2.5 exposure contributes to lung inflammation progression. Our results provide evidence that curcumin in anti-inflammation therapeutics could serve as a beneficial chemopreventive agent.
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Affiliation(s)
- Yeak-Wun Quek
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan; Division of thoracic surgery, Department of surgery, Chung Shan medical university hospital, Taiwan; Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Yu-Ting Kang
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan
| | - Hsu Chih Huang
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan; Division of thoracic surgery, Department of surgery, Chung Shan medical university hospital, Taiwan
| | - Hui-Yi Chang
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan
| | - I-Chieh Huang
- National Taiwan University Hospital, Department of Laboratory Medicine, 100, Taiwan; School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan
| | - Ko-Huang Lue
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan; Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
| | - Jiunn-Liang Ko
- Institute of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan; Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
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Jacob S, Kather FS, Morsy MA, Boddu SHS, Attimarad M, Shah J, Shinu P, Nair AB. Advances in Nanocarrier Systems for Overcoming Formulation Challenges of Curcumin: Current Insights. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:672. [PMID: 38668166 PMCID: PMC11054677 DOI: 10.3390/nano14080672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/03/2024] [Accepted: 04/10/2024] [Indexed: 04/29/2024]
Abstract
Curcumin, an organic phenolic molecule that is extracted from the rhizomes of Curcuma longa Linn, has undergone extensive evaluation for its diverse biological activities in both animals and humans. Despite its favorable characteristics, curcumin encounters various formulation challenges and stability issues that can be effectively addressed through the application of nanotechnology. Nano-based techniques specifically focused on enhancing solubility, bioavailability, and therapeutic efficacy while mitigating toxicity, have been explored for curcumin. This review systematically presents information on the improvement of curcumin's beneficial properties when incorporated, either individually or in conjunction with other drugs, into diverse nanosystems such as liposomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, solid-lipid nanoparticles, and nanostructured lipid carriers. Additionally, the review examines ongoing clinical trials and recently granted patents, offering a thorough overview of the dynamic landscape in curcumin delivery. Researchers are currently exploring nanocarriers with crucial features such as surface modification, substantial loading capacity, biodegradability, compatibility, and autonomous targeting specificity and selectivity. Nevertheless, the utilization of nanocarriers for curcumin delivery is still in its initial phases, with regulatory approval pending and persistent safety concerns surrounding their use.
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Affiliation(s)
- Shery Jacob
- Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab Emirates;
| | - Fathima Sheik Kather
- Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab Emirates;
| | - Mohamed A. Morsy
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia; (M.A.M.); (M.A.); (A.B.N.)
- Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt
| | - Sai H. S. Boddu
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates;
- Center of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Mahesh Attimarad
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia; (M.A.M.); (M.A.); (A.B.N.)
| | - Jigar Shah
- Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India;
| | - Pottathil Shinu
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Anroop B. Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia; (M.A.M.); (M.A.); (A.B.N.)
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14
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Eslaminejad T, Nematollahi-Mahani SN, Sargazi ML, Ansari M, Mirzaie V. Evaluating the effects of curcumin nano-chitosan on miR-221 and miR-222 expression and Wnt/β-catenin pathways in MCF-7, MDA-MB-231 and SKBR3 cell lines. Diagn Pathol 2024; 19:35. [PMID: 38365810 PMCID: PMC10870642 DOI: 10.1186/s13000-024-01468-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 02/12/2024] [Indexed: 02/18/2024] Open
Abstract
BACKGROUND Breast cancer is one of the most common diseases worldwide that affects women of reproductive age. miR-221 and miR-222 are two highly homogeneous microRNAs that play pivotal roles in many cellular processes and regulate the Wnt/β-catenin signaling pathway. Curcumin (CUR), a yellow polyphenolic compound, targets numerous signaling pathways relevant to cancer therapy. The main aim of this study was to compare the ability of chitosan curcumin nanoparticle (CC-CUR) formulation with the curcumin in modulating miR-221 and miR-222 expression through Wnt/β-catenin signaling pathway in MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. METHOD Chitosan-cyclodextrin-tripolyphosphate containing curcumin nanoparticles (CC-CUR) were prepared. Cytotoxicity of the CUR and CC-CUR was evaluated. Experimental groups including CC-CUR, CUR and negative control were designed. The expression of miR-221 and miR-222 and Wnt/β-catenin pathway genes was measured. RESULTS The level of miR-221 and miR-222 and β-catenin genes decreased in MCF-7 and MDA-MB-231 cells and WIF1 gene increased in all cells in CC-CUR group. However, the results in SK-BR-3 cell line were unexpected; since miRs and WIF1 gene expressions were increased following CC-CUR administration and β-catenin decreased by administration of CUR. CONCLUSION Although the composite form of curcumin decreased the expression of miR-221 and miR-222 in MCF-7 and MDA cells, with significant decreasing of β-catenin and increasing of WIF1 gene in almost all three cell lines, we can conclude than this formulation exerts its effect mainly through the Wnt/β-catenin pathway. These preliminary findings may pave the way for the use of curcumin nanoparticles in the treatment of some known cancers.
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Affiliation(s)
- Touba Eslaminejad
- Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Marzieh Lotfian Sargazi
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mehdi Ansari
- Departments of Drug and Food Control, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Vida Mirzaie
- Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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15
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Zhang S, Wang Y, Wang B, Zeng Y, Li J, Wang X, Hu C, Weng Z, Wang Z. Effect of curcumin on malignant hepatocytes and mitochondria studied using atomic force microscopy. Micron 2024; 177:103573. [PMID: 38043195 DOI: 10.1016/j.micron.2023.103573] [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: 10/07/2023] [Revised: 11/15/2023] [Accepted: 11/20/2023] [Indexed: 12/05/2023]
Abstract
Mitochondria are emerging as potential targets for the cancer treatment. In this study, the effects of curcumin on the activity, migration, and mitochondrial membrane potential (MMP) of malignant hepatocytes (SMMC-7721 cells) were determined using cell viability, migration, and MMP assays. Changes in the morphology and biomechanics of SMMC-7721 cells and their mitochondria were studied using both optical microscopy and atomic force microscopy (AFM). The cell survival rate, migration and MMP depended on the concentration of curcumin. Optical microscopy studies showed that curcumin altered the cell morphology. AFM studies showed that the changes in the morphology and nanomechanics of SMMC-7721 cells and their mitochondria, were induced by curcumin. As the concentration of curcumin increased, the cell length, width, and adhesion decreased, but the height, roughness and Young's modulus increased. In contrast, the mitochondrial length, width, height and roughness increased, but the adhesion and Young's modulus decreased. There was a close relationship between mitochondria and cells in terms of function, morphology and biomechanics. This study shows the effects of curcumin on SMMC-7721 cells and their mitochondria from biology and biophysics perspectives. The findings aid in comprehensively understanding the interactions between mitochondria and malignant hepatocytes.
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Affiliation(s)
- Shengli Zhang
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Ying Wang
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Bowei Wang
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Yi Zeng
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Jiani Li
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Xingyue Wang
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Cuihua Hu
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China
| | - Zhankun Weng
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China.
| | - Zuobin Wang
- International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun 130022, China; Zhongshan Institute of Changchun University of Science and Technology, Zhongshan 528400, China; Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun 130022, China; JR3CN & IRAC, University of Bedfordshire, Luton LU1 3JU, UK.
