Atranorin, an antimicrobial metabolite from lichen Parmotrema rampoddense exhibited in vitro anti-breast cancer activity through interaction with Akt activity.

Atranorin (ATR), lichenized secondary metabolite and depside molecule with several biological potentials such as antimicrobial, anticancer, anti-inflammatory, antinociceptive, wound healing and photoprotective activities. Cytotoxic reports of ATR are documented in several cancer cells and in vivo models but its molecular interaction studies are poorly understood. Therefore, in this present investigation, we have used the in silico studies with biological validation of the molecular targets for the anti-breast cancer mechanism of ATR. The molecular docking studies with the breast cancer oncoproteins such as Bcl-2, Bax, Akt, Bcl-w and Bcl-xL revealed the highest interaction was observed with the Akt followed by Bax, Bcl-xL and Bcl-2 & least with the Bcl-w proteins. The cytotoxicity studies showed ATR selectively inhibited MDA MB-231 and MCF-7 breast cancer cells in differential and dose-dependent manner with the IC50 concentration of 5.36 ± 0.85 µM and 7.55 ± 1.2 µM respectively. Further mechanistic investigations revealed that ATR significantly inhibited ROS production and significantly down-regulated the anti apoptotic Akt than Bcl-2, Bcl-xL and Bcl-w proteins with a significant increase in the Bax level and caspases-3 activity in the breast cancer cells when comparison with Akt inhibitor, ipatasertib. In vitro biological activities well correlated with the molecular interaction data suggesting that atranorin had higher interaction with Akt than Bax and Bcl-2 but weak interaction with Bcl-w and Bcl-xL. In this present study, the first time we report the interactions of atranorin with molecular targets for anti-breast cancer potential. Hence, ATR represents the nature-inspired molecule for pharmacophore moiety for design in targeted therapy.Communicated by Ramaswamy H. Sarma.

Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.