Topical application of neem leaves prevents wrinkles formation in UVB-exposed hairless mice

•Topical application of NLE to photoaged mice skin was very effective.•The increased type I procollagen and elastin were detected after treatment with NLE.•NLE modulated the biomarkers of skin aging including ROS, AP-1, MAPKs, IL-6, MMP-1, and TGF-β1.

Azadirachta indica A. Juss. (Neem) has been used in India for the treatment of skin problems for centuries. However, no skin photoaging-related research has been performed with this agent. In the present study, neem leaf extract at 1, 10, and 50 μg/mL was investigated for its skin anti-aging effects in UVB-irradiated NHDFs and hairless mice. Regulation of molecular signaling pathways by neem leaf extract during UVB exposure was investigated in both in vitro and in vivo models. UVB-irradiated skin model treated with neem leaf extract showed increased type I procollagen and elastin as a result of enhanced synthesis via two pathways. Firstly, transforming growth factor TGF-β1 is up-regulated. Secondly, intracellular reactive oxygen species (ROS), transcription activator AP-1 protein expression, and MAPK are down-regulated. The down-regulation of signaling molecules caused the suppression of type I procollagen degrading enzymes such as matrix metalloproteinase-1 and type I procollagen synthesis inhibitor such as interleukin-6. In particular, topical application of neem leaf to UVB-irradiated hairless mice was shown to be very effective in treating the symptoms of skin aging such as wrinkles, thickening, water loss, and erythema. Therefore, our results indicated that neem leaf ethanolic extract is a promising anti-aging candidate for topical therapy products.

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