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Kumar MN, Dandela R, Gopinath P. A Review on zerumbone and its semisynthetic Analogs: Synthesis and Implications in Medicinal chemistry. Bioorg Chem 2025; 154:108074. [PMID: 39732090 DOI: 10.1016/j.bioorg.2024.108074] [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: 09/28/2024] [Revised: 12/05/2024] [Accepted: 12/15/2024] [Indexed: 12/30/2024]
Abstract
Natural products and their semisynthetic analogs have long standing history in generating and identifying lead and drug candidates for various therapeutic areas. Zerumbone 1, a unique 11 membered monocyclic sesquiterpene natural product is isolated from Zingiber zerumbet (L. Smith) and related species. The presence of divinyl ketone along with an isolated double bond with all trans double bond geometries, provides great opportunities to create unique and complex molecular scaffolds. Various chemistries to synthesize semisynthetic analogs and their biological properties are discussed in detail. Broad spectrum biological activities and identified potential targets for zerumbone could potentially lead to the generation of lead compounds for therapeutic applications especially for cancer.
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Affiliation(s)
- Murthi Nandha Kumar
- Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India
| | - Rambabu Dandela
- Department of Industrial and Engineering Chemistry, Institute of Chemical Technology, Indianoil Odisha Campus, Samantpuri, Bhubaneswar 751013, India.
| | - Pushparathinam Gopinath
- Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203, Tamil Nadu, India.
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Zolotareva K, Dotsenko PA, Podkolodnyy N, Ivanov R, Makarova AL, Chadaeva I, Bogomolov A, Demenkov PS, Ivanisenko V, Oshchepkov D, Ponomarenko M. Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma. Int J Mol Sci 2024; 25:12802. [PMID: 39684516 DOI: 10.3390/ijms252312802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes' promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services-PANTHER, DAVID, STRING, MetaScape, and GeneMANIA-as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.
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Affiliation(s)
- Karina Zolotareva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Polina A Dotsenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Nikolay Podkolodnyy
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Institute of Computational Mathematics and Mathematical Geophysics, SB RAS, Novosibirsk 630090, Russia
| | - Roman Ivanov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Aelita-Luiza Makarova
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
| | - Irina Chadaeva
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Anton Bogomolov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Pavel S Demenkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
| | - Vladimir Ivanisenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Dmitry Oshchepkov
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
- Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia
| | - Mikhail Ponomarenko
- Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (ICG SB RAS), Novosibirsk 630090, Russia
- Kurchatov Genome Center at the ICG SB RAS, Novosibirsk 630090, Russia
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Yu J, Jiang S, Liu Y. Zerumbone Inhibits the Viability, Motility, and Angiogenesis of Human Retinal Microvascular Endothelial Cells (HRCECs) by Inhibiting Vascular Endothelial Growth Factor. Curr Eye Res 2024; 49:1201-1207. [PMID: 38856031 DOI: 10.1080/02713683.2024.2363479] [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: 06/02/2023] [Accepted: 05/29/2024] [Indexed: 06/11/2024]
Abstract
PURPOSE To uncover the possible effects of zerumbone on the viability, motility, and angiogenesis of human retinal microvascular endothelial cells and to clarify the mechanism. METHODS 5-Ethynyl-2'-deoxyuridine assays were conducted to confirm the effects of zerumbone on the viability of human retinal microvascular endothelial cells. Wound healing, tube formation, and immunoblot assays were conducted to confirm the role of zerumbone in human retinal microvascular endothelial cell motility and angiogenesis, and regulation on vascular endothelial growth factor expression. ELISA was performed to confirm its effects on vascular endothelial growth factor secretion. Colivelin was used to activate the STAT3. RESULTS We revealed that zerumbone suppressed the viability of human retinal microvascular endothelial cells. Zerumbone restrained the motility and angiogenesis of human retinal microvascular endothelial cells via targeting STAT3 and regulating the expression and secretion of vascular endothelial growth factor in vitro. Zerumbone treatment suppressed the angiogenesis, whereas Colivelin treatment reversed the suppression of angiogenesis caused by zerumbone. CONCLUSION Zerumbone restrained the viability, motility and angiogenesis of human retinal microvascular endothelial cells by inhibiting vascular endothelial growth factor expression.
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Affiliation(s)
- Jiexin Yu
- Department of Ophthalmology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Shule Jiang
- Department of Ophthalmology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Yanli Liu
- Department of Ophthalmology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
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Bejarano E, Domenech-Bendaña A, Avila-Portillo N, Rowan S, Edirisinghe S, Taylor A. Glycative stress as a cause of macular degeneration. Prog Retin Eye Res 2024; 101:101260. [PMID: 38521386 PMCID: PMC11699537 DOI: 10.1016/j.preteyeres.2024.101260] [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: 01/05/2024] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 03/25/2024]
Abstract
People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health. The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes. In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using in vitro and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease.
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Affiliation(s)
- Eloy Bejarano
- Department of Biomedical Sciences, School of Health Sciences and Veterinary School, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | - Alicia Domenech-Bendaña
- Department of Biomedical Sciences, School of Health Sciences and Veterinary School, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | | | - Sheldon Rowan
- JM USDA Human Nutrition Research Center on Aging at Tufts University, United States
| | - Sachini Edirisinghe
- Tufts University Friedman School of Nutrition Science and Policy, United States
| | - Allen Taylor
- Tufts University Friedman School of Nutrition Science and Policy, United States.
