silver nanoparticles modulate S/JAK/STAT and P13K/Akt/PTEN signalling pathways in the kidney of streptozotocin-induced diabetic rats.

Objectives: Diabetes nephropathy (DN) is one of the complications of diabetes mellitus (DM) marked by gradual progressive loss of renal function. SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways are among the chain of interactions implicated in the onset, progression and pathology of DN. (bitter melon) is often used in folk medicine as therapy for DM due to its hypoglycemic properties. This study was designed to evaluate silver nanoparticles' therapeutic effect on DN-induced by streptozotocin (STZ) in Wistar rats.

Methods: The nanoparticles used was synthesized using the filtrate from the plant methanolic extract added to 1 mM concentration of aqueous silver nitrate. DM was induced in Wistar rats by intraperitoneal injection of STZ (65 mg/kg). The animals' treatment groups were divided into; Diabetic control (65 mg/kg STZ), Control, and groups treated with silver nitrate (10 mg/kg), nanoparticles (50 mg/kg), metformin (100 mg/kg), and plant extract (100 mg/kg). Treatment was terminated after 11 days. RT-PCR determined renal mRNA expression of Akt, PI3k, PTEN, TGF-β, JAK2, STAT3, STAT5, SOCS3, SOCS4 and glucokinase (GCK). Consequently, characterized compounds from identified from literatures were docked with PI3K, JAK2 and TGF-β and STAT3 to retrieve potential hits.

Results: Oral administration of nanoparticles (50 mg/kg) to STZ-induced diabetic untreated rats significantly (( 0.05) down-regulated the mRNA expression of Akt, PI3k, TGF-β, JAK2, STAT3 and upregulated the mRNA expression of PTEN, SOCS3 and SOCS4, thus establishing the role of nanoparticles in alleviating DN in diabetic rats. Additionally, there was a significant up-regulation of glucose metabolizing gene (glucokinase) upon administering nanoparticles. Molecular docking results showed 12 compounds from bitter melon with docking score ranging from -6.114 kcal/mol to -8.221 kcal/mol that are likely to exert anti-diabetic properties.

Conclusion: Observation drawn from this study suggests that nanoparticles ameliorate DN through regulation of SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways.