Herbal composition Gambigyeongsinhwan (4) from Curcuma longa, Alnus japonica, and Massa Medicata Fermentata inhibits lipid accumulation in 3T3-L1 cells and regulates obesity in Otsuka Long-Evans Tokushima Fatty rats

Ethnopharmacological relevance: Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal. composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata. Materials and methods: The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red 0 staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor a (PPARa) transactivation assay. Results: GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPAR gamma, aP2, and C/EBPcc) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARa target genes. GGH(4) and the individual components also increased PPARa reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARa antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARa target genes in OLETF rats. Conclusions: These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARa activation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.