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16
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Majeed M, Nagabhushanam K, Noureddin M, Paulose S, Barik C, Saklecha S, Mundkur L. A scientifically validated combination of garcinol, curcuminoids, and piperine for mild to moderate nonalcoholic steatohepatitis patients-results from a randomized, double-blind, placebo-controlled study. Front Nutr 2023; 10:1201186. [PMID: 38170037 PMCID: PMC10760641 DOI: 10.3389/fnut.2023.1201186] [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: 04/06/2023] [Accepted: 11/30/2023] [Indexed: 01/05/2024] Open
Abstract
Background Garcinol is a naturally occurring compound from the fruit rind of the Garcinia indica, with antioxidant, anti-inflammatory, and anticancer properties. Curcuminoids are the active molecule from the rhizome of Curcuma longa, studied extensively for its health benefits as an anti-inflammatory and antioxidant activities. Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic steatohepatitis characterized by liver fat and inflammation. Objective To evaluate the clinical efficacy and safety of Garcinol, Curcuminoids and piperine (GCP) combination in patients with mild to moderate NASH in a randomized, double-blind, placebo-controlled study. Methods The patients received one tablet (450 mg) of GCP containing garcinol-50 mg, curcuminoids -250 mg and piperine 5 mg or a placebo (450 mg of microcrystalline cellulose) twice daily for 90 days. Changes in circulating aspartate aminotransferase (AST), alanine transaminase (ALT) levels, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) using Fibroscan were compared from baseline to day 90. Anthropometric parameters, serum levels of lipids, Interleukin (IL-6), hsCRP, and adiponectin were estimated. Safety was evaluated by laboratory parameters and by monitoring adverse events. Results Seventy-two patients were randomized and 63 (GCP = 32, Placebo = 31) completed the study. The mean age of the patients was 48.3 ± 8.7 years (36 males and 27 females). The mean reduction in AST (U/L) was 9.53 in GCP and 3.16 in placebo (p < 0.001) and that of ALT (U/L) was 13.47 in GCP and 7.43 in Placebo (p = 0.002). The liver stiffness and CAP scores showed a better reduction in GCP (0.56 kPa and 12.38 db/m) compared to placebo (0.064 kPa and 10.42 db/m) p < 0.05. Consequently, the noninvasive Fibroscan-AST (FAST) score reduction was also found to be significant in GCP compared to placebo. Additionally, body weight, lipid levels, hsCRP, and IL-6 in serum decreased, while adiponectin levels increased in GCP-supplemented participants compared to placebo. The combination of garcinol and curcuminoids was well tolerated with no significant changes in hematological and clinical laboratory parameters during the 90-day supplementation. Conclusion Our results suggest that GCP could be a possible supplement for the management of NASH.Clinical trial registration: https://clinicaltrials.gov/, identifier CTRI/2019/11/022147.
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Affiliation(s)
- Muhammed Majeed
- Sami-Sabinsa Group Limited, Bangalore, Karnataka, India
- Sabinsa Corporation, East Windsor, NJ, United States
| | | | - Mazen Noureddin
- Houston Liver Institute, Houston Research Institute, Houston, TX, United States
| | - Shaji Paulose
- Sami-Sabinsa Group Limited, Bangalore, Karnataka, India
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Hoffman TR, Emsley SA, Douglas JC, Reed KR, Esquivel AR, Koyack MJ, Paddock BE, Videau P. Assessing Curcumin Uptake and Clearance and Their Influence on Superoxide Dismutase Activity in Drosophila melanogaster. BIOTECH 2023; 12:58. [PMID: 37754202 PMCID: PMC10526445 DOI: 10.3390/biotech12030058] [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: 08/03/2023] [Revised: 08/25/2023] [Accepted: 09/04/2023] [Indexed: 09/28/2023] Open
Abstract
While normal levels of reactive oxygen and nitrogen species (RONS) are required for proper organismal function, increased levels result in oxidative stress. Oxidative stress may be managed via the scavenging activities of antioxidants (e.g., curcumin) and the action of enzymes, including superoxide dismutase (SOD). In this work, the uptake and clearance of dietary curcuminoids (consisting of curcumin, demethoxycurcumin, and bisdemethoxycurcumin) was assessed in Drosophila melanogaster larvae following chronic or acute exposure. High levels of curcuminoid uptake and loss were observed within a few hours and leveled off within eight hours post treatment onset. The addition or removal of curcuminoids from media resulted in corresponding changes in SOD activity, and the involvement of each of the three SOD genes was assessed for their contribution to total SOD activity. Taken together, these data provide insight into the uptake and clearance dynamics of curcuminoids and indicate that, while SOD activity generally increases following curcuminoid treatment, the individual SOD genes appear to contribute differently to this response.
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Affiliation(s)
- Tammy R. Hoffman
- Department of Biology, Southern Oregon University, Ashland, OR 97520, USA
| | - Sarah A. Emsley
- Department of Biology, Southern Oregon University, Ashland, OR 97520, USA
| | - Jenna C. Douglas
- Department of Biology, Southern Oregon University, Ashland, OR 97520, USA
| | - Kaela R. Reed
- Department of Chemistry, Southern Oregon University, Ashland, OR 97520, USA
| | - Abigail R. Esquivel
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA
| | - Marc J. Koyack
- School of Arts and Sciences, Gwynedd Mercy University, Gwynedd Valley, PA 19437, USA
| | - Brie E. Paddock
- Department of Biology, Southern Oregon University, Ashland, OR 97520, USA
| | - Patrick Videau
- Department of Biology, Southern Oregon University, Ashland, OR 97520, USA
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18
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Cherian A, Vadivel V, Thiruganasambandham S, Madhavankutty S. Phytocompounds and their molecular targets in immunomodulation: a review. J Basic Clin Physiol Pharmacol 2023; 34:577-590. [PMID: 34786892 DOI: 10.1515/jbcpp-2021-0172] [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: 06/17/2021] [Accepted: 10/24/2021] [Indexed: 11/15/2022]
Abstract
Immune cells are important for the healthy function of every organ. The homeostasis of the immune system is selfregulated by T-cells, B-cells, and natural killer cells. The immunomodulation process of immune cells is part of the immunotherapy. According to therapeutic methods of immune responses are categorized as inducing (immunostimulant), amplification (immune booster), attenuation (immunomodulation), and prevention (immunosuppressive) actions. The prevalence of chronic immunological diseases like viral infections, allergies, and cancer is mainly due to the over-activation of the immune system. Further, immunomodulators are reported to manage the severity of chronic immunological disorders. Moreover, these immunomodulator-acting proteins are identified as potential molecular targets for the regulation of the immune system. Moreover, natural compound like phytocompounds are known to bind these targets and modulates the immune system. The specialized phytocompounds like curcumin, quercetin, stilbenes, flavonoids, and lignans are shown the immunomodulatory actions and ameliorate the immunological disorders. The present scenario of a COVID-19 pandemic situation has taught us the need to focus on strengthening the immune system and the development of the most promising immunotherapeutics. This review is focused on an overview of various phytocompounds and their molecular targets for the management of immunological disorders via immunosuppressants and immunostimulants actions.
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Affiliation(s)
- Ayda Cherian
- Pharmaceutical Chemistry, SRM College of Pharmacy, Kattankulathur, Tamil Nadu, India
| | - Velmurugan Vadivel
- Pharmaceutical Chemistry, SRM College of Pharmacy, SRMIST, Kattankulathur, Chengalpattu District, Tamil Nadu, India
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19
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Tuong DTC, Moniruzzaman M, Smirnova E, Chin S, Sureshbabu A, Karthikeyan A, Min T. Curcumin as a Potential Antioxidant in Stress Regulation of Terrestrial, Avian, and Aquatic Animals: A Review. Antioxidants (Basel) 2023; 12:1700. [PMID: 37760003 PMCID: PMC10525612 DOI: 10.3390/antiox12091700] [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: 07/10/2023] [Revised: 08/21/2023] [Accepted: 08/28/2023] [Indexed: 09/29/2023] Open
Abstract
Stress has brought about a variety of harmful impacts on different animals, leading to difficulties in the management of animal husbandry and aquaculture. Curcumin has been recognized as a potential component to ameliorate the adverse influence of animal stress induced by toxicity, inflammation, diseases, thermal effect, and so on. In detail, this compound is known to offer various outstanding functions, including antibacterial properties, antioxidant effects, immune response recovery, and behavioral restoration of animals under stress conditions. However, curcumin still has some limitations, owing to its low bioavailability. This review summarizes the latest updates on the regulatory effects of curcumin in terms of stress management in terrestrial, avian, and aquatic animals.
