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Wan Q, Luo S, Lu Q, Guan C, Zhang H, Deng Z. Protective effects of puerarin on metabolic diseases: Emphasis on the therapeutical effects and the underlying molecular mechanisms. Biomed Pharmacother 2024; 179:117319. [PMID: 39197190 DOI: 10.1016/j.biopha.2024.117319] [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: 06/21/2024] [Revised: 08/16/2024] [Accepted: 08/21/2024] [Indexed: 09/01/2024] Open
Abstract
Metabolic diseases (MetD) such as diabetes mellitus, obesity, and hyperlipidemia have become global health challenges. As a naturally occurring plant component, puerarin has been verified to possess a wide range of pharmacological effects including lowering blood glucose, improving insulin resistance, and regulating lipid metabolism, which has attracted extensive attention in recent years, and its potential in the treatment of MetD has been highly acclaimed. In addition, puerarin has exhibited antioxidant, anti-inflammatory, and cardiovascular protective effects, which are of great significance in the prevention and treatment of MetD. This article comprehensively summarizes the research progress of puerarin in the treatment of MetD and explores its pharmacological mechanisms, clinical applications, and future perspectives. More importantly, this review provided a list of the involved molecular mechanims in treating MetD of puerarin. Taking into account these conclusions, it may provide a strong foundation for the optimized use of puerarin in the treatment of patients suffering from MetD.
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Affiliation(s)
- Qiang Wan
- Department of Medical Cardiology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, China; Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang 330006, China.
| | - Sang Luo
- Graduate School, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Qiwen Lu
- Graduate School, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Chengyan Guan
- Graduate School, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Hao Zhang
- Graduate School, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Zhiyan Deng
- Department of Gastroenterology, Jinhua TCM Hospital Affiliated to Zhejiang Chinese Medical University, Jinhua 321017, China.
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Bai YL, Han LL, Qian JH, Wang HZ. Molecular Mechanism of Puerarin Against Diabetes and its Complications. Front Pharmacol 2022; 12:780419. [PMID: 35058775 PMCID: PMC8764238 DOI: 10.3389/fphar.2021.780419] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/07/2021] [Indexed: 01/17/2023] Open
Abstract
Puerarin is a predominant component of Radix Puerarin. Despite its anti-tumor and anti-virus effects and efficacy in improving cardiovascular or cerebrovascular diseases and preventing osteoporosis, it has been shown to protect against diabetes and its complications. This review summarizes the current knowledge on Puerarin in diabetes and related complications, aiming to provide an overview of antidiabetic mechanisms of Puerarin and new targets for treatment.
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Affiliation(s)
- Yi-Ling Bai
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ling-Ling Han
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jun-Hui Qian
- Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hao-Zhong Wang
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Mo L, Zhao GL, Li XF, Xiao XL, He N, Ma JJ, Yu YG. Evaluation of the digestion and transport profiles and potential immunocompetence of puerarin and its acylated derivatives. Food Funct 2021; 12:5949-5958. [PMID: 34031685 DOI: 10.1039/d1fo00555c] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Acylation has become one of the most widely used methods to improve the lipid solubility and bioavailability of flavonoids. In this study, puerarin acid esters (PAES) with different chain lengths were synthesized via biocatalytic acylation. This was the first study to evaluate the digestion and transport profiles and immunocompetence of PAES. The relationship between the digestion and transport profiles and potential immunocompetence of the acylated derivatives in Caco-2 cell monolayers was also explored. Puerarin and PAES remained stable in gastric phases, whereas different degrees of hydrolysis of PAES were found in the intestine. PAES with less than 12 carbon chains were positively correlated with the degree of hydrolysis, while those with more than 12 carbon chains showed higher resistance to hydrolysis by the artificial human digestive juice. The apparent permeability coefficients of puerarin, puerarin acetate, puerarin propanoate, puerarin butyrate, puerarin hexanoate, puerarin octanate and puerarin laurate were 1.62 ± 0.09, 1.70 ± 0.15, 1.89 ± 0.19, 1.86 ± 0.18, 2.29 ± 0.12, 4.06 ± 1.01 and 2.32 ± 0.88 × 10-6 cm s-1, respectively, in Caco-2 cell monolayers. The results of the immune factor assays indicated that puerarin propanoate, puerarin hexanoate and puerarin myristate could significantly promote the secretion of IL-6, TNF-α and IL-10. These findings suggested that a better absorption could be predicted after oral intake using PAES. Meanwhile, the concentration of esters and their metabolites (puerarin) found in the digestion and transport profiles directly affected their potential immunocompetence.
