Proteomic Analysis of Human Follicular Fluid Reveals the Pharmacological Mechanisms of the Chinese Patent Drug Kunling Pill for Improving Diminished Ovarian Reserve

Haiyan Wang; Dan Cao; Meixian Wang; Yanbin Shi; Bowen Wei; Shiyuan Jiang; Yangyu Jiang; Hui Lian; Xiaoou Xue; Zhiqiang Ma; Jian Li

doi:10.1155/2022/5929694

Proteomic Analysis of Human Follicular Fluid Reveals the Pharmacological Mechanisms of the Chinese Patent Drug Kunling Pill for Improving Diminished Ovarian Reserve

Evid Based Complement Alternat Med. 2022 May 28:2022:5929694. doi: 10.1155/2022/5929694. eCollection 2022.

Authors

Haiyan Wang^{1

2}, Dan Cao¹, Meixian Wang², Yanbin Shi², Bowen Wei¹, Shiyuan Jiang¹, Yangyu Jiang¹, Hui Lian¹, Xiaoou Xue³, Zhiqiang Ma⁴, Jian Li¹

Affiliations

¹ Department of Histology and Embryology, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China.
² Reproductive and Genetic Medical Center, Dalian Women and Children's Medical Group, Dalian 116000, Liaoning, China.
³ Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
⁴ School of Chinese Pharmacy, Beijing Key Lab for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Abstract

Objective: To explore the pharmacological mechanism of a Chinese patent drug (Kunling Pill (KLP)) on improving diminished ovarian reserve based on proteomic analysis.

Methods: A total of 18 patients divided into three groups (the normal ovary reserve (NOR), diminished ovary reserve (DOR), and KLP groups) undergoing assisted reproductive technology by standard ovarian stimulation protocols were recruited to collect follicular fluid. Data-independent acquisition mass spectrometry was used to identify differentially expressed proteins by nano-LC-MS/MS. Bioinformatic analysis was conducted to predict the functions and pathways of the identified proteins. Clinical, hormonal, and biochemical parameters were also analyzed in the three groups.

Results: A total of 144 differentially expressed proteins were screened out, including 56 proteins that were downregulated and 88 proteins that were upregulated in the DOR group compared with the NOR group, while 27 proteins were shared in the KLP-treated group. Among them, 10 proteins were upregulated and 17 proteins were downregulated in the KLP-treated group compared with the DOR group. The most enriched biological processes accounted for 28 GO terms, including cellular process, biological regulation, metabolic process, and regulation of biological process. Significant pathways were associated with fatty acid elongation, fatty acid degradation, fatty acid metabolism, nicotinate and nicotinamide metabolism, and valine, leucine, and isoleucine degradation.

Conclusion: Our study provides the proteome profiles of human follicular fluid from DOR patients treated by KLP. Functional analyses of proteome datasets revealed that core proteins (SAA1, MIF, and PRDX5) and related pathways (fatty acid metabolism, nicotinate and nicotinamide metabolism, and tyrosine and purine metabolism) are possible pharmacological mechanisms through which KLP improves DOR. Therefore, these findings may help better understand the complex mechanisms through which DOR is treated by the Chinese patent drug KLP.