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Biography

Mennatallah A. Ali is currently a Lecturer at Pharmacology & Therapeutics Department, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria since 2008. I obtained my Ph.D. degree in Pharmacology from Faculty of Pharmacy, Cairo University in 2015. The Master degree of Pharmacology and Experimental Therapeutics was obtained from Medical Research Institute, Alexandria University in 2012. My Bachelor degree in Pharmaceutical Sciences was from Faculty of Pharmacy, Ain Shams University in 2007. I worked as a community pharmacist since her graduation as I am keen on patient counseling and advising. My research motivation is to explore the underlying molecular mechanisms that potentiate the therapeutic beneficial effects of any antidiabetic agent and to discover any new compounds that can be used as adjuvants to treat diabetes mellitus.

Abstract

There has been a recent explosion of interest in the notion that metaflammation and activation of the innate immune system are closely involved in the pathogenesis of type 2 diabetes mellitus (T2DM).
Hence, we assessed the potential antidiabetic effect of leflunomide (10 mg/kg every other day) and sulfasalazine (100 mg/kg/day), in a comparison with pioglitazone (5 mg/kg/day) as a reference drug, using neonatal STZ animal model. All treatments were gavaged for 8 weeks. Leflunomide and
sulfasalazine lowered significantly the n5-STZ-induced elevation in body weight, blood glucose, and HOMA index. Moreover, they amended successfully serum lipid profile and increased serum insulin level. Additionally, leflunomide and sulfasalazine showed antioxidant (Nrf2, keap1), antiinflammatory (NF-κB, TNF-α) and anti-apoptotic (caspase-3, cytochrome c) capabilities. Both drugs showed comparable effects on almost all the parameters, however, pioglitazone effect was superior to both. On the molecular level, drugs have improved the hepatic insulin (glucokinase, pinsulin receptor, p-Akt, IRS-1), lipogenic (SREBP-1c, PGC-1α) and Wnt/β-catenin (p-GSK-3β, β- catenin, FOXO) signaling pathways. All treatments also showed decreases in the hepatic 8-oxoguanine content. The present results clearly proved that altered immune responses play a key role in T2DM and that the immunomodulatory drugs can gain insights as prospective antidiabetic
agents.