Supplementation with a phenolic-rich fraction from Ilex kudingcha improves inflammatory stress, gastrocnemius weights, and foreleg muscle grip strength in murine squamous cell carcinoma (SCC7)-bearing mice

Abstract

Ethanol supernatant of Ilex kudingcha methanol extract (ESIKME) was identified to be rich in phenolic compounds and inhibited murine squamous cell carcinoma (SCC)-7 growth through slightly restoring adaptive immunity and Th1-inclination immune balance in the SCC7-bearing mice. To further evaluate the inhibitory effects and mechanisms of ESIKME against SCC7-induced inflammation status, the effects of ESIKME on inflammatory stress and related cachexia induced by SCC7 cells were investigated in vitro and in vivo. Chemical components of ESIKME were measured using an advanced LC-MS/MS analysis. SCC7 cells were treated with mouse splenocyte (SCM) and macrophage conditioned media (MCM) cultured without/with ESIKME in vitro. SCC7-bearing mice were orally administered with ESIKME for 26 days in vivo. Cachexia-related biomarkers in the SCC7-bearing mice were analyzed. Most of the detected compounds in ESIKME were polymeric or oxidized phenolic compounds. Either SCM or MCM without ESIKME significantly inhibited SCC7 cell growth. The high-dose ESIKME-administered group (400 mg/kg b.w./day) had significantly higher body weights, feed efficiency, and energy efficiency than the dietary control (DC) group, suggesting non-adverse toxic effects for ESIKME supplementation in the SCC7-bearing mice. The DC group had a higher TNF-α and TNF-α/IL-10 secretion ratio but lower anti-inflammatory IL-10 cytokine secretions by macrophages than the vehicle control group. ESIKME administration dose-dependently and significantly reversed these adverse statuses. Medium dose ESIKME (100 mg/kg b.w./day) decreased tumor sizes but increased gastrocnemius weights and foreleg muscle grip strength. Our results suggest that ESIKME alleviated inflammatory stress and related cachexia in vitro and in vivo.