Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell-Based Assays
Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell-Based Assays
Chia-Chuan Chang,1 Wei Yuan,2 Yun-Lian Lin,3 Ren-Shyan Liu,4 Yi-Chen Juan,5 Wan-Hua Sun,6 Huey Jen Tsay,7 Hsiu-Chen Huang,8 Yu-Ching Lee,9,10 and Hui-Kang Liu11,12
1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
2Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
3Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan
4Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
5Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
6Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
7Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei, Taiwan
8Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan
9The Centre of Translational Medicine, Taipei Medical University, Taipei, Taiwan
10The Ph.D. Program for Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
11Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan
12Ph.D. Program for the Clinical Drug Discovery from Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
Received 11 July 2016; Revised 24 October 2016; Accepted 3 November 2016
Academic Editor: Darren R. Williams
Copyright © 2016 Chia-Chuan Chang et al. 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.
Abstract
Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycemic bioactivities. In animal experiments, blood glucose, the homeostasis model assessment (HOMA)-index assessment, glucose tolerance test, and in vivo glucose uptake were all measured. Additional effects of PRExt on obesity and hepatic steatosis were evaluated by serum and histological analysis. Results. PRExt provides multiple hypoglycemic effects including the enhancement of glucose-mediated insulin secretion. Pentagalloylglucose and polyphenol-enriched fraction are two insulinotropic constituents. Moreover, PRExt intraperitoneal injection causes acute hypoglycemic effects on fasted db/db mice. Oral administration of PRExt (200 mg/kg b.w.) gradually reduces blood glucose in db/db mice to the level similar to that in C57J/B6 mice after 30 days. The improvement of glucose intolerance, HOMA-index, and in vivo glucose uptake is evident in addition to the weight loss effect and attenuation of hepatic steatosis. Conclusion. PRExt is an effective antidiabetic herbal extract with multiple hypoglycemic bioactivities.
1. Introduction
Diabetes mellitus (DM) is a major health issue, affecting more than 180 million people worldwide. Type 2 diabetes (T2D) affects more people than does type 1 diabetes and the typical comorbidities are central obesity and fatty liver [1]. Hyperglycemia in T2D patients is the consequence of both insulin resistance and beta-cell dysfunction or failure [2]. Therefore, an effective antidiabetic agent should both improve insulin sensitivity and enhance beta-cell function. Herbal medicine containing multiple hypoglycemic constituents has a great potential for fulfilling such requirement.
Radix Paeoniae Rubra (Chi Shao) is prescribed in Traditional Chinese Medicine (TCM) to enhance blood circulation and eliminate blood stasis and is usually employed for treating diabetics, for instance, Xue-Fu-Zhu-Yu decoction and Keishi-Bukuryo-Gan [3, 4]. Recently, we demonstrated that an ethanol extract of Radix Paeoniae Rubra could suppress transcription of the hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene [5].
It was identified that the insulin sensitizing effect of chemical constituents from Radix Paeoniae Rubra is modulated by the inhibition of protein-tyrosine phosphatase 1B [6]. Pentagalloylglucose, another Radix Paeoniae Rubra constituent, acts like an insulin mimetic by binding to the insulin receptor [2, 7]. Additionally, pentagalloylglucose and tannin acids inhibit adipogenesis and counteract obesity [8–10]. Several pharmacological effects of paeoniflorin have been demonstrated, including hypoglycemic, hypolipidemic, and antifatty liver (...truncated)