Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish.
Female
Humans
Animals
Cricetinae
Polycystic Ovary Syndrome
/ pathology
Cricetulus
Zebrafish
/ metabolism
Reactive Oxygen Species
/ metabolism
Antioxidants
/ metabolism
CHO Cells
Molecular Docking Simulation
Signal Transduction
Testosterone
Oxidative Stress
Guanine Nucleotide Exchange Factors
/ genetics
Death Domain Receptor Signaling Adaptor Proteins
/ genetics
apoptosis
nimbin
polycystic ovarian syndrome
testosterone
zebrafish
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
26
09
2022
received:
17
08
2022
accepted:
16
10
2022
medline:
13
4
2023
pubmed:
1
12
2022
entrez:
30
11
2022
Statut:
ppublish
Résumé
Polycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi-natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti-androgenic property of N2 on testosterone-induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone-induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in-silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in-vitro and in-vivo and altered the expression of PCOS key genes.
Substances chimiques
nimbin
N4CTG7K9IU
Reactive Oxygen Species
0
Antioxidants
0
Testosterone
3XMK78S47O
DENND1A protein, human
0
Guanine Nucleotide Exchange Factors
0
Death Domain Receptor Signaling Adaptor Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1449-1461Subventions
Organisme : DST-FIST
ID : SR/FST/CST266/2015(c)
Organisme : Science and Engineering Research Board
ID : SERB-SRG/2019/001133
Informations de copyright
© 2022 John Wiley & Sons Ltd.
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