Abstract

We had tested antiobesity effect of 52 traditional herbal formulas in 3T3-L1 adipocyte, and Banhasasim-tang (BHSST) was chosen as one of the effective medications to inhibit triglyceride accumulation. We investigated the antiobesity effect of BHSST on 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese mice. In addition, we evaluated the acute toxicity of BHSST in Sprague Dawley (SD) rats. Differentiated 3T3-L1 cells were treated with various concentrations of BHSST for 8 days. Accumulated triglyceride level and the expressions of adipogenesis-related genes and proteins were subsequently investigated. To evaluate the single oral toxicity of BHSST, the SD rats of each sex were administered a single dose (5000 mg/kg) of BHSST via oral gavage; the control group received vehicle only. After a single administration, the mortality, clinical signs, gross findings, and body weight were monitored for 15 days. Male C57BL/6J mice were fed HFD for 4 weeks to induce obesity and randomly received 50 mg/kg of Orlistat (n=12, OR), 200 mg/kg of BHSST (n=12, B200), and 1000 mg/kg of BHSST (n=12, B1000) for another 8 weeks. BHSST suppressed the triglyceride contents and lipid accumulation in a dose-dependent manner in 3T3-L1 adipocytes. BHSST also downregulated the adipogenesis-related gene levels and protein expression compared with those in undifferentiated adipocytes. In a single oral dose toxicity study, there was no adverse effect on mortality, clinical signs, body weight changes, and gross findings in the treatment group. HFD-fed mice treated with BHSST showed significantly reduced body weight gain, food efficiency ratio, and white adipose tissue weight. The medial lethal dose (LD50) of BHSST was 5000 mg/kg/day body weight for each sex in the rats. BHSST decreased the body weight gain in HFD-fed obese mice and inhibited triglyceride accumulation via a cascade of multiple factors at the mRNA and protein levels in 3T3-L1 adipocytes.

Highlights

  • Obesity is a result of chronic energy imbalance, which causes several metabolic disorders such as hyperglycemia, hypertension, and insulin resistance [1]

  • No significant toxicity was observed at concentrations up to 500 μg/ml of BHSST in adipocytes

  • All experiments with 3T3L1 adipocyte were performed under 500 μg/ml of BHSST

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Summary

Introduction

Obesity is a result of chronic energy imbalance, which causes several metabolic disorders such as hyperglycemia, hypertension, and insulin resistance [1]. The worldwide prevalence of obese and overweight individuals has increased more than threefold since 1975. In 2016, 1.9 billion adults over the age of 18 and 41 million children under the age of 5 were overweight or obese [2]. Along with an increasing number of overweight or obese people, the market for weight-loss products has been rapidly growing. The use of herbal medicine to manage weight control has received much attention in recent decades. Studies have shown that various herbal medicines are effective for the treatment obesity in clinical trials [3, 4] and their underlying mechanisms or components have been elucidated through in vitro and in vivo experiments [5,6,7]. To determine the safety and efficacy of herbal medicine, it is a necessary factor to develop antiobesity drugs

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