Pharmacodynamic study of hederacoside C and its derivative on lipopolysaccharide induced acute kidney injury in mice
Objective To synthesize C-28 deglycosylated derivative of hederasaponin C via enzymatic hydrolysis,and to assess their effects on lipopolysaccharide-induced acute kidney injury in mice.Methods Hederasaponin C was hydrolyzed by α-L rhamnosidase,and its derivative were obtained after separation and purification.Male BALB/c mice were injected intraperitoneally with lipopolysaccharide(LPS)to induce glomerulonephritis.Seventy mice were randomly divided into control group,model group,dexamethasone positive drug group,hederasaponin C low and high dose(20,40 mg·kg-1)groups,hederasaponin C derivative low and high dose(20,40 mg·kg-1)groups.10 mice in each group were given the drug 2 h before modeling and 6 h after modeling.Blood samples were collected from the eyeballs 6 h after the last administration.WBC and Neu were counted by automatic biochemical analyzer.The reagent kit method was used to measure the levels of animal serum creatinine(CRE)and urea nitrogen(BUN).The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)in serum and kidney were detected by ELISA.Hematoxylin-eosin(HE)was used to detect pathological changes in renal tissues.Results Compared to the model group,the counts of WBC,Neu,CRE,BUN and TNF-α,IL-6 and IL-1β in serum and kidney tissue of hederasaponin C group and its derivative group were significantly decreased(P＜0.05,0.01,and 0.001),and renal tissue injury was significantly reduced.Compared with hederasaponin C group,the counts of WBC,Neu and BUN in hederasaponin C derivative group significantly decreased at the same dose(P＜0.05,0.01,and 0.001).At low dose,CRE levels in serum and the release of IL-6 and IL-1β in renal tissue were significantly inhibited(P＜0.001).The degree of renal pathological injury was significantly improved at high dose.Conclusion Both hederasaponin C and its C-28 deglycosylation derivative can attenuate LPS-induced renal tissue damage in mice,with the derivative demonstrating enhanced efficacy at equivalent dosages.At the same dose,the efficacy of the C-28 desugarated derivative of hederasaponin C was better than that of hederasaponin C.
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