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Li J, Li ZP, Xu SS, Wang W. Unraveling the biological link between diabetes mellitus and prostate cancer: Insights and implications. World J Diabetes 2024; 15:1367-1373. [PMID: 38983816 PMCID: PMC11229951 DOI: 10.4239/wjd.v15.i6.1367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/15/2024] [Accepted: 04/18/2024] [Indexed: 06/11/2024] Open
Abstract
This article is a comprehensive study based on research on the connection between diabetes mellitus (DM) and prostate cancer (PCa). It investigates the potential role of DM as an independent risk factor for PCa, delving into the biological links, including insulin resistance and hormonal changes. The paper critically analyzes previous studies that have shown varying results and introduces mendelian randomization as a method for establishing causality. It emphasizes the importance of early DM screening and lifestyle modifications in preventing PCa, and proposes future research directions for further under-standing the DM - PCa relationship.
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Affiliation(s)
- Jian Li
- Department of Interventional Oncology, Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Si-Si Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Wei Wang
- Department of Interventional Oncology, Municipal Hospital Affiliated to Taizhou University, Taizhou 318000, Zhejiang Province, China
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Chan JSW, Lim XY, Japri N, Ahmad IF, Tan TYC. Zingiber zerumbet: A Scoping Review of its Medicinal Properties. PLANTA MEDICA 2024; 90:204-218. [PMID: 38035621 PMCID: PMC10869203 DOI: 10.1055/a-2219-9801] [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: 06/13/2023] [Accepted: 11/01/2023] [Indexed: 12/02/2023]
Abstract
Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.
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Affiliation(s)
- Janice Sue Wen Chan
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam, Selangor,
Malaysia
| | - Xin Yi Lim
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam, Selangor,
Malaysia
| | - Norfarahana Japri
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam, Selangor,
Malaysia
| | - Ida Farah Ahmad
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam, Selangor,
Malaysia
| | - Terence Yew Chin Tan
- Herbal Medicine Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Setia Alam, Shah Alam, Selangor,
Malaysia
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Gandhi GR, Hillary VE, Antony PJ, Zhong LLD, Yogesh D, Krishnakumar NM, Ceasar SA, Gan RY. A systematic review on anti-diabetic plant essential oil compounds: Dietary sources, effects, molecular mechanisms, and safety. Crit Rev Food Sci Nutr 2023; 64:6526-6545. [PMID: 36708221 DOI: 10.1080/10408398.2023.2170320] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is a multifaceted metabolic syndrome defined through the dysfunction of pancreatic β-cells driven by a confluence of genetic and environmental elements. Insulin resistance, mediated by interleukins and other inflammatory elements, is one of the key factors contributing to the progression of T2DM. Many essential oils derived from dietary plants are beneficial against various chronic diseases. We reviewed the anti-diabetic properties of dietary plant-derived essential oil compounds, with a focus on their molecular mechanisms by modulating specific signaling pathways and other critical inflammatory mediators involved in insulin resistance. High-quality literature published in the last 12 years, from 2010 to 2022, was collected from the Scopus, Web of Science, PubMed, and Embase databases using the search terms "dietary plants," "essential oils," "anti-diabetic," "insulin resistance," "antihyperglycemic," "T2DM," "anti-diabetic essential oils," and anti-diabetic mechanism." According to the results, the essential oil compounds, including cinnamaldehyde, carvacrol, zingerone, sclareol, zerumbone, myrtenol, thujone, geraniol, citral, eugenol, thymoquinone, thymol, citronellol, α-terpineol, and linalool have been demonstrated to contain strong anti-diabetic effects via modulating various signal transduction pathways linked to glucose metabolism. Additionally, in diabetes-related animal models, they can also considerably reduce the expression of TNF-α, IL-1β, IL-4, IL-6, iNOS, and COX-2. The main signaling molecules regulated by these compounds include AMPK, GLUT4, Caspase-3, PPARγ, PPARα, NF-κB, p-IκBα, MyD88, MCP-1, SREBP-1c, AGEs, RAGE, VEGF, Nrf2/HO-1, and SIRT-1. They can also significantly inhibit the generation of TBARS and MDA, reduce oxidative stress, increase insulin levels, adiponectin, and glycoprotein enzymes, boost antioxidant enzymes like SOD, CAT, and GPx, as well as reduce glutathione and vital glycolytic enzymes. Besides, they can significantly lower the levels of liver enzymes and lipid profile markers. Moreover, most essential oil compounds are generally safe based on animal studies. In conclusion, dietary plant-derived essential oil compounds have potential anti-diabetic effects by influencing different signaling pathways and molecular targets linked to glucose metabolism, and should be safe and beneficial against diabetes and related complications.
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Affiliation(s)
- Gopalsamy Rajiv Gandhi
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, India
| | - Varghese Edwin Hillary
- Division of Phytochemistry and Drug-Design, Department of Biosciences, Rajagiri College of Social Sciences (Autonomous), Kochi, India
| | | | - Linda L D Zhong
- Biomedical Sciences and Chinese Medicine, School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | - Devarajan Yogesh
- Department of Biochemistry, University of Madras, Chennai, India
| | | | - Stanislaus Antony Ceasar
- Division of Plant Molecular Biology and Biotechnology, Department of Biosciences, Rajagiri College of Social Sciences, Kochi, India
| | - Ren-You Gan
- Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
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Yong PH, New SY, Azzani M, Wu YS, Chia VV, Ng ZX. Potential of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review. Endocr Regul 2023; 58:26-39. [PMID: 38345496 DOI: 10.2478/enr-2024-0004] [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] [Indexed: 02/15/2024] Open
Abstract
Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.