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Affiliation(s)
- Do Thi Cat Tuong
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea; (D.T.C.T.); (E.S.); (S.C.); (A.S.)
| | - Mohammad Moniruzzaman
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea; (D.T.C.T.); (E.S.); (S.C.); (A.S.)
| | - Elena Smirnova
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea; (D.T.C.T.); (E.S.); (S.C.); (A.S.)
| | - Sungyeon Chin
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea; (D.T.C.T.); (E.S.); (S.C.); (A.S.)
| | - Anjana Sureshbabu
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea; (D.T.C.T.); (E.S.); (S.C.); (A.S.)
| | - Adhimoolam Karthikeyan
- Subtropical Horticulture Research Institute, Jeju National University, Jeju 63243, Republic of Korea;
| | - Taesun Min
- Department of Animal Biotechnology, Bio-Resources Computing Research Center, Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
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20
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Heidari H, Shojaei M, Askari G, Majeed M, Bagherniya M, Barreto GE, Sahebkar A. The impact of curcumin on migraine: A comprehensive review. Biomed Pharmacother 2023; 164:114910. [PMID: 37216708 DOI: 10.1016/j.biopha.2023.114910] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 05/18/2023] [Accepted: 05/18/2023] [Indexed: 05/24/2023] Open
Abstract
Migraine, a neurovascular condition, is a chronic and lifelong disease that affects about 15% of the population worldwide. Although the exact pathophysiology and etiology of migraine are still unclear, oxidative stress, inflammation, and neuroendocrine imbalances are identified as the critical risk factors for migraine attacks. Curcumin is an active component and a polyphenolic diketone compound extracted from turmeric. Curcumin is a promising candidate for preventing and controlling migraine due to its anti‑inflammatory, antioxidative, anti-protein aggregate, and analgesic effects. In the present review, we have evaluated experimental and clinical studies investigating the impact of liposomal curcumin and nano-curcumin on the frequency and severity of migraine attacks in patients. Although the results are promising, more studies should be conducted in this area to show the exact efficacies of curcumin on clinical symptoms of migraine and investigate its potential mechanisms.
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Affiliation(s)
- Hajar Heidari
- Food Security Research Center, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrnaz Shojaei
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Muhammed Majeed
- Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ, 08520, USA
| | - Mohammad Bagherniya
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - George E Barreto
- Department of Biological Sciences, University of Limerick, Limerick, Ireland.
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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21
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Hussein HA, Khaphi FL. The Apoptotic Activity of Curcumin Against Oral Cancer Cells Without Affecting Normal Cells in Comparison to Paclitaxel Activity. Appl Biochem Biotechnol 2023; 195:5019-5033. [PMID: 37032374 DOI: 10.1007/s12010-023-04454-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2023] [Indexed: 04/11/2023]
Abstract
Until now, chemotherapy, which has a series of side effects, has been the most widely employed treatment for different types of cancer. However, bioactive products have been utilized as alternative medicines for tumors due to their bioactivities with low or no side effects in normal cells. This research reported for the first time that curcumin (CUR) and paclitaxel (PTX) have significant anti-cancer activity against normal human gingival fibroblast (HGF) and tongue squamous cell carcinoma fibroblast (TSCCF) cell lines. The results showed that CUR (13.85 µg mL-1) and PTX (8.17 µg mL-1) significantly inhibited TSCCF cell viability, with no significant effect on normal HGF cells. SEM showed morphological changes in cells treated with CUR and PTX, especially with TSCCF cells, compared to HGF normal cells. For TSCCF, the results showed the highest necrosis was achieved with CUR (58.8%) and PTX (39%) as compared to the control (2.99%). For normal HGF cells, the highest early and late apoptosis was achieved with PTX. Further, DCFH-DA analyses showed no significant ROS stimulation in TSCCF and HGF cell lines treated with CUR and PTX. The 1H NMR analysis results show the presence of methoxy and hydroxyl groups and aromatic hydrogens in the CUR structure. In conclusion, the results confirmed that CUR is more specific to the oral cancer cells but not normal cells by inducing apoptosis in a dose- and time-dependent manner, with decreased TSCCF cell viability, and the cytotoxicity of CUR and PTX is not through the ROS pathway.
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Affiliation(s)
- Hanaa Ali Hussein
- College of Dentistry, University of Basrah 61004, Basic Science Branch, Al-Bara'iyah Street, Al-Sadir Teaching Hospital, Basrah city, 61001, Basrah, Iraq.
| | - Fatin L Khaphi
- College of Dentistry, University of Basrah 61004, Basic Science Branch, Al-Bara'iyah Street, Al-Sadir Teaching Hospital, Basrah city, 61001, Basrah, Iraq
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22
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Luo W, Bai L, Zhang J, Li Z, Liu Y, Tang X, Xia P, Xu M, Shi A, Liu X, Zhang D, Yu P. Polysaccharides-based nanocarriers enhance the anti-inflammatory effect of curcumin. Carbohydr Polym 2023; 311:120718. [PMID: 37028867 DOI: 10.1016/j.carbpol.2023.120718] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 02/11/2023] [Accepted: 02/14/2023] [Indexed: 02/27/2023]
Abstract
Curcumin (CUR) has been discovered to have many biological activities, including anti-inflammatory, anti-cancer, anti-oxygenation, anti-human immunodeficiency virus, anti-microbial and exhibits a good effect on the prevention and treatment of many diseases. However, the limited properties of CUR, including the poor solubility, bioavailability and instability caused by enzymes, light, metal irons, and oxygen, have compelled researchers to turn their attention to drug carrier application to overcome these drawbacks. Encapsulation may provide potential protective effects to the embedding materials and/or have a synergistic effect with them. Therefore, nanocarriers, especially polysaccharides-based nanocarriers, have been developed in many studies to enhance the anti-inflammatory capacity of CUR. Consequently, it's critical to review current advancements in the encapsulation of CUR using polysaccharides-based nanocarriers, as well as further study the potential mechanisms of action where polysaccharides-based CUR nanoparticles (the complex nanoparticles/Nano CUR-delivery systems) exhibit their anti-inflammatory effects. This work suggests that polysaccharides-based nanocarriers will be a thriving field in the treatment of inflammation and inflammation-related diseases.
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Affiliation(s)
- Wei Luo
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Liangyu Bai
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Zhangwang Li
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Yinuo Liu
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Xiaoyi Tang
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Panpan Xia
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China; Branch of Nationlal Clinical Research Center for Metabolic Diseases, Nanchang 330006, China
| | - Minxuan Xu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China; Branch of Nationlal Clinical Research Center for Metabolic Diseases, Nanchang 330006, China
| | - Ao Shi
- School of Medicine, St.George University of London, London, UK
| | - Xiao Liu
- Cardiology Department, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong.
| | - Peng Yu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China; Branch of Nationlal Clinical Research Center for Metabolic Diseases, Nanchang 330006, China.
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23
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Sadeghi M, Dehnavi S, Asadirad A, Xu S, Majeed M, Jamialahmadi T, Johnston TP, Sahebkar A. Curcumin and chemokines: mechanism of action and therapeutic potential in inflammatory diseases. Inflammopharmacology 2023; 31:1069-1093. [PMID: 36997729 PMCID: PMC10062691 DOI: 10.1007/s10787-023-01136-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 01/09/2023] [Indexed: 04/01/2023]
Abstract
Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed.
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Affiliation(s)
- Mahvash Sadeghi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sajad Dehnavi
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Asadirad
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Suowen Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | | | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Medicine, The University of Western Australia, Perth, Australia.
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91779-48564, Iran.
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24
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Kang H. Regulation of Acetylation States by Nutrients in the Inhibition of Vascular Inflammation and Atherosclerosis. Int J Mol Sci 2023; 24:ijms24119338. [PMID: 37298289 DOI: 10.3390/ijms24119338] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
Atherosclerosis (AS) is a chronic metabolic disorder and primary cause of cardiovascular diseases, resulting in substantial morbidity and mortality worldwide. Initiated by endothelial cell stimulation, AS is characterized by arterial inflammation, lipid deposition, foam cell formation, and plaque development. Nutrients such as carotenoids, polyphenols, and vitamins can prevent the atherosclerotic process by modulating inflammation and metabolic disorders through the regulation of gene acetylation states mediated with histone deacetylases (HDACs). Nutrients can regulate AS-related epigenetic states via sirtuins (SIRTs) activation, specifically SIRT1 and SIRT3. Nutrient-driven alterations in the redox state and gene modulation in AS progression are linked to their protein deacetylating, anti-inflammatory, and antioxidant properties. Nutrients can also inhibit advanced oxidation protein product formation, reducing arterial intima-media thickness epigenetically. Nonetheless, knowledge gaps remain when it comes to understanding effective AS prevention through epigenetic regulation by nutrients. This work reviews and confirms the underlying mechanisms by which nutrients prevent arterial inflammation and AS, focusing on the epigenetic pathways that modify histones and non-histone proteins by regulating redox and acetylation states through HDACs such as SIRTs. These findings may serve as a foundation for developing potential therapeutic agents to prevent AS and cardiovascular diseases by employing nutrients based on epigenetic regulation.
