Evaluating the antidiabetic effects of Chinese herbal medicine: Xiao-Ke-An in 3T3-L1 cells and KKAy mice using both conventional and holistic omics approaches.
BACKGROUND
Xiao-Ke-An (XKA) is a Chinese medicine widely used for treating type 2 diabetes mellitus (T2D). It is composed of eight herbal medicines traditionally used for T2D, including Rehmannia glutinosa Libosch, Anemarrhena asphodeloides Bunge, Coptis chinensis Franch, etc. The aim of the present study was to investigate the antidiabetic effects of XKA with both conventional and holistic omics approaches.


METHODS
The antidiabetic effect of XKA was first investigated in 3T3-L1 cells to study the effect of XKA on adipogenesis in vitro. Oil Red O staining was performed to determine the lipid accumulation. The intracellular total cholesterol (TC) and triglyceride (TG) contents in XKA treated 3T3-L1 cells were also evaluated. The therapeutic effects of XKA was further evaluated in KKAy mice with both conventional and holistic omics approaches. Body weight, fasting and non-fasting blood glucose, and oral glucose tolerance were measured during the experiment. At the time of sacrifice, serum was collected for the measurement of TG, TC, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). The liver, kidney, spleen, pancreas, heart and adipose tissues were harvested and weighted. The liver was used for further microarray experiment. Omics approaches were adopted to evaluate the holistic rebalancing effect of XKA at molecular network level.


RESULTS
XKA significantly inhibited adipogenic differentiation, lowered the intracellular TC and TG contents in 3T3-L1 cells. XKA improved the glucose homeostasis and lipid metabolism, ameliorated insulin resistance in KKAy mice. Furthermore, XKA also exhibited effective therapeutic effects by reversing the molecular T2D disease network from an unbalanced state.


CONCLUSIONS
This study investigated the antidiabetic effects of XKA with both conventional and holistic omics approaches, providing both phenotypic evidence and underlying action mechanisms for the clinical use of XKA treating T2D.
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. paulyzz@126.com.
Zhenzhong
Z
Yang
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. wanglinli1990@163.com.
Linli
L
Wang
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. 1194299708@qq.com.
Feng
F
Zhang
State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. lizheng1@gmail.com.
Zheng
Z
Li
D041721:3T3-L1 Cells; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice
D001786:Blood Glucose; D004365:Drugs, Chinese Herbal