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Affiliation(s)
- Phaik Har Yong
- School of Bioscience, Faculty of Pharmacy & Biomedical Sciences, MAHSA University, Selangor, Malaysia
| | - Shin Yee New
- School of Bioscience, Faculty of Pharmacy & Biomedical Sciences, MAHSA University, Selangor, Malaysia
| | - Meram Azzani
- Department of Public Health Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, 47000, Sungai Buloh, Selangor, Malaysia and Centre of Occupational Safety, Health and Wellbeing, Universiti Teknologi MARA, , Malaysia
| | - Yuan Seng Wu
- Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Selangor, Malaysia
- Department of Medical Education, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Selangor, Malaysia
| | - Vi Vien Chia
- School of Bioscience, Faculty of Pharmacy & Biomedical Sciences, MAHSA University, Selangor, Malaysia
| | - Zhi Xiang Ng
- School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, Selangor, Malaysia
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Alharbi KS, Nadeem MS, Afzal O, Alzarea SI, Altamimi ASA, Almalki WH, Mubeen B, Iftikhar S, Shah L, Kazmi I. Gingerol, a Natural Antioxidant, Attenuates Hyperglycemia and Downstream Complications. Metabolites 2022; 12:metabo12121274. [PMID: 36557312 PMCID: PMC9782005 DOI: 10.3390/metabo12121274] [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: 11/09/2022] [Revised: 12/04/2022] [Accepted: 12/08/2022] [Indexed: 12/23/2022] Open
Abstract
Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of genetic, environmental, and immunologic variables in people with type 1 diabetes. These factors cause pancreatic beta cell death and insulin insufficiency. Insulin resistance and irregular insulin production cause hyperglycemia in type 2 diabetes patients. Hyperglycemia activates a number of complicated interconnected metabolic processes. Hyperglycemia is a major contributor to the onset and progression of diabetes' secondary complications such as neuropathy, nephropathy, retinopathy, cataracts, periodontitis, and bone and joint issues. Studies on the health benefits of ginger and its constituent's impact on hyperglycemia and related disorders have been conducted and gingerol proved to be a potential pharmaceutically active constituent of ginger (Zingiber officinale) that has been shown to lower blood sugar levels, because it possesses antioxidant properties and it functions as an antioxidant in the complicated biochemical process that causes hyperglycemia to be activated. Gingerol not only helps in treating hyperglycemia but also shows effectivity against diseases related to it, such as cardiopathy, kidney failure, vision impairments, bone and joint problems, and teeth and gum infections. Moreover, fresh ginger has various gingerol analogues, with 6-gingerol being the most abundant. However, it is necessary to investigate the efficacy of its other analogues against hyperglycemia and associated disorders at various concentrations in order to determine the appropriate dose for treating these conditions.
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Affiliation(s)
- Khalid Saad Alharbi
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Correspondence: (M.S.N.); (I.K.)
| | - Obaid Afzal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia
| | - Abdulmalik S. A. Altamimi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia
| | - Bismillah Mubeen
- Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54000, Pakistan
| | - Saima Iftikhar
- School of Biological Sciences, University of Punjab, Lahore 54000, Pakistan
| | - Luqman Shah
- Department of Biochemistry, Faculty of Science, Hazara University, Mansehra 21300, Pakistan
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Correspondence: (M.S.N.); (I.K.)
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Karimi R, Bakhshi A, Dayati P, Abazari O, Shahidi M, Savaee M, Kafi E, Rahmanian M, Naghib SM. Silymarin reduces retinal microvascular damage in streptozotocin-induced diabetic rats. Sci Rep 2022; 12:15872. [PMID: 36151457 PMCID: PMC9508129 DOI: 10.1038/s41598-022-20297-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 09/12/2022] [Indexed: 11/29/2022] Open
Abstract
Diabetic retinopathy is a severe microvascular problem in diabetes mellitus. Silymarin is a flavonoid compound, and according to previous studies, it is a bioactive compound with potent antioxidant and anti-inflammatory properties. This investigation aims to peruse the impact of silymarin against diabetic retinopathy in streptozotocin (STZ)-provoked rats. Thirty-two adult male Wistar rats were randomly allocated into the control group, STZ group, STZ + silymarin (50 mg/kg), and STZ + silymarin (100 mg/kg). STZ rats received silymarin every day until 2 months after diabetes induction. The serum and retinal tissues were collected 2 months after silymarin treatment to determine biochemical and molecular analyses. Silymarin markedly lowered the serum glucose concentration in diabetic rats. Silymarin reduced the increased levels of advanced glycosylated end products (AGEs), the receptors for AGEs (RAGE), and reactive oxygen species (ROS) in diabetic rats. Silymarin also attenuated the phosphorylation of p38 MAP kinase and nuclear factor (NF)-κB p65 and diminished diabetes-induced overexpression of inflammatory cytokines, vascular endothelial growth factor (VEGF), adhesion molecules, and extracellular matrix proteins in STZ rats. Our data suggested that silymarin has protective effects against diabetic retinopathy, which might be related to the inhibition of the AGEs/RAGE axis and its antioxidant and anti-inflammatory activities.
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Affiliation(s)
- Rahman Karimi
- Department of Cell & Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Ali Bakhshi
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Parisa Dayati
- Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Omid Abazari
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Maryamsadat Shahidi
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mohamadreza Savaee
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Ehsan Kafi
- Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Mehdi Rahmanian
- Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 1517964311, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology (IUST), Tehran, Iran.
