Cardioprotection by isosteviol derivate JC105: A unique drug property to activate ERK1/2 only when cells are exposed to hypoxia‐reoxygenation

Abstract

In the present study, we have investigated potential cardioprotective properties of Isosteviol analogue we recently synthesized and named JC105. Treatment of heart embryonic H9c2 cells with JC105 (10 μM) significantly increased survival of cells exposed to hypoxia‐reoxygenation. JC105 (10 μM) activated ERK1/2, DRP1 and increased levels of cardioprotective SUR2A in hypoxia‐reoxygenation, but did not have any effects on ERK1/2, DRP1 and/or SUR2A in normoxia. U0126 (10 μM) inhibited JC105‐mediated phosphorylation of ERK1/2 and DRP1 without affecting AKT or AMPK, which were also not regulated by JC105. Seahorse bioenergetic analysis demonstrated that JC105 (10 μM) did not affect mitochondria at rest, but it counteracted all mitochondrial effects of hypoxia‐reoxygenation. Cytoprotection afforded by JC105 was inhibited by U0126 (10 μM). Taken all together, these demonstrate that (a) JC105 protects H9c2 cells against hypoxia‐reoxygenation and that (b) this effect is mediated via ERK1/2. The unique property of JC105 is that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non‐stress conditions.

Isosteviol plays a protective role on hepatic ischemia and reperfusion injury in mice through MAPK/NF-κB signaling pathway

“…According to previous literature reports ISV has positive anti-in ammatory and anti-apoptotic effects in the brain, intestine and heart, and has certain effects on the immune system in the body [15,20] . Therefore, we tested whether it can improve the liver function by using ISV in the treatment process of hepatic I/R injury.…”