PMID- 34707679
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211030
IS  - 1741-427X (Print)
IS  - 1741-4288 (Electronic)
IS  - 1741-427X (Linking)
VI  - 2021
DP  - 2021
TI  - Hyperin Alleviates Triptolide-Induced Ovarian Granulosa Cell Injury by Regulating 
      AKT/TSC1/mTORC1 Signaling.
PG  - 9399261
LID - 10.1155/2021/9399261 [doi]
LID - 9399261
AB  - Premature ovarian insufficiency (POI) is characterized by the loss of ovarian 
      function before 40 years of age and affects approximately 1% of women worldwide. 
      Caragana sinica is a traditional Miao (a Chinese ethnic minority) medicine that 
      improves ovarian function and follicular development. In the present study, we 
      aimed to investigate the effect of active ingredients of C. sinica on POI and 
      determine underlying mechanisms. Herein, the chemical composition of the C. 
      sinica compound was analyzed using ultra-high-performance liquid chromatography, 
      which identified hyperin (HR) as one of the main ingredients in C. sinica. Then, 
      interaction targets of HR and POI were predicted and analyzed using network 
      pharmacology and bioinformatics. The effect of HR on triptolide (TP)-induced 
      granulosa cell injury was evaluated, and the underlying mechanism was explored 
      based on bioinformatic results. A total of 100 interaction targets for POI and HR 
      were obtained. The protein-protein interaction network of identified interaction 
      targets emphasized the topological importance of AKT1. Kyoto Encyclopedia of 
      Genes and Genomes (KEGG) analysis revealed that HR might regulate POI by 
      modulating the mechanistic target of rapamycin (mTOR) signaling pathway. In 
      addition, the KEGG graph of the mTOR signaling pathway revealed that AKT 
      phosphorylation inhibits the TSC1/2, while TSC1/2 activation inhibits the 
      expression of mTORC1. The fundamental experiment revealed that HR increased 
      proliferation, progesterone receptor levels, and estradiol levels decreased by TP 
      in KGN cells. Additionally, HR alleviated TP-induced apoptosis and G1/G1 phase 
      arrest in KGN cells. Western blotting demonstrated that HR increased the 
      phosphorylation of AKT and mTORC1 and decreased TSC1 expression in TP-induced KGN 
      cells. Collectively, our findings revealed that HR alleviates TP-induced 
      granulosa cell injury by regulating AKT/TSC1/mTORC1 signaling, providing insight 
      into the treatment of POI.
CI  - Copyright (c) 2021 Fang You et al.
FAU - You, Fang
AU  - You F
AD  - The Second Clinical College, Guizhou University of Chinese Medicine, Guiyang 
      550000, China.
FAU - Cao, Junyan
AU  - Cao J
AD  - The Second Clinical College, Guizhou University of Chinese Medicine, Guiyang 
      550000, China.
FAU - Cheng, Li
AU  - Cheng L
AD  - The Second Clinical College, Guizhou University of Chinese Medicine, Guiyang 
      550000, China.
FAU - Liu, Xiaogu
AU  - Liu X
AD  - The Second Clinical College, Guizhou University of Chinese Medicine, Guiyang 
      550000, China.
FAU - Zeng, Li
AU  - Zeng L
AUID- ORCID: 0000-0002-9039-6509
AD  - The Second Clinical College, Guizhou University of Chinese Medicine, Guiyang 
      550000, China.
LA  - eng
PT  - Journal Article
DEP - 20211018
PL  - United States
TA  - Evid Based Complement Alternat Med
JT  - Evidence-based complementary and alternative medicine : eCAM
JID - 101215021
PMC - PMC8545507
COIS- All authors declare that they have no conflicts of interest.
EDAT- 2021/10/29 06:00
MHDA- 2021/10/29 06:01
PMCR- 2021/10/18
CRDT- 2021/10/28 06:37
PHST- 2021/07/26 00:00 [received]
PHST- 2021/08/31 00:00 [revised]
PHST- 2021/09/18 00:00 [accepted]
PHST- 2021/10/28 06:37 [entrez]
PHST- 2021/10/29 06:00 [pubmed]
PHST- 2021/10/29 06:01 [medline]
PHST- 2021/10/18 00:00 [pmc-release]
AID - 10.1155/2021/9399261 [doi]
PST - epublish
SO  - Evid Based Complement Alternat Med. 2021 Oct 18;2021:9399261. doi: 
      10.1155/2021/9399261. eCollection 2021.