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Salaramoli S, Mehri S, Yarmohammadi F, Hashemy SI, Hosseinzadeh H. The effects of ginger and its constituents in the prevention of metabolic syndrome: A review. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2022; 25:664-674. [PMID: 35949312 PMCID: PMC9320212 DOI: 10.22038/ijbms.2022.59627.13231] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 03/06/2022] [Indexed: 11/06/2022]
Abstract
Metabolic syndrome is a multifactorial disorder characterized by hyperglycemia, hyperlipidemia, obesity, and hypertension risk factors. Moreover, metabolic syndrome is the most ordinary risk factor for cardiovascular disease (CVD). Numerous chemical drugs are being synthesized to heal metabolic risk factors. Still, due to their abundant side effects, herbal medicines have a vital role in the treatment of these abnormalities. Ginger (Zingiber officinale Roscoe, Zingiberaceae) plant has been traditionally used in medicine to treat disorders, including CVD. The unique ginger properties are attributed to the presence of [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol, which through different mechanisms can be beneficial in metabolic syndrome. Ginger has a beneficial role in metabolic syndrome treatment due to its hypotensive, anti-obesity, hypoglycemic, and hypolipidemic effects. It can significantly reduce atherosclerotic lesion areas, VLDL and LDL cholesterol levels, and elevate adenosine deaminase activity in platelet and lymphocytes. Also, it promotes ATP/ADP hydrolysis. In the current article review, the critical properties of ginger and its constituents' effects on the metabolic syndrome with a special focus on different molecular and cellular mechanisms have been discussed. This article also suggests that ginger may be introduced as a therapeutic or preventive agent against metabolic syndrome after randomized clinical trials.
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Affiliation(s)
- Sanaz Salaramoli
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soghra Mehri
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding authors: Soghra Mehri. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. ; Hossein Hosseinzadeh. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98-51-38819042; Fax: +98-51-38823251;
| | - Fatemeh Yarmohammadi
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran,Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran,Corresponding authors: Soghra Mehri. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. ; Hossein Hosseinzadeh. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Tel: +98-51-38819042; Fax: +98-51-38823251;
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12
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Xia S, Weng T, Jin R, Yang M, Yu M, Zhang W, Wang X, Han C. Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds. BURNS & TRAUMA 2022; 10:tkac001. [PMID: 35291229 PMCID: PMC8918758 DOI: 10.1093/burnst/tkac001] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 12/07/2021] [Accepted: 01/03/2022] [Indexed: 12/17/2022]
Abstract
Background Gelatin methacryloyl (GelMA) hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing. Advanced glycation end product (AGE), interacting with its particular receptor (AGER), gives rise to reactive oxygen species (ROS) and apoptosis. Curcumin (Cur) has excellent antioxidant activity and regulates intracellular ROS production and apoptosis. In this study, we developed a Cur-incorporated 3D-printed GelMA to insert into adipose-derived stem cells (ADSCs) and applied it to diabetic wounds. Methods GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated. We used structural characterization, western blot, ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity, and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB (NF-κB) p65 pathway. Results A 10% GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs. The circular mesh structure demonstrated printability of 10% GelMA and Cur-GelMA bioinks. The incorporation of Cur into the 10% GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis. Furthermore, Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing. Conclusions The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs. The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.
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Affiliation(s)
- Sizhan Xia
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Tingting Weng
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Ronghua Jin
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Min Yang
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Meirong Yu
- Clinical Research Center, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Wei Zhang
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Xingang Wang
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
| | - Chunmao Han
- Department of Burns and Wound Care Center, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou 310000, China
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Khazeei Tabari MA, Mirjalili R, Khoshhal H, Shokouh E, Khandan M, Hasheminasabgorji E, Hafezi-Moghadam A, Bagheri A. Nature against Diabetic Retinopathy: A Review on Antiangiogenic, Antioxidant, and Anti-Inflammatory Phytochemicals. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4708527. [PMID: 35310030 PMCID: PMC8926515 DOI: 10.1155/2022/4708527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 02/09/2022] [Accepted: 02/18/2022] [Indexed: 11/17/2022]
Abstract
Background and Purpose. Diabetes mellitus (DM), hyperglycemia, and hypertension can result in diabetic retinopathy (DR), which is a major cause of blindness on a global scale. Development of DR is associated with decreased endothelial cells, increased basal membrane thickness, permeation of the retinal blood barrier, and neovascularization in patients. The purpose of the present review is to provide an overview of the findings regarding applications of phytochemicals for DR treatment and could be a beneficial resource for further clinical studies and also a basis for pharmaceutical purposes for drug design. Materials and Methods. A narrative literature review was performed from electronic databases including Web of Science, PubMed, and Scopus to analyze the effects of different phytochemicals to prevent or treat oxidation, angiogenesis, and inflammation in diabetic retinopathy. The inclusion criteria were original studies, which included the effects of different phytochemicals on diabetic retinopathy. The exclusion criteria included studies other than original articles, studies which assessed the effects of phytochemicals on nondiabetic retinopathy, and studies which used phytochemical-rich extracts. Results and Conclusions. Studies have shown that increased levels of inflammatory cytokines, angiogenic, and oxidative stress factors are involved in the progression and pathogenesis of DR. Therefore, phytochemicals with their anti-inflammatory, antiangiogenic, and antioxidant properties can prevent DR progression and retinal damage through various cellular mechanisms. It is also shown that some phytochemicals can simultaneously affect the inflammation, oxidation, and angiogenesis in DR.