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Affiliation(s)
- Lan Mo
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
| | - Guang-Lei Zhao
- State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510641, China
| | - Xiao-Feng Li
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
| | - Xing-Long Xiao
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
| | - Ning He
- The Laboratory of Advanced Design and Manufacturing for Precision Biomedical Devices, College of Mechanical and Vehicle Engineering, Hunan University, Changsha, 410082, China
| | - Juan-Juan Ma
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
| | - Yi-Gang Yu
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
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Zhang D, Li M. Puerarin prevents cataract development and progression in diabetic rats through Nrf2/HO‑1 signaling. Mol Med Rep 2019; 20:1017-1024. [PMID: 31173182 PMCID: PMC6625395 DOI: 10.3892/mmr.2019.10320] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Accepted: 04/17/2019] [Indexed: 12/30/2022] Open
Abstract
Puerarin is the major bioactive ingredient isolated from the dry root of Pueraria lobata, a plant used in traditional Chinese medicine. Puerarin has been used to treat diabetes and cataracts in China; however, its underlying mechanism of action remains unclear. The aim of the present study was to investigate the effectiveness and mechanism of puerarin in preventing cataracts in diabetic rats. Diabetes was induced by streptozocin (STZ) administration and rats were intraperitoneally injected with puerarin (25, 50 and 100 mg/kg). Blood glucose levels and cataract development were examined in the different experimental groups. In addition, the expression levels of markers associated with oxidative stress, including nuclear factor erythroid 2 like 2 (Nrf2) and heme oxygenase‑1 (HO‑1), were analyzed. The present results suggested that treatment with puerarin at 25, 50 and 100 mg/kg significantly reduced blood glucose levels and the incidence of cataract in STZ‑induced diabetic rats. Additionally, puerarin treatment reduced oxidative stress, restoring the levels of malondialdehyde and glutathione, and the activity of glutathione peroxidase. Furthermore, puerarin administration decreased the expression levels of retinal vascular endothelial growth factor and interleukin‑1β and increased the mRNA expression levels of Nrf2 and HO‑1, thus inhibiting oxidative stress. The present findings suggested that puerarin had hypoglycemic effects and that it prevented cataract development and progression in diabetic rats by reducing oxidative stress through the Nrf2/HO‑1 signaling pathway.
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Affiliation(s)
- Duzhen Zhang
- Department of Ophthalmology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| | - Man Li
- Department of Ophthalmology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
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Chen X, Yu J, Shi J. Management of Diabetes Mellitus with Puerarin, a Natural Isoflavone FromPueraria lobata. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2019; 46:1771-1789. [DOI: 10.1142/s0192415x18500891] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Diabetes mellitus (DM) has become one of the most challenging public health problems globally. The increasing prevalence and mortality rates call for more effective therapeutic agents, especially for DM complications. Traditional herbs have a long clinical application history for DM treatment. Puerarin is a natural isoflavone from Pueraria lobata (Wild.) Ohwi which has been consumed both as a functional food and herb in Eastern Asia countries. Documented data has shown that puerarin has cardio-protective, neuroprotective, anti-oxidative, anti-inflammatory and many other effects. In this review, we will summarize the beneficial effects and underlying mechanisms of puerarin on DM and complications. Puerarin may directly benefit DM by decreasing blood glucose levels, improving insulin resistance, protecting islets, inhibiting inflammation, decreasing oxidative stress and inhibiting Maillard reaction and advanced glycation end products (AGEs) formation. Furthermore, puerarin may also benefit DM indirectly by retarding and improving a series of DM complications, such as cardiovascular complications, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, etc. However, comprehensive studies of its effect and mechanisms are needed. In addition, its efficacy is relatively low, which is partially due to its pharmacokinetics profiles. Though puerarin shows low toxicity to experimental animals, its safety on human remains to be clarified. Collectively, we suggest that puerarin might be a potential adjuvant agent for the treatment of DM and DM complications in future.
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Affiliation(s)
- Xiuping Chen
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563003, P. R. China
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, P. R. China
| | - Jie Yu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, P. R. China
| | - Jingshan Shi
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563003, P. R. China
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Wang T, Liu Y, Huang C, Mansai HAA, Wei W, Zhang X, Li X, Liu S, Yang S. Puerarin promotes MIN6 cell survival by reducing cellular reactive oxygen species. Mol Med Rep 2018; 17:7281-7286. [PMID: 29568901 DOI: 10.3892/mmr.2018.8731] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 07/25/2017] [Indexed: 11/05/2022] Open
Abstract
Type 1 diabetes is caused by destruction of the pancreatic β‑cells and, to date, no cure has been developed. Promoting the survival of pancreatic β‑cells may be beneficial for patients with type 1 diabetes. Puerarin is an estrogen analogue that been demonstrated in previous studies to be able to decreased blood glucose in patients with type 1 diabetes. Similar results were demonstrated in previous studies which additionally demonstrated that puerarin was able to decreased blood glucose in type 1 diabetic mice by protecting pancreatic β‑cells. However, the mechanism underlying the function of puerarin in pancreatic β‑cells remains unclear. Therefore, the present study sought to investigate the detailed function of puerarin in pancreatic β‑cells. In the present study, H2O2 was used to induce apoptosis. It was observed that puerarin significantly decreased H2O2‑induced apoptosis in mouse insulinoma MIN6 cells. It was additionally observed that puerarin decreased the levels of intracellular reactive oxygen species and mitochondrial superoxide in MIN6 cells. The protective effect of puerarin was markedly decreased by 6‑aminonicotinamide, an inhibitor of glucose‑6‑phosphate dehydrogenase (G6PD). In conclusion, the results of the present study suggested that puerarin may increase the activity of G6PD, decreased the level of oxidative stress in MIN6 cells, protect mitochondria and promote MIN6 cell survival. Investigating the mechanism underlying the effect of puerarin in MIN6 cells may provide a novel approach for development of a cure for type 1 diabetes.
