Sanshool improves UVB-induced skin photodamage by targeting JAK2/STAT3-dependent autophagy

Abstract

Ultraviolet radiation is markedly increased because of pollution and the depletion of the stratospheric ozone layer. Excessive exposure to sunlight can negatively affect the skin, resulting in sunburn, photo-aging, or skin cancer. In this study, we first determined the photoprotective effect of sanshool, a major component in Zanthoxylum bungeanum, on UVB-irradiated responses in human dermal fibroblasts (HDFs) and nude mouse. We found that sanshool treatment can protect cells against the effects of UVB irradiation by (i) increasing cell viability, (ii) inhibiting MMP expression, and (iii) inducing autophagy. We also used the recombinant CSF2 or anti-CSF2 antibody co-cultured with human dermal fibroblasts (HDFs) and found that CSF2 contributes to sanshool-induced autophagy. Sanshool hindered the UVB-induced activation of JAK2-STAT3 signaling in HDFs, thereby inhibiting the expression of MMPs and activation of autophagic flux. Exposure of the dorsal skin of hairless mice to UVB radiation and subsequent topical application of sanshool delayed the progression of skin inflammation, leading to autophagy and inhibiting the activation of JAK2-STAT3 signaling. These results provide a basis for the study of the photoprotective effect of sanshool and suggest that it can be potentially used as an agent against UVB-induced skin damage in humans.

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

“…For western blotting, the total protein extracts from each sample were processed as previously described [72][73][74][75]. The total proteins were loaded into the SDS-PAGE (sodium dodecyl sulfate-polyacrylamide) gel and separated by their molecular weight via electrophoresis (PAGE).…”

Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis

“…Treating with the autophagy activator rapamycin (100nM, 3h) could drastically improving the cleavage of LC3 and promoting the shikonin-induced cell death ( Figure 4D and S1). [37] Shikonin-treatment along with the known autophage inhibitor 3-MA (10μM), Bafilomycin A1 (100nM) and HCQ (50μM) 3h early than shikonin enhanced shikonin-induced accumulation of p62 and LC3. All these results suggest that shikonin might be able to induce autophagic death by induced autophagy but inhibit the degradation of autophagolysosome.…”

Identification of the candidate genes related to sanshool biosynthesis in Zanthoxylum bungeanum by comparative RNA sequencing analysis

“…8a) 37 . Because polyunsaturated acid is a precursor of sanshool biosynthesis 11 and because most of the unigenes in group I were upregulated at DAF50 and DAF90 compared with DAF30 and the sanshool content increases with pericarp development (the numbing and anaesthetic sensation was stronger during pericarp development), we inferred that these enzymes might play important roles in the biosynthesis of polyunsaturated alkyl chains of sanshools. Group II included three enzymes: branched-chain amino acid aminotransferase (BCAT), alanine-glyoxylate transaminase (AGXT), and aspartate aminotransferase (ASP).…”

“…Sanshools are a set of polyunsaturated fatty acid amides that possess long-chain unsaturated fatty acid structures and an isobutyl or hydroxylated isobutyl chain linked to the amide moiety ( Fig. 7a) 11,36 . Thus combining the above results indicates that the genes involved in fatty acid biosynthesis and metabolism and amino acid transport and metabolism were dynamically regulated at the transcriptional level during pericarp development, which suggests it is important to identify the genes related to sanshool biosynthesis.…”

“…Due to their potential economic value, many studies have focused on separating sanshools and their analogues, identifying their chemical structures 9 , artificially synthesising sanshools, and exploring their pharmacological effects 10,11 . However, due to the lack of genomic information, molecular synthesis pathways and the related genes remain to be elucidated.…”