Long Dan Xie Gan Formula Granule Promotes Pro-Inflammatory Cytokine Expression in Female Guinea Pigs with Recurrent Genital Herpes

Objective To explore the effects of Long Dan Xie Gan formula granule(LDXGFG)on regulation of pro-inflammatory cytokines in female guinea pigs with recurrent genital herpes(herpes simplex virus 2,HSV-2).Methods Levels of pro-inflammatory cytokines in blood of HSV-2-infected guinea pigs,including IL-6,IL-8,IL-10,IL-12,IFN-α,IFN-β,IFN-γ,and TNF-α,were detected by ELISA;corresponding gene expression levels in tissues were detected by real-time PCR.Results IL-6,IL-10,IL-12,IFN-α,IFN-γand TNF-αdecreased significantly in both blood and diseased tissues after infection with recurrent genital herpes.Upon feeding LDXGFG to HSV-2-infected guinea pigs,IL-6,IL-10,IL-12,IFN-α,IFN-γand TNF-αdemonstrated significant increases,similar to the effects of acyclovir(ACV).LDXGFG promoted the expression of pro-inflammatory cytokines in blood and tissue,with a stronger effect than ACV.Moreover,LDXGFG demonstrated broader effects than ACV.Conclusion The present results suggest that LDXGFG can serve as an alternative,inexpensive,and long-term treatment for HSV-2 infection.

Advanced Oxidation Protein Products Regulate the Pharmacokinetics of Aloe-emodin,Emodin,Rhein,and Chrysophanol in Chronic Kidney Disease Rats

Background:As accelerators and products of the progression of chronic kidney disease(CKD),advanced oxidation protein products(AOPPs)affect the function of the liver.Huang Gan granules(HGGs)are commonly used to prevent the progression of CKD,but the pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs in CKD remain unknown.Objective:To investigate the influence and its molecular mechanism of AOPPs on the in vivo pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs.Methods:We constructed 5/6 nephrectomised(5/6 nx),adenine-induced(adenine)and AOPP-treated rat models.After oral administration of HGG,the concentrations of aloe-emodin,emodin,rhein,and chrysophanol in the plasma samples were detected by high-performance liquid chromatography(HPLC),and their pharmacokinetics were analysed with the PKSolver software.The plasma concentrations of IL-6 and TNF-αare detected by enzyme linked immunosorbent assay(ELISA).The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-αand IL-6 on the mRNA expression of CYP1A2 and CYP3A4.Result:The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear(R R^(2)>0.9931),precision(<9.4%)and accuracy(±10%).In 5/6 nx,adenine and AOPPs-treated rats,the concentrations of TNF-αand IL-6 were increased.In 5/6 nx and adenine rats,the pharmacokinetic parameters(t_(1/2),MRT_(0-∞)and AUC_(0-∞))of aloe-emodin,emodin,rhein,and chryso-phanol were,respectively,significantly increased and correlated with the concentration of AOPPs.In AOPPs-treated rats,the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.Conclusion:In summary,inflammatory cytokine production may be one of the important causes in AOPPs’regulat-ing the pharmacokinetic of aloe-emodin,emodin,rhein,and chrysophanol in the CKD rats.Studies of aloe-emodin,emodin,rhein,and chrysophanol in CKD facilitate the appropriate prescription of HGGs in the clinical.