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Affiliation(s)
- Hyunju Kang
- Department of Food and Nutrition, Keimyung University, Daegu 42601, Republic of Korea
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25
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Córdova A, Drobnic F, Noriega-González D, Caballero-García A, Roche E, Alvarez-Mon M. Is Curcumine Useful in the Treatment and Prevention of the Tendinopathy and Myotendinous Junction Injury? A Scoping Review. Nutrients 2023; 15:384. [PMID: 36678255 PMCID: PMC9860696 DOI: 10.3390/nu15020384] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 01/04/2023] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Physical activity in general and sports in particular, is a mechanism that produces stress and generates great force in the tendon and in the muscle-tendon unit, which increases the risk of injury (tendinopathies). Eccentric and repetitive contraction of the muscle precipitates persistent microtraumatism in the tendon unit. In the development of tendinopathies, the cellular process includes inflammation, apoptosis, vascular, and neuronal changes. Currently, treatments with oral supplements are frequently used. Curcumin seems to preserve, and even repair, damaged tendons. In this systematic review, we focus more especially on the benefits of curcumin. The biological actions of curcumin are diverse, but act around three systems: (a) inflammatory, (b) nuclear factor B (NF-κB) related apoptosis pathways, and (c) oxidative stress systems. A bibliographic search is conducted under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a basis for reporting reliable systematic reviews to perform a Scoping review. After analysing the manuscripts, we can conclude that curcumin is a product that demonstrates a significant biological antialgic, anti-inflammatory, and antioxidant power. Therefore, supplementation has a positive effect on the inflammatory and regenerative response in tendinopathies. In addition, curcumin decreases and modulates the cell infiltration, activation, and maturation of leukocytes, as well as the production of pro-inflammatory mediators at the site of inflammation.
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Affiliation(s)
- Alfredo Córdova
- Department of Biochemistry, Molecular Biology and Physiology, Faculty of Health Sciences, GIR Physical Exercise and Aging, University of Valladolid, Campus Duques de Soria, 42004 Soria, Spain
| | - Franchek Drobnic
- Medical Department, Wolverhampton Wanderers FC, Wolverhampton WV1 4QR, UK
| | - David Noriega-González
- Department of Surgery, Ophthalmology, Otorhinolaryngology and Physiotherapy, Faculty of Medicine, Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain
| | - Alberto Caballero-García
- Department of Anatomy and Radiology, Faculty of Health Sciences, GIR Physical Exercise and Aging, University of Valladolid, Campus Los Pajaritos, 42004 Soria, Spain
| | - Enrique Roche
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain
- Department of Applied Biology-Nutrition, Institute of Bioengineering, University Miguel Hernández, 03202 Elche, Spain
- Alicante Institute for Health and Biomedical Research (ISABIAL), 03010 Alicante, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialty, Faculty of Medicine and Health Sciences, University of Alcalá, 28871 Alcalá de Henares, Spain
- Immune System Diseases-Rheumatology and Oncology Service, University Hospital “Príncipe de Asturias”, 28871 Alcalá de Henares, Spain
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Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases. Arch Toxicol 2023; 97:3-38. [PMID: 36260104 DOI: 10.1007/s00204-022-03391-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/26/2022] [Indexed: 02/07/2023]
Abstract
Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.
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Mirza S, Penny C, Jain NK, Rawal RM. Curcumin mediated dendritic cell maturation by modulating cancer associated fibroblasts-derived exosomal miRNA-146a. J Cancer Res Ther 2023; 19:S649-S657. [PMID: 38384034 DOI: 10.4103/jcrt.jcrt_1286_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/20/2022] [Indexed: 02/23/2024]
Abstract
BACKGROUND Though cancer associated fibroblasts (CAFs), being a main component of tumor microenvironment (TME), are known to modulate immune response through secretion of various growth hormones, exosomes carrying miRNAs and cytokines; their effect on dendritic cells (DCs) are yet to be elucidated. Thus, aim of this study was to assess the effect of miRNAs and cytokines released by lung-CAFs and to evaluate immunomodulatory potential of curcumin on DC maturation through modulating their TME. MATERIAL AND METHODS To check the effect of CAFs derived exosomes on DC maturation, we cultured imDCs in the presence of CAFs derived conditioned media (CAFs-CM) and characterized by the presence of maturation markers CD80, CD83, CD86 and CTLA4 using qRT-PCR. Additionally, expression of miR-221, miR-222, miR-155, miR-142-3p and miR-146a was assessed to evaluate the role of epigenetic regulators on DC maturation. Likewise, cytokine profiling of CAFs-CM as well as CAFs-CM treated with curcumin was also conducted using ELISA. RESULTS Results revealed the generation of regulatory DCs which were characterized by decreased expression of maturation markers in the presence of CAFs-CM. In addition, such DCs showed higher expression of epigenetic regulator miR-146a which was positively correlated with increased expression of anti-inflammatory cytokines like IL-6, IL-10, TGF-β and decreased expression of TNF-α (pro-inflammatory). Moreover, curcumin had the potential to convert regulatory DCs generated by CAFs into mDCs, which were characterized by high expression of co-stimulatory molecules, low expression of CTLA4, lower levels of immune suppressive cytokines production and lower levels of miR-146a. CONCLUSION Collectively, these findings provide insight into understanding the immunomodulatory role of curcumin in targeting CAFs and modulating TME, thus enhancing antitumor immune response in DC based therapy.
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Affiliation(s)
- Sheefa Mirza
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India
- Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Clement Penny
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Nayan K Jain
- Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India
| | - Rakesh M Rawal
- Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India
- Division of Medicinal Chemistry and Pharmacogenomics, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
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28
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Potential Properties of Natural Nutraceuticals and Antioxidants in Age-Related Eye Disorders. LIFE (BASEL, SWITZERLAND) 2022; 13:life13010077. [PMID: 36676026 PMCID: PMC9863869 DOI: 10.3390/life13010077] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 12/23/2022] [Accepted: 12/25/2022] [Indexed: 12/29/2022]
Abstract
Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders.
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29
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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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30
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Wang Y, Xu S, Han C, Huang Y, Wei J, Wei S, Qin Q. Modulatory effects of curcumin on Singapore grouper iridovirus infection-associated apoptosis and autophagy in vitro. FISH & SHELLFISH IMMUNOLOGY 2022; 131:84-94. [PMID: 36206994 DOI: 10.1016/j.fsi.2022.09.074] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/30/2022] [Accepted: 09/30/2022] [Indexed: 06/16/2023]
Abstract
Singapore grouper iridovirus (SGIV) with high pathogenicity can cause great economic losses to aquaculture industry. Thus, it is of urgency to find effective antiviral strategies to combat SGIV. Curcumin has been demonstrated effective antiviral activity on SGIV infection. However, the molecular mechanism behind this action needs to be further explanations. In view of the fact that apoptosis (type I programmed cell death) and autophagy (type II programmed cell death) were key regulators during SGIV infection, we aimed to investigate the relevance between antiviral activity of curcumin and SGIV-associated programmed and clarify the role of potential signaling pathways. Our results showed that curcumin suppressed SGIV-induced apoptosis. At the same time, the activities of caspase-3/8/9 and activating protein-1 (AP-1), P53, nuclear factor-κB (NF-ΚB) promoters were inhibited. Besides, the activation of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen activate protein kinase (p38 MAPK) signal pathways were suppressed in curcumin-treated cells. On the other hand, curcumin down-regulated protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway to promote autophagy representing by increased LC3 II and Beclin1 expression. Curcumin also hindered the transition of cells from G1 to S phase, as well as down-regulating the expression of CyclinD1. Our findings revealed the resistance curcumin induced to the effects of DNA virus on cell apoptosis and autophagy and the insights gained from this study may be of assistance to understand the molecular mechanism of curcumin against DNA virus infection.
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Affiliation(s)
- Yuexuan Wang
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China
| | - Suifeng Xu
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China
| | - Chengzong Han
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China
| | - Youhua Huang
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China
| | - Jingguang Wei
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China
| | - Shina Wei
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
| | - Qiwei Qin
- College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 528478, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266000, China.
