Anti-adipogenic activity of 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl from dendrobium ellipsophyllum in 3t3-l1 preadipocytes

Abstract

Obesity and its global prevalence have become a threat to human health due to not only the abnormal lipid accumulation in the body as a result of aberrant expression levels in adipocyte differentiation and lipogenesis but also the underdeveloped pharmacotherapy. Recently, the bioactive compounds from the natural products have gained a lot of attention due to undertaking prophylactic and therapeutic effects on obesity. Here, we probed how 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB) extracted from an Thai orchid (Dendrobium ellipsophyllum) could exert its roles on the differentiation and function of murine (3T3-L1) and human (PCS-210-010) preadipocytes and offer some implications to modulate obesity. Cytotoxic effects of TDB on preadipocytes (Half maximum inhibitory concentration; IC50 = ~36 µM) were two-fold higher than those detected on adipocytes (IC50 = ~72 µM), and no significant difference was detected in cytotoxic profiles between both cells. TDB in a dose-dependent manner decreased cellular lipid accumulation and enhanced lipolysis of both cell lines assessed at early differentiation and during maturation. Underlining molecular mechanisms proved that TDB paused the cell cycle progression by regulating inducers and inhibitors in mitotic clonal expansion, leading to growth arrest of preadipocytes at the G0/G1 phase. The compound also governed adipocyte differentiation by repressing expressions of crucial adipogenic regulators and effectors through deactivating the AKT/GSK-3β signaling pathway and activating the AMPK-ACC pathway. To this end, TDB has shown its pharmaceutical potential for modulating adipocyte development and function, and it would be a promising candidate for further assessments as a therapeutic agent to defeat obesity.