Anti-HIV bioactive components in Pinus yunnanensis cones and their in vivo absorption-metabolism profiles based on...

Pinus yunnanensis, an endemic plant to Yunnan, China, produces reproductive cones whose extract (PAE) has shown anti-HIV activity in prior in vitro cellular studies. However, its anti-HIV active components and their in vivo absorption and metabolic behavior remain unclear. This study aims to screen the potential anti-HIV active components from PAE and systematically investigate their sequential metabolism using an integrated strategy combining in vivo sequential metabolism, network pharmacology, and molecular docking. In this study, a total of 146 compounds were detected in PAE; sequential metabolism analysis further identified 139 prototype components and 59 metabolites with significant differences constituents, 79 of these prototype components were predicted to be anti-HIV-active substances. Following further screening, the top 20 core components were included in subsequent analyses, and four compounds-3,4-Divanillyltetrahydrofuran, Pimaric acid, Leoheteronin A, and Isopimaric acid-were identified as the most promising core candidates. Network pharmacology revealed that their anti-HIV effects may be mediated through interactions with key targets such as AKT1, IL6, IL1B, and TNF, and by modulating critical signaling pathways including AGE-RAGE and TNF. Molecular docking confirmed strong binding affinity (binding energy <-5.0 kcal/mol) between these components and the core targets. This study systematically elucidates the in vivo absorption and metabolism rules of potential anti-HIV components in PAE, transforming static component identification into a holistic and dynamic pharmacokinetic profile, and lays an important material foundation for subsequent relevant studies.