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Sadegha S, Varshochian R, Dadras P, Hosseinzadeh H, Sakhtianchi R, Mirzaie ZH, Shafiee A, Atyabi F, Dinarvand R. Mesoporous silica coated SPIONs containing curcumin and silymarin intended for breast cancer therapy. Daru 2022; 30:331-341. [PMID: 36197594 PMCID: PMC9715905 DOI: 10.1007/s40199-022-00453-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 09/21/2022] [Indexed: 12/04/2022] Open
Abstract
INTRODUCTION Super-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2@SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7. METHODS Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy. RESULTS The MTT results showed that the IC50 of CUR + SIL loaded mSiO2@SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis. CONCLUSION In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.
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Affiliation(s)
- Soosan Sadegha
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Varshochian
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pegah Dadras
- Trita Nanomedicine Research Center (TNRC), Trita Third Millennium Pharmaceuticals, Zanjan, Iran
| | - Hosniyeh Hosseinzadeh
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Ramin Sakhtianchi
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Hadavand Mirzaie
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Shafiee
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Atyabi
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Rassoul Dinarvand
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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Evidence for Multilevel Chemopreventive Activities of Natural Phenols from Functional Genomic Studies of Curcumin, Resveratrol, Genistein, Quercetin, and Luteolin. Int J Mol Sci 2022; 23:ijms232314957. [PMID: 36499286 PMCID: PMC9737263 DOI: 10.3390/ijms232314957] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/02/2022] [Accepted: 11/10/2022] [Indexed: 12/02/2022] Open
Abstract
Herein, I present an updated and contextualized literature review of functional genomic studies of natural phenols in the context of cancer. I suggest multilevel chemopreventive and anticancer mechanisms of action, which are shared by multiple dietary natural phenols. Specifically, I cite evidence that curcumin and resveratrol have multilevel anti-cancer effects through: (1) inducing either p53-dependent or p53-independent apoptosis in cancer cell lines, (2) acting as potent regulators of expression of oncogenic and anti-oncogenic microRNAs, and (3) inducing complex epigenetic changes that can switch off oncogenes/switch on anti-oncogenes. There is no simple reductionist explanation for anti-cancer effects of curcumin and resveratrol. More generally, multilevel models of chemoprevention are suggested for related natural phenols and flavonoids such as genistein, quercetin, or luteolin.
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Mahmoudi A, Atkin SL, Jamialahmadi T, Banach M, Sahebkar A. Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study. Nutrients 2022; 14:4344. [PMID: 36297027 PMCID: PMC9609422 DOI: 10.3390/nu14204344] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 01/30/2023] Open
Abstract
Background: Liver cirrhosis is a life-threatening seqsuel of many chronic liver disorders of varying etiologies. In this study, we investigated protein targets of curcumin in liver cirrhosis based on a bioinformatics approach. Methods: Gene/protein associations with curcumin and liver cirrhosis were probed in drug−gene and gene−diseases databases including STITCH/DGIdb/DisGeNET/OMIM/DISEASES/CTD/Pharos and SwissTargetPrediction. Critical clustering groups (MCODE), hub candidates and critical hub genes in liver cirrhosis were identified, and connections between curcumin and liver cirrhosis-related genes were analyzed via Venn diagram. Interaction of hub genes with curcumin by molecular docking using PyRx-virtual screening tools was performed. Results: MCODE analysis indicated three MCODEs; the cluster (MCODE 1) comprised 79 nodes and 881 edges (score: 22.59). Curcumin database interactions recognized 318 protein targets. Liver cirrhosis genes and curcumin protein targets analysis demonstrated 96 shared proteins, suggesting that curcumin may influence 20 candidate and 13 hub genes, covering 81% of liver cirrhosis critical genes and proteins. Thirteen shared proteins affected oxidative stress regulation, RNA, telomerase activity, cell proliferation, and cell death. Molecular docking analysis showed the affinity of curcumin binding hub genes (Binding affinity: ΔG < −4.9 kcal/mol). Conclusions: Curcumin impacted on several critical liver cirrhosis genes mainly involved in extracellular matrix communication, focal adhesion, and the response to oxidative stress.
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Affiliation(s)
- Ali Mahmoudi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Stephen L. Atkin
- School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Bahrain
| | - Tannaz Jamialahmadi
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), 93-338 Lodz, Poland
- Cardiovascular Research Center, University of Zielona Gora, 65-417 Zielona Gora, Poland
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Chen CJ, Shang HS, Huang YL, Tien N, Chen YL, Hsu SY, Wu RSC, Tang CL, Lien JC, Lee MH, Lu HF, Hsia TC. Bisdemethoxycurcumin suppresses human brain glioblastoma multiforme GBM 8401 cell migration and invasion via affecting NF-κB and MMP-2 and MMP-9 signaling pathway in vitro. ENVIRONMENTAL TOXICOLOGY 2022; 37:2388-2397. [PMID: 35735092 DOI: 10.1002/tox.23604] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/01/2022] [Accepted: 06/08/2022] [Indexed: 06/15/2023]
Abstract
Human glioblastoma (GBM) is one of the common cancer death in adults worldwide, and its metastasis will lead to difficult treatment. Finding compounds for future to develop treatment is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was isolated from the rhizome of turmeric (Curcuma longa), which has been shown to against many human cancer cells. In the present study, we evaluated the antimetastasis activity of BDMC in human GBM cells. Cell proliferation, cell viability, cellular uptake, wound healing, migration and invasion, and western blotting were analyzed. Results indicated that BDMC at 1.5-3 μM significantly decreased the cell proliferation by MTT assay. BDMC showed the highest uptake by cells at 3 h. After treatment of BDMC at 12-48 h significantly inhibited cell motility in GBM 8401 cells by wound healing assay. BDMC suppressed cell migration and invasion at 24 and 48 h treatment by transwell chamber assay. BDMC significantly decreased the levels of proteins associated with PI3K/Akt, Ras/MEK/ERK pathways and resulted in the decrease in the expressions of NF-κB, MMP-2, MMP-9, and N-cadherin, leading to the inhibition of cell migration and invasion. These findings suggest that BDMC may be a potential candidate for the antimetastasis of human GBM cells in the future.
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Affiliation(s)
- Chiung-Ju Chen
- Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Hung-Sheng Shang
- Division of Clinical Pathology, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Graduate Institute of Clinical of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yuan-Li Huang
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung City, Taiwan
| | - Ni Tien
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yung-Liang Chen
- Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan
| | - Sheng-Yao Hsu
- Department of Ophthalmology, An Nan Hospital, China Medical University, Tainan, Taiwan
- Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Rick Sai-Chuen Wu
- Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Lun Tang
- Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jin-Cherng Lien
- School of Pharmacy, China Medical University, Taichung, Taiwan
| | - Mei-Hui Lee
- Department of Genetic Counseling Center, Changhua Christian Hospital, Changhua, Taiwan
| | - Hsu-Feng Lu
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung City, Taiwan
- Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Te-Chun Hsia
- Department of Respiratory Therapy, China Medical University, Taichung, Taiwan
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
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Nowowiejska J, Baran A, Flisiak I. Psoriasis and neurodegenerative diseases—a review. Front Mol Neurosci 2022; 15:917751. [PMID: 36226313 PMCID: PMC9549431 DOI: 10.3389/fnmol.2022.917751] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/31/2022] [Indexed: 11/26/2022] Open
Abstract
Psoriasis is a chronic skin disease with underlying genetic, inflammatory and immunological background, which is a great medical problem, currently regarded as a systemic condition. Neurodegenerative diseases (NDs) are characterized by a progressive loss of nervous tissue, which affects elderly people more frequently; therefore, it is suspected that, due to society's aging, morbidity is going to increase. We performed a thorough review in order to investigate for the first time whether psoriasis may predispose to different particular neurodegenerative diseases—Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). PubMed search resulted in the retrieval of 833 records, of which 77 eligible were included in the review. Our thorough analysis revealed there are some potential links between psoriasis and NDs (inflammation, oxidative stress, genetics, cardiometabolic disorders), but there is no strong evidence that psoriasis may predispose to NDs. Based on the evidence, it seems that the risk of PD in psoriatics is not increased, and the evidence for increased risk of AD slightly prevails the data that state the opposite. ALS risk does not seem to be increased in psoriatics. The paucity of original studies does not allow for the formulation of definitive conclusions but encourages to perform further investigations.
