Anti-Inflammatory Activity of Sarcoaldosterol A Isolated From Heteroxenia fuscescens: Insights From In Vitro, In Silico, and Spectroscopic Studies.

Abstract

Chronic inflammation is a key factor in the progression of many diseases, driving ongoing efforts to identify new and effective anti-inflammatory agents. Sarcoaldosterol A, a polyhydroxylated gorgostane steroid isolated from Heteroxenia fuscescens, was evaluated for its anti-inflammatory activity using in vitro studies, molecular docking, and quantum chemical calculations. Its structure was elucidated on the basis of 1D NMR, HR-ESI-MS, and comparison with literature. Sarcoaldosterol A significantly inhibited pro-inflammatory mediators nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and Toll-like receptor 4 (TLR-4), while upregulating the anti-inflammatory cytokine interleukin-10 (IL-10). It also showed moderate inhibition of cyclooxygenase-2 (COX-2) (IC₅₀ = 18.57 ± 0.61 µg/mL). Molecular docking confirmed COX-2 binding affinity, and quantum calculations elucidated its chemical stability and reactivity. As the first reported polyhydroxylated gorgostane steroid with such activity, Sarcoaldosterol A holds promising candidate for future exploration as a molecular scaffold in inflammation-related drug discovery.