Chinese yam extract and adenosine attenuated LPS-induced cardiac dysfunction by inhibiting RAS and apoptosis via the ER-mediated activation of SHC/Ras/Raf1 pathway

Purpose: This study aimed to examine the effects of the Chinese yam extract and adenosine on lipopolysaccharide (LPS)-induced cardiac anomalies and the underlying mechanisms involved. Methods: Chinese yam extract [1630 mg/kg, intragastric (i.g.), 2 times/day] and adenosine (50 mg/kg, i.g., 2 times/day) were administered for 3 days, followed by the induction of sepsis by injecting LPS intraperitoneally [10 mg/kg, 2h prior, intraperitoneally (i.p.)]. Also, estrogen receptor (ER)-unspecific antagonist Faslodex (ICI182,780, 0.5 mg/kg, i.p.) was administered 30 min before the treatments of Chinese yam extract or adenosine to evaluate whether the observed effects elicited by yam and adenosine were mediated via ERs. The heart function and the levels of pro-inflammatory cytokines, reversed mitogen-activated protein kinases (MAPKs), renin-angiotensin system (RAS), apoptosis markers, ER, and SHC/Ras/Raf1 were examined. The antagonistic effect of ICI182,780 (1 mu M) and FTS (1 mu M) against the Chinese yam extract (0.1 mg/ml) and adenosine (5 mu M) in LPS (20 mu g/ml, 24 h)-induced H9c2 cells was also investigated. Results: The Chinese yam extract and adenosine improved heart function, downregulated pro-inflammatory cytokines, reversed MAPK and RAS, transformed the apoptosis markers, and increased the expression of ER and SHC/Ras/Raf1 following LPS challenge. These effects could be blocked by ICI182,780. FTS could not block the expression of ER on the Chinese yam extract and adenosine interposed on LPS-induced H9c2 cells, demonstrating that ER might be the upstream signaling regulator of SHC/Ras/Raf1. Conclusion: The Chinese yam extract and adenosine ameliorated LPS-induced cardiac contractility through the inhibition of RAS and apoptosis possibly via an ER-SHC/Ras/Raf1-dependent mechanism.