ABSTRACT
Diabetes has emerged as one the leading detrimental factors for human life expectancy worldwide. The disease is mainly considered as outcome of dysregulation in glucose metabolism, resulting in consistent high glucose concentration in blood. At initial stages, the diabetes particularly type 2 diabetes, is manageable by lifestyle interventions such as regular physical activity and diet with less carbohydrates. However, in advance stage, regular intake of external insulin dose and medicines like metformin are recommended. The long-term consumption of metformin is associated with several side effects such as nausea, vomiting, diarrhoea, lectic acidosis etc., In this scenario, several plant-based medicines have shown promising potential for the prevention and treatment of diabetes. Berberine is the bioactive compound present in the different plant parts of berberis family. Biochemical studies have shown that berberine improve insulin sensitivity and insulin secretion. Additionally, berberine induces glucose metabolism by activating AMPK signaling and inhibition of inflammation. A series of studies have demonstrated the antidiabetic potential of berberine at in vitro, pre-clinical and clinical trials. This review provides comprehensive details of preventive and therapeutic potential of berberine against diabetes.
ABSTRACT
Nephropathy has become the most common reason for end-stage renal disease worldwide. The progression of end-stage renal disease occurs caused by decreased glomerular filtration rate, damage to capillaries in renal glomeruli or a higher risk of cardiovascular morbidity and mortality in diabetic patients. The involvement of mechanism in the development of nephropathy via generation of AGEs, the elevation of growth factors, altered hemodynamic and metabolic factors, inflammatory mediators, oxidative stress and dyslipidaemia. The prevalence of chronic kidney disease in India will rise from 3.7 million in 1990 to 7.63 million in 2020 becoming the main cause of mortality and morbidity. The pathogenesis of nephropathy mediates by various molecules that cause alterations in the structure and function of the kidney like growth factors, endothelins, transforming growth factor (TGF-ß), and Angiotensin-converting enzymes (ACE), fibronectin and proinflammatory cytokines, mast cells and dyslipidemia. Growth factors like VEGF, IGFs, PDGF, EGFR and TGF-ß contribute to excessive extracellular matrix accumulation, together with thickening of the glomerular and tubular basement membranes and an increase in the mesangial matrix, leading to glomerulosclerosis and tubulointerstitial fibrosis. Oxidative stress and inflammation factors like TNF-α, IL-1 and IL-6 are hypothesized to play a role in the development of pathological changes in nephropathy like renal hyperfiltration and hypertrophy, thickening of the glomerular basement membrane (GBM), glomerular lesion and tubulointerstitial fibrosis. Dyslipidemia is involved in the progression of nephropathy by impaired action of lipoprotein lipase, lecithincholesterol acyltransferase (LCAT) and cholesteryl ester transferase protein (CETP) resulting in the increased level of LDL-C, Triglyceride level and decrease HDL-C that enhance macrophage infiltration, excessive extracellular matrix production and accelerate inflammation with the development of proteinuria. Interruption in the RAS, oxidative stress and dyslipidemia have yielded much better results in terms of reno-protection and progression of nephropathy. In this review, we would focus on various factors that have been shown to contribute to renal injury in many experimental models of nephropathy.
