Comprehensive Evaluation of Tectona grandis L.f.: Integrated In Vitro and In Silico Analysis of Steroid 5α-Reductase Inhibition and Anti-Inflammatory Properties.

The extract of Tectona grandis L.f. leaves along with its major bioactive constituents, (+)-Eperua-8,13-dien-15-oic acid (1) and (+)-Eperua-7,13-dien-15-oic acid (2), has demonstrated moderate inhibitory activity against the steroid 5α-reductase enzyme (5α-R), a key factor in androgenetic alopecia (AGA) pathogenesis. In this study, molecular interactions between these compounds and 5α-reductase type 1 (SRD5A1) were investigated, revealing binding affinities of -8.01 kcal/mol for 1 and -8.81 kcal/mol for 2. Moreover, their anti-inflammatory properties were evaluated via in vitro assays assessing nitric oxide inhibition and the suppression of pro-inflammatory cytokines, interleukin-1β (IL-1β) and interleukin-6 (IL-6). The results showed that 2 exhibited a stronger binding affinity to endothelial nitric oxide synthase (eNOS) (-9.00 kcal/mol) and demonstrated more selective inhibition of IL-6 (IC50 = 9.30 ± 2.65 μM, binding affinity = -6.83 kcal/mol) due to the presence of attractive charge interactions. This integrated experimental and computational approach highlights T. grandis bioactive compounds as promising dual-action candidates, simultaneously targeting 5α-reductase activity and cytokine-mediated inflammation and offering new mechanistic insights relevant to AGA management.