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Affiliation(s)
- Tianxi Wang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Yijie Liu
- Division of Gastroenterology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Caoxin Huang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Hussen Amir Ahmed Mansai
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Wenjing Wei
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Xiaofang Zhang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Xuejun Li
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Suhuan Liu
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
| | - Shuyu Yang
- Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
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Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats. Nutr Diabetes 2018; 8:1. [PMID: 29330446 PMCID: PMC5851431 DOI: 10.1038/s41387-017-0009-6] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Revised: 10/02/2017] [Accepted: 10/22/2017] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Type 2 diabetes is characterized by dyslipidemia and the accumulation of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a natural isoflavonoid isolated from the root of the plant Pueraria lobata, has been shown to have antidiabetic activity. However, the lipid-reducing effect of puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS We examined the effect of puerarin on mitochondrial function and the oxidation of fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced diabetic rats. RESULTS Puerarin effectively alleviated dyslipidemia and decreased the accumulation of intramyocellular lipids by upregulating the expression of a range of genes involved in mitochondrial biogenesis, oxidative phosphorylation, the detoxification of reactive oxygen species, and the oxidation of fatty acids in the muscle of diabetic rats. Also, the effect of puerarin on mitochondrial biogenesis might partially involve the function of the μ-opioid receptor. In addition, puerarin decreased the trafficking of fatty acid translocase/CD36 to the plasma membrane to reduce the uptake of fatty acids by myocytes. In vitro studies confirmed that puerarin acted directly on muscle cells to promote the oxidation of fatty acids in insulin-resistant myotubes treated with palmitate. CONCLUSIONS Puerarin improved the performance of mitochondria in muscle and promoted the oxidation of fatty acids, which thus prevented the accumulation of intramyocellular lipids in diabetic rats. Our findings will be beneficial both for elucidating the mechanism of the antidiabetic activity of puerarin and for promoting the therapeutic potential of puerarin in the treatment of diabetes.
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Chen X, Wang L, Fan S, Song S, Min H, Wu Y, He X, Liang Q, Wang Y, Yi L, Gao Q. Puerarin acts on the skeletal muscle to improve insulin sensitivity in diabetic rats involving μ-opioid receptor. Eur J Pharmacol 2018; 818:115-123. [DOI: 10.1016/j.ejphar.2017.10.033] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 10/05/2017] [Accepted: 10/18/2017] [Indexed: 01/19/2023]
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Chadha R, Bhalla Y, Jain A, Chadha K, Karan M. Dietary Soy Isoflavone: A Mechanistic Insight. Nat Prod Commun 2017. [DOI: 10.1177/1934578x1701200439] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Soy, a major component of the diet for centuries contains the largest concentration of isoflavones, a class of phytoestrogens. A variety of health benefits are associated with the consumption of soy primarily because of the isoflavones genistein, daidzein, and glycitein with a potential protective effect against a number of chronic diseases. Owing to the pharmaceutical and nutraceutical properties allied with isoflavonoids and their use in functional foods, there is a growing interest in these compounds. This review throws light on the chemistry, and significant pharmacological and biopharmaceutical aspects of soy isoflavones. This article critically describes the mechanisms of action, infers conclusions and shows opportunity for future research.
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Affiliation(s)
- Renu Chadha
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Yashika Bhalla
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Ankita Jain
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Kunal Chadha
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Maninder Karan
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
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Fang K, Dong H, Wang D, Gong J, Huang W, Lu F. Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta-analysis of randomized controlled trials. Mol Nutr Food Res 2016; 60:1602-14. [PMID: 27004555 DOI: 10.1002/mnfr.201501024] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Revised: 02/28/2016] [Accepted: 03/06/2016] [Indexed: 12/12/2022]
Abstract
SCOPE The aim of this meta-analysis was to investigate whether soy isoflavones, a type of phytoestrogen, would affect glucose homeostasis in menopausal women. METHODS AND RESULTS Studies concerning about the relationship between soy isoflavone treatment and glucose metabolism were searched on MEDLINE and WEB OF SCIENCE (updated through April 2015) and EMBASE (1990-April 2015). Seventeen randomized controlled trials (RCTs) with a total number of 1529 menopausal women were identified for meta-analysis. Soy isoflavones were found to show great significance for the improvement of glucose metabolism, though marked heterogeneity was found between studies. The overall results showed that the average difference in fasting blood glucose values between women assigned to soy isoflavones and women in placebo groups was -0.22 mmol/L (95% CI: -0.38 to -0.07 mmol/L) under a random-effects model. In addition, the effect of soy isoflavones on insulin was also significant: -0.43 μIU/mL (95% CI: -0.71 to -0.14 μIU/mL), as was the effect on homeostasis model assessment insulin resistance (HOMA-IR): -0.52 (95% CI: -0.76 to -0.28). CONCLUSION Although the results displayed a significant tendency in favor of soy isoflavones, it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity.
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Affiliation(s)
- Ke Fang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Hui Dong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Dingkun Wang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Jing Gong
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Wenya Huang
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Fuer Lu
- Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
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Liu AC, Zhao LX, Yu SW, Lou HX. Pre-treatment with puerarin affects pharmacokinetics of warfarin, but not clopidogrel, in experimental rats. Chin J Nat Med 2016; 13:257-63. [PMID: 25908622 DOI: 10.1016/s1875-5364(15)30012-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Indexed: 12/26/2022]
Abstract
The present study was designed to determine the effects of puerarin pre-treatment on the pharmacokinetics of the oral anticoagulant agent warfarin and the antiplatelet agent clopidogrel in rats. In the treatment group, rats was gavaged with warfarin or clopidogrel after repeated treatment with puerarin at intraperitoneal doses of 20, 60, or 200 mg·kg(-1) for 7 days, while rats in the control group were administrated only with the same dose warfarin or clopidogrel. Plasma samples were obtained at the prescribed times and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The results showed that rats treated with puerarin at all the test doses of 20, 60 and 200 mg·kg(-1) were found to affect the pharmacokinetics of warfarin, but not clopidogrel, suggesting a potential herb-drug interaction between puerarin and warfarin.