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Obaidi I, Blanco Fernández A, McMorrow T. Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism. Int J Mol Sci 2022; 23:ijms23179569. [PMID: 36076967 PMCID: PMC9455736 DOI: 10.3390/ijms23179569] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/17/2022] [Accepted: 08/17/2022] [Indexed: 12/31/2022] Open
Abstract
Targeted therapies are the most attractive options in the treatment of different tumours, including kidney cancers. Such therapies have entered a golden era due to advancements in research, breakthroughs in scientific knowledge, and a better understanding of cancer therapy mechanisms, which significantly improve the survival rates and life expectancy of patients. The use of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) as an anticancer therapy has attracted the attention of the scientific community and created great excitement due to its selectivity in targeting cancerous cells with no toxic impacts on normal tissues. However, clinical studies disappointingly showed the emergence of resistance against TRAIL. This study aimed to employ curcumin to sensitise TRAIL-resistant kidney cancerous ACHN cells, as well as to gain insight into the molecular mechanisms of TRAIL sensitization. Curcumin deregulated the expression of apoptosis-regulating micro Ribonucleic Acid (miRNAs), most notably, let-7C. Transfecting ACHN cells with a let-7C antagomir significantly increased the expression of several cell cycle protein, namely beta (β)-catenin, cyclin dependent kinase (CDK)1/2/4/6 and cyclin B/D. Further, it overexpressed the expression of the two key glycolysis regulating proteins including hypoxia-inducible factor 1-alpha (HIF-1α) and pyruvate dehydrogenase kinase 1 (PDK1). Curcumin also suppressed the expression of the overexpressed proteins when added to the antagomir transfected cells. Overall, curcumin targeted ACHN cell cycle and cellular metabolism by promoting the differential expression of let-7C. To the best of our knowledge, this is the first study to mechanistically report the cancer chemosensitisation potential of curcumin in kidney cancer cells via induction of let-7C.
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Affiliation(s)
- Ismael Obaidi
- NatPro Centre for Natural Product Research, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, D02 W272 Dublin, Ireland
- College of Pharmacy, University of Babylon, Babylon 51002, Iraq
- Correspondence: (I.O.); (T.M.); Tel.: +353-8-6064-2626 (I.O.); +353-1-716-2317 (ext. 6819) (T.M.)
| | - Alfonso Blanco Fernández
- Flow Cytometry Core Technology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, D04 V1W8 Dublin, Ireland
| | - Tara McMorrow
- Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland
- Correspondence: (I.O.); (T.M.); Tel.: +353-8-6064-2626 (I.O.); +353-1-716-2317 (ext. 6819) (T.M.)
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Mahmoudi A, Atkin SL, Nikiforov NG, Sahebkar A. Therapeutic Role of Curcumin in Diabetes: An Analysis Based on Bioinformatic Findings. Nutrients 2022; 14:3244. [PMID: 35956419 PMCID: PMC9370108 DOI: 10.3390/nu14153244] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/19/2022] [Accepted: 07/26/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Diabetes is an increasingly prevalent global disease caused by the impairment in insulin production or insulin function. Diabetes in the long term causes both microvascular and macrovascular complications that may result in retinopathy, nephropathy, neuropathy, peripheral arterial disease, atherosclerotic cardiovascular disease, and cerebrovascular disease. Considerable effort has been expended looking at the numerous genes and pathways to explain the mechanisms leading to diabetes-related complications. Curcumin is a traditional medicine with several properties such as being antioxidant, anti-inflammatory, anti-cancer, and anti-microbial, which may have utility for treating diabetes complications. This study, based on the system biology approach, aimed to investigate the effect of curcumin on critical genes and pathways related to diabetes. METHODS We first searched interactions of curcumin in three different databases, including STITCH, TTD, and DGIdb. Subsequently, we investigated the critical curated protein targets for diabetes on the OMIM and DisGeNET databases. To find important clustering groups (MCODE) and critical hub genes in the network of diseases, we created a PPI network for all proteins obtained for diabetes with the aid of a string database and Cytoscape software. Next, we investigated the possible interactions of curcumin on diabetes-related genes using Venn diagrams. Furthermore, the impact of curcumin on the top scores of modular clusters was analysed. Finally, we conducted biological process and pathway enrichment analysis using Gene Ontology (GO) and KEGG based on the enrichR web server. RESULTS We acquired 417 genes associated with diabetes, and their constructed PPI network contained 298 nodes and 1651 edges. Next, the analysis of centralities in the PPI network indicated 15 genes with the highest centralities. Additionally, MCODE analysis identified three modular clusters, which highest score cluster (MCODE 1) comprises 19 nodes and 92 edges with 10.22 scores. Screening curcumin interactions in the databases identified 158 protein targets. A Venn diagram of genes related to diabetes and the protein targets of curcumin showed 35 shared proteins, which observed that curcumin could strongly interact with ten of the hub genes. Moreover, we demonstrated that curcumin has the highest interaction with MCODE1 among all MCODs. Several significant biological pathways in KEGG enrichment associated with 35 shared included the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway, TNF signaling, and JAK-STAT signaling pathway. The biological processes of GO analysis were involved with the cellular response to cytokine stimulus, the cytokine-mediated signaling pathway, positive regulation of intracellular signal transduction and cytokine production in the inflammatory response. CONCLUSION Curcumin targeted several important genes involved in diabetes, supporting the previous research suggesting that it may have utility as a therapeutic agent in diabetes.
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Affiliation(s)
- Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Stephen L. Atkin
- School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen 15503, Bahrain
| | - Nikita G. Nikiforov
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Feng W, Liu J, Cheng H, Zhang D, Tan Y, Peng C. Dietary compounds in modulation of gut microbiota-derived metabolites. Front Nutr 2022; 9:939571. [PMID: 35928846 PMCID: PMC9343712 DOI: 10.3389/fnut.2022.939571] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/24/2022] [Indexed: 11/29/2022] Open
Abstract
Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.
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Affiliation(s)
- Wuwen Feng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hao Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dandan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuzhu Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Key Laboratory of the Ministry of Education for Standardization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Thuy LT, Kang N, Choi M, Lee M, Choi JS. Dendrimeric micelles composed of polyamidoamine dendrimer-peptide-cholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection. J IND ENG CHEM 2022. [DOI: 10.1016/j.jiec.2022.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
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Fetoni AR, Paciello F, Troiani D. Cisplatin Chemotherapy and Cochlear Damage: Otoprotective and Chemosensitization Properties of Polyphenols. Antioxid Redox Signal 2022; 36:1229-1245. [PMID: 34731023 DOI: 10.1089/ars.2021.0183] [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] [Indexed: 12/30/2022]
Abstract
Significance: Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including redox imbalance caused by reactive oxygen species production and lipid peroxidation, activation of inflammation, and p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies to reduce side effect toxicities while preserving or enhancing the antineoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, that is, normal cells undergoing stressful conditions versus cancer cells. Critical Issues: This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/cross talk between the cell's defenses, inflammatory molecules, and the key signaling molecules of signal transducers and activators of transcription 3 (STAT-3), nuclear factor κ-B (NF-κB), p53, and nuclear factor erythroid 2-related factor 2 (Nrf-2). Future Directions: We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols. Antioxid. Redox Signal. 36, 1229-1245.
