PMID- 27845267 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20170703 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 195 DP - 2017 Jan 4 TI - Protective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovaries. PG - 173-181 LID - S0378-8741(16)31750-0 [pii] LID - 10.1016/j.jep.2016.11.014 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Kuntai capsule, a traditional Chinese medicine, has been widely used for the clinical treatment of menopausal syndrome. However, its mechanisms remain poorly understood. Considering that aging ovaries are the primary cause of menopause, this study was designed to investigate the effects and mechanisms of Kuntai capsule on ovarian function in a novel mice model with accelerated aging ovaries. MATERIALS AND METHODS: Seventy-five female C57BL/6 mice were chosen for this study. Fifteen of the mice were separated into the normal control group (NC). The remaining sixty were used to establish the novel accelerated aging ovary model by superovulation and oxidative stress and then by randomly dividing the mice into four equal groups. One group was considered the model group (Mod). The other three groups were treated with low (0.4g/kg), middle (0.8g/kg) and high (1.6g/kg) doses of Kuntai capsule intragastrically every day for 4 weeks. During the treatment, the body weight and fur condition of all mice were recorded. All the mice were forced to swim to record their exhaustive swimming time (EST), which measures their strength. Mice were then sacrificed for sampling. Ovarian reserve was evaluated using follicle counts and AMH expression. Ovarian function was evaluated using estrous cycle, sex hormone level and litter experiments. Ovarian follicles were categorized and counted to estimate ovarian reserve, and ovarian histologic sections were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to detect apoptotic cells. The ultrastructure of ovarian cells was observed using transmission electron microscopy. Western blotting was used to measure expression of Bax, Bcl2, AMH and SOD2 protein. RESULTS: Compared with the NC GROUP, the Mod group clearly displayed worse fur condition and ovarian function. These situations showed some improvement after Kuntai capsule treatment. Specifically, the fur condition and the EST of the Kuntai capsule groups were superior to the fur condition and EST of the Mod group. In cases of damaged ovarian function, Kuntai capsule can regulate the estrous cycles, increase hormone secretion and fertility and significantly decrease atretic follicles. The transmission electron microscopy results revealed that Kuntai capsule rescued the ovarian ultrastructure of mice. TUNEL staining confirmed that the apoptotic cells were reduced after Kuntai capsule treatment. Western blotting revealed that Kuntai capsule can increase AMH, SOD2, and Bcl2 protein expression and decrease Bax expression. CONCLUSIONS: Kuntai capsule may improve damaged ovarian function, which may be related to its antioxidant and anti-apoptosis effects. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Zhang, Jinjin AU - Zhang J AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: 824754662@qq.com. FAU - Fang, Li AU - Fang L AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: 1228043956@qq.com. FAU - Shi, Liangyan AU - Shi L AD - Department of Obstetrics and Gynecology, Hubei Province, Maternity and Child Health Care Hospital, Wuhan, Hubei 430030, PR China. Electronic address: 416234083@qq.com. FAU - Lai, Zhiwen AU - Lai Z AD - Maternal and Child Health Hospital of Zigong, Sichuan 643000, China. Electronic address: 124075212@aa.com. FAU - Lu, Zhiyong AU - Lu Z AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: 553654372@qq.com. FAU - Xiong, Jiaqiang AU - Xiong J AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: 292539238@qq.com. FAU - Wu, Meng AU - Wu M AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: 651377251@qq.com. FAU - Luo, Aiyue AU - Luo A AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: aiyueluo@163.com. FAU - Wang, Shixuan AU - Wang S AD - Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China. Electronic address: sxwang@tjh.tjmu.edu.cn. LA - eng PT - Journal Article DEP - 20161111 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Antioxidants) RN - 0 (Bax protein, mouse) RN - 0 (Capsules) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-2-Associated X Protein) RN - 0 (kuntai capsule) RN - 114100-40-2 (Bcl2 protein, mouse) RN - 66H7ZZK23N (Ozone) RN - 80497-65-0 (Anti-Mullerian Hormone) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (superoxide dismutase 2) SB - IM EIN - J Ethnopharmacol. 2017 Feb 23;198:608-609. PMID: 28190630 EIN - J Ethnopharmacol. 2019 Mar 1;231:570-571. PMID: 30551927 MH - Administration, Oral MH - Age Factors MH - Animals MH - Anti-Mullerian Hormone/metabolism MH - Antioxidants/administration & dosage/*pharmacology MH - Apoptosis/drug effects MH - Capsules MH - Cytoprotection MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/administration & dosage/*pharmacology MH - Estrous Cycle/drug effects MH - Female MH - Fertility/drug effects MH - Inhalation Exposure MH - Mice, Inbred C57BL MH - Muscle Strength MH - Organ Size MH - Ovarian Follicle/drug effects/ultrastructure MH - Ovarian Reserve/*drug effects MH - Ovary/*drug effects/metabolism/physiopathology/ultrastructure MH - Oxidative Stress/*drug effects MH - Ozone/toxicity MH - Pregnancy MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Superovulation MH - Superoxide Dismutase/metabolism MH - Time Factors MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Accelerated aging ovary OT - Estradiol (PubChem CID:5757) OT - Kuntai capsule OT - Model OT - Ovarian function OT - Progesterone (PubChem CID:5994) EDAT- 2016/11/16 06:00 MHDA- 2017/07/04 06:00 CRDT- 2016/11/16 06:00 PHST- 2016/05/08 00:00 [received] PHST- 2016/09/18 00:00 [revised] PHST- 2016/11/05 00:00 [accepted] PHST- 2016/11/16 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] PHST- 2016/11/16 06:00 [entrez] AID - S0378-8741(16)31750-0 [pii] AID - 10.1016/j.jep.2016.11.014 [doi] PST - ppublish SO - J Ethnopharmacol. 2017 Jan 4;195:173-181. doi: 10.1016/j.jep.2016.11.014. Epub 2016 Nov 11.