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Affiliation(s)
- Mohammad Amin Khazeei Tabari
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Razie Mirjalili
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hooman Khoshhal
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Elahe Shokouh
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohanna Khandan
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
- USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Elham Hasheminasabgorji
- Department of Clinical Biochemistry and Medical Genetics, Faculty of Medicine, Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ali Hafezi-Moghadam
- Molecular Biomarkers Nano-Imaging Laboratory, Brigham and Women's Hospital, Boston, MA, USA
- Department of Radiology, Harvard Medical School, Boston, MA, USA
| | - Abouzar Bagheri
- Department of Clinical Biochemistry and Medical Genetics, Faculty of Medicine, Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran
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14
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Zerumbone suppresses high glucose and LPS-induced inflammation in THP-1-derived macrophages by inhibiting the NF-κB/TLR signaling pathway. Nutr Res 2022; 100:58-69. [DOI: 10.1016/j.nutres.2022.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 12/28/2021] [Accepted: 01/16/2022] [Indexed: 02/06/2023]
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Bioactive Compounds from Zingiber montanum and Their Pharmacological Activities with Focus on Zerumbone. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app112110205] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The genus Zingiber consists of about 85 species and many of these species are used as food, spices, and medicines. One of the species, Zingiber montanum (J. Koenig) Link ex A. Dietr. is native to Southeast Asia and has been extensively used as traditional medicines and food. The aim of this review was to collect and critically analyze the scientific information about the bioactive compounds and pharmacological activities of Z. montanum with focus on one of the main components, zerumbone (ZER). Various studies have reported the analysis of volatile constituents of the essential oils from Z. montanum. Similarly, many phenylbutanoids, flavonoids and terpenes were also isolated from rhizomes. These essential oils, extracts and compounds showed potent antimicrobial, anti-inflammatory and antioxidant activities among others. Zerumbone has been studied widely for its anticancer, anti-inflammatory, and other pharmacological activities. Future studies should focus on the exploration of various pharmacological activities of other compounds including phenylbutanoids and flavonoids. Bioassay guided isolation may result in the separation of other active components from the extracts. Z. montanum could be a promising source for the development of pharmaceutical products and functional foods.
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Ai X, Yu P, Hou Y, Song X, Luo J, Li N, Lai X, Wang X, Meng X. A review of traditional Chinese medicine on treatment of diabetic retinopathy and involved mechanisms. Biomed Pharmacother 2020; 132:110852. [DOI: 10.1016/j.biopha.2020.110852] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 10/01/2020] [Accepted: 10/04/2020] [Indexed: 02/06/2023] Open
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Shrikanth CB, Nandini CD. AMPK in microvascular complications of diabetes and the beneficial effects of AMPK activators from plants. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 73:152808. [PMID: 30935723 DOI: 10.1016/j.phymed.2018.12.031] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 12/19/2018] [Accepted: 12/23/2018] [Indexed: 05/15/2023]
Abstract
BACKGROUND Diabetes mellitus is a multifactorial disorder with the risk of micro- and macro-vascular complications. High glucose-induced derangements in metabolic pathways are primarily associated with the initiation and progression of secondary complications namely, diabetic nephropathy, neuropathy, and retinopathy. Adenosine monophosphate-activated protein kinase (AMPK) has emerged as an attractive therapeutic target to treat various metabolic disorders including diabetes mellitus. It is a master metabolic regulator that helps in maintaining cellular energy homeostasis by promoting ATP-generating catabolic pathways and inhibiting ATP-consuming anabolic pathways. Numerous pharmacological and plant-derived bioactive compounds that increase AMP-activated protein kinase activation has shown beneficial effects by mitigating secondary complications namely retinopathy, nephropathy, and neuropathy. PURPOSE The purpose of this review is to highlight current knowledge on the role of AMPK and its activators from plant origin in diabetic microvascular complications. METHODS Search engines such as Google Scholar, PubMed, Science Direct and Web of Science are used to extract papers using relevant key words. Papers mainly focusing on the role of AMPK and AMPK activators from plant origin in diabetic nephropathy, retinopathy, and neuropathy was chosen to be highlighted. RESULTS According to results, decrease in AMPK activation during diabetes play a causative role in the pathogenesis of diabetic microvascular complications. Some of the plant-derived bioactive compounds were beneficial in restoring AMPK activity and ameliorating diabetic microvascular complications. CONCLUSION AMPK activators from plant origin are beneficial in mitigating diabetic microvascular complications. These pieces of evidence will be helpful in the development of AMPK-centric therapies to mitigate diabetic microvascular complications.
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Affiliation(s)
- C B Shrikanth
- Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka 570 020, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-CFTRI campus, Mysuru, Karnataka 570 020, India
| | - C D Nandini
- Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka 570 020, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-CFTRI campus, Mysuru, Karnataka 570 020, India.
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Akbari A, Nasiri K, Heydari M. Ginger ( Zingiber officinale Roscoe) extract can improve the levels of some trace elements and total homocysteine and prevent oxidative damage induced by ethanol in rat eye. AVICENNA JOURNAL OF PHYTOMEDICINE 2020; 10:365-371. [PMID: 32850293 PMCID: PMC7430965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Acute and chronic ethanol consumption cause oxidative stress and ginger improves suchconditions. In this study, the protective effects of ginger were studied on indices of oxidative stress, total homocysteinelevel and the level of the some of the oxidative stress-associated trace elements against toxicity induced by ethanol in rat eye. MATERIALS AND METHODS Twenty-four adult male Sprague-Dawley rats were randomly allocated into four groups and treated daily for 28 days as follows: group I: control;group II: ginger (1g/kg/day ginger extract by oral gavage); group III: ethanol (4g/kg/day ethanol by oral gavage) and group IV: ginger+ethanol. At the end of the experimental period, eye tissue sera were used for determination of different parameters. Furthermore, in vitro antioxidant potential and total phenol content of ginger extract were determined. RESULTS In ethanol group, significant changes in oxidative stress markers and levels of homocysteine and some trace elements, compared to other groups, were observed (p<0.05 for all cases). However,these parameters significantly ameliorated with pretreatment with ginger in ginger+ethanol group (p<0.05 for all cases), and had no significant differencesinthese parameters betweenginger and control group were found. CONCLUSION It can be concluded that ginger extract has protective effects against toxicity induced by ethanol in the eye of male rat.
