Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

Mechanism of Baihu Renshen decoction on T2DM rats based on mitochondrial autophagy mediated by PINK1/Parkin

Background:This study will be aimed at investigating the effects of Baihu Renshen decoction(BHRS)on type 2 diabetes rats and on macromolecular enzyme 1(PINK1)/E3 ubiquitin protein ligase(Parkin)pathway.Methods:The experiment was divided into four groups:control group,model group,metformin group and BHRS low-dose group and high-dose group.Forty male rats were selected as samples and randomly assigned to at least one test group.Finally,there are 18 rats in each group.Except for the control group,the rats within the different teams got a high-fat diet associate in nursing an intraperitoneal injection of streptozotocin to make a type 2 diabetes mellitus(T2DM)rat model.The organic chemistry and inflammatory indexes of rats in every cluster were analyzed and compared once four weeks of intragastric administration of comparable reagents to review the therapeutic impact of BHRS on T2DM.In addition,we determined the pathological changes of ductal gland tissue of T2DM rats after treatment,and compared the expression of mitochondrial phagocytosis related proteins in ductal gland tissue of rats in each group.Results:FBG,LDL-C,TC,TG,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were elevated in the model group compared to the control group,while HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were decreased(P<0.05 or P<0.01).The expressions of FBG,TC,TG,LDL-C,MDA,IL-1,IL-6,TNF-,and mitophagy-related proteins COXIV,P62,VDAC1,and TOM20 were lowered in the BHRS group,while the expressions of HOMA-,HDL-C,SOD,GSH-Px,and mitophagy-related proteins PINK1,Parkin,and LC3II/I were(P<0.05 or P<0.01).After therapy with BHRS,hematoxylin-eosin staining showed that the intensity of pancreatic acinar staining increased,and islet cells became clear boundaries that were,regularly arranged,and with reduced vacuoles reduced.Conclusion:BHRS has a clear therapeutic effect on T2DM,which may be achieved by regulating mitochondrial autophagy through the PINK1/Parkin pathway.

Clinical efficacy of Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease

Background:To observe the clinical effect of Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease.Methods:90 patients with non-alcoholic fatty liver disease in our hospital from January 2021 to January 2022 were randomly divided into observation group and control group,45 cases in each group.All patients received routine lifestyle intervention and the control group received oral polyene phosphatidylcholine capsules 2 capsules/time(456 mg),three times daily;45 cases in the observation group were given Qingre Quzhuo capsule(Jiyao Z2017040,0.5 g/grain)2.5 g/time,3 times/day,for 12 weeks.The clinical efficacy,liver function,liver transient elastography controlled attenuation index value,lipid metabolism,oxidation and antioxidant indexes were compared between the two groups after treatment.Results:The observation indexes of the two groups after treatment were better than those before treatment(P<0.05).After treatment,the total effective rate of the observation group was higher than that of the control group.Lipid metabolism indexes and oxidation indexes were lower than those in the control group.All antioxidant indexes were higher than control group.The decrease of liver transient elastography controlled attenuation index value was better than that of the control group and the difference was statistically significant(P<0.05).There was no significant difference in the decrease of alanine aminotransferase between the observation group and the control group after treatment.The decrease of r-glutamyltransferase was statistically significant(P<0.05).Conclusion:Qingre Quzhuo capsule in the treatment of non-alcoholic fatty liver disease can improve liver function,regulate lipid metabolism indexes of patients,improve the antioxidant capacity of liver cells and improve the controlled attenuation index value of liver transient elastography.In addition,it is superior to polyene phosphatidylcholine in regulating lipid metabolism,antioxidant capacity and controlled attenuation index value of patients with non-alcoholic fatty liver disease which is safe and worthy of promotion.

Clinical observation of Furongtongmai capsule on the lower extremity Atherosclerotic Occlusive Disease after Intervention Operation

目的探讨复荣通脉胶囊对下肢动脉硬化闭塞症（ASO）股浅动脉段介入术后再狭窄（ISR）的影响. 方法：接受股浅动脉支架植入术的连续 110例下肢动脉硬化闭塞症患者,随机分为处理组和对照组,每组 55例,两组患者均口服阿司匹林 100mg/d,氯吡格雷 75mg/d,处理组在此基础上加用复荣通脉胶囊口服.持续治疗 6个月,比较两组患者治疗后临床疗效、踝肱指数（ABI）的情况,高敏C 反应蛋白（Hs-CPR）及 ISR. 结果：术后6个月,两组Hs-CRP 血浆水平处理组较对照组降低明显（P 〈 0.05）;ABI处理组较对照组升高明显（P 〈 0.05）;处理组和对照组术后 6个月ISR发生率比较差异有统计学意义（9.09% vs 27.78%, P 〈 0.05） 结论：复荣通脉胶囊对ASO 患者股动脉介入术后 hs-CRP 产生抑制作用,改善踝肱指数,降低支架ISR发生率.