Mitigation of letrozole induced polycystic ovarian syndrome associated inflammatory response and endocrinal dysfunction by Vitex negundo seeds.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women that necessitates effective and safe treatment alternatives. This study aimed to evaluate the therapeutic efficacy of Vitex negundo seed in a letrozole-induced PCOS rat model. RESULTS: Findings of the present study demonstrated that administration of hydro-ethanolic extract of Vitex negundo (VNE) effectively restored endocrino-metabolic imbalances associated with PCOS, along with correction of antioxidant enzymes level, proinflammatory cytokines, and apoptotic bio-markers. LC-MS analysis confirmed the presence of cinnamic acid, plumbagin and nigundin B as the prominent phytochemicals in VNE. The observed beneficial effects could be attributed to the active compounds in Vitex negundo extract, which exhibited hypoglycemic, hypolipidemic, and catabolic effects on body weight. Additionally, the extract contributed to hormonal balance regulation by modulating the steroidogenic enzymes, specifically by tuning gonadotropins level and correcting the LH:FSH ratio, through the modulation of ERα signalling and downregulation of NR3C4 expression. The antioxidant properties of phytochemicals in Vitex negundo seed were apparent through the correction of SOD and catalase activity. While it's anti-inflammatory and antiapoptotic action were associated with the regulation of mRNA expression of TNF-α, IL-6, BAX, Bcl2. Molecular docking study further indicated the molecular interaction of above mentioned active phytocompounds of VNE with ERα, NR3C4 and with TNFα that plays a critical mechanistic gateway to the regulation of hormone signalling as well as synchronizing the inflammation cascade. Furthermore, the histomorphological improvement of the ovaries supported the ameliorative action of Vitex negundo extract in the letrozole-induced PCOS model. CONCLUSIONS: This study indicates the potential of Vitex negundo seed as a multifaceted therapeutic option for PCOS. VNE offers a holistic strategy for PCOS with antiandrogenic, anti-inflammatory, and antioxidant properties, driven by its major compounds like cinnamic acid, plumbagine, and nigundin B.

n-Butanol fraction of moringa seed attenuates arsenic intoxication by regulating the uterine inflammatory and apoptotic pathways.

The adverse effects of arsenic-chelating drugs make it essential to replace invasive chelating therapy with non-invasive oral therapy for arsenic poisoning. The goal of the current investigation was to determine whether the uterine damage caused by arsenization could be repaired by the n-butanol fraction of Moringa oleifera seed (NB). The rats were orally administered with arsenic (10 mg/kg BW) for the initial 8 days, followed by NB (50 mg/kg) for the next 8 days without arsenic. The probable existence of different components in NB was evaluated by HPLC-MS. Pro and anti-inflammatory indicators were assessed by RT-PCR and western blot. ESR-α was detected via immunostaining. Arsenic-exposed rats had significantly increased lipid peroxidation and decreased antioxidant enzyme activity, which were markedly reduced after NB treatment. Weaker ESR-α expression and distorted uterine histomorphology following arsenication were retrieved significantly by NB. Meaningful restoration by NB was also achieved for altered mRNA and protein expression of various inflammatory and apoptotic indicators. Molecular interaction predicted that glucomoringin and methyl glucosinolate of moringa interact with the catalytic site of caspase-3 in a way that limits its activity. However, NB was successful in restoring the arsenic-mediated uterine hypofunction. The glucomoringin and methyl glucosinolate present in n-butanol fraction may play a critical role in limiting apoptotic event in the arsenicated uterus.