Abstract
Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. The leaves of RG (LR) is an important vegetative organ of the plant. At present, the total glycosides of RG (TLR) were extracted from RG, and developed a national second class of new drugs to the Dihuangye total glycoside capsule (DTG). Additionally, DTG has the effect of nourishing yin and tonifying kidney, promoting blood circulation and blood cooling, and applicable to chronic glomerulonephritis mild to Qi and Yin Deficiency. Moreover, diabetic nephropathy (DN) rats model was induced by intraperitoneal injection of a small dose of streptozotocin (45 mg/kg) and high-fat diet and plus 5% glucose drinking water. Over 15 days, after oral administration TLR and DTG in DN rats, samples from serum, urine and kidney were collected for biochemical indicators measurements, pathological analysis, western blotting and metabolomics. Therefore, the analytical results of biochemical indicators, histopathological observations and western blotting showed that TLR and DTG exhibited a significant effect in renal protection. And 27 endogenous metabolites (12 in serum and 15 in urine) could be tentatively identified in the process of DN in rats using metabolomics method. Those endogenous metabolites were chiefly involved in sphingolipid metabolism; pentose, glucuronate interconversion; terpenoid backbone biosynthesis; purine metabolism and retinol metabolism. After drug intervention, these endogenous metabolites turned back to normal level some extent (P < 0.05). Furthermore, TLR and DTG prevent high glucose-induced glomerular mesangial cells (GMCs) by inhibiting TGF-β1 and Wnt/β-catenin signaling pathway, providing a powerful supports to develop a new therapeutic agent for DN. This study paved the way for further exploration of the pathogenesis of DN, early diagnosis and the evaluation of curative effect.
Highlights
Traditional Chinese medicine (TCM) with multi-components and multi-targets has been used in clinical for over 4000 years in China due to its efficacy and low side-effects (Yokozawa et al, 1986)
serum urea nitrogen (BUN) reagent kit, low density lipoprotein (LDL) reagent kit, total cholesterol (T-CHO) reagent kit, TG reagent kit, serum creatinine (Scr) reagent kit, urine protein (UP) reagent kit, serum β2-microglobulin (β2-MG) reagent kit were bought from Nanjing Jiancheng Bioengineering Institute (Nanjing, China)
Compared with diabetic nephropathy (DN) model group, the levels of creatinine, urea nitrogen, 24-h urinary protein and renal histopathology were significantly improved in the administration groups, and the expression levels of Wnt4, β-catenin and TGF-β1 protein was significantly decreased, especially total glycosides of RG (TLR) treatment
Summary
Traditional Chinese medicine (TCM) with multi-components and multi-targets has been used in clinical for over 4000 years in China due to its efficacy and low side-effects (Yokozawa et al, 1986). LR is officially listed in the Beijing standard of Chinese herbal medicines, and it has the effect of heat-clearing, promoting blood circulation, supplementing Qi and nourishing yin and tonifying kidney (Beijing Municipal Health Bureau, 1988). The major active components of DTG is the phenylethanoid glycosides, which is extracted from LR, and phenylethanoid glycosides are a class of natural glycosides containing hydroxyl groups, methoxy substituted phenethyl or cinnamoyl groups, usually containing β-glucose as the parent nucleus, and are widely present in dicotyledonous plants (Jiménez and Riguera, 1994). DTG can increased glomerular permeability and reduced glomerular hyperfiltration, reducing proteinuria and the protection of renal function (Shen et al, 2010)
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