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Affiliation(s)
- Anna Rita Fetoni
- Department of Head and Neck Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Fabiola Paciello
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Diana Troiani
- Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy
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Umar S, Kan P, Carter MJ, Shitabata P. Treatment-Refractory Central Centrifugal Cicatricial Alopecia Responsive to a Novel Botanical Treatment. Clin Cosmet Investig Dermatol 2022; 15:609-619. [PMID: 35422647 PMCID: PMC9004676 DOI: 10.2147/ccid.s358618] [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: 01/15/2022] [Accepted: 03/31/2022] [Indexed: 01/06/2023]
Abstract
Purpose Central centrifugal cicatricial alopecia (CCCA) is the most common cause of scarring alopecia in women of African descent. However, current treatments for CCCA, such as immunosuppressants and immunomodulatory pharmaceutical agents, have suboptimal efficacy and undesirable side effects. This case series reports the therapeutic effect of a new botanical formulation (Dr. UGro Gashee) in four patients with histologically supported diagnoses of CCCA. The formulations contain at least three phytoactive ingredients that affect multiple targets in the cascade of pathophysiologic events contributing to CCCA. Possible mechanisms of action include anti-inflammatory effects, inhibiting proinflammatory cytokines, and the net antifibrotic effect of inhibiting transforming growth factor-beta while upregulating AMP-activated protein kinase and peroxisome proliferator-associated receptor-gamma activity. Patients and Methods Four African American women with treatment-refractory CCCA were treated with a new topical botanical formula (cosmeceutical) alone or in combination with its oral formulation (nutraceutical) for 8 weeks to 1 year. The cosmeceutical and nutraceutical treatments contain similar phytoactive ingredient profiles. Treatment outcomes were collected using documented patient reports and images and by direct observation. Results In all patients, scalp pruritus cessation occurred within 2 weeks of treatment, and significant hair regrowth was observed within 2 months. All patients reported a high satisfaction level without adverse effects. Conclusion Patients with treatment-refractory CCCA responded to the novel botanical treatment reported in this study. Further evaluations in a controlled trial with more patients are warranted.
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Affiliation(s)
- Sanusi Umar
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.,Division of Dermatology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.,Dr. U Hair and Skin Clinic, Manhattan Beach, CA, USA
| | - Petrina Kan
- Department of Molecular Biology, University of California at Los Angeles, Los Angeles, CA, USA
| | | | - Paul Shitabata
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.,Division of Dermatology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.,Dermatopathology Institute, Torrance, CA, USA
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Mohammadi A, Khanbabaei H, Zandi F, Ahmadi A, Haftcheshmeh SM, Johnston TP, Sahebkar A. Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases. Microb Pathog 2022; 166:105552. [DOI: 10.1016/j.micpath.2022.105552] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 04/16/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022]
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Chen L, Yue B, Liu Z, Luo Y, Ni L, Zhou Z, Ge X. Study on the Preparation, Characterization, and Stability of Freeze-Dried Curcumin-Loaded Cochleates. Foods 2022; 11:foods11050710. [PMID: 35267344 PMCID: PMC8908975 DOI: 10.3390/foods11050710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 11/16/2022] Open
Abstract
Curcumin (CUR), a polyphenolic substance extracted from plants, has extensive pharmacological activities. However, CUR is difficult to be absorbed in the body due to its poor stability and low solubility. Studies have found that cochleates can be used as a new delivery system to encapsulate bioactive agents for the purpose of improving its stability and bioavailability. In this study, thin-film dispersion and trapping methods were used to prepare curcumin-loaded cochleates (CUR-Cochs). Then CUR-Cochs were characterized and the encapsulation efficiency was determined by HPLC. In addition, the freeze-drying process of CUR-Cochs was studied and related characterization was performed. CCK-8 assay was used to detect the cytotoxicity of cochleates carrier. Additionally, H2O2-induced cellular oxidative damage model were used to evaluate its antioxidant capacity. The results showed that the structure of CUR-Cochs was a spiral cylinder with an average particle size of 463.8 nm and zeta potential of −15.47 mV. The encapsulation efficiency was the highest (83.66 ± 0.8)% with 1:50 CUR-to-lipid mass ratio. In vitro results showed that cochleates had negligible cytotoxicity and owned antioxidant capacity, which provided the possibility for their applications in food and medicine. In general, the method herein might be a promising method to encapsulate CUR for further use as a bioactive agent in functional foods.
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Affiliation(s)
- Lijuan Chen
- Department of Food Science and Technology, College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing 210037, China; (L.C.); (Z.L.); (Y.L.)
| | - Bowen Yue
- Department of Pharmacy, Medical College of China Three Gorges University, Yichang 443002, China; (B.Y.); (L.N.)
| | - Zhiming Liu
- Department of Food Science and Technology, College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing 210037, China; (L.C.); (Z.L.); (Y.L.)
| | - Yali Luo
- Department of Food Science and Technology, College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing 210037, China; (L.C.); (Z.L.); (Y.L.)
| | - Lu Ni
- Department of Pharmacy, Medical College of China Three Gorges University, Yichang 443002, China; (B.Y.); (L.N.)
| | - Zhiyong Zhou
- Department of Pharmacy, Medical College of China Three Gorges University, Yichang 443002, China; (B.Y.); (L.N.)
- Correspondence: (Z.Z.); (X.G.); Tel.: +86-0717-639-6818 (Z.Z.); +86-025-8542-7844 (X.G.)
| | - Xuemei Ge
- Department of Food Science and Technology, College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing 210037, China; (L.C.); (Z.L.); (Y.L.)
- Correspondence: (Z.Z.); (X.G.); Tel.: +86-0717-639-6818 (Z.Z.); +86-025-8542-7844 (X.G.)
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Pemmaraju DB, Ghosh A, Gangasani JK, Murthy U, Naidu V, Rengan AK. Herbal biomolecules as nutraceuticals. HERBAL BIOMOLECULES IN HEALTHCARE APPLICATIONS 2022:525-549. [DOI: 10.1016/b978-0-323-85852-6.00025-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Ma Y, Lee G, Heo SY, Roh YS. Oxidative Stress Is a Key Modulator in the Development of Nonalcoholic Fatty Liver Disease. Antioxidants (Basel) 2021; 11:antiox11010091. [PMID: 35052595 PMCID: PMC8772974 DOI: 10.3390/antiox11010091] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 12/14/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and scientific studies consistently report that NAFLD development can be accelerated by oxidative stress. Oxidative stress can induce the progression of NAFLD to NASH by stimulating Kupffer cells, hepatic stellate cells, and hepatocytes. Therefore, studies are underway to identify the role of antioxidants in the treatment of NAFLD. In this review, we have summarized the origins of reactive oxygen species (ROS) in cells, the relationship between ROS and NAFLD, and have discussed the use of antioxidants as therapeutic agents for NAFLD.
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Affiliation(s)
- Yuanqiang Ma
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Korea; (Y.M.); (G.L.)
| | - Gyurim Lee
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Korea; (Y.M.); (G.L.)
| | - Su-Young Heo
- College of Veterinary Medicine, Jeonbuk National University, Jeonju 54896, Korea
- Correspondence: (S.-Y.H.); (Y.-S.R.)
| | - Yoon-Seok Roh
- College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Korea; (Y.M.); (G.L.)
- Correspondence: (S.-Y.H.); (Y.-S.R.)
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Rodrigues FC, Kumar NVA, Hari G, Pai KSR, Thakur G. The inhibitory potency of isoxazole-curcumin analogue for the management of breast cancer: A comparative in vitro and molecular modeling investigation. CHEMICAL PAPERS 2021; 75:5995-6008. [DOI: 10.1007/s11696-021-01775-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/04/2021] [Indexed: 12/22/2022]
Abstract
AbstractCurcumin, a potent phytochemical derived from the spice element turmeric, has been identified as a herbal remedy decades ago and has displayed promise in the field of medicinal chemistry. However, multiple traits associated with curcumin, such as poor bioavailability and instability, limit its effectiveness to be accepted as a lead drug-like entity. Different reactive sites in its chemical structure have been identified to incorporate modifications as attempts to improving its efficacy. The diketo group present in the center of the structural scaffold has been touted as the group responsible for the instability of curcumin, and substituting it with a heterocyclic ring contributes to improved stability. In this study, four heterocyclic curcumin analogues, representing some broad groups of heterocyclic curcuminoids (isoxazole-, pyrazole-, N-phenyl pyrazole- and N-amido-pyrazole-based), have been synthesized by a simple one-pot synthesis and have been characterized by FTIR, 1H-NMR, 13C-NMR, DSC and LC–MS. To predict its potential anticancer efficacy, the compounds have been analyzed by computational studies via molecular docking for their regulatory role against three key proteins, namely GSK-3β—of which abnormal regulation and expression is associated with cancer; Bcl-2—an apoptosis regulator; and PR which is a key nuclear receptor involved in breast cancer development. One of the compounds, isoxazole-curcumin, has consistently indicated a better docking score than the other tested compounds as well as curcumin. Apart from docking, the compounds have also been profiled for their ADME properties as well as free energy binding calculations. Further, the in vitro cytotoxic evaluation of the analogues was carried out by SRB assay in breast cancer cell line (MCF7), out of which isoxazole-curcumin (IC50–3.97 µM) has displayed a sevenfold superior activity than curcumin (IC50–21.89 µM). In the collation of results, it can be suggested that isoxazole-curcumin behaves as a potential lead owing to its ability to be involved in a regulatory role with multiple significant cancer proteins and hence deserves further investigations in the development of small molecule-based anti-breast cancer agents.
