Paeonia suffruticosa Andrews Root Extract Ameliorates Photoaging via Regulating IRS1/PI3K/FOXO Pathway

Junxi Liu Youyun Liu Feifei Wang Yonglei Yuan Hongyu Ma Liping Qu ^*

• Yunnan Botanee Bio-technology Group Co., Ltd., Yunnan, China

The root of Paeonia suffruticosa Andrews (P. suffruticosa Andr.), is a traditional Chinese medicine. Numerous studies have shown that it possesses anti-inflammatory, antioxidant, and antiaging effects due to its rich content of bioactive compounds such as polyphenols and paeonol. Thus, it finds extensively applied in the fields of medicine and cosmetics. However, there are few reports on the photoprotective effects of P. suffruticosa Andr. root bark, this study aims to investigate its research in this area.This study utilized P. suffruticosa Andr. root bark sourced from Kunming, Yunnan Province, China. The P. suffruticosa Andr. root extract (PSAE) was obtained using AB-8 resin, with a total phenolic content of 48.9%. Antioxidant activity studies have shown that PSAE effectively inhibits DPPH radicals, superoxide anions, hydroxyl radicals, and ABTS radicals, while also increasing the inhibition rates of collagenase and hyaluronidase. The photoprotective effect of PSAE was assessed using HaCaT cells, HFF cells, and a 3D Reconstructed Human full T-SkinTM model. The findings demonstrated that PSAE notably decreased the UV-induced rise in reactive oxygen species (ROS) levels and senescence-associated β-galactosidase (SA-β-gal) activity. Mechanistic investigations via RT-qPCR, WB, IF, H＆E staining, Masson's trichrome staining and IHC staining analyses revealed that PSAE inhibited the overexpression of IRS1 and its downstream effectors PI3K, AKT, and mTOR induced by UV irradiation. Consequently, this led to alleviated suppression of FOXO and activation of the Nrf2 pathway, thereby mitigating oxidative damage, genetic damage, and collagen degradation associated with photoaging. Human efficacy assessment was conducted by evaluating parameters such as transepidermal water loss (TEWL), epidermal moisture content, roughness and elasticity confirming the efficacy of PSAE in humans.In summary, this study elucidated the mechanism through which PSAE attenuates UV-induced photoaging damage by modulating the IRS/PI3K/FOXO signaling pathway, thereby providing strong support for its application in cosmetic anti-aging formulations.