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

Abstract

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.

Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model

“…This finding is crucial, as CD31 is a key marker for vascular dynamics in PCOS [ 34 ]. The research not only corroborates existing literature on exosomes’ regulatory roles in cellular signaling [ 35 ] but also distinctively highlights their specific impact on angiogenic processes within PCOS [ 36 ]. By demonstrating how BMSCs-Exo can target and potentially reverse abnormal angiogenic patterns indicated by CD31 expression, the study offers novel insight into PCOS pathophysiology.…”

Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic Fungus Aphanomyces invadans

“…The cancer cell proliferation inhibitory activity was calculated through the MTT assay on MCF-7 cells and the GE18 peptide (24 and 48 h exposure challenge) [ 24 , 25 ]. The standard protocol, as mentioned in Section 3.2.2 , has been followed.…”

Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish

“…The lipoxidation levels were quantified by their fluorescence intensity. The fluorescence intensity was assessed using Image J software [ 24 , 25 , 26 , 27 ].…”