title: Protective effects and mechanisms investigation of Kuntai capsule on the ovarian function of a novel model with accelerated aging ovaries.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and Gynecology, Hubei Province, Maternity and Child Health Care Hospital, Wuhan, Hubei 430030, PR China. Electronic address: 416234083@qq.com.
authors.forename: Liangyan
authors.initials: L
authors.lastname: Shi
authors.affiliation: Maternal and Child Health Hospital of Zigong, Sichuan 643000, China. Electronic address: 124075212@aa.com.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Lai
authors.affiliation: 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.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Aiyue
authors.initials: A
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002214:Capsules; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D019570:Inhalation Exposure; D008810:Mice, Inbred C57BL; D053580:Muscle Strength; D009929:Organ Size; D006080:Ovarian Follicle / Q000187:drug effects / Q000648:ultrastructure; D065851:Ovarian Reserve / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D010126:Ozone / Q000633:toxicity; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013480:Superovulation; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D054304:Anti-Mullerian Hormone; D000975:Antioxidants; D002214:Capsules; D004365:Drugs, Chinese Herbal; D010126:Ozone; D019253:Proto-Oncogene Proteins c-bcl-2; D013482:Superoxide Dismutase; D051028:bcl-2-Associated X Protein; D000099156:Superoxide Dismutase 2; C494827:Bax protein, mouse; C000620717:kuntai capsule; C052617:Bcl2 protein, mouse
keywords: Accelerated aging ovary; Estradiol (PubChem CID:5757); Kuntai capsule; Model; Ovarian function; Progesterone (PubChem CID:5994)