Rehmannioside D mitigates disease progression in rats with experimental-induced diminished ovarian reserve via Forkhead Box O1/KLOTHO axis

Yan Liang; Huimin Wang; Jin Chen; Lingyan Chen; Xiaoyong Chen

doi:10.4196/kjpp.2023.27.2.167

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자료유형: 학술저널

저자정보: Yan Liang (Department of Traditional Chinese Medicine Maternal and Child Health Hospital of Jiangxi Province Nanchang Jiangxi 330006 China) Huimin Wang (Department of Traditional Chinese Medicine Maternal and Child Health Hospital of Jiangxi Province Nanchang Jiangxi 330006 China) Jin Chen (Department of Traditional Chinese Medicine Maternal and Child Health Hospital of Jiangxi Province Nanchang Jiangxi 330006 China) Lingyan Chen (Department of Traditional Chinese Medicine Maternal and Child Health Hospital of Jiangxi Province Nanchang Jiangxi 330006 China) Xiaoyong Chen (Department of Traditional Chinese Medicine Maternal and Child Health Hospital of Jiangxi Province Nanchang Jiangxi 330006 China)

저널정보: 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제27권 제2호

발행연도: 2023.2

수록면: 167 - 176 (10page)

DOI: 10.4196/kjpp.2023.27.2.167

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This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E2 expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis

#Forkhead Box O1 #KLOTHO #Ovarian reserve #Rehmannioside D

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