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Affiliation(s)
- An-Chang Liu
- Qilu hospital of Shandong University, Jinan 250012, China
| | - Li-Xia Zhao
- Qilu hospital of Shandong University, Jinan 250012, China
| | - Shu-Wen Yu
- Jinan Central Hospital Affiliated to Shandong University, Jinan 250011, China
| | - Hong-Xiang Lou
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
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Interactions between herbs and antidiabetics: an overview of the mechanisms, evidence, importance, and management. Arch Pharm Res 2014; 38:1281-98. [PMID: 25475096 DOI: 10.1007/s12272-014-0517-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Accepted: 11/10/2014] [Indexed: 02/08/2023]
Abstract
Complementary and alternative therapies are quickly gaining importance because they are perceived to be free of side effects due to their natural origin. However, herbal remedies are complex mixtures of bioactive entities, which may interact with prescription drugs through pharmacokinetic or pharmacodynamic mechanisms and sometimes result in life-threatening consequences. In particular, diabetes patients are often treated with multiple medications due to different comorbidities, and such patients use antidiabetic medications for their entire lives; thus, it is important to make the public aware of herb interactions with antidiabetic drugs. In this paper, we summarize the reports available on the interaction of herbal remedies with oral hypoglycemic agents and describe mechanisms, preclinical or clinical evidence, importance, and management strategies.
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13
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Ma JZ, Yang LX, Shen XL, Qin JH, Deng LL, Ahmed S, Xu HX, Xue DY, Ye JX, Xu G. Effects of Traditional Chinese Medicinal Plants on Anti-insulin Resistance Bioactivity of DXMS-Induced Insulin Resistant HepG2 Cells. NATURAL PRODUCTS AND BIOPROSPECTING 2014; 4:197-206. [PMID: 25089237 PMCID: PMC4111871 DOI: 10.1007/s13659-014-0028-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Accepted: 06/16/2014] [Indexed: 06/03/2023]
Abstract
ABSTRACT Medicinal plants have a long history of use in China to treat diabetic symptoms. Ancient Chinese medical manuscripts and ethnobotanical surveys document plant remedies that continue to be actively used in China for the treatment of diabetic symptoms. Based on a systematic ancient Chinese medical manuscripts review in combination with ethnobotanical survey, 16 medicinal plants for the traditional treatment of diabetic symptoms were identified for the evaluation of anti-insulin resistance bioactivity. The biological activity of 16 medicinal plants was tested on dexamethasone (DXMS)-induced insulin resistant HepG2 cells. The result shows that 11 of the 16 medicinal plants enhanced glucose uptake of DXMS-induced insulin resistant HepG2 cells, thereby demonstrating their ability to increase insulin sensitivity, other five medicinal plants including Astragalus membranaceus were found ineffective. The study shows that ancient Chinese medical manuscripts and ethnobotanical surveys on plants for the prevention and treatment of diabetic symptoms provide a promising knowledge base for drug discovery to mitigate the global diabetes epidemic.
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Affiliation(s)
- Jun-Zeng Ma
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201 People’s Republic of China
| | - Li-Xin Yang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201 People’s Republic of China
- College of Life and Environmental Science, Minzu University of China, 27 ZhongGuanCun South Avenue, Beijing, 100086 China
| | - Xiao-Ling Shen
- Laboratory of Chinese Herbal Drug Discovery, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405 People’s Republic of China
| | - Ji-Huan Qin
- Laboratory of Chinese Herbal Drug Discovery, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405 People’s Republic of China
| | - Li-Lan Deng
- Southwest Forestry University, Kunming, 650224 People’s Republic of China
| | - Selena Ahmed
- College of Life and Environmental Science, Minzu University of China, 27 ZhongGuanCun South Avenue, Beijing, 100086 China
- Sustainable Food and Bioenergy Systems Program, Department of Health and Human Development, Montana State University, Bozeman, MT 59717 USA
| | - Hong-Xi Xu
- Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 People’s Republic of China
| | - Da-Yuan Xue
- College of Life and Environmental Science, Minzu University of China, 27 ZhongGuanCun South Avenue, Beijing, 100086 China
| | - Jiang-Xia Ye
- Southwest Forestry University, Kunming, 650224 People’s Republic of China
| | - Gang Xu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201 People’s Republic of China
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14
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Maji AK, Pandit S, Banerji P, Banerjee D. Pueraria tuberosa: a review on its phytochemical and therapeutic potential. Nat Prod Res 2014; 28:2111-27. [PMID: 24980468 DOI: 10.1080/14786419.2014.928291] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Amal K. Maji
- Department of Botany and Forestry, Vidyasagar University, Midnapore 721102, India
| | - Subrata Pandit
- Ulysses Research Foundation, 125, Rash Behari Avenue, Kolkata 700029, India
| | - Pratim Banerji
- Ulysses Research Foundation, 125, Rash Behari Avenue, Kolkata 700029, India
| | - Debdulal Banerjee
- Department of Botany and Forestry, Vidyasagar University, Midnapore 721102, India
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Ulbricht C, Costa D, Dam C, D'Auria D, Giese N, Isaac R, LeBlanc Y, Rusie E, Weissner W, Windsor RC. An evidence-based systematic review of kudzu (Pueraria lobata) by the Natural Standard Research Collaboration. J Diet Suppl 2014; 12:36-104. [PMID: 24848872 DOI: 10.3109/19390211.2014.904123] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
An evidence-based systematic review of kudzu (Pueraria lobata) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
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16
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El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: Review on potential mechanistic perspectives. World J Diabetes 2014; 5:176-197. [PMID: 24748931 PMCID: PMC3990312 DOI: 10.4239/wjd.v5.i2.176] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 01/07/2014] [Accepted: 03/14/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying.
