Abstract
Background and AimIncreasing 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.MethodsObesity 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.ResultsIn 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.ConclusionThis evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via regulating distribution of gut flora and gut permeability.
Highlights
Obesity, which was officially declared a disease by the World Health Organization (WHO) in 1997 [1], is a serious and alarming global public health issue as it can increase the risk of hyperlipidemia, hypertension, diabetes, coronary-heart diseases, and certain cancers [2]
Co-treatment of LPS-induced cells with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) resulted in significant, concentrationdependent inhibition of Nitric Oxide (NO) production (P,0.01)
Treatment with LPS caused a marked increase in transcription of tumor necrosis factor alpha (TNF-a), cyclooxygenase 2 (COX-2), and interlukin 6 (IL-6) genes (P,0.01 versus normal)
Summary
Obesity, which was officially declared a disease by the World Health Organization (WHO) in 1997 [1], is a serious and alarming global public health issue as it can increase the risk of hyperlipidemia, hypertension, diabetes, coronary-heart diseases, and certain cancers [2]. Overweight and obesity are generally regarded as the consequences of an imbalance in energy homeostasis, on the basis of accumulating evidence, obesity is recognized as a chronic and systemic inflammatory disease, where adipose tissue plays a vital endocrine role [4]. Crosstalk among the cellular constituents of adipose tissue, such as adipocytes, and endothelial and immune cells leads to augmentation of inflammatory mediators. These mediators exert important systemic effects that can result in development of insulin resistance, dysmetabolism, and cardiovascular disease [4]. 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
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