Browsing by Author "Elekofehinti OO"

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    Activation of NRF2/HO-1 Pathway by aqueous methanolic leaf extract of Triclisia gilletii and selected identified compounds in Triclisia gilletii, modulates crystal binding genes (CD44/OPN) in Ethane-1,2-diol-induced nephrolithic rats
    (2021) Olayeriju OS; Elekofehinti OO; Olaleye MT; Akindahunsi AA
    Background Moonseed vine (Triclisia gilletii Staner) a member of the Menispermaceae family, has been previously investigated and reported in our laboratory to exhibit antilithiatic potentials against ethane-1,2-diol induced nephrolithiasis. However, the mechanism underlying its action is not clear. Purpose Mechanism of action of aqueous methanolic leaf extact of Triclisia gilletii (TGAMLE 100 mg/kg) in comparison with compounds identified in TGAMLE (Quercetin (20 mg/kg), oleanolic acid (10 mg/kg), stigmasterol (20 mg/kg), and sitosterol (20 mg/kg)) was investigated against ethane-1,2-diol administered rats. Methods The mRNA expression of antioxidant marker genes (nuclear factor erythroid- 2 – related factor- 2 (NRF2) and Heme oxygenase-1 (HO-1)) and crystal binding genes (CD44 and osteopontin (OPN)) were assessed using RT-PCR. Results Ethane-1,2-diol administration down-regulated antioxidant marker genes (NRF2 and HO-1) and up-regulated mRNA expression of CD44 with no significant difference in OPN when compared with control. TGAMLE and its derived compounds significantly activated the NRF2/HO-1 pathway by up-regulating its expression and modify crystal binding molecules (CD44/OPN). Overall, the additive effects of the compounds present in the extract revealed a better efficacy in attenuating NRF2/HO-1 pathway as well as the expression of crystal binding molecules. Conclusion The present study concludes the nephro-protective effect and underlying mechanism of TGAMLE against ethane-1,2-diol exposed rats and suggests that TGAMLE or compounds in TGAMLE could be an alternative agent against kidney stones.
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    Co-administration of metformin and gallic acid modulates JAK/STAT signaling pathway and glutathione metabolism in fructose-fed streptozotocin diabetic Rats
    (2022) Elekofehinti OO; Ariyo EO; Iwaloye O; Obafemi TO
    Background Incidence of diabetes Mellitus (DM) is on the rise with each passing year in spite of available therapies in the management of DM. Metformin, a standard antidiabetic drug, and gallic acid (GA) are some of the compounds with established antidiabetic properties. However, there is dearth of information on their combination on JAK/STAT signaling pathway and glutathione metabolism in diabetic model. This study investigated the combined effect of metformin and GA on diabetic rats. Methods Forty male wistar rats were divided into 5 groups viz: diabetic control, normal control, Metformin (100 mg/kg), GA (100 mg/kg) and GA (100 mg/kg) + Metformin (100 mg/kg). Diabetes was induced by administration of 10% fructose for 14 days followed by injection of streptozotocin (40 mg/kg). The therapy was administered for a total of 21 days. The pancreatic mRNA expression of antioxidant genes (glutamate cysteine ligase catalytic subunits (GCLC), glutamate cysteine ligase modifier subunits (GCLM) and Glutathione Synthetase (GSS), inflammatory genes (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and proteins of the Janus Kinase/ Signal Transducer and Activator of Transcription pathway (Janus Kinase (JAK), Signal Transducer and Activator of Transcription (STAT), were quantified using reverse-transcriptase polymerase chain reaction (RT-PCR). Metformin and GA were also docked with Insulin, GSS, and Janus Kinase 2 (JAK2) to determine their binding affinity. Results Rats treated with co-administration of GA and metformin significantly (p < 0.05) decreased fasting blood glucose level in comparison with groups treated with gallic acid only and metformin only. The gene expression analysis shows that co-administering metformin and gallic acid protects the pancreas of STZ-induced rats by increasing glutathione production, alleviating inflammation (IL-1, IL-6, IFN-), and modulating the JAK/STAT signaling pathway though upregulation of GCLC, GCLM, GSS mRNA expression and IL-1, IL-6, TNF-α, JAK2, STAT3 and STA5 mRNA expression. Conclusion This study showed that the combination therapy of metformin and GA modulated JAK/STAT pathway mediated by the cytokines, and replenished glutathione in the pancreas of diabetic rats.