Two Triterpenoids, ARM-2 and RA-5, From Exhibit the Potential to Modulate Lipolysis and Lipogenesis in Cultured 3T3-L1 Adipocytes.

Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPAR, SREBP-1, and AMPK, with lower binding affinity to C/EBP, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with K and IC values ranging from 28.7 to 52.9 M and 27.6 to 35.8 M, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 M) was comparable to 50 M lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPAR, C/EBP, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 M was similar to 50 M lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.