Research Paper Volume 14, Issue 20 pp 8321—8345
Jian-Pi-Yi-Shen decoction inhibits mitochondria-dependent granulosa cell apoptosis in a rat model of POF
- 1 Department of Nephrology, The Fourth of Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), Guangzhou University of Traditional Chinese Medicine, Shenzhen, China
- 2 Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China
- 3 College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China
- 4 Department of Internal Medicine, Liaoning Provincial Corps Hospital of Chinese People’s Armed Police Forces, Shenyang, China
- 5 Department of Endocrinology and Metabolism, The Fourth People’s Hospital of Shenyang, Shenyang, China
- 6 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China
- 7 NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, China
- 8 College of Basic Medical Science, Chinese Capital Medical University, Beijing, China
Received: July 12, 2022 Accepted: September 23, 2022 Published: October 27, 2022
https://doi.org/10.18632/aging.204320How to Cite
Copyright: © 2022 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). In vivo experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. In vitro experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 μg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. In vivo, JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. In vitro, JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.
Abbreviations
POF: premature ovarian failure; CTX: cyclophosphamide; GnRH-a: gonadotropin releasing hormone agonist; ET: embryo transfer; DHGCT: Da-Huang-Gan-Cao-Tang; YPFS: Yu-Ping-Feng-San; CKD: chronic kidney disease; TCM: traditional Chinese medicine; JPYS: Jian-Pi-Yi-Shen decoction; HPLC: high-performance liquid chromatography; SD: Sprague-Dawley; EDTA: ethylene diamine tetraacetic acid; EF: ejection fraction; FSH: follicle stimulating hormone; E2: oestradiol; ELISA: Enzyme-linked immunosorbent assay; Cyt-c: cytochrome C; DAPI: 4’,6-diamidino-2-phenylindole; DCFH-DA: 2’,7’-Dichlorodihydrofluorescein diacetate; ELISA: euzymelinked immunosorbent assay; PBS: phosphate buffer saline; ATP: adenosine triphosphate; MMP: mitochondrial membrane potential; mPTP: mitochondrial permeability transition pore; RT-qPCR: Real-time quantitative Polymerase Chain Reaction; ROS: reactive oxygen species; SD: Sprague-Dawley; RCR: respiratory control rate; HE: hematoxylin-eosin; PBS: phosphate buffer saline; POI: primary ovarian insufficiency; GC: granulose cells; CsA: Cyclosporine A; CyP-D: cyclophilin D; Drp1: dynamin-related protein 1; PGC-1α: PPARγ coactivator-1-α; ASK1: Apoptosis signal-regulating kinase 1; MAP3K: mitogen-activated kinase kinase kinase; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling.