Drug Design, Development and Therapy (Jul 2021)

Qilin Pill Exerts Therapeutic Effect on Resection-Induced Premature Ovarian Insufficiency Rats by Inhibiting the MAPK and PI3K-AKT Signaling Pathways

  • Li D,
  • Jia Y,
  • Hou Y,
  • Chen D,
  • Zheng C,
  • Chen L,
  • Zhou L,
  • Sun Z

Journal volume & issue
Vol. Volume 15
pp. 3331 – 3345

Abstract

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Debao Li,1– 3 Yuling Jia,2,3 Yiwen Hou,2,3 Dingshi Chen,2,3 Chiyang Zheng,2,3 Lifen Chen,2,3 Li Zhou,2,3 Zuyue Sun2,3 1School of Pharmacy, Fudan University, Shanghai, 201203, People’s Republic of China; 2National Health Commission (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, 200032, People’s Republic of China; 3Reproductive and Developmental Research Institute of Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Li Zhou; Zuyue SunShanghai Institute for Biomedical and Pharmaceutical Technologies, No. 2140 Xietu Road, Shanghai, 200032, People’s Republic of ChinaEmail [email protected]; [email protected]: The Qilin pill (QLP) is a traditional Chinese compound prescription comprising 15 herbs that has demonstrated significant therapeutic effects on premature ovarian insufficiency (POI) in recent years. However, a pharmacological evaluation of QLP on ovarian function remains to be conducted, and the key mechanism of QLP treatment on POI is unclear.Methods: Premature ovarian insufficiency rats were established by bilateral partial ovariectomy. The model rats were administrated with low (QLP-L), medium (QLP-M) and high (QLP-H) doses of QLP for 4 weeks to evaluate the ovarian function in terms of estrous cycle, hormone level, and follicle count. The mechanism of QLP in the treatment of POI was systematically explored by network pharmacology, and expression levels of the MAPK and PI3K-AKT signaling pathways were verified by Western blotting and molecular docking.Results: The rat model of resection-induced POI was successfully established, and QLP could significantly recover the estrous cycle, decrease serum FSH levels, and decelerate follicle depletion after 4 weeks of administration. The optimal dose of QLP in the experiment was preliminarily determined to be 0.9 g/kg. Based on the network pharmacology methods, we constructed the compound-target network and protein protein interaction (PPI) network of QLP for the treatment of POI. The experimental verification of the enrichment analysis showed that QLP inhibited the MAPK and PI3K-AKT signaling pathways, and the key compounds and key targets involved were verified by molecular docking.Conclusion: QLP exerted significant therapeutic effects on resection-induced POI rats, and this was achieved by the inhibition of the MAPK and PI3K-AKT signaling pathways. This study is the first to systematically investigate the effects and mechanism of QLP on POI rats, which will provide valuable guidance in clinic.Keywords: Qilin pill, premature ovarian insufficiency, network pharmacology, MAPK signaling pathway, PI3K-AKT signaling pathway

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