43 - The beneficial potential of polyherbal formulation in protecting against streptozotocin-nicotinamide-induced cardiomyopathy through Nrf2-regulated anti-inflammation, anti-oxidant and anti-fibrosis in C57BL/6J mice

Abstract

The study investigates the effects of methanolic extracts of Terminalia paniculata(MTP), Piper nigrum (MPN), Gymnema sylvetsris (MGS)and a combination of their poly herbalformulation (PHF) againststreptozotocin (STZ)-nicotinamide (NAD)-induced diabetic cardiomyopathy (DCM) in C57BL/6J mice. MTP (200 mg/kg body weight (BW)), MPN (200 mg/kg BW), MGS (100 mg/kg BW) and PHF (500 mg/kg BW) were administered orally for 45 days to diabetic mice, and their biochemical parameters and cardiac markers (AST, ALT, LDH, troponin and cardiotroponin) as well as antioxidant profile were estimated. Heart antioxidant mRNA expressions, such as SOD, CAT, GpX, GST, GR, Nrf2, NF-kB, GCLC, GCLM by RT-PCR and their protein expressions by western blot were observed along with histopathological changes in the aortain control and experimental mice, and these effects were compared with gliclazide. Treatment with MTP, MPN, MGS, PHF and gliclazide for 45 days resulted in significant modulations in the levels of biochemical parameters, cardiac marker enzymes and oxidative markers. We also found PHF effectively altered the expressions of mRNA levels and protein levels of antioxidants, anti-inflammatory and anti-fibrosis in diabetic mice. The histopathological alteration of aorta reduced most of the pathological alterations with PHF treatment. The effect of PHF was more pronounced than that of the MTP, MPN, and MGS and brought back all the parameters to nearnormal. Thus, the present findings suggest that this combination of PHF may be considered as an effective therapeutic agent for the treatment of DCM by regulation of Nrf2-mediated oxidative stress, anti-inflammatory and anti-fibrosis markers, and restoration of cardiac damage.