An in vitro study reveals the anti-obesity effects of 7- methoxy-3-methyl-5-((E)-prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran from Myristica fragrans.

Adipogenesis, the maturation process of preadipocytes, is closely associated with the development of obesity and other complex metabolic syndromes. Herein, we investigated the effect of 7- methoxy-3-methyl-5-((E)- prop-1-enyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (TM), a benzofuran, isolated from the mace of Myristica fragrans Houtt on adipogenesis in 3T3-L1 preadipocytes to extrapolate whether this compound has any anti-obesity potential. For this, 3T3-L1 preadipocytes were induced to differentiate in the presence of various concentrations of TM (1, 5, 10 µM) and analyzed for triglyceride (TG) accumulation and the expression of proteins and genes involved in lipogenesis and lipolysis associated with adipogenesis. Results showed that TM significantly reduced TG accumulation and expression of marker proteins of adipocyte differentiation (peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and fatty acid-binding protein 4) and increased the secretion of glycerol in a dose-dependent manner. There was a significant dose-dependent decrease in the expression of fatty acid synthase, stearoyl-CoA desaturase-1, sterol regulatory element-binding transcription factor 1c, and acetyl-CoA carboxylase 1 and an increase in carnitine palmitoyltransferase 1, acyl-CoA oxidase, and peroxisome proliferator-activated receptor α in TM treated cells. The phosphorylation of cAMP-activated protein kinase was also increased, which in turn activated the phosphorylation of acetyl-CoA carboxylase in mature adipocytes. Also, there was an increase in glucose uptake by TM, suggesting its insulin-sensitizing potential. This is the first report on the anti-obesity effects of TM from Myristica fragrans on adipogenesis and lipid metabolism in 3T3-L1 adipocytes and demands detailed in vivo study for developing TM as anti-obesity therapeutics.

Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways.

Deoxyelephantopin, a sesquiterpene lactone extracted and purified from Elephantopus scaber, has been shown to exhibit antitumor and hepatoprotective activities. The purpose of this study was to investigate the antiproliferative and apoptosis-inducing properties of deoxyelephantopin in SiHa cells and to elucidate the underlying molecular mechanisms. Deoxyelephantopin inhibited growth of SiHa cells and triggered apoptosis. Apoptosis was accompanied by sequential activation of caspases (8, 9, 3, and 7) and reactive oxygen species (ROS) production. Downregulation of antiapoptotic proteins (Bcl2 and Bcl-xL) and upregulation of apoptotic protein (bax) were also detected. Our results demonstrated that deoxyelephantopin-induced G2/M phase arrest was associated with a marked increase in the levels of p53 and p21 and a decrease in phospho-signal transducer and activator of transcription 3 (pSTAT3-Tyr705), cyclin-dependent kinase 1 (cdc2), and cyclin B1. The expression of p-Akt and p-mTOR was downregulated. p-ERK was inhibited while p-JNK and p-p38 was activated on deoxyelephantopin treatment. Our findings provided the first evidence that STAT3/p53/p21 signaling, MAPK pathway, PI3k/Akt/mTOR pathway, caspase cascades, and ROS play critical roles in deoxyelephantopin-induced G2/M phase arrest and apoptosis of SiHa cells.