Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds

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Abstract

Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed.

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SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.

Michelle Pacholec, John Bleasdale, Boris Chrunyk … (2010)

Sirtuins catalyze NAD(+)-dependent protein deacetylation and are critical regulators of transcription, apoptosis, metabolism, and aging. There are seven human sirtuins (SIRT1-7), and SIRT1 has been implicated as a key mediator of the pathways downstream of calorie restriction that have been shown to delay the onset and reduce the incidence of age-related diseases such as type 2 diabetes. Increasing SIRT1 activity, either by transgenic overexpression of the Sirt1 gene in mice or by pharmacological activation by small molecule activators resveratrol and SRT1720, has shown beneficial effects in rodent models of type 2 diabetes, indicating that SIRT1 may represent an attractive therapeutic target. Herein, we have assessed purported SIRT1 activators by employing biochemical assays utilizing native substrates, including a p53-derived peptide substrate lacking a fluorophore as well as the purified native full-length protein substrates p53 and acetyl-CoA synthetase1. SRT1720, its structurally related compounds SRT2183 and SRT1460, and resveratrol do not lead to apparent activation of SIRT1 with native peptide or full-length protein substrates, whereas they do activate SIRT1 with peptide substrate containing a covalently attached fluorophore. Employing NMR, surface plasmon resonance, and isothermal calorimetry techniques, we provide evidence that these compounds directly interact with fluorophore-containing peptide substrates. Furthermore, we demonstrate that SRT1720 neither lowers plasma glucose nor improves mitochondrial capacity in mice fed a high fat diet. SRT1720, SRT2183, SRT1460, and resveratrol exhibit multiple off-target activities against receptors, enzymes, transporters, and ion channels. Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.

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Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas.

Omer Coskun, Mehmet Kanter, Ahmet Korkmaz … (2005)

The aim of the present study was the evaluation of possible protective effects of quercetin (QE) against beta-cell damage in experimental streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg kg(-1) for diabetes induction. QE (15 mg kg(-1) day, intraperitoneal (i.p.) injection) was injected for 3 days prior to STZ administration; these injections were continued to the end of the study (for 4 weeks). It has been believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). In order to determine the changes of cellular antioxidant defense system, antioxidant enzymes such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in pancreatic homogenates. Moreover we also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, if there is an imbalance between oxidant and antioxidant status. Pancreatic beta-cells were examined by immunohistochemical methods. STZ induced a significant increase lipid peroxidation, serum NO concentrations and decreased the antioxidant enzyme activity. Erythrocyte MDA, serum NO and pancreatic tissue MDA significantly increased (P < 0.05) and also the antioxidant levels significantly decreased (P < 0.05) in diabetic group. QE treatment significantly decreased the elevated MDA and NO (P < 0.05), and also increased the antioxidant enzyme activities (P < 0.05). QE treatment has shown protective effect possibly through decreasing lipid peroxidation, NO production and increasing antioxidant enzyme activity. Islet cells degeneration and weak insulin immunohistochemical staining was observed in STZ induced diabetic rats. Increased staining of insulin and preservation of islet cells were apparent in the QE-treated diabetic rats. These findings suggest that QE treatment has protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic beta-cell integrity.

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Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus.

Jayesh Bhatt, Sabin Thomas, Moola Nanjan (2012)

Resveratrol is a naturally occurring polyphenolic compound. Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus (DM). We hypothesized, therefore, that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus (T2DM). The present clinical study was therefore carried out to test the hypothesis. Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital, Ootacamund, India, in a prospective, open-label, randomized, controlled trial. Patients were randomized into control and intervention groups. The control group received only oral hypoglycemic agents, whereas the intervention group received resveratrol (250 mg/d) along with their oral hypoglycemic agents for a period of 3 months. Hemoglobin A(1c), lipid profile, urea nitrogen, creatinine, and protein were measured at the baseline and at the end of 3 months. The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c) (means ± SD, 9.99 ± 1.50 vs 9.65 ± 1.54; P < .05), systolic blood pressure (mean ± SD, 139.71 ± 16.10 vs 127.92 ± 15.37; P < .05), total cholesterol (mean ± SD, 4.70 ± 0.90 vs 4.33 ± 0.76; P < .05), and total protein (mean ± SD, 75.6 ± 4.6 vs 72.3 ± 6.2; P < .05) in T2DM. No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed. Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Evid Based Complement Alternat Med

Journal ID (iso-abbrev): Evid Based Complement Alternat Med

Journal ID (publisher-id): ECAM

Title: Evidence-based Complementary and Alternative Medicine : eCAM

Publisher: Hindawi Publishing Corporation

ISSN (Print): 1741-427X

ISSN (Electronic): 1741-4288

Publication date (Print): 2013

Publication date (Electronic): 4 April 2013

Publication date PMC-release: 4 April 2013

Volume: 2013

Electronic Location Identifier: 378657

Affiliations

¹Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan

²Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan

³Institute of Chemistry, University of the Philippines, Diliman, Quezon City 1100, Philippines

⁴Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Academia Sinica Road, Section 2, Nankang, Taipei 115, Taiwan

⁵Graduate Institute of Immunology, China Medical University, Taichung 404, Taiwan

⁶Center for Neuropsychiatry, China Medical University Hospital, Taichung 404, Taiwan

⁷Institute of Pharmacology, Yang-Ming University, Taipei 112, Taiwan

⁸Institute of Zoology, National Taiwan University, Taipei 106, Taiwan

⁹Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan

Author notes

*Wen-Chin Yang: wcyang@ 123456gate.sinica.edu.tw

Academic Editor: William C. Cho

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Yenshou Lin https://orcid.org/0000-0002-9169-3273

Wen-Chin Yang https://orcid.org/0000-0001-6410-2581

Article

DOI: 10.1155/2013/378657

PMC ID: 3638592

PubMed ID: 23662132

SO-VID: 5f2b2e0a-2967-467e-938a-b6251d05d847

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This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds

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Most cited references 204

SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1.

Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas.

Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus.

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