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Liu AC, Zhao LX, Xing J, Gao J, Lou HX. LC-MS/MS method for the determination of a new puerarin derivative and its application in pharmacokinetic studies in rats. Chin J Nat Med 2013; 11:566-71. [PMID: 24359785 DOI: 10.1016/s1875-5364(13)60102-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Indexed: 11/25/2022]
Abstract
AIM To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of dehydrated puerarin in rat plasma, and its application for pharmacokinetic studies. METHODS A plasma sample was pretreated by one-step protein precipitation by the addition of five volumes of methanol. The chromatographic separation was achieved on a Zorbax SB-C18 column (4.6 mm × 150 mm I.D. 5.0 μm, Agilent, USA) at 40 °C at a flow rate of 0.6 mL·min(-1) by an isocratic elution consisting of 10 mmol·L(-1) ammonium acetate in methanol and water containing 0.1% formic acid in a ratio of 20 : 80 (V/V). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction monitoring (MRM) mode. An atmospheric pressure chemical ionization (APCI) interface in positive ionization mode was used by monitoring the transitions from m/z 399.1→281.0 (dehydrated puerarin) and m/z 271.0→215.0 (internal standard, IS). RESULTS Calibration curves were linear in the concentration range from 1.50 to 5400 ng·mL(-1), and the lower limit of quantification (LLOQ) was 1.50 ng·mL(-1) in rat plasma. The accuracy and precision values, which were calculated from three different sets of quality control samples analyzed in sextuplicate on three different days, ranged from 95.73% to 103.18%, and from 4.33% to 7.86%, respectively. CONCLUSION The method was successfully applied to assess the pharmacokinetics of dehydrated puerarin after oral administration in rats.
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Affiliation(s)
- An-Chang Liu
- Qilu Hospital of Shandong University, Jinan 250012, China
| | - Li-Xia Zhao
- Qilu Hospital of Shandong University, Jinan 250012, China
| | - Jie Xing
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Jian Gao
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
| | - Hong-Xiang Lou
- School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
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Kim J, Kim CS, Sohn E, Lee YM, Jo K, Kim JS. KIOM-79 protects AGE-induced retinal pericyte apoptosis via inhibition of NF-kappaB activation in vitro and in vivo. PLoS One 2012; 7:e43591. [PMID: 22916281 PMCID: PMC3423361 DOI: 10.1371/journal.pone.0043591] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Accepted: 07/23/2012] [Indexed: 12/19/2022] Open
Abstract
KIOM-79 is an herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix and Euphorbiae radix. In the present study, we determined the efficacy and possible mechanism of KIOM-79 on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in Zucker diabetic fatty (ZDF) rats. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg body weight) once a day orally for 13 weeks. KIOM-79 significantly inhibited pericyte apoptosis which were induced by the AGE-BSA treatment. The KIOM-79 treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB) through the inhibition of inhibitory κB kinase complex. In addition, the oral administration of KIOM-79 inhibited the changes in retinal vasculature (vascular hyperpermeability, acellular capillary). KIOM-79 strongly inhibited pericyte apoptosis, NF-κB activation and the expression of pro-apoptotic Bax and tumor necrosis factor-α. Our results suggest that KIOM-79 may exert inhibitory effects on AGE-induced pericyte apoptosis by blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.
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Affiliation(s)
- Junghyun Kim
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Chan-Sik Kim
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Eunjin Sohn
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Yun Mi Lee
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Kyuhyung Jo
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
| | - Jin Sook Kim
- Traditional Korean Medicine (TKM) Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea
- * E-mail:
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19
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Wong KH, Li GQ, Li KM, Razmovski-Naumovski V, Chan K. Kudzu root: traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases. JOURNAL OF ETHNOPHARMACOLOGY 2011; 134:584-607. [PMID: 21315814 DOI: 10.1016/j.jep.2011.02.001] [Citation(s) in RCA: 262] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Revised: 01/25/2011] [Accepted: 02/05/2011] [Indexed: 05/23/2023]
Abstract
Kudzu root (Gegen in Chinese) is the dried root of Pueraria lobata (Willd.) Ohwi, a semi-woody, perennial and leguminous vine native to South East Asia. It is often used interchangeably in traditional Chinese medicine with thomson kudzu root (Fengen in Chinese), the dried root of P. thomsonii, although the Chinese Pharmacopoeia has separated them into two monographs since the 2005 edition. For more than 2000 years, kudzu root has been used as a herbal medicine for the treatment of fever, acute dysentery, diarrhoea, diabetes and cardiovascular diseases. Both English and Chinese literatures on the traditional applications, phytochemistry, pharmacological activities, toxicology, quality control and potential interactions with conventional drugs of both species have been included in the present review. Over seventy phytochemicals have been identified in kudzu root, with isoflavonoids and triterpenoids as the major constituents. Isoflavonoids, in particular puerarin, have been used in most of the pharmacological studies. Animal and cellular studies have provided support for the traditional uses of kudzu root on cardiovascular, cerebrovascular and endocrine systems, including diabetes and its complications. Further studies to define the active phytochemical compositions, quality standards and clinical efficacy are warranted. Strong interdisciplinary collaboration to bridge the gap between traditional medicine and modern biomedical medicine is therefore needed for the development of kudzu root as an effective medicine for the management of diabetes and cardiovascular diseases.