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Affiliation(s)
- Abolfazl Akbari
- Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran,Corresponding Author: Tel:+989187610484, Fax:+9871322866940,
| | - Khadijeh Nasiri
- Department of Exercise Physiology, Faculty of Sport Science, University of Mazandaran, Babolsar, Iran
| | - Mojtaba Heydari
- Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Wang M, Niu J, Ou L, Deng B, Wang Y, Li S. Zerumbone Protects against Carbon Tetrachloride (CCl 4)-Induced Acute Liver Injury in Mice via Inhibiting Oxidative Stress and the Inflammatory Response: Involving the TLR4/NF-κB/COX-2 Pathway. Molecules 2019; 24:molecules24101964. [PMID: 31121820 PMCID: PMC6571963 DOI: 10.3390/molecules24101964] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/10/2019] [Accepted: 05/15/2019] [Indexed: 12/11/2022] Open
Abstract
The natural compound Zerumbone (hereinafter referred to as ZER), a monocyclic sesquiterpenoid, has been reported to possess many pharmacological properties, including antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanism of ZER against acute liver injury (ALI) in CCl4-induced mice models. ICR mice were pretreated intraperitoneally with ZER for five days, then received a CCl4 injection two hours after the last ZER administration and were sacrificed 24 h later. Examination of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the histopathological analysis confirmed the hepatoprotective effect of ZER. Biochemical assays revealed that ZER pretreatment recovered the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), restored the glutathione (GSH) reservoir, and reduced the production of malondialdehyde (MDA), all in a dose-dependent manner. Furthermore, administration of ZER in vivo reduced the release amounts of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and inhibited the increased protein levels of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB) p-p65, and cyclooxygenase (COX-2). Further studies in lipopolysaccharide (LPS)-induced Raw264.7 inflammatory cellular models verified that ZER could inhibit inflammation via inactivating the TLR4/NF-κB/COX-2 pathway. Thus, our study indicated that ZER exhibited a hepatoprotective effect against ALI through its antioxidant and anti-inflammatory activities and the possible mechanism might be mediated by the TLR4/NF-κB/COX-2 pathway. Collectively, our studies indicate ZER could be a potential candidate for chemical liver injury treatment.
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Affiliation(s)
- Meilin Wang
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
| | - Jingling Niu
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
| | - Lina Ou
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
| | - Bo Deng
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
| | - Yingyi Wang
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
| | - Sanqiang Li
- Medical College, Henan University of Science and Technology, Luoyang 471023, China.
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A critical review on anti-angiogenic property of phytochemicals. J Nutr Biochem 2019; 71:1-15. [PMID: 31174052 DOI: 10.1016/j.jnutbio.2019.04.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/12/2019] [Accepted: 04/25/2019] [Indexed: 12/14/2022]
Abstract
Angiogenesis, a process involved in neovascularization, has been found to be associated with several metabolic diseases like cancer, retinopathy etc. Thus, currently, the focus on anti-angiogenic therapy for treatment and prevention of diseases has gained significant attention. Currently available Food and Drug Administration (FDA) approved drugs are targeting either vascular endothelial growth factor or it's receptor, but in the long term, these approaches were shown to cause several side effects and the chances of developing resistance to these drugs is also high. Therefore, identification of safe and cost-effective anti-angiogenic molecules is highly imperative. Over the past decades, dietary based natural compounds have been studied for their anti-angiogenic potential which provided avenues in improving the angiogenesis based therapy. In this review, major emphasis is given to the molecular mechanism behind anti-angiogenic effect of natural compounds from dietary sources.
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Rossino MG, Casini G. Nutraceuticals for the Treatment of Diabetic Retinopathy. Nutrients 2019; 11:nu11040771. [PMID: 30987058 PMCID: PMC6520779 DOI: 10.3390/nu11040771] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/19/2019] [Accepted: 03/28/2019] [Indexed: 02/07/2023] Open
Abstract
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.
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Affiliation(s)
| | - Giovanni Casini
- Department of Biology, University of Pisa, via San Zeno 31, 56127 Pisa, Italy.
- Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, 56124 Pisa, Italy.
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Kim JW, Yang D, Jeong H, Park IS, Lee MH, Lim CW, Kim B. Dietary zerumbone, a sesquiterpene, ameliorates hepatotoxin-mediated acute and chronic liver injury in mice. Phytother Res 2019; 33:1538-1550. [PMID: 30868670 DOI: 10.1002/ptr.6346] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 02/06/2019] [Accepted: 02/21/2019] [Indexed: 12/19/2022]
Abstract
Acute liver injury (ALI) is a life-threatening clinical syndrome. Long-lasting liver injury can lead to chronic hepatic inflammation and fibrogenic responses. Zerumbone (ZER), the main constituent of rhizomes of Zingiber zerumbet Smith, has a variety of functions including anticancer activity. We investigated the role of ZER on the progression of hepatotoxin-induced liver injury. Single or repeated injection of CCl4 was used to induce acute or chronic liver injury, respectively. Mice were orally administered with ZER (10, 50 mg/kg) during the experimental period. Histopathologic analysis and serum biochemical levels revealed that ZER had hepatoprotective activities against ALI. Similar effects of ZER on injured livers were confirmed by analyses of inflammation and apoptosis-related genes. Western blot analysis showed that protein levels of apoptotic molecules were decreased, whereas antiapoptotic protein levels were conversely increased in injured livers treated with ZER. Furthermore, chronic liver injury and its associated fibrogenesis in mice were reduced by ZER treatment. These findings from our in vivo experiments further indicate that ZER could alleviate hepatocellular toxicity and inhibit activation of primary hepatic stellate cells. Our results suggest that ZER might have potential as a safe and prophylactic alternative to prevent acute and chronic liver injury.
