|
|
Pharmacy Information 2026
β-谷甾醇通过调控CYP17A1/CYP19A1改善多囊卵巢综合征的作用机制研究
|
Abstract:
多囊卵巢综合征(PCOS)是一种常见的内分泌代谢性疾病，以高雄激素血症、排卵障碍和卵巢多囊样改变为主要特征。本研究基于网络药理学方法从52个治疗PCOS的中药方剂中筛选出高频活性成分β-谷甾醇，并探讨其通过调控CYP17A1和CYP19A1表达改善PCOS的作用机制。通过构建DHEA诱导的PCOS小鼠模型，以灌胃的方法在给予β-谷甾醇干预后，检测小鼠体重、动情周期、卵巢组织形态及卵巢组织中CYP17A1、CYP19A1和AR的表达变化。结果显示，β-谷甾醇可明显改善PCOS小鼠的体重、恢复动情周期、减少囊状卵泡数量，显著下调卵巢组织中CYP17A1、AR的mRNA和蛋白表达水平，并上调CYP19A1的mRNA和蛋白表达水平。本研究首次系统揭示β-谷甾醇通过调控类固醇激素合成通路关键酶表达改善PCOS的分子机制，为中医药治疗PCOS提供新的理论依据和潜在治疗策略。
Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disorder characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovarian morphology. Based on network pharmacology analysis of 52 traditional Chinese medicine prescriptions for PCOS, this study identified β-sitosterol as a high-frequency active component and investigated its mechanism in improving PCOS by regulating the expression of CYP17A1 and CYP19A1. A DHEA-induced PCOS mouse model was established, and after intervention with β-sitosterol via oral gavage, changes in body weight, estrous cycle, ovarian morphology, and the expression levels of CYP17A1, CYP19A1, and AR in ovarian tissues were measured. The results showed that β-sitosterol significantly improved body weight, restored the estrous cycle, reduced the number of cystic follicles, markedly downregulated the mRNA and protein expression levels of CYP17A1 and AR in ovarian tissues, and upregulated the mRNA and protein expression levels of CYP19A1. This study systematically reveals for the first time the molecular mechanism by which β-sitosterol ameliorates PCOS by regulating key enzymes in the steroid hormone synthesis pathway, providing a new theoretical basis and potential therapeutic strategy for traditional Chinese medicine in treating PCOS.
| [1] | Palomba, S., Piltonen, T.T. and Giudice, L.C. (2020) Endometrial Function in Women with Polycystic Ovary Syndrome: A Comprehensive Review. Human Reproduction Update, 27, 584-618. https://doi.org/10.1093/humupd/dmaa051 |
| [2] | Dapas, M. and Dunaif, A. (2022) Deconstructing a Syndrome: Genomic Insights into PCOS Causal Mechanisms and Classification. Endocrine Reviews, 43, 927-965. https://doi.org/10.1210/endrev/bnac001 |
| [3] | Hoeger, K.M., Dokras, A. and Piltonen, T. (2020) Update on PCOS: Consequences, Challenges, and Guiding Treatment. The Journal of Clinical Endocrinology & Metabolism, 106, e1071-e1083. https://doi.org/10.1210/clinem/dgaa839 |
| [4] | Rosenfield, R.L. and Ehrmann, D.A. (2016) The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocrine Reviews, 37, 467-520. https://doi.org/10.1210/er.2015-1104 |
| [5] | Walters, K.A., Bertoldo, M.J. and Handelsman, D.J. (2018) Evidence from Animal Models on the Pathogenesis of PCOS. Best Practice & Research Clinical Endocrinology & Metabolism, 32, 271-281. https://doi.org/10.1016/j.beem.2018.03.008 |
| [6] | Li, Y., Chen, C., Ma, Y., Xiao, J., Luo, G., Li, Y., et al. (2019) Multi-System Reproductive Metabolic Disorder: Significance for the Pathogenesis and Therapy of Polycystic Ovary Syndrome (PCOS). Life Sciences, 228, 167-175. https://doi.org/10.1016/j.lfs.2019.04.046 |
| [7] | Shahid, R., Iahtisham‐Ul‐Haq, Mahnoor, Awan, K.A., Iqbal, M.J., Munir, H., et al. (2022) Diet and Lifestyle Modifications for Effective Management of Polycystic Ovarian Syndrome (PCOS). Journal of Food Biochemistry, 46, e14117. https://doi.org/10.1111/jfbc.14117 |
| [8] | Gadalla, M.A., Norman, R.J., Tay, C.T., Hiam, D.S., Melder, A., Pundir, J., et al. (2020) Medical and Surgical Treatment of Reproductive Outcomes in Polycystic Ovary Syndrome: An Overview of Systematic Reviews. International Journal of Fertility and Sterility, 13, 257-270. |
| [9] | Zhou, X.Y., Zhou, L. and Sun, Z.Y. (2016) Research Progress in Mechanism of Traditional Chinese Medicine Treatment of Polycystic Ovary Syndrome. China Journal of Chinese Materia Medica, 41, 3715-3720. |
| [10] | 姚曼曼, 马丽亚, 张大伟, 等. 多囊卵巢综合征相关信号通路及其中医药调控研究进展[J]. 中国实验方剂学杂志, 2025, 31(3): 301-312. |
