Sanshool

α-Sanshool (Neoherculin) is a natural product isolated from Zanthoxylum bungeanum. Sanshool can ameliorate UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy.

Method: Human dermal fibroblasts (HDFs) were pretreated with α-Sanshool (10–40 μM) and then exposed to UVB irradiation (40 mJ/cm²). After 24 h, cell viability was assessed by CCK-8 assay, MMP-1 and MMP-3 expression was detected by ELISA and Western blot, and ROS levels were measured using DCF-DA probe combined with flow cytometry.
Result: α-Sanshool dose-dependently increased the cell viability of UVB-irradiated HDFs, significantly inhibited UVB-induced secretion and protein expression of MMP-1 and MMP-3, and reduced ROS production [1].
Method: HDFs were treated with α-Sanshool (40 μM) for 24 h, or treated with Sanshool following UVB irradiation. The expression of JAK2, p-JAK2, STAT3, p-STAT3, AKT, and p-AKT was detected by Western blot. In some experiments, cells were pretreated with the JAK2 inhibitor AZD1480 to observe changes in autophagic flux and cell viability.
Result: UVB irradiation upregulated the phosphorylation levels of JAK2, STAT3, and AKT in HDFs, while α-Sanshool treatment significantly inhibited this phosphorylation activation. AZD1480 pretreatment further enhanced α-Sanshool-induced autophagy and improved cell viability, suggesting that α-Sanshool exerts its protective effects through inhibition of the JAK2/STAT3 pathway [1].

Method: Six-week-old female nude mice were topically applied with α-Sanshool (20 mg/kg) on the dorsal skin. After 30 min, the mice were exposed to UVB irradiation (300 mJ/cm²) three times per week for 2 weeks. Erythema scores were evaluated, and skin sections were subjected to H&E staining, Verhoeff elastic fiber staining, LC3 immunofluorescence staining, and immunohistochemical staining for JAK2, STAT3, and AKT.
Result: Topical application of α-Sanshool significantly alleviated erythema, scaling, and dryness on the dorsal skin of UVB-irradiated mice. H&E staining revealed reduced epidermal thickening and inflammatory infiltration, while Verhoeff staining showed increased elastic fibers and improved collagen density. Immunofluorescence staining demonstrated an increase in LC3-positive punctate structures, and immunohistochemistry showed decreased expression of JAK2, STAT3, and AKT, consistent with the in vitro results [1].