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Affiliation(s)
- Jong-Won Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Daram Yang
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Hyeneui Jeong
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Il Song Park
- Division of Advanced Materials Engineering, Research Center for Advanced Materials Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju, Republic of Korea
| | - Min-Ho Lee
- Deptartment of Dental Biomaterials and Institute of Biodegradable material, Institute of Oral Bioscience and BK21 plus project, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea
| | - Chae Woong Lim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
| | - Bumseok Kim
- Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea
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Singh YP, Girisa S, Banik K, Ghosh S, Swathi P, Deka M, Padmavathi G, Kotoky J, Sethi G, Fan L, Mao X, Halim CE, Arfuso F, Kunnumakkara AB. Potential application of zerumbone in the prevention and therapy of chronic human diseases. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.12.020] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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Resveratrol exhibits an effect on attenuating retina inflammatory condition and damage of diabetic retinopathy via PON1. Exp Eye Res 2018; 181:356-366. [PMID: 30503749 DOI: 10.1016/j.exer.2018.11.023] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 11/07/2018] [Accepted: 11/25/2018] [Indexed: 12/18/2022]
Abstract
Diabetic retinopathy (DR), an obstacle of the visual microvascular system, is a serious complication of diabetic patients. Paraoxonase 1 (PON1) has been extensively evaluated as a genetic candidate for diabetic microvascular complications, and PON1 is associated with DR. In this study, the biological functions of PON1 and its related proteins were determined via gene ontology (GO) enrichment analysis; we demonstrated that treatment with resveratrol alleviated retinal inflammatory activities to evaluate its protective effects on streptozotocin (STZ)-induced diabetic rats and high-glucose (HG) stimulated rat retinal endothelial cells (RRECs). The GO enrichment analysis suggested that PON1 may regulate inflammatory responses and microvascular complications in DR. In an in vivo study, resveratrol significantly recovered the insulin level and PON1 expression and activity, as well as clearly reduced the retinal vascular permeability, retinal AGEs, LDL, Ox-LDL, caspase3 activity, retinal damage, IL-1β, IL-6, TNFα, VEGF, IFNγ and MCP-1 in STZ-diabetic rats. Moreover, resveratrol reduced the caspase3 activity and Ox-LDL expression in HG stimulated RRECs. However, its protective effect was a deficiency in PON1-silenced RRECs. PON1 is a pivotal modulator in the role of resveratrol in reversing the RREC damage induced by HG. Furthermore, we found that resveratrol exhibits an effect on attenuating the retinal inflammatory condition and damage of DR via PON1. Our study suggests that resveratrol-induced PON1 in the retina may be a promising therapeutic strategy to prevent diabetes-related retinopathy.
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Shrikanth CB, Chilkunda ND. Zerumbone Ameliorates High Glucose-Induced Reduction in AMP-Activated Protein Kinase Phosphorylation in Tubular Kidney Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2017; 65:9208-9216. [PMID: 28971677 DOI: 10.1021/acs.jafc.7b02379] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
AMP-activated protein kinase (AMPK) plays an important role in pathophysiology of diabetes and its complications. In recent years, its role in kidney as a therapeutic target in ameliorating diabetic kidney damage is receiving renewed attention. Efforts on identifying AMPK modulators from dietary sources have gained prominence because of the tremendous potential it harbors. We therefore, examined the effect of a few bioactives on AMPK phosphorylation in kidney tubular cells. AMPK phosphorylation at Thr172 was reduced (0.42 ± 0.05-fold change compared to the control; p < 0.01 vs control) after treatment with high glucose (30 mM) for 48 h and restored by zerumbone (1.59 ± 0.20; p < 0.01 vs high glucose) but not by other tested modulators. Zerumbone also increased the phosphorylation of downstream target of AMPK, the acetyl-CoA carboxylase (ACC) without affecting the mitochondrial membrane potential and ADP/ATP ratio. Thus, zerumbone could potentially be explored as a therapeutic agent in bringing about energy homeostasis in diabetes where high glucose suppresses the AMPK pathway.