| [11] | Hopkins, A.L. (2007) Network Pharmacology. Nature Biotechnology, 25, 1110-1111. https://doi.org/10.1038/nbt1007-1110 |
| [12] | Wang, N., Zheng, Y., Gu, J., Cai, Y., Wang, S., Zhang, F., et al. (2017) Network-Pharmacology-Based Validation of TAMS/CXCL-1 as Key Mediator of XIAOPI Formula Preventing Breast Cancer Development and Metastasis. Scientific Reports, 7, Article No. 14513. https://doi.org/10.1038/s41598-017-15030-3 |
| [13] | Lyu, M., Yan, C., Liu, H., Wang, T., Shi, X., Liu, J., et al. (2017) Network Pharmacology Exploration Reveals Endothelial Inflammation as a Common Mechanism for Stroke and Coronary Artery Disease Treatment of Danhong Injection. Scientific Reports, 7, Article No. 15427. https://doi.org/10.1038/s41598-017-14692-3 |
| [14] | Hong, M., Li, S., Tan, H., Cheung, F., Wang, N., Huang, J., et al. (2017) A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of Traditional Hepatoprotective Chinese Herbal Medicines. Molecules, 22, Article No. 632. https://doi.org/10.3390/molecules22040632 |
| [15] | Diamanti-Kandarakis, E. and Dunaif, A. (2012) Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications. Endocrine Reviews, 33, 981-1030. https://doi.org/10.1210/er.2011-1034 |
| [16] | Nestler, J.E. (2000) Insulin Resistance and the Polycystic Ovary Syndrome: Recent Advances. Current Opinion in Endocrinology & Diabetes, 7, 345-349. https://doi.org/10.1097/00060793-200012000-00009 |
| [17] | Nisenblat, V. and Norman, R.J. (2009) Androgens and Polycystic Ovary Syndrome. Current Opinion in Endocrinology, Diabetes & Obesity, 16, 224-231. https://doi.org/10.1097/med.0b013e32832afd4d |
| [18] | Reddy, K.R., Deepika, M.L.N., Supriya, K., Latha, K.P., Rao, S.S.L., Rani, V.U., et al. (2014) CYP11A1 Microsatellite (tttta)n Polymorphism in PCOS Women from South India. Journal of Assisted Reproduction and Genetics, 31, 857-863. https://doi.org/10.1007/s10815-014-0236-x |
| [19] | Nelson, V.L., Qin, K., Rosenfield, R.L., Wood, J.R., Penning, T.M., Legro, R.S., et al. (2001) The Biochemical Basis for Increased Testosterone Production in Theca Cells Propagated from Patients with Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism, 86, 5925-5933. https://doi.org/10.1210/jcem.86.12.8088 |
| [20] | Akhtar, M., Wright, J.N. and Lee-Robichaud, P. (2011) A Review of Mechanistic Studies on Aromatase (CYP19) and 17α-Hydroxylase-17,20-Lyase (cyp17). The Journal of Steroid Biochemistry and Molecular Biology, 125, 2-12. https://doi.org/10.1016/j.jsbmb.2010.11.003 |
| [21] | Garg, D. and Merhi, Z. (2016) Relationship between Advanced Glycation End Products and Steroidogenesis in PCOS. Reproductive Biology and Endocrinology, 14, 1-3. https://doi.org/10.1186/s12958-016-0205-6 |
| [22] | Ashraf, S., Nabi, M., Rasool, S.u.A., Rashid, F. and Amin, S. (2019) Hyperandrogenism in Polycystic Ovarian Syndrome and Role of CYP Gene Variants: A Review. Egyptian Journal of Medical Human Genetics, 20, Article No. 25. https://doi.org/10.1186/s43042-019-0031-4 |
| [23] | Sujith Kumar, M.S., Mawlong, I. and Singh, D. (2016) Phytosterol Recovery from Oilseeds: Recent Advances. Journal of Food Process Engineering, 40, e12466. https://doi.org/10.1111/jfpe.12466 |
| [24] | Feng, S., Belwal, T., Li, L., Limwachiranon, J., Liu, X. and Luo, Z. (2020) Phytosterols and Their Derivatives: Potential Health‐Promoting Uses against Lipid Metabolism and Associated Diseases, Mechanism, and Safety Issues. Comprehensive Reviews in Food Science and Food Safety, 19, 1243-1267. https://doi.org/10.1111/1541-4337.12560 |
| [25] | Ambavade, S.D., Misar, A.V. and Ambavade, P.D. (2014) Pharmacological, Nutritional, and Analytical Aspects of Β-Sitosterol: A Review. Oriental Pharmacy and Experimental Medicine, 14, 193-211. https://doi.org/10.1007/s13596-014-0151-9 |
| [26] | Babu, S. and Jayaraman, S. (2020) An Update on β-Sitosterol: A Potential Herbal Nutraceutical for Diabetic Management. Biomedicine & Pharmacotherapy, 131, Article ID: 110702. https://doi.org/10.1016/j.biopha.2020.110702 |