Graphic abstract
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Wang M, Wang R, Li L, Yan Y, Jia S, Jiang H, Du Z. Quantitative proteomics of plasma and liver reveals the mechanism of turmeric in preventing hyperlipidemia in mice. Food Funct 2021; 12:10484-10499. [PMID: 34555841 DOI: 10.1039/d1fo01849c] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hyperlipidemia is manifested by abnormal levels of circulating lipids and may lead to various cardiovascular diseases. Studies have demonstrated that turmeric supplemented in food can effectively prevent hyperlipidemia. The aim of this study is to elucidate the underlying mechanism. 27 male C57BL/6J mice were randomly divided into three groups, which were fed with a standard diet, a high-fat diet and a high-fat diet supplemented with turmeric powder (2.0% w/w), respectively. After eight weeks of feeding, turmeric intervention significantly reduced the plasma TC, TG, and LDL-C levels and the LDL-C/HDL-C ratio of mice compared with high-fat diet fed mice. TMT-based proteomic analysis showed that the expression of 24 proteins in mouse plasma and 76 proteins in mouse liver was significantly altered by turmeric, respectively. Bioinformatics analysis showed that differential proteins in the plasma were mainly involved in complement and coagulation cascades and the cholesterol metabolism pathway. The differential proteins in the liver were mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis and the PPAR signaling pathway. Key differential proteins were successfully validated by western blot analysis. This study is the first to reveal the preventive mechanism of turmeric on hyperlipidemia from proteomics. The results showed that dietary turmeric could prevent hyperlipidemia through regulating the expression of proteins in metabolism pathways.
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Affiliation(s)
- Meiqin Wang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Runjing Wang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Lieyao Li
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Yingfei Yan
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Shuailong Jia
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Hongliang Jiang
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Zhifeng Du
- Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
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Rujirachotiwat A, Suttamanatwong S. Curcumin upregulates transforming growth factor-β1, its receptors, and vascular endothelial growth factor expressions in an in vitro human gingival fibroblast wound healing model. BMC Oral Health 2021; 21:535. [PMID: 34657625 PMCID: PMC8522235 DOI: 10.1186/s12903-021-01890-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 10/06/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Curcumin accelerates healing of oral wounds; however, the responsible mechanisms remain underexplored. Our hypothesis is curcumin regulates the expression of wound healing-related genes in human gingival fibroblasts (hGFs). This study investigated whether curcumin regulates transforming growth factor (TGF)-β1, type I TGF-β receptor (TGF-βRI), type II TGF-β receptor (TGF-βRII), and vascular endothelial growth factor (VEGF) expression in unwounded hGFs and an in vitro hGF wound healing model. METHODS The cytotoxicity of curcumin was evaluated using the MTT assay. Unwounded hGFs were treated with non-cytotoxic concentrations of curcumin for 24 h. Gene expression was determined by quantitative polymerase chain reaction. Then, hGFs were treated with 1 µM curcumin in an in vitro wound healing model. PD98059 pretreatment was performed to determine whether extracellular signal-regulated kinase (ERK) signaling was required for regulation of gene expression by curcumin. RESULTS Curcumin at 0.1-20 µM caused no significant change in cell viability. In unwounded hGFs, curcumin had no significant effect on TGF-β1, TGF-βRI, TGF-βRII, or VEGF expression. Conversely, curcumin significantly upregulated the expression of these genes in the in vitro wound healing model. PD98059 significantly attenuated the curcumin-stimulated TGF-βRI, TGF-βRII, and VEGF expression, whereas it had no effect on TGF-β1 expression. CONCLUSIONS Curcumin upregulated TGF-β1, TGF-βRI, TGF-βRII, and VEGF expression in an in vitro hGF wound healing model. The ERK pathway is required for TGF-βRI, TGF-βRII, and VEGF induction by curcumin. Our findings support the development of curcumin as a therapeutic agent for gingival ulcers.
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Affiliation(s)
- Auspreeya Rujirachotiwat
- Graduate Program in Pediatric Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.,Banphue Hospital, 134 Moo 2, Plubphue Road, Banphue District, Udonthani, 41160, Thailand
| | - Supaporn Suttamanatwong
- Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
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Nahar N, Mohamed S, Mustapha NM, Fong LS, Mohd Ishak NI. Gallic acid and myricetin-rich Labisia pumila extract mitigated multiple diabetic eye disorders in rats. J Food Biochem 2021; 45:e13948. [PMID: 34622461 DOI: 10.1111/jfbc.13948] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 09/06/2021] [Accepted: 09/09/2021] [Indexed: 12/15/2022]
Abstract
Diabetes affected about a quarter of a billion people globally, and one out of four diabetics has eye or vision problems. This study investigated whether gallic acid and myricetin-rich Labisia pumila extract (LP) consumption would help prevent diabetic eye disorders and some probable biochemistry involved relating to inflammation, vascular leakage, and oxidative tension. Male rats were divided into four groups (n = 6), namely healthy control, diabetic non-treated control, and hyperglycemic rats treated with 150 or 300 mg/kg LP. Intraperitoneal injection of 60 mg/kg streptozotocin was used to induce diabetes. Rats were fed in the morning and evening. Diabetic retinopathy was graded in rats using a dilated retinal digital ophthalmoscopy. Rats were sacrificed at 12 weeks and the retina, optic nerve, cornea, lens, sclera, ciliary bodies, iris, and conjunctiva were examined histologically. The diabetic rats consuming LP for 10 weeks showed dose-dependent, histopathologically-reduced eye abnormalities (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal changes). The LP significantly suppressed inflammation [increased serum tumor necrosis factor-α (TNF-α), prostaglandin-E2 (PGE2)], vascular leakage [claudin-1], abnormal vascularization [vascular endothelial growth factor (VEGF)], oxidative tension [malondialdehyde/reduced glutathione ratio], and hyperglycemia [fasting blood glucose] of the diabetic rats. The LP consumption was significantly protective against diabetic eye disorders and optic nerve dysfunction which were related to inflammation, vascular leakage, abnormal vascularization, and oxidative tension, which most likely influenced eye hemorrhage and collagen cross-linkage. PRACTICAL APPLICATIONS: The study shows that gallic acid and myricetin-rich Labisia pumila (LP) leaf consumption may be used as a complementary therapy for managing diabetes (fasting blood glucose) and preventing diabetic eye disorders (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal abnormalities). The LP consumptions reduced the serum biomarkers for inflammation (serum tumor necrosis factor-α TNF-α; prostaglandin-E2), vascular leakage/abnormalities (claudin-1 and vascular endothelial growth factor VEGF), and oxidative tension (malondialdehyde/reduced glutathione MDA/GSH ratio). The LP was eye-protective probably by normalizing fasting blood glucose, reducing inflammation, oxidative tension, vascular leakage, and irregular vascularization.
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Affiliation(s)
- Nazmun Nahar
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Serdang, Malaysia
| | - Suhaila Mohamed
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang, Serdang, Malaysia
| | | | - Lau Seng Fong
- Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Serdang, Malaysia
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Moludi M, Rashidian A, Asghari MH, Nassireslami E, Yousefi Zoshk M, Hami Z, Paknejad B, Chamanara M. Curcumin induces potent cytotoxic effects on myeloma cells independent of caspase activation. TOXIN REV 2021. [DOI: 10.1080/15569543.2021.1892763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Milad Moludi
- Department of Pharmacology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
- Toxicology Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Amir Rashidian
- Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Asghari
- Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ehsan Nassireslami
- Department of Pharmacology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
- Toxicology Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Mojtaba Yousefi Zoshk
- Department of Pediatrics, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Zahra Hami
- Toxicology Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Babak Paknejad
- Department of Pharmacology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mohsen Chamanara
- Department of Pharmacology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
- Toxicology Research Center, Aja University of Medical Sciences, Tehran, Iran
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