Ginsenoside Re, Produces Multi-targeted Potent Antidiabetic Effects Via Estrogen Receptor Signaling Pathway in Rat, an Alternative Multi-Targeted Therapeutic for Type 2 Diabetes
Jingxian Gao
Department of Pharmacology, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Chengdu 610075, Sichuan, China and Department of Physiology, College of Basic Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Xianli Meng *
Department of Pharmacology, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Chengdu 610075, Sichuan, China.
Bayin Zabu
Department of Pharmacology, Academy of Mongolian Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China and Department of Internal Medicine, Hohhot Hospital for Traditional Mongolian and Chinese Medicine, 9 Baotou Street, Hohhot 100191, Inner Mongolia, China.
Yi Zhang
Department of Pharmacology, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, 37 Shierqiao Road, Chengdu 610075, Sichuan, China.
Siqinbilig Wu
Department of Pharmacology, Academy of Mongolian Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Huhe Muren
Department of Pharmacology, Academy of Mongolian Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Ni Ha
Department of Pharmacology, Academy of Mongolian Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Qinnuan Sun
Department of Pathology, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Tang Jisi
Department of Pharmacology, Academy of Mongolian Medicine, Inner Mongolia Medical University, 5 Xinhua Street, Hohhot 010059, Inner Mongolia, China.
Changxi Bai *
*Author to whom correspondence should be addressed.
Abstract
Aims: To identify more effective ginsenoside for type 2 diabetes (T2D) and clarify whether the ginsenoside characterizing estrogenic multi-targeted antidiabetic effects.
Study Design: Identifying more effective ginsenoside through preclinical evaluation of antidiabetic effects of representative ginsenosides with T2D rat model, and further test pharmacological mechanism underlying the potent antidiabetic effects of the ginsenoside in the same model.
Place and Duration of Study: Key laboratory for Pharmacy, Inner Mongolia Medical University, March 2018 to November 2020.
Methodology: Used a total of 240 female adult rats. Rat model of T2D induced by high-fat diet fed and streptozotocin. Five tapes of representative ginsenosides (Rb1, Rd, Rg3, Re, Rg1) administrated at low (20 mg/kg daily) and high (40 mg/ kg daily) doses to T2D rats with orally for 4 weeks. Detect testing indexes with biochemical, histological, Quantitative Real-Time PCR, and western blots analysis.
Results: Ginsenoside Re (Re), very significantly lowered blood glucose (P<0.01), lipids (P<0.001), free fatty acid (P<0.001), and glucagon (P<0.01) levels, markedly improved impaired insulin sensitivity (P<0.01), ameliorated oxidative stress (P<0.01) and inflammation (P<0.01) in T2D rats, exhibited potent antidiabetic effects. Moreover, Re, phosphorylate serine/threonine kinase (Akt) (P<0.01) and endothelial nitric oxide synthase (eNOS) (P<0.01), up regulates B-cell lymphoma-2 (P<0.01) and insulin gene expression (P<0.01), down regulates glucagon gene expression(P<0.01), reverse impaired glucagon-like peptide 1 (P<0.01); exhibits multi-targeted effects; these effects of Re were inhibited by estrogen receptor (ER) inhibitor (ICI-182,780) (P<0.01). Functionally, the antidiabetic effects of Re were sequentially inhibited by inhibitor of ER, Akt, and eNOS, respectively (P<0.01).
Conclusion: These findings, revealed a novel pharmacological property of Re that characterized in multi-targeted potent antidiabetic effects mediated by ER/Akt/eNOS/NO signaling pathway, provide the first evidence for the potential use of Re, as a multi-targeted therapeutic for T2D, particularly, a novel candidate for replacement of estrogen therapy and NO therapy in diabetes.
Keywords: Ginsenoside Re, Type 2 diabetes, Multiple targeted antidiabetic effects, Estrogen receptor signaling pathway, Nitric oxide, An alternative multi - targeted therapy