PMID- 37802816
OWN - NLM
STAT- MEDLINE
DCOM- 20231009
LR  - 20231018
IS  - 1001-5302 (Print)
IS  - 1001-5302 (Linking)
VI  - 48
IP  - 17
DP  - 2023 Sep
TI  - [Qirong Tablets inhibits apoptosis of ovarian granulosa cells via PI3K/Akt/ HIF-1 
      signaling pathway].
PG  - 4774-4781
LID - 10.19540/j.cnki.cjcmm.20230424.501 [doi]
AB  - This study aims to observe the effect and explore the mechanism of Qirong Tablets 
      in the treatment of premature ovarian insufficiency(POI) in mice via the 
      phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible 
      factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly 
      divided into normal group, model group, positive control group, Qirong Tablets 
      low-, medium-and high-dose group. The normal group was intraperitoneally injected 
      with the same amount of normal saline, and the other groups were 
      intraperitoneally injected with cyclophosphamide 120 mg.kg~(-1).d~(-1) once to 
      establish a POI animal model. After the model was successfully established, the 
      low-, medium-and high-dose groups of Qirong Tablets were administered orally with 
      0.6, 1.2, 2.4 mg.kg~(-1).d~(-1) respectively. The positive control group was 
      given 0.22 mg.kg~(-1).d~(-1) Clementine Tablets by intragastric administration, 
      and the normal group and model group were given intragastric administration with 
      the same amount of normal saline, and the treatment was 28 d as a course of 
      treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was 
      employed to measure the levels of estradiol(E_2), follicle-stimulating 
      hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in 
      peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian 
      tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and 
      Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), 
      Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with 
      the normal group, the modeling of POI caused loose or destroyed ovarian tissue 
      with vacuolar structures, edema and fibrosis in the ovarian interstitium, 
      disordered or loose arrangement of granulosa cells, and reduced normal follicles. 
      Compared with the model group, drug interventions restored the ovarian tissue and 
      follicles at all the development stages and reduced atretic follicles. Compared 
      with the normal group, the modeling of POI lowered the serum level of E_2 and 
      AMH(P<0.01), and elevated the level of FSH and LH(P<0.01). Compared with 
      the model group, high-dose Qirong Tablets elevated the levels of E_2 and 
      AMH(P<0.05), and lowered the levels of FSH and LH(P<0.05). Compared with 
      the normal group, the modeling of POI up-regulated the protein levels of PI3K, 
      Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in 
      the ovarian tissue(P<0.01). Compared with the model group, low-, medium-, and 
      high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, 
      Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the 
      ovarian tissue(P<0.05). In conclusion, Qirong Tablets can up-regulate the 
      expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. 
      Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, 
      thereby delaying ovarian aging, improving reproductive axis function, and 
      strengthening ovarian reserve capacity, which may be associated with the 
      inhibition of PI3K/Akt/HIF-1 pathway.
FAU - Nan, Nan
AU  - Nan N
AD  - Ningxia Medical University Yinchuan 750000, China.
FAU - DU, Xiao-Li
AU  - DU XL
AD  - Ningxia Medical University Yinchuan 750000, China Ningxia Key Laboratory of 
      Integrated Traditional Chinese and Western Medicine for Prevention and Treatment 
      of Regional Diseases with High Incidence, Key Laboratory of Ningxia Minority 
      Medicine Modernization of Ministry of Education Yinchuan 750000, China.
FAU - Chen, Miao
AU  - Chen M
AD  - Ningxia Medical University Yinchuan 750000, China.
FAU - Luo, Jia-Qi
AU  - Luo JQ
AD  - Ningxia Medical University Yinchuan 750000, China.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhongguo Zhong Yao Za Zhi
JT  - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese 
      materia medica
JID - 8913656
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (Saline Solution)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Female
MH  - Animals
MH  - *Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - bcl-2-Associated X Protein
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Caspase 3/metabolism
MH  - Saline Solution/pharmacology/therapeutic use
MH  - Signal Transduction
MH  - Granulosa Cells
MH  - *Primary Ovarian Insufficiency/drug therapy
MH  - Follicle Stimulating Hormone/pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Apoptosis
OTO - NOTNLM
OT  - PI3K/Akt/HIF-1
OT  - Qirong Tablets
OT  - mice
OT  - ovarian tissue
OT  - premature ovarian insufficiency
EDAT- 2023/10/07 00:41
MHDA- 2023/10/09 06:41
CRDT- 2023/10/06 22:03
PHST- 2023/10/09 06:41 [medline]
PHST- 2023/10/07 00:41 [pubmed]
PHST- 2023/10/06 22:03 [entrez]
AID - 10.19540/j.cnki.cjcmm.20230424.501 [doi]
PST - ppublish
SO  - Zhongguo Zhong Yao Za Zhi. 2023 Sep;48(17):4774-4781. doi: 
      10.19540/j.cnki.cjcmm.20230424.501.