Explore the multitarget mechanism of tetrahydrocurcumin preventing on UV-induced photoaging mouse skin

Abstract

UV induced photoaging is the main external factor of skin aging. In this study, we tested the protective effects of tetrahydrocurcumin on UV-induced skin photoaging of KM mice and researched the multi-target mechanism through RNA sequencing technology. Mouse experiments show that tetrahydrocurcumin strongly changed in skin appearance, epidermal thickness, and wrinkle-related parameters in UV-irradiated mice. RNA-seq result show that we found 29 differentially expressed mRNA transcripts in UV mice relative to Ctrl rats (18 up-regulated and 11 down-regulated) and 7 significantly dysregulated mRNAs were obtained in the THC group compared to the UV group (1 up-regulated and 6 down-regulated), respectively. Spink7, Edn3, Stab2 may be the key target genes of tetrahydrocurcumin in preventing aging. Bioinformatics analysis shows that the response to muscle contraction and melanin biosynthetic GO term and Inflammation related pathway such as PPAR, MAPK would involve in effects of tetrahydrocurcumin. The results of this study indicated that tetrahydrocurcumin can improve the appearance through anti-inflammatory, improving extracellular matrix and inhibiting melanin production. It could be suggested as a protective measure in the prevention of UV-induced photoaging.

Keywords: Mechanisms; RNA-seq; Skin photoaging; Tetrahydrocurcumin.

Figure 1

Chemical structures of tetrahydrocurcumin.

Figure 2

THC treatment improved photoaging appearance. Ctrl (control), UV(UVA + UVB), THC(UVA + UVB + THC THC100 mg/kg in 0.5% sodium carboxymethyl cellulose). (A) Photograph on the dorsal skin of KM mice at week 10 after indicated THC treatment and UVA irradiation. (B) Different group with equivalent UVA fluence radiation on photoaging was evaluated by Bissett scoring. Values presented are the means ± standard deviation (N = 12/group). ∗P < 0.05, ∗∗P < 0.01 Indicate compared to Ctrl group, compared to, #P < 0.05, ##P < 0.01 Indicate compared to UV group.

Figure 3

THC treatment improved skin tissue structure, collagen fibers and elastic fiber’s structure (A) H & E (B) Masson’s trichrome (C) Verhoeff prior. Ctrl (control group), UV (UVA + UVB group), THC (UVA + UVB + THC group THC100 mg/kg in 0.5% sodium carboxymethyl cellulose).

Figure 4

The detection results of SOD, MDA, GSH-Px and Hyp in mouse skin tissue. Ctrl group (control group), UV group (UVA + UVB group), THC group (UVA + UVB + THC group, THC100 mg/kg in 0.5% sodium Carboxymethyl cellulose).Values presented are the means ± standard deviation (N = 12/group). ∗P < 0.05, ∗∗P < 0.01 Indicate compared to Ctrl group, compared to, #P < 0.05, ##P < 0.01 Indicate compared to UV group.

Figure 5

Altered mRNA profiles in Photoaging Mice Skins. BG (control group), MG (UVA + UVB group) TG (UVA + UVB + THC group, THC100 mg/kg in 0.5% sodium Carboxymethyl cellulose). (A)Heat map of significant mRNA (padj<0.05) from Ctrl and UV irradiated and THC treatment groups with green and red spectrum colors indicating down regulated and up regulated expression, respectively. (B)Venn diagrams shows overlaps of differentially expressed genes (padj<0.05 |log2 (fold change) | >1) between experimental groups. Three gene increased in UV group but decrease in THC group.

Figure 6

GO and KEGG Pathway Analyses of the mRNA. (A) Gene Ontology (GO) drew Scatter plot, the top 30 biological process were significantly enriched (P < 0.05). (B) KEGG Dazzle, the top 20 were significantly enriched (P < 0.05).

Figure 7

qRT-PCR Confirmation of Sequencing mRNAs. Ctrl (control group), UV group (UVA + UVB group), THC group (UVA + UVB + THC group, THC100 mg/kg in 0.5% sodium Carboxymethyl cellulose). (A) qRT-PCR showed that the result consistent with the RNA-seq data in terms of the expression levels of the validated mRNAs. (Red represents the blank control group, blue represents the model control group, and orange represents the tetrahydrocurcumin group, ∗P < 0.05, ∗∗P < 0.01). (B) qRT-PCR showed that Spink7, Edn3 and stab2 genes were significantly up-regulated after UV irradiation and down regulated after THC, which was consistent with the results of high-throughput sequencing (∗P < 0.05, ∗∗P < 0.01).