Effects of Jiangtang Fanglong Wan on hearing in an animal model of diabetes

Objective ; To study effects of Jiangtang Fanglong Wan （glucose-lowering and deafness-preventing capsule） on hearing in an animal model of diabetes. Methods Wistar rats were used to create a diabetes model by intraperitoneal injection of streptozotocin （STZ, 55 mg/kg）. Forty rats were randomly selected to receive Jiangtang Fanglong Wan （ 10 g/kg/ day） through intragastric garage （treatment group） or normal saline （control group）. Auditory brainstem responses （ABRs） were recorded at Months 1, 2 and 3. Results ABR latencies and wave intervals were similar between the two groups at Month 1 （P 〉 0.05）. ABR latencies and wave intervals were shorter in the treatment group than those of the control group at Months 2 and 3 （P 〈 0.05 and P 〈 0.01, respectively）. Conclusion Our results suggest that Jiangtang Fanglong Wan may have a beneficial effect in preventing and treating hearing impairment associated with diabetes.

The Mechanism of Action of Qihuang Jiangtang Capsule in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.

Danzhi Jiangtang capsule(丹蛭降糖胶囊)reduces renal injury in rats with diabetes induced by high fat diet and streptozotocin via downregulating toll-like receptor 4-nuclear factor-κB pathway and apoptosis

OBJECTIVE:To investigate the effect and mechanisms of Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)on renal injury in streptozotocin(STZ)-induced diabetes of rats.METHODS:Sprague-Dawley rats were fed with high fat diet for 6 weeks followed by streptozotocin(STZ,35 mg/kg)injection.These rats were then treated with DJC(270,540 and 1080 mg/kg)daily for 8 weeks.RESULTS:A combination of high fat diet and STZ significantly increased blood glucose creatinine,urea nitrogen,and urine albumin in rats.Meanwhile,the glomerular and tubular lesions were observed in rats fed with high fat diet and injected with STZ.These biochemical and pathological changes were significantly attenuated by DJC treatments in a dose-dependent manner.Mechanistically,DJC treatments significantly decreased toll-like receptor 4(TLR4),mitogen-activated protein kinase(MAPK),and nuclear factor-κB(NF-κB)signals in the kidney of rats fed with high fat diet and injected with STZ.Terminal deoxynucleotidyl transferase dU TP nick end labeling staining and caspase-8 levels showed that renal apoptosis was increased in rats fed with high fat diet and injected with STZ,and this was attenuated by DJC treatments.CONCLUSIONS:DJC treatments protect against diabetic kidney disease,and the mechanism may be closely related to downregulation of TLR4/MAPK/NF-κB pathways and apoptosis.This study provides further evidence of using DJC as a potential therapeutic option for diabetic kidney disease.

Qizhi Jiangtang capsule(芪蛭降糖胶囊)activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways

OBJECTIVE:To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule(芪蛭降糖胶囊,QZJT)on diabetic kidney disease(DKD)treatment.METHODS:This experiment used db/db mice and podocytes(MPC5)to develop DKD model.Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters(24-h urinary albumin,serum creatinine,blood urine nitrogen),pathological kidney injury,and podocyte integrity.Moreover,autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy.Additionally,Western blotting was applied to detect the expression of podocyte marker protein(podocin),autophagy-associated proteins,and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway changes in vivo and in vitro.RESULTS:QZJT significantly reduced urine protein,blood nitrogen urea,and serum creatinine and showed histological restoration of renal tissues.QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice.QZJT increased autophagic vesicles in mice and cultured podocytes.QZJT also upregulated microtubuleassociated protein 1 light chain 3-II(LC3-II)/(LC3-I)and Beclin-1 and downregulated phosphorylated-PI3K(pPI3K),p-AKT,and p-mTOR in db/db mice and MPC5 cells.However,autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells.CONCLUSIONS:These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.

Danzhi Jiangtang capsule(丹蛭降糖胶囊) alleviate hyperglycemiaand periodontitis via Wnt/β-catenin signaling in diabetic rats

OBJECTIVE:To elucidate whether Danzhi Jiangtang capsule(丹蛭降糖胶囊,DJC)has treatment effects on diabetic periodontitis and the potential mechanism.METHODS:One week after the induction of diabetes by streptozotocin(STZ),60 male Wistar rats were ligated by orthodontic ligation thread in cervical portion of bilateral maxillary first molar to induce diabetic periodontitis.Periodontitis was exanimated by tooth tissue morphology after 4 weeks.And then all rats were divided into 5 groups:diabetic periodontitis group(DP,n=20),periodontal basic treatment group(DP+BT,n=20),periodontal basic treatment+DJC treatment group(DP+BT+DJC,n=20)and additional Wnt/β-catenin inhibitor group(DP+BT+DJC+WIKI4/21 H7,n=20).Eight weeks after different interventions,fasting plasma glucose(FPG),C-peptide and glycosylated hemoglobin(Hb Alc)of rats were measured and then all rats were sacrificed.The paraffin sections of periodontal tissue were executed hematoxylin-eosin(HE)staining and immunohistochemical examination.The m RNA and protein levels of inflammatory cytokines were evaluated by quantitative polymerase chain reaction(Q-PCR)and Western blotting(WB).The protein levels of Wnt/β-catenin signaling molecules were measured by WB.RESULTS:The blood glucose and C-peptide concentrations in DP,DP+BT and DP+BT+DJC groups were gradually reduced,with gradually decreased distance of CEJ-A and the percentage of periodontal ligament(PDL),as well as gradually increased Hb Alc.The number of monocytes and leukocytes in the junctional epithelium and periodontal connective tissue was markedly decreased in DP+BT+DJC group(P<0.05),which was slightly reduced in DP+BT group comparing to DP group.The protein levels of Wnt1 andβ-catenin were obviously up-regulated with DJC treatment,while the SOST and DDK1 were markedly down-regulated with DJC treatment.The expression levels of BGP were lowest in DP group and highest in DP+BT+DJC group,while the tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and metalloproteinase-3(MMP-3)were highest in DP group and lowest in DP+BT+DJC group.All these changes could be reversed by Wnt/β-catenin inhibitor.CONCLUSION:DJC can improve the hyperglycemia and both distal alveolar bone loss and alveolar bone loss in furcation area of diabetic periodontitis rats by reducing the inflammation of gingival tissue and regulating the expressions of BGP,TNF-α,IFN-γand MMP-3 potentially through Wnt/β-catenin signaling.

Clinical Study on Treatment of Incipient Diabetic Nephropathy by Integrated Traditional Chinese and Western Medicine

Objective: To explore the curative effect of integrated traditional Chinese and western medicinal (TCM-WM) therapy on incipient diabetic nephropathy (DN).Methods: One hundred patients with incipient DN were randomly divided into two groups, the treated group (50 cases) was treated with TCM-WM therapy, which was carried out by using Jiangtang Jianshenling (JTJSL) capsule, a Chinese preparation for supplementing Qi and nourishing Yin, on the basis of effectively controlling blood glucose with western medicine. The 50 patients in the control group were treated with western medicine alone. The course of treatment was three months. Changes of symptoms, signs and related laboratory parameters were observed before and after treatment.Results: The total effective rate in the treated group was 90% while that in the control group 58%, the difference between the two groups was significant (P<0.05). The related parameters including 24 hrs urinary albumin excretion, blood sugar, microalbuminuria, blood and urine β2-microglobulin, blood lipids and hemorrheologic parameters were all improved after treatment in the treated group (P<0.05 or P<0.01).Conclusion: The curative effect of TCM-WM was better than that of western medicine alone in treating incipient DN.