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Affiliation(s)
- Ka H Wong
- Herbal Medicines Research and Education Centre, Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia
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20
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Liu IM, Cheng JT. Mediation of Endogenous β-Endorphin in the Plasma Glucose-Lowering Action of Herbal Products Observed in Type 1-Like Diabetic Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2010; 2011:987876. [PMID: 19095661 PMCID: PMC3147137 DOI: 10.1093/ecam/nen078] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2008] [Accepted: 11/14/2008] [Indexed: 01/01/2023]
Abstract
Recently, there have been advances in the development of new substances effective in managing diabetic disorders. Opioid receptors couple multiple systems to result in various biological effects, although opioids are best known for analgesia. In the present review, we used our recent data to describe the advance in plasma glucose-lowering action of herbal products, especially the mediation of β-endorphin in glucose homeostasis of insulin-deficient diabetes. In type 1-like streptozotocin-induced diabetic rats, we identified many products purified from herbs that show a dose-dependent plasma glucose-lowering action. Increase in β-endorphin secretion from the adrenal gland may activate peripheral opioid μ-receptors (MOR) to enhance the expression of muscle glucose transporters and/or to reduce hepatic gluconeogenesis at the gene level, thereby leading to improved glucose utilization in peripheral tissues for amelioration of severe hyperglycemia. It has also been observed that stimulation of α(1)-adrenoceptors (α(1)-ARs) in the adrenal gland by some herbal products is responsible for the increase in β-endorphin secretion via a phospholipase C-protein kinase dependent pathway. However, an increase in β-endorphin secretion from the adrenal gland by herbal products can function via another receptor. New insights into the mediation of endogenous β-endorphin activation of peripheral MOR by herbal products for regulation of glucose homeostasis without the presence of insulin have been established. Therefore, an increase in β-endorphin secretion and/or direct stimulation of peripheral MOR via an insulin-independent action might serve as the potential target for development of a therapeutic agent or promising adjuvant in intensive plasma glucose control.
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Affiliation(s)
- I M Liu
- Department of Pharmacy, Tajen University, Yen-Pou, Ping Tung Shien, Taiwan
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21
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Zhao L, Li W, Han F, Hou L, Baillargeon JP, Kuang H, Wang Y, Wu X. Berberine reduces insulin resistance induced by dexamethasone in theca cells in vitro. Fertil Steril 2010; 95:461-3. [PMID: 20840879 DOI: 10.1016/j.fertnstert.2010.07.1090] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2010] [Revised: 07/10/2010] [Accepted: 07/30/2010] [Indexed: 10/19/2022]
Abstract
Theca cells with dexamethasone-induced insulin resistance showed defective glucose uptake and excessive testosterone production, both of which were effectively antagonized by berberine. Therefore, insulin-resistant theca cells may contribute to the pathogenesis of hyperandrogenism in polycystic ovary syndrome.
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Affiliation(s)
- Lu Zhao
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China
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22
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KIOM-79 Prevents Lens Epithelial Cell Apoptosis and Lens Opacification in Zucker Diabetic Fatty Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2010; 2011. [PMID: 20953387 PMCID: PMC2952320 DOI: 10.1155/2011/717921] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Revised: 04/23/2010] [Accepted: 06/30/2010] [Indexed: 11/18/2022]
Abstract
Damage of lens epithelial cells (LECs) has been implicated in cataract formation. The aim of this study was to investigate the protective effect of KIOM-79, a combination of four plant extracts, on LECs. We examined the levels of advanced glycation end products (AGEs), nuclear factor-kappaB (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in LECs during cataract development using the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. KIOM-79 was orally administered by gavage to ZDF rats once a day for 13 weeks. Apoptosis was detected by TUNEL assay, and NF-κB activation and iNOS expression were studied by southwestern histochemistry and immunohistochemistry, respectively. In diabetic cataractous lenses, TUNEL-positive LECs were markedly increased 20-fold, and AGEs were highly accumulated (2.7-fold) in LECs. In addition, both NF-κB activation, and iNOS expression were significantly enhanced 3- to 5-fold, respectively, compared to levels found in normal ZL rats. However, the administration of KIOM-79 delayed the development of diabetic cataracts and prevented LEC apoptosis (70%) through the inhibition of AGEs, NF-κB-activation and iNOS expression. These observations suggest that KIOM-79 is useful in inhibiting diabetic cataractogenesis and acts through an antiapoptotic mechanism to protect LECs from injury.
