Synergistic action of carvedilol and clomiphene in mitigating the behavioral phenotypes of letrozole-model of PCOS rats by modulating the NRF2/NFKB pathway.

INTRODUCTION: Psychiatric and cognitive impairment has been observed in premenopausal women with a hormonal disorder called polycystic ovary syndrome (PCOS). This study aimed to explore the possibility of combining pharmacological agents: Carvedilol and Clomiphene citrate, with antiestrogenic, antioxidant and anti-inflammatory properties in letrozole-induced PCOS rats. METHODS: PCOS was induced in rats by the administration of letrozole (1 mg/kg) daily for 21 days. They were subsequently divided into four groups, each receiving either the vehicle or Clomiphene citrate (1 mg/kg) or Carvedilol or a combination of Clomiphene citrate and Carvedilol, respectively from days 22-36. Neurobehavioral studies were conducted on day 35 (Elevated plus maze and Y maze) and day 36 (Novel object recognition). The serum levels of the antioxidants Superoxide dismutase, Catalase, Interleukin 1B (IL-1B), and the gene expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), Nuclear Factor k-Beta (NFKB), and acetylcholine esterase in the frontal brain homogenate was determined. RESULT: Both Carvedilol and the combination therapy reversed the anxiety-like behavior, while Clomiphene citrate and the combination therapy ameliorated the spatial and non-spatial memory impairment observed in PCOS rats. Carvedilol, Clomiphene citrate, and the combination therapy increased the serum concentration of SOD and Catalase and decreased the serum concentration of IL-1B. The combination therapy up-regulated the NRF-2, NFKB, and acetylcholine esterase gene expression. CONCLUSION: Study showed that the combination of carvedilol and clomiphene citrate has anxiolytic potential and improved cognitive functions in PCOS rats. This might have been achieved by carvedilol and clomiphene citrate's ability to modulate the cholinergic system and the Nrf2 pathway while downregulating the NFκB signaling pathway.

Long-term spatial memory and morphological changes in hippocampus of Wistar rats exposed to smoke from Carica papaya leaves

Objective:To investigate the effects of smoking of dried leaves of Carica papaya (pawpaw) based on ethnopharmacological information which indicated that smoking of papaya leaves could influence motor performance and learning. Methods:Twenty-four rats were used for the study, and were grouped into four groups. Groups 1 served as the control (not exposed to papaya leaves smoke), while Groups 2, 3 and 4 were exposed to smoke from 6.25 g, 12.50 g and 18.75 g of dry pawpaw leaves respectively in a smoking chamber twice daily for 21 d with each exposure lasting for 3 min. Lastly, hippocampus was harvested in each group for histological study. Results: The results showed that there were significant (P Conclusions: In conclusion, the findings from this study has demonstrated that smoking of papaya leaves has the ability to maintain an intact long-term spatial memory at all doses but retrieving such memory is faster with the low and medium dosages.