Network pharmacology, machine learning, and experiments uncover β-sitosterol targeting HSP90AA1 in medicinal-edible black soybean against aging

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2026.1749856...

Published: 2026-02-16T00:00:00Z

The study used network pharmacology, machine learning, and experiments to investigate the antiaging mechanism of β-sitosterol from black soybeans. The analysis identified 63 overlapping targets between black soybean components and aging-related genes, with PPI networks favoring HSP90AA1 and BCL2 as master regulators. Molecular docking showed high-affinity binding of β-sitosterol to HSP90AA1 via hydrogen bonds with amino acid ILE-214 in the 9-236 region. In UVA-induced human skin fibroblast cell models, β-sitosterol attenuated photoaging markers, restored the cell cycle, and enhanced antioxidant defenses. β-Sitosterol increased the expression of HSP90AA1, stabilized BCL2 and p53, thereby mitigating oxidative damage. Inhibition of HSP90AA1 abolished these effects and confirmed its key role. β-Sitosterol thus fights skin photoaging by regulating the p53-BCL2 signaling axis via HSP90AA1.