Jian-Pi-Yi-Shen decoction inhibits mitochondria-dependent granulosa cell apoptosis in a rat model of POF

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.

Transcription factor c-fos induces the development of premature ovarian insufficiency by regulating MALAT1/miR-22-3p/STAT1 network

“…The human ovarian granulosa-like tumour cell line KGN was purchased from Feiya Biotechnology Ltd. KGN was cultured in DMEM/F12 medium (10,569,044, Gibco, Carlsbad, CA) appended to 10% FBS (10,099,141, Gibco), penicillin (100 U/mL) and streptomycin (100 U/mL) (15,070,063, Gibco) in a cell incubator at 37 °C with 5% CO 2 . KGN cells were cultured with 250 μM CTX for 48 h to construct an in vitro POI cell model [ 15 , 16 ].…”

Network Pharmacology and In Vivo Validation to Explore the Potential Active Ingredients and Mechanisms of Ziyin Buyang Formula in Diminished Ovarian Reserve

“…12 In clinical settings, several traditional Chinese medicine(TCM) formulas are usually used to treat ovarian dysfunction and are believed to have curative effects. For example, the Erzhi Tiangui recipe could obviously improve ovarian reactivity and oocyte quality in elderly sterile women receiving IVF-ET 13 ; Jian-Pi-Yi-Shen decoration could improve mitochondrial function and alleviate apoptosis through the apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase (ASK1/JNK) pathway in a rat model of POF, 14 and the Zuogui pill improved immune inflammatory injury in the ovary and exerted therapeutic effects on POF. 15 Successful DOR treatment according to Professor Xia, a master of TCM, requires the restoration of the yin-yang balance in the patient's body.…”