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Abstract
In management of metabolic syndrome, the traditional Chinese medicine (TCM) is an excellent representative in alternative and complementary medicines with a complete theory system and substantial herb remedies. In this article, basic principle of TCM is introduced and 25 traditional Chinese herbs are reviewed for their potential activities in the treatment of metabolic syndrome. Three herbs, ginseng, rhizoma coptidis (berberine, the major active compound) and bitter melon, were discussed in detail on their therapeutic potentials. Ginseng extracts made from root, rootlet, berry and leaf of Panax quinquefolium (American ginseng) and Panax ginseng (Asian ginseng), are proved for anti-hyperglycemia, insulin sensitization, islet protection, anti-obesity and anti-oxidation in many model systems. Energy expenditure is enhanced by ginseng through thermogenesis. Ginseng-specific saponins (ginsenosides) are considered as the major bioactive compounds for the metabolic activities of ginseng. Berberine from rhizoma coptidis is an oral hypoglycemic agent. It also has anti-obesity and anti-dyslipidemia activities. The action mechanism is related to inhibition of mitochondrial function, stimulation of glycolysis, activation of AMPK pathway, suppression of adipogenesis and induction of low-density lipoprotein (LDL) receptor expression. Bitter melon or bitter gourd (Momordica charantia) is able to reduce blood glucose and lipids in both normal and diabetic animals. It may also protect beta cells, enhance insulin sensitivity and reduce oxidative stress. Although evidence from animals and humans supports the therapeutic activities of ginseng, berberine and bitter melon, multi-center large-scale clinical trials have not been conducted to evaluate the efficacy and safety of these herbal medicines.
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Affiliation(s)
- Jun Yin
- Pennington Biomedical Research Center, Louisiana State University System, USA
| | - Hanjie Zhang
- Pennington Biomedical Research Center, Louisiana State University System, USA
| | - Jianping Ye
- Pennington Biomedical Research Center, Louisiana State University System, USA
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24
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Park SY, Choi YH, Lee W. Dangnyohwan improves glucose utilization and reduces insulin resistance by increasing the adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima Fatty rats. JOURNAL OF ETHNOPHARMACOLOGY 2008; 115:473-482. [PMID: 18068920 DOI: 10.1016/j.jep.2007.10.040] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2005] [Revised: 09/19/2007] [Accepted: 10/15/2007] [Indexed: 05/25/2023]
Abstract
AIM OF THE STUDY Dangnyohwan (DNH) has been used for treatment of diabetes mellitus. However, the exact cellular and molecular mechanisms underlying the beneficial effects of DNH are not well understood. Therefore, we investigated how DNH improves hyperglycemia and insulin resistance in obese-type diabetes model. METHODS AND MATERIALS We examined the effect of DNH on the expression of glucose transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in muscle and adipose tissues from Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats. RESULTS DNH ameliorated hyperglycemia and impaired glucose tolerance (IGT) observed in 26- and 42-week-old male OLETF rats. The basal and insulin-stimulated [14C]2-Deoxyglucose (2DG) uptake was significantly increased in adipocytes from DNH-treated OLETF rats, as compared with untreated OLETF rats. The expression level of GLUT4 was markedly decreased (by 90-95%) in the adipose tissue of OLETF rats, whereas DNH treatment drastically increased the expression of GLUT4 within 8 weeks. DNH improved GLUT4 recruitment stimulated by insulin in both the 26- and 42-week-old OLETF rat adipocytes. CONCLUSION These results suggest that DNH could exert the beneficial effects on hyperglycemia and insulin resistance by increasing the expression and insulin-stimulated translocation of GLUT4 in OLETF rat adipocytes.
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Affiliation(s)
- Seung Y Park
- Department of Biochemistry, College of Medicine, Dongguk University, 707 Sukjang-dong, Kyungju, Kyungpook 780-714, Republic of Korea
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25
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Yu BC, Chang CK, Su CF, Cheng JT. Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2007; 377:529-40. [PMID: 18080810 DOI: 10.1007/s00210-007-0240-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2007] [Accepted: 11/26/2007] [Indexed: 11/29/2022]
Abstract
In the present study, we investigated the mechanism(s) for glucose-lowering action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent manner and increased plasma beta-endorphin-like immunoreactivity (BER) dose-dependently in diabetic rats. Both of these responses to andrographolide were abolished by the pretreatment of animals with prazosin or N-(2-(2-cyclopropylmethoxy) ethyl) 5-choro-alpha-dimethyl-1H-indole-3-thylamine (RS17053) at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by alpha1-ARs antagonists. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of andrographolide, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Andrographolide failed to lower plasma glucose in the presence of opioid micro-receptor antagonists and in the opioid micro-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with andrographolide resulted in the reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These effects were also blocked by opioid micro-receptor antagonists. In conclusion, our results suggest that andrographolide may activate alpha1-ARs to enhance the secretion of beta-endorphin which can stimulate the opioid micro-receptors to reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However, the roles of other endogenous opioid peptides or the mixture of several opioid peptides in the activation of opioid micro-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.
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Affiliation(s)
- Bu Chin Yu
- Institute of Basic Medical Science, and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, 70101, Republic of China
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Kim YS, Jung DH, Kim NH, Lee YM, Jang DS, Song GY, Kim JS. KIOM-79 inhibits high glucose or AGEs-induced VEGF expression in human retinal pigment epithelial cells. JOURNAL OF ETHNOPHARMACOLOGY 2007; 112:166-72. [PMID: 17383127 DOI: 10.1016/j.jep.2007.02.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2006] [Revised: 02/09/2007] [Accepted: 02/18/2007] [Indexed: 05/14/2023]
Abstract
We evaluated whether KIOM-79, a mixture of extracts obtained from Puerariae lobata, Magnolia officinalis, Glycyrrhiza uralensis and Euphorbia pekinensis, could inhibit vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells cultured under high glucose (HG, 25mM) or S100b (a specific ligand of the receptor for advance glycation end products (RAGE), 5microg/ml). In this study, the effect of KIOM-79 on HG or S100b-induced VEGF expression was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, RT-PCR, ELISA, and Western blot on human RPE cells. The MTT assay (p<0.01) revealed that KIOM-79 (up to 1mg/ml) had no effect on cell growth. HG or S100b induced an increase in expression of VEGF at both mRNA and protein levels (p<0.05; p<0.01 versus control). The increase in VEGF expression by HG or S100b was dose- and time-dependently prevented by KIOM-79 (p<0.05 versus 25mM glucose; p<0.01 versus S100b). Also, KIOM-79 inhibited protein kinase C (PKC)-alpha/beta(alpha) and p38 mitogen-activated protein kinase (MAPK) activation. Our results demonstrate that KIOM-79 can inhibit VEGF expression via inhibition of the MAPK and PKC pathway.
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Affiliation(s)
- Young Sook Kim
- Department of Herbal Pharmaceutical Development, Korea Institute of Oriental Medicine, 461-24 Jeonmin-dong, Yuseng-gu, Daejeon 305-811, Republic of Korea
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Abstract
This paper is the 27th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over 30 years of research. It summarizes papers published during 2004 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.
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Affiliation(s)
- Richard J Bodnar
- Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, Flushing, NY 11367, USA.
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Meezan E, Meezan EM, Jones K, Moore R, Barnes S, Prasain JK. Contrasting effects of puerarin and daidzin on glucose homeostasis in mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2005; 53:8760-7. [PMID: 16248582 DOI: 10.1021/jf058105e] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Puerarin and daidzin are the major isoflavone glucosides found in kudzu dietary supplements. In this study, we demonstrated that puerarin significantly improves glucose tolerance in C57BL/6J-ob/ob mice, an animal model of type 2 diabetes mellitus, blunting the rise in blood glucose levels after i.p. administration of glucose. In contrast, daidzin, the O-glucoside, had a significant but opposite effect, impairing glucose tolerance as compared to saline-treated controls. When they were administered i.p. with (14)C-glucose to C57BL/6J lean mice, puerarin inhibited glucose uptake into tissues and incorporation into glycogen, while daidzin stimulated glucose uptake, showing an opposite effect to puerarin. Puerarin also antagonized the stimulatory effect of decyl-beta-D-thiomaltoside, an artificial primer of glycogen synthesis, which increases (14)C-glucose uptake and incorporation into glycogen in mouse liver and heart. A liquid chromatography-tandem mass spectrometry procedure was used to investigate the metabolism and bioavailability of puerarin and daidzin. The blood puerarin concentration-time curve by i.p. and oral administration indicated that puerarin was four times more bioavailable via i.p. injection than via the oral route of administration. This may account for the increased hypoglycemic effect seen in the i.p. glucose tolerance test vs that seen orally. Our results suggest that puerarin is rapidly absorbed from the intestine without metabolism, while daidzin is hydrolyzed to the aglycone daidzein. The opposing effects of puerarin and daidzin on glucose homeostasis may have implications for the activity of dietary supplements that contain both of these isoflavonoids.
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Affiliation(s)
- Elias Meezan
- Department of Pharmacology & Toxicology, Comprehensive Cancer Center Mass Spectrometry Shared Facility, and Purdue-UAB Botanicals Center for Age-Related Diseases, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Li D, Park SH, Shim JH, Lee HS, Tang SY, Park CS, Park KH. In vitro enzymatic modification of puerarin to puerarin glycosides by maltogenic amylase. Carbohydr Res 2004; 339:2789-97. [PMID: 15542087 DOI: 10.1016/j.carres.2004.09.017] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2004] [Accepted: 09/22/2004] [Indexed: 11/19/2022]
Abstract
Puerarin (daidzein 8-C-glucoside), the most abundant isoflavone in Puerariae radix, is prescribed to treat coronary heart disease, cardiac infarction, problems in ocular blood flow, sudden deafness, and alcoholism. However, puerarin cannot be given by injection due to its low solubility in water. To increase its solubility, puerarin was transglycosylated using various enzymes. Bacillus stearothermophilus maltogenic amylase (BSMA) was the most effective transferase used compared with Thermotoga maritima maltosyl transferase (TMMT), Thermus scotoductus 4-alpha-glucanotransferase (TS4alphaGTase), and Bacillus sp. I-5 cyclodextrin glucanotransferase (BSCGTase). TMMT and TS4alphaGTase lacked acceptor specificity for puerarin, which lacks an O-glucoside linkage between D-glucose and 7-OH-daidzein. The yield exceeded 70% when reacting 1% puerarin (acceptor), 3.0% soluble starch (donor), and 5U/100 microL BSMA at 55 degrees C for 45 min. The two major transfer products of the BSMA reaction were purified using C(18) and GPC chromatography. Their structures were identified as alpha-d-glucosyl-(1-->6)-puerarin and alpha-D-maltosyl-(1-->6)-puerarin using ESI+ TOF MS-MS and 13C NMR spectroscopy. The solubility of the transfer products was 14 and 168 times higher than that of puerarin, respectively.
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Affiliation(s)
- Dan Li
- National Laboratory for Functional Food Carbohydrate and Center for Agricultural Biomaterials, School of Agricultural Biotechnology, Seoul National University, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea
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