Exploring the protective effect of ShengMai-Yin and Ganmaidazao decoction combination against type 2 diabetes mellitus with nonalcoholic fatty liver disease by network pharmacology and validation in KKAy mice.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

ShengMai-Yin and Ganmaidazao decoction are classic formulas in traditional Chinese medicine. Individually, Shengmai-Yin is used to treat cardiovascular diseases, and Ganmaidazao decoction for therapy of mental disorders. The combination of Shengmai-Yin and Ganmaidazao decoction (SGD) is normally used as adjuvant therapy for type 2 diabetes mellitus (T2DM).

AIM OF THE STUDY:

The central aim is to elucidate the pharmacological efficacy of SGD and its mechanism in the treatment of T2DM with non-alcoholic fatty liver disease (NAFLD).

MATERIALS AND METHODS:

Active ingredients in SGD and their drug targets were identified using network analysis followed by experimental validation. First, existing databases were mined for information relevant to SGD, including pharmacological actions, chemical components, physicochemical characteristics, potential targets, and implicated diseases. Candidate patterns obtained with the network analysis were then tested in a KKAy mouse model of T2DM with NAFLD. Various doses of SGD were administered, followed by measurements of fasting blood glucose, oral glucose tolerance tests, insulin tolerance tests, markers of lipid metabolism - including free fatty acids (FFA), triglycerides (TG), and total cholesterol (TC) - liver histology, and expression levels of implicated molecules including PI3K/AKT and PPARα.

RESULTS:

Over 300 potential active compounds with their physicochemical characteristics and 562 candidate targets were collected, and then the network of them was constructed. Follow-up pathway and functional enrichment analyses indicated that SGD influences metabolism-related signaling pathways including PI3K-Akt, AMPK, and PPAR. In validation experiments, treatment of KKAy mice with SGD reduced serum levels of glucose, TC, TG, and FFA, decreased numbers of crown-like structures in visceral adipose tissue, reduced adipocyte size, and lowered liver lipid deposits. Further, SGD improved liver metabolism by increasing the expressions of PPARα, HSL, and PI3K/Akt, and decreasing expressions of SREBP-1 and FASN, inhibiting lipid biosynthesis, and increasing insulin sensitivity.

CONCLUSION:

Experimental validation of network analysis revealed anti-diabetic effects of the plant product SGD, manifested most notably by improved serum profiles and diminished insulin resistance. These experimental results may have clinical implications.

• Authors: Senlin Li, Ying Qian, Rui Xie, Yangsha Li, Zhao Jia, Zijun Zhang, Rongrong Huang, Lingling Tuo, Yihong Quan, Zhihong Yu, Jue Liu, Ming Xiang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 242 Pg. 112029 (Oct 05 2019) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 31216433 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Blood Glucose
• Drug Combinations
• Drugs, Chinese Herbal
• Hypoglycemic Agents
• Phytochemicals
• Protective Agents
• fructus schizandrae, radix ginseng, radix ophiopogonis drug combination
• ganmaidazao
• Proto-Oncogene Proteins c-akt
• Glucose

Topics

• Animals
• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy, metabolism)
• Drug Combinations
• Drugs, Chinese Herbal (chemistry, therapeutic use)
• Glucose (metabolism)
• Hypoglycemic Agents (chemistry, therapeutic use)
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Male
• Mice
• Molecular Targeted Therapy
• Non-alcoholic Fatty Liver Disease (blood, drug therapy, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phytochemicals (analysis, therapeutic use)
• Protective Agents (chemistry, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)