Aloe Vera Gel and Rind-Derived Nanoparticles Mitigate Skin Photoaging via Activation of Nrf2/ARE Pathway

Zixuan Sun,1,2,* Yuzhou Zheng,2,* Tangrong Wang,2,* Jiaxin Zhang,2 Jiali Li,2 Zhijing Wu,2 Fan Zhang,2 Tingxin Gao,2 Li Yu,2 XueZhong Xu,1 Hui Qian,2 Yulin Tan1 1Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, People’s Republic of China; 2Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Qian, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, People’s Republic of China, Email [email protected] Yulin Tan, Department of General Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, 213017, People’s Republic of China, Email [email protected]: Skin aging is the primary external manifestation of human aging, and long-term exposure to ultraviolet radiation is the leading cause of photoaging, which can lead to actinic keratosis and skin cancer in severe cases. Traditional treatments may pose safety risks and cause side effects. As an emerging research direction, plant-derived exosome-like nanoparticles (PDNPs) show promise in combating aging. Aloe vera, known for its natural active ingredients that benefit the skin, aloe-derived exosome-like nanoparticles (ADNPs) have not yet been studied for their potential in delaying skin aging.Methods: In this study, nanoparticles were isolated from two different sites, aloe vera gel and aloe vera rind (gADNPs and rADNPs), and characterized by TEM, SEM, AFM, NTA and BCA. The effects were evaluated by constructing in vitro and in vivo models and using RT-qPCR, immunofluorescence, and histopathological analysis.Results: The results first revealed the exceptional anti-aging effects of ADNPs. We found that ADNPs promoted the nuclear translocation of Nrf2, alleviated oxidative stress and DNA damage induced by UV exposure, and inhibited the elevation of β-gal and SASP. In vivo, ADNPs reduced MDA and SOD levels in mouse skin tissue and delayed skin photoaging. Moreover, safety assessments confirmed the excellent biocompatibility of ADNPs.Conclusion: ADNPs delay skin photoaging through the Nrf2/ARE pathway, holding potential clinical application value, and may provide new therapeutic strategies for future medical cosmetology and skin disease prevention. Keywords: aloe vera, anti-aging, nanoparticles, skin photoaging, cellular senescence, antioxidants