β-N-Oxalyl-L-α,β-diaminopropionic acid from Panax notoginseng plays a major role in the treatment of type 2 diabetic nephropathy

Abstract

Background: Diabetic nephropathy (DN) is one of the most serious and dangerous chronic complications of diabetes mellitus.Panax notoginseng has been widely used with great efficacy in the long-term treatment of kidney disease. However, the mechanism by which it exerts its effects has not been fully elucidated.

Aim: We sought to identify the major components ofPanax notoginseng that are effective in reducing the symptoms of DN in vitro and in vivo.

Methods: Inhibition of cell proliferation and collagen secretion were used to screen the ten most highly concentrated components ofPanax notoginseng. The STZ-induced DN rat model on a high-fat-high-glucose diet was used to investigate the renal protective effect of Panax notoginseng and dencichine and their underlying molecular mechanisms.

Results: Among the ten components analysed, dencichine (β-N-oxalyl-L-α,β-diaminopropionic acid) was the most protective against DN. Dencichine andPanax notoginseng attenuated glucose and lipid metabolic disorders in STZ-induced DN rats on a high-fat-high-glucose diet. In the untreated DN rats, we observed albuminuria, renal failure, and pathological changes. However, treatment with dencichine and Panax notoginseng alleviated these symptoms. We also observed that dencichine suppressed the expression of TGF-β1 and Smad2/3, which mediates mesangial cell proliferation and extracellular matrix (ECM) accumulation in the glomerulus, and enhanced the expression of Smad7, the endogenous inhibitor of the TGF-β1/Smad signalling pathway.

Conclusion: From these results, we concluded that dencichine is the main compound inPanax notoginseng that is responsible for alleviating renal injury in the experimental DN model. Its mechanism may be related to the reduction of the deposition of ECM in glomeruli and inhibition of the epithelial mesenchymal transformation (EMT) by inhibition of the TGF-β1/Smad signalling pathway.

Keywords: Dencichine; Diabetic nephropathy; Extracellular matrix; Panax notoginseng; TGF-β1/Smad signalling pathway; β-N-oxalyl-L-α,β-diaminopropionic acid.