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

Purpose: Metformin and Houttuynia cordata are representative anti-diabetic 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.Meth...

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Main Authors: Jing-Hua Wang, Shambhunath Bose, Na Rae Shin, Young-Won Chin, Young Hee Choi, Hojun Kim
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fendo.2018.00620/full
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author Jing-Hua Wang
Shambhunath Bose
Na Rae Shin
Young-Won Chin
Young Hee Choi
Hojun Kim
author_facet Jing-Hua Wang
Shambhunath Bose
Na Rae Shin
Young-Won Chin
Young Hee Choi
Hojun Kim
author_sort Jing-Hua Wang
collection DOAJ
description Purpose: Metformin and Houttuynia cordata are representative anti-diabetic 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.
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spelling doaj.art-d51bb684695b4066ae8c727ca3a06db42022-12-21T23:21:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-10-01910.3389/fendo.2018.00620385130Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic EndotoxemiaJing-Hua Wang0Shambhunath Bose1Na Rae Shin2Young-Won Chin3Young Hee Choi4Hojun Kim5Department of Oriental Rehabilitation Medicine, Dongguk University, Goyang, South KoreaNosQuest, Seongnam-si, South KoreaDepartment of Oriental Rehabilitation Medicine, Dongguk University, Goyang, South KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang, South KoreaCollege of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Seoul, South KoreaDepartment of Oriental Rehabilitation Medicine, Dongguk University, Goyang, South KoreaPurpose: Metformin and Houttuynia cordata are representative anti-diabetic 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.https://www.frontiersin.org/article/10.3389/fendo.2018.00620/fullHouttuynia cordatatype 2 diabeteshigh fat dietgut microbiotaendotoxin
spellingShingle Jing-Hua Wang
Shambhunath Bose
Na Rae Shin
Young-Won Chin
Young Hee Choi
Hojun Kim
Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
Frontiers in Endocrinology
Houttuynia cordata
type 2 diabetes
high fat diet
gut microbiota
endotoxin
title Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
title_full Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
title_fullStr Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
title_full_unstemmed Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
title_short Pharmaceutical Impact of Houttuynia Cordata and Metformin Combination on High-Fat-Diet-Induced Metabolic Disorders: Link to Intestinal Microbiota and Metabolic Endotoxemia
title_sort pharmaceutical impact of houttuynia cordata and metformin combination on high fat diet induced metabolic disorders link to intestinal microbiota and metabolic endotoxemia
topic Houttuynia cordata
type 2 diabetes
high fat diet
gut microbiota
endotoxin
url https://www.frontiersin.org/article/10.3389/fendo.2018.00620/full
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