Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.
OBJECTIVE
Increasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia.


METHODS
Obesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group) or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg) (LPS control group). While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models.


RESULTS
In cell-based studies, treatment with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6) in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO)-1 and claudin-1, and normalized trans epithelial electric resistance (TEER) and horseradish peroxidase (HRP) flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes.


CONCLUSIONS
This evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via regulating distribution of gut flora and gut permeability.
Department of Oriental Rehabilitation Medicine, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea ; Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, People's Republic of China.
Jing-Hua
JH
Wang
College of Pharmacy, Dongguk University-Seoul, Goyang, Gyeonggi-do, Republic of Korea.
Shambhunath
S
Bose
Department of Oriental Rehabilitation Medicine, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.
Gi-Cheol
GC
Kim
Department of Oriental Otorhinolaryngology, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.
Seung-Ug
SU
Hong
Department of Oriental Otorhinolaryngology, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.
Ji-Hun
JH
Kim
Department of Pathology, College of Oriental Medicine, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.
Jai-Eun
JE
Kim
Department of Oriental Rehabilitation Medicine, Dongguk University, Goyang, Gyeonggi-do, Republic of Korea.
Hojun
H
Kim
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D019446:Endotoxemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D031239:Lonicera / Q000737:chemistry*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D054892:Metagenome; D051379:Mice; D064307:Microbiota; D009569:Nitric Oxide / Q000096:biosynthesis; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D010539:Permeability / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide