Abstract: 　　Cherimolacyclopeptide A is a monomeric component isolated from the fruits of Annonacherimolia Mill. It has been applied as a cosmetic ingredient for its remarkable anti-inflammatory activity, while systematic scientific research on its anti-aging effect remains insufficient. This study was designed to investigate the protective effect of cherimolacyclopeptide A on UVB-induced photoaged skin in mice and evaluate its regulatory impact on autophagic levels. A mouse model of skin photoaging was established, HE staining and Masson staining were used to observe skin tissue lesions and epidermal thickness; CD31, a vascular marker, was employed to detect the effect of UVB on subcutaneous blood vessels in the dorsal skin of mice. Immunofluorescence staining was performed to determine the expression of aging-related proteins Sirt1, P53, P21 and AMPK in the dorsal skin tissue. Western blot analysis was conducted to detect the expression of AMPK, p-AMPK, ULK1, p-ULK1, ATG5, ATG13, Beclin1, P62 and LC3Ⅱ/Ⅰ in mouse dorsal skin tissue and HUVECs. The experimental results demonstrated that cherimolacyclopeptide A significantly ameliorated UVB-induced skin tissue damage and restored the regular structure of the epidermal layer. Moreover, cherimolacyclopeptide A regulated the abnormal activation of AMPK and its downstream autophagy-related proteins (ATG5, ATG13, Beclin1, P62, LC3Ⅱ/Ⅰ), as well as mitochondrial dysfunction (P<0.05, P<0.01, P<0.001). Collectively, these findings indicate that cherimolacyclopeptide A exerts a protective effect against UVB-induced photoaging. It maintains skin homeostasis by modulating autophagic disorders and inhibiting excessive autophagic activation in skin tissue and HUVECs, thereby exhibiting favorable anti-aging activity.
　　Funding: Yunnan Characteristic Plant Extraction Laboratory- Development and Industrialization of Novel Repair Series Products Based on Yunnan Specialty Plants Regulating Multiple Barrier Mechanisms of the Skin (2025YKZY003); Yunnan Characteristic Plant Extraction Laboratory- Development and Industrialization of Post-medical Class II Medical Devices (2025YKZY012).