Abstract
Podocytes injury was a crucial factor resulting in diabetic nephropathy (DN). Erzhi formula extract (EZF) was a clinical effective Chinese medicine on DN, but its mechanism was unclear. In this study, the main compounds of EZF and their pharmacokinetics in rat were detected by HPLC-MS/MS. And then, blood glucose, urine protein, renal index, renal microstructural (HE/PAS staining), inflammatory factors (IL-β, TNF-α, IL-6), and protein/mRNA expression related to the function of podocyte (CD2AP and Podocin) in DN rats were investigated after the oral administration of EZF. The concentrations of specnuezhenide and wedelolactone in rat kidney were 7.19 and 0.057 mg/kg, respectively. The Tmax of specnuezhenide and wedelolactone were 2.0 and 1.50 h, respectively. Their Cmax were, respectively, 30.24 ± 2.68 and 6.39 ± 0.05 μg/L. Their AUC(0-∞) were 123.30 ± 2.68 and 16.56 ± 0.98 μg/L⁎h, respectively. Compared with the model group, the blood glucose and the 24-hour urinary protein were significantly decreased (P < 0.05) after 16 weeks' treatment of EZF. The expressions of Podocin and CD2AP protein/mRNA were increased (P < 0. 05). The deteriorate of glomerular morphology was alleviated under the treatment of EZF. EZF prominently decreased the levels of inflammatory factors (P < 0.05). MDA was significantly decreased (P < 0.05) with the significant increase of SOD activity (P < 0.05) in EZF groups. All the results proved that EZF repaired glomerular mesangial matrix, protected renal tubule, and improved renal function in DN rats by upregulating the expression of Podocin and CD2AP protein/mRNA in podocytes.
Highlights
In recent years, effective monomers or extracts from natural plants have been widely applied to the treatment of diabetic nephropathy (DN) [1,2,3]
All the results proved that EZF repaired glomerular mesangial matrix, protected renal tubule, and improved renal function in DN rats by upregulating the expression of Podocin and CD2AP protein/mRNA in podocytes
The polyclonal antibody of rabbit CD2AP was provided by Beijing Boosen biological (G3828, Bioss Antibodies, China); TRIzol Reagent was provided by Life Technologies (50175111, Life Technologies, USA); M-MLV reverse transcription kit was obtained from American Invitrogen Company (RP1105, Invitrogen Co., Ltd., USA)
Summary
Effective monomers or extracts from natural plants have been widely applied to the treatment of diabetic nephropathy (DN) [1,2,3]. Erzhi formula extract (EZF) contained lots of active compounds such as specnuezhenide, wedelolactone, oleanolic acid, acetyl oleanolic acid, and ursolic acid [6, 7]. Among these compounds, oleanolic acid ameliorated DN and protected renal microstructural by reducing oxidative stress and endoplasmic reticulum stress in type II diabetic rats [8,9,10,11]. By replicating the DN in rats, the effects of EZF on blood glucose, proteinuria, renal index, pathological changes of renal tissue, expression of Podocin/CD2AP protein and mRNA, the IL-β, TNF-α, IL6, and MDA levels, and SOD activity in renal tissue were evaluated. We described the mechanism of EZF in treating and reversing the DN
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
