Scutellariae Radix and Atractylodis Macrocephalae Rhizoma pairs ameliorate preeclampsia via PI3K/AKT/eNOS pathway

Shujun Sun^1,2Jie Li¹Dingmei Qin¹Xiaoxiao Yang¹Huilin Zhang¹Yue Yang³Mengmeng Li¹Ruihua Jin⁴Jianye Dai^3*Yong Liu^1,5*

• ¹Fuyang Teachers College, Fuyang, China
• ²Anhui Rural Revitalization Collaborative Technology Service Center, Fuyang, China
• ³School of Pharmacy, Lanzhou University, Lanzhou, Gansu Province, China
• ⁴Fuyang Women's and Children's Hospital, Fuyang, Jiangsu Province, China
• ⁵Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang, China

Preeclampsia stands as a leading cause of maternal mortality. Scutellariae Radix and Atractylodis Macrocephalae Rhizoma (SA) is a commonly employed traditional Chinese medicine pair in the treatment of preeclampsia, yet the underlying mechanisms of their protective effects against preeclampsia remain elusive. In this study, the N-nitro-L-arginine methyl ester (L-NAME) was utilized to establish a preeclamptic pregnant mouse model, and the protective effects of SA were systematically evaluated. A comprehensive approach integrating network pharmacology analysis, quantitative proteomics, and in vitro experiments was adopted to probe into the relevant mechanisms.The results demonstrated that SA could significantly ameliorate the systolic blood pressure, urinary protein levels, and pathological damage in the kidneys and placenta of mice.Moreover, in vitro experiments further validated the promoting effects of SA, baicalin, and atractylenolide I on the proliferation and migration of HTR-8/SVneo cells. Baicalin and atractylenolide I are the main active and quality control components of SA. Network pharmacology analysis, quantitative proteomics and molecular docking revealed that the PI3K/Akt pathway is a potential mechanism through which SA alleviates preeclampsia. Further investigations showed that SA could reverse L-NAME-induced inhibition of the PI3K/p-Akt/Akt signaling pathway, upregulating eNOS expression and ultimately alleviating vasoconstriction and other preeclampsiarelated symptoms. In conclusion, SA has the capacity to improve preeclampsia-induced increases in blood pressure and urinary protein, holding promise as a novel strategy for the treatment of preeclampsia.