AUTHOR=Wang Jing-Hua , Bose Shambhunath , Shin Na Rae , Chin Young-Won , Choi Young Hee , Kim Hojun 

TITLE=Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00620

DOI=10.3389/fendo.2018.00620

ISSN=1664-2392

ABSTRACT=<p><bold>Purpose:</bold> Metformin and <italic>Houttuynia cordata</italic> are representative anti-diabetic therapeutic agents in western and oriental medicinal fields, respectively. The present study examined the therapeutic effects of <italic>houttuynia cordata</italic> extract (HCE) and metformin in combination in a dysmetabolic mouse model.</p><p><bold>Methods:</bold> Metabolic disorders were induced in C57BL/6J mice by high fat diet (HFD) for 14 weeks.</p><p><bold>Results:</bold> 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 <italic>Escherichia coli</italic> and <italic>Bacteriodetes fragilis</italic>, but not universal Gram-positive bacteria.</p><p><bold>Conclusions:</bold> 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.</p>