Abstract

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean medicine is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in Korean medicine lacks experimental evidence. According to Shennong's Classic of Materia Medica, the earliest book of herbal medicine, Bupleuri Radix (BR) and Scutellariae Radix (SR) possess the Sangsoo relationship, which means they have synergistic features when used together. Therefore these two are frequently used together in prescriptions such as Sosiho-Tang. In this study, we used the network pharmacological method to predict the interaction between these two herbs and then investigated the effects of BR, SR, and their combination on obesity in 3T3-L1 adipocytes. BR, SR, and BR-SR mixture significantly decreased lipid accumulation and the expressions of two major adipogenic factors, peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer-binding protein-alpha (C/EBPα), and their downstream genes, Adipoq, aP2, and Lipin1 in 3T3-L1 cells. In addition, the BR-SR mixture had synergistic effects compared with BR or SR on inhibition of adipogenic-gene expressions. BR and SR also inhibited the protein expressions of PPARγ and C/EBPα. Furthermore, the two extracts successfully activated AMP-activated protein kinase alpha (AMPK α), the key regulator of energy metabolism. When compared to those of BR or SR, the BR-SR mixture showed higher inhibition rates of PPARγ and C/EBPα, along with higher activation rate of AMPK. These results indicate a new potential antiobese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in Korean medicine.

Highlights

  • The epidemiology of obesity is constantly increasing, becoming a health threat all over the world

  • Bupleuri Radix (BR) and Scutellariae Radix (SR), both originated from China, were purchased from Omniherb Co. (Daegu, Republic of Korea) identified by a specialist of herbs. 100 g of BR was extracted in 1000 ml of distilled water at 100∘C for 4 h. 100 g of SR was extracted by the same method

  • The compound-target relevance showed that these two herbs share two major antiobese targets: adipogenesis and energy expenditure

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Summary

Introduction

The epidemiology of obesity is constantly increasing, becoming a health threat all over the world. The World Health Organization has reported that over 1.4 billion adults worldwide are overweight (BMI ≥ 25 kg/m2) or obese (BMI ≥ 30 kg/m2) [1]. There are only 5 treatments (orlistat, lorcaserin, liraglutide, phentermine/topiramate, and bupropion/naltrexone) approved by the United States Food and Drug Administration. Despite their efficacies, adverse effects of these drugs lead to search for other options [2]. Pharmacological approach for obesity treatment can be subcategorized into two methods: inhibiting lipid accumulation or consuming accumulated lipids.

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