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ObjectiveTo investigate the effect of modified Taohe Chengqitang on NOD-like receptor protein 3 （NLRP3） inflammasome activation in rats with diabetic cardiomyopathy. MethodSPF male SD rats aged 3-4 weeks were randomly divided into a normal group and an experimental group. The rats in the experimental group were fed on a high-fat diet for 4 weeks and then received intraperitoneal injection of streptozotocin （STZ） at 35 mg·kg-1 to induce the diabetes model. The rats in the experimental group were randomly divided into model group， low- and high-dose modified Taohe Chengqitang groups （11.7 g·kg-1 and 23.4 g·kg-1）， and metformin hydrochloride group （67.5 mg·kg-1） according to the fast blood glucose （FBG）. The cardiac function and structure of rats were detected by ultrasonic imaging after 8 weeks of continuous intragastric administration. Blood samples from the femoral artery were collected to detect FBG， triglyceride （TC）， and total cholesterol （TG） of rats. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in rat myocardium. Serum levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease 1 （Caspase-1）， and phosphorylated nuclear factor kappa-B p65 （p-NF-κB p65） in the myocardium was detected by Western blot. ResultCompared with the normal group， the model group showed increased levels of FBG， TC， and TG （P<0.01）， decreased left ventricular ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.05）， myocardial hypertrophy and myocardial fibrosis as revealed by HE staining， increased serum levels of 1L-1β and 1L-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.01）. Compared with the model group， the modified Taohe Chengqitang groups and the metformin group showed reduced levels of FBG， TC， and TG （P<0.05）， restored EF and FS （P<0.05）， improved pathological changes in myocardial tissues， and decreased serum levels of IL-1β and IL-18 and protein expression of NLRP3， ASC， Caspase-1， and p-NF-κB p65 in myocardial tissues （P<0.05）. The improvement was more significant in the high-dose modified Taohe Chengqitang group （P<0.05）. ConclusionModified Taohe Chengqitang can protect the myocardium by inhibiting the activation of NLRP3 inflammasomes.
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Taohe Chengqitang is a classical prescription published in The Catalogue of Ancient Classic Recipes (The First Batch). This study systematically summarized traditional Chinese medicine (TCM) ancient books and modern clinical reports on Taohe Chengqitang and investigated its origin， composition， basis, and historical evolution in processing requirements， dosage， preparation and administration， and functions. The findings indicated different opinions on drug basis， preparation of decoction pieces, and drug dosage conversion. Based on sufficient literature review, the actual development needs of classical prescriptions, and the usage habits of modern clinical practice， this study recommended dried mature seeds of Prunus persica or P. davidiana for Persicae Semen， dried twigs of Cinnamomum cassia for Cinnamomi Ramulus， honey-fried Glycyrrhiza uralensis for Glycyrrhizae Radix et Rhizoma, raw Rheum palmatum, R. tanguticum, or R. offìcinale for Rhei Radix et Rhizoma, and mirabilite for Natrii Sulfas. In terms of drug dosage， the doses directed converted from weights and measures in the Han dynasty were large. According to the common doses in modern clinical practice, conversion was carried out based on 6 g of Cinnamomi Ramulus, 6 g of Natrii Sulfas, 6 g of Glycyrrhizae Radix et Rhizoma, and 12 g of Rhei Radix et Rhizoma. The weight of Persicae Semen should be determined according to the actual measurement. In terms of preparation and administration, the drugs in the pot were decocted with 1 400 mL of water to obtain 500 mL of decoction, which was filtered and slightly boiled in the presence of Natrii Sulfas. About 100 mL of warm decoction was taken before meals， three times a day. It was recorded in the ancient books that Taohe Chengqitang was indicated for the syndromes of heat invading the bladder and accumulating inside in the case of released exterior syndrome in Taiyang. After symptom-based flexible application by doctors, it is currently commonly used in the treatment of diabetic nephropathy， constipation， chronic renal failure, and other diseases.
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Taohe Chengqitang is a classical prescription published in The Catalogue of Ancient Classic Recipes (The First Batch). This study systematically summarized traditional Chinese medicine (TCM) ancient books and modern clinical reports on Taohe Chengqitang and investigated its origin， composition， basis, and historical evolution in processing requirements， dosage， preparation and administration， and functions. The findings indicated different opinions on drug basis， preparation of decoction pieces, and drug dosage conversion. Based on sufficient literature review, the actual development needs of classical prescriptions, and the usage habits of modern clinical practice， this study recommended dried mature seeds of Prunus persica or P. davidiana for Persicae Semen， dried twigs of Cinnamomum cassia for Cinnamomi Ramulus， honey-fried Glycyrrhiza uralensis for Glycyrrhizae Radix et Rhizoma, raw Rheum palmatum, R. tanguticum, or R. offìcinale for Rhei Radix et Rhizoma, and mirabilite for Natrii Sulfas. In terms of drug dosage， the doses directed converted from weights and measures in the Han dynasty were large. According to the common doses in modern clinical practice, conversion was carried out based on 6 g of Cinnamomi Ramulus, 6 g of Natrii Sulfas, 6 g of Glycyrrhizae Radix et Rhizoma, and 12 g of Rhei Radix et Rhizoma. The weight of Persicae Semen should be determined according to the actual measurement. In terms of preparation and administration, the drugs in the pot were decocted with 1 400 mL of water to obtain 500 mL of decoction, which was filtered and slightly boiled in the presence of Natrii Sulfas. About 100 mL of warm decoction was taken before meals， three times a day. It was recorded in the ancient books that Taohe Chengqitang was indicated for the syndromes of heat invading the bladder and accumulating inside in the case of released exterior syndrome in Taiyang. After symