ArticleFrontiers in pharmacology2026
Dihydromyricetin attenuates fibrosis-associated features of hypertrophic scar with accompanying changes in PI3K/AKT/mTOR-related signaling.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
This study investigated whether dihydromyricetin (DHM) attenuates fibrosis-associated features in hypertrophic scar (HS) and whether these effects are accompanied by changes in PI3K/AKT/mTOR-related signaling. Network pharmacology identified overlapping targets between DHM and HS, and subsequent protein-protein interaction and enrichment analyses highlighted AKT1 as a candidate hub target potentially associated with PI3K/AKT/mTOR-related signaling. Molecular docking and 50-ns molecular dynamics simulation further indicated a stable predicted interaction pattern between DHM and AKT1. For experimental validation, hypertrophic scar tissues, paired normal skin tissues, hypertrophic scar fibroblasts (HSFs), and paired normal skin fibroblasts (NSFs) were examined. Compared with paired normal controls, HS tissues and HSFs showed increased expression of collagen I, collagen III, and α-SMA. Untreated HSFs also exhibited higher basal p-AKT/AKT and p-mTOR/mTOR ratios than paired NSFs. In HSFs, DHM reduced the CCK-8 viability signal and the expression of fibrosis-related markers, and these changes were accompanied by decreased phosphorylation of AKT and mTOR. Live/dead staining did not show an obvious increase in PI-positive dead cells after 15 μM DHM treatment, suggesting that the decrease in CCK-8 signal may reflect reduced metabolic activity and growth inhibition rather than extensive acute cell death. Treatment with LY294002 alone and combined treatment with DHM and LY294002 further supported the involvement of PI3K/AKT/mTOR-related signaling in the regulation of fibrosis-associated features in HSFs. In a rabbit ear hypertrophic scar model, DHM improved gross scar appearance, reduced the scar elevation index, decreased the collagen-positive area fraction in Masson's trichrome-stained sections, and alleviated histopathological alterations. Together, these findings indicate that DHM attenuated fibrosis-associated features of HS
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