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Affiliation(s)
- Chomanahalli B Shrikanth
- Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute , Mysuru, 570 020, Karnataka India
| | - Nandini D Chilkunda
- Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute , Mysuru, 570 020, Karnataka India
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Gu JF, Su SL, Guo JM, Zhu Y, Zhao M, Duan JA. The aerial parts of Salvia miltiorrhiza Bge. strengthen intestinal barrier and modulate gut microbiota imbalance in streptozocin-induced diabetic mice. J Funct Foods 2017. [DOI: 10.1016/j.jff.2017.06.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Minassi A, Pollastro F, Chianese G, Caprioglio D, Taglialatela-Scafati O, Appendino G. Carbonyl Activation in Electrophilic Polyene Cyclizations: A Toolbox for the Design of Isoprenoid Libraries. Angew Chem Int Ed Engl 2017; 56:7935-7938. [DOI: 10.1002/anie.201703455] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Indexed: 12/15/2022]
Affiliation(s)
- Alberto Minassi
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | - Federica Pollastro
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | - Giuseppina Chianese
- Dipartimento di Farmacia; Università di Napoli Federico II; Via Montesano 49 80131 Napoli Italy
| | - Diego Caprioglio
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | | | - Giovanni Appendino
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
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Minassi A, Pollastro F, Chianese G, Caprioglio D, Taglialatela-Scafati O, Appendino G. Carbonyl Activation in Electrophilic Polyene Cyclizations: A Toolbox for the Design of Isoprenoid Libraries. Angew Chem Int Ed Engl 2017. [DOI: 10.1002/ange.201703455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Alberto Minassi
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | - Federica Pollastro
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | - Giuseppina Chianese
- Dipartimento di Farmacia; Università di Napoli Federico II; Via Montesano 49 80131 Napoli Italy
| | - Diego Caprioglio
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
| | | | - Giovanni Appendino
- Dipartimento di Scienze del Farmaco; Università del Piemonte Orientale; L.go Donegani 2 28100 Novara Italy
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Gopalan G, Dhanya BP, Saranya J, Reshmitha TR, Baiju TV, Meenu MT, Nair MS, Nisha P, Radhakrishnan KV. Metal-Free trans
-Aziridination of Zerumbone: Synthesis and Biological Evaluation of Aziridine Derivatives of Zerumbone. European J Org Chem 2017. [DOI: 10.1002/ejoc.201700410] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Greeshma Gopalan
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Bhandara Purayil Dhanya
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Jayaram Saranya
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Thankappan Remadevi Reshmitha
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Agroprocessing and Technology Division; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Thekke Veettil Baiju
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Murugan Thulasi Meenu
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Mangalam S. Nair
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Prakasan Nisha
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Agroprocessing and Technology Division; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
| | - Kokkuvayil Vasu Radhakrishnan
- Academy of Scientific and Innovative Research (AcSIR); CSIR-NIIST; 695019 Thiruvananthapuram India
- Organic Chemistry Section; National Institute for Interdisciplinary Science and Technology (CSIR); 695019 Thiruvananthapuram India
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31
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Haque MA, Jantan I, Arshad L, Bukhari SNA. Exploring the immunomodulatory and anticancer properties of zerumbone. Food Funct 2017; 8:3410-3431. [DOI: 10.1039/c7fo00595d] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Plant-derived immunomodulators and anti-cancer agents have attracted a lot of interest from natural product scientists for their efficacy and safety, and their significant contribution towards understanding targeted drug action and drug delivery mechanisms.
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Affiliation(s)
- Md. Areeful Haque
- Drug and Herbal Research Centre
- Faculty of Pharmacy
- Universiti Kebangsaan Malaysia
- 50300 Kuala Lumpur
- Malaysia
| | - Ibrahim Jantan
- Drug and Herbal Research Centre
- Faculty of Pharmacy
- Universiti Kebangsaan Malaysia
- 50300 Kuala Lumpur
- Malaysia
| | - Laiba Arshad
- Drug and Herbal Research Centre
- Faculty of Pharmacy
- Universiti Kebangsaan Malaysia
- 50300 Kuala Lumpur
- Malaysia
| | - Syed Nasir Abbas Bukhari
- Drug and Herbal Research Centre
- Faculty of Pharmacy
- Universiti Kebangsaan Malaysia
- 50300 Kuala Lumpur
- Malaysia
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32
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Dhanya BP, Gopalan G, Reshmitha TR, Saranya J, Sharathna P, Shibi IG, Nisha P, Radhakrishnan KV. Synthesis and in vitro evaluation of zerumbone pendant derivatives: potent candidates for anti-diabetic and anti-proliferative activities. NEW J CHEM 2017. [DOI: 10.1039/c7nj01098b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A series of zerumbone pendant derivatives were synthesized and evaluated for their α-glucosidase, α-amylase and glycation inhibition activities.
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Affiliation(s)
- B. P. Dhanya
- Academy of Scientific and Innovative Research (AcSIR)
- CSIR-NIIST
- Thiruvananthapuram-695019
- India
- Organic Chemistry Section
| | - Greeshma Gopalan
- Academy of Scientific and Innovative Research (AcSIR)
- CSIR-NIIST
- Thiruvananthapuram-695019
- India
- Organic Chemistry Section
| | - T. R. Reshmitha
- Agroprocessing and Natural Products Division
- National Institute for Interdisciplinary Science and Technology (CSIR)
- Thiruvananthapuram-695 019
- India
| | - J. Saranya
- Organic Chemistry Section
- National Institute for Interdisciplinary Science and Technology (CSIR)
- Thiruvananthapuram-695019
- India
| | - P. Sharathna
- Academy of Scientific and Innovative Research (AcSIR)
- CSIR-NIIST
- Thiruvananthapuram-695019
- India
- Organic Chemistry Section
| | - I. G. Shibi
- Department of Chemistry
- Thiruvananthapuram
- India
| | - P. Nisha
- Academy of Scientific and Innovative Research (AcSIR)
- CSIR-NIIST
- Thiruvananthapuram-695019
- India
- Agroprocessing and Natural Products Division
| | - K. V. Radhakrishnan
- Academy of Scientific and Innovative Research (AcSIR)
- CSIR-NIIST
- Thiruvananthapuram-695019
- India
- Organic Chemistry Section
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Liu WY, Tzeng TF, Liu IM. Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways. Molecules 2016; 21:molecules21121708. [PMID: 27973425 PMCID: PMC6273957 DOI: 10.3390/molecules21121708] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 12/07/2016] [Accepted: 12/09/2016] [Indexed: 12/22/2022] Open
Abstract
Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.
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Affiliation(s)
- Wayne Young Liu
- Center for Basic Medical Science, Collage of Health Science, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan.
- Department of Urology, Jen-Ai Hospital, Taichung 41625, Taiwan.
| | - Thing-Fong Tzeng
- Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan.
| | - I-Min Liu
- Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Pingtung 90741, Taiwan.
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