TY - JOUR
T1 - Pharmaceutical impact of houttuynia cordata and metformin combination on high-fat-diet-induced metabolic disorders
T2 - Link to intestinal microbiota and metabolic endotoxemia
AU - Wang, Jing Hua
AU - Bose, Shambhunath
AU - Shin, Na Rae
AU - Chin, Young Won
AU - Choi, Young Hee
AU - Kim, Hojun
N1 - Publisher Copyright:
Copyright © 2018 Wang, Bose, Shin, Chin, Choi and Kim.
PY - 2018
Y1 - 2018
N2 - Purpose: Metformin and Houttuynia cordata are representative antidiabetic therapeutic agents in western and oriental medicinal fields, respectively. The present study examined the therapeutic effects of houttuynia cordata extract (HCE) and metformin in combination in a dysmetabolic mouse model. Methods: Metabolic disorders were induced in C57BL/6J mice by high fat diet (HFD) for 14 weeks. Results: Combination of metformin and HCE significantly lowered body weight, abdominal fat, perirenal fat, liver and kidney weights, but did not change epididymal fat in HFD-fed animals. Metformin + HCE treatment markedly attenuated the elevated serum levels of TG, TC, AST, ALT, and endotoxin and restored the depleted HDL level. Both HCE and metformin + HCE treatment ameliorated glucose tolerance and high level of fasting blood glucose in association with AMPK activation. Moreover, treatment with HCE + metformin dramatically suppressed inflammation in HFD-fed animals via inhibition of proinflammatory cytokines (MCP-1 and IL-6) and LPS receptor (TLR4). Histopathological findings showed that exposure of HFD-treated animals to metformin + HCE ameliorated fatty liver, shrinkage of intestinal villi and adipocytes enlargement. Furthermore, HCE and metformin + HCE treatments markedly modulated the abundance of gut Gram-negative bacteria, including Escherichia coli and Bacteriodetes fragilis, but not universal Gram-positive bacteria. Conclusions: Overall, HCE and metformin cooperatively exert their therapeutic effects via modulation of gut microbiota, especially reduction of Gram-negative bacteria, resulting in alleviation of endotoxemia.
AB - Purpose: Metformin and Houttuynia cordata are representative antidiabetic therapeutic agents in western and oriental medicinal fields, respectively. The present study examined the therapeutic effects of houttuynia cordata extract (HCE) and metformin in combination in a dysmetabolic mouse model. Methods: Metabolic disorders were induced in C57BL/6J mice by high fat diet (HFD) for 14 weeks. Results: Combination of metformin and HCE significantly lowered body weight, abdominal fat, perirenal fat, liver and kidney weights, but did not change epididymal fat in HFD-fed animals. Metformin + HCE treatment markedly attenuated the elevated serum levels of TG, TC, AST, ALT, and endotoxin and restored the depleted HDL level. Both HCE and metformin + HCE treatment ameliorated glucose tolerance and high level of fasting blood glucose in association with AMPK activation. Moreover, treatment with HCE + metformin dramatically suppressed inflammation in HFD-fed animals via inhibition of proinflammatory cytokines (MCP-1 and IL-6) and LPS receptor (TLR4). Histopathological findings showed that exposure of HFD-treated animals to metformin + HCE ameliorated fatty liver, shrinkage of intestinal villi and adipocytes enlargement. Furthermore, HCE and metformin + HCE treatments markedly modulated the abundance of gut Gram-negative bacteria, including Escherichia coli and Bacteriodetes fragilis, but not universal Gram-positive bacteria. Conclusions: Overall, HCE and metformin cooperatively exert their therapeutic effects via modulation of gut microbiota, especially reduction of Gram-negative bacteria, resulting in alleviation of endotoxemia.
KW - Endotoxin
KW - Gut microbiota
KW - High fat diet
KW - Houttuynia cordata
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85055868445&partnerID=8YFLogxK
U2 - 10.3389/fendo.2018.00620
DO - 10.3389/fendo.2018.00620
M3 - Article
AN - SCOPUS:85055868445
SN - 1664-2392
VL - 9
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
IS - OCT
M1 - 00620
ER -