Sanggenol L Reduces LPS-induced Myocardial Injury and Inflammation by Activating PI3K/AKT/mTOR and Inhibiting NF-κB in Rats

Abstract

Background The manifestation of severe sepsis is sepsis-induced myocardial dysfunction (SIMD), which is the chief cause of elevated death in sepsis patients. Sepsis mainly attacks the heart, and the effective switch of the inflammatory cascades is of prodigious implication in relieving sepsis-allied myocardial impairments. Natural antioxidants with anti-inflammatory and antiapoptotic properties are promptly required as typical anti-septic agents. Purpose: Morus alba root bark contains a flavonoid sanggenol L (SL), which exhibits antioxidant, apoptotic, and anti-inflammatory activities. Nevertheless, the anti-septic action of SL has not yet been described. Hence, we explored the antioxidative, antiapoptotic, and anti-inflammatory actions of SL on lipopolysaccharide (LPS)-triggered sepsis in rats. Methods Rats were divided into four sets: group 1: control, group 2: LPS (20 mg/kg bw), group 3: LPS (20 mg/kg bw) + dexamethasone (2 mg/kg bw), and group 4: LPS (20 mg/kg bw) + SL (10 mg/kg bw). We assessed cardiotoxicity, antioxidants, cytokines, histopathology, protein expressions of apoptosis, and inflammatory enzymes. Results Data unveiled that SL inhibited toxicity markers, oxidative stress, inflammation, apoptosis, and histological changes. SL effectively attenuated LPS-induced acute myocardial injury by stimulating the PI3K/AKT/mTOR signaling and suppressing the nuclear factor kappa B (NF-κB) pathway. Conclusion Thus, SL might be a possible anti-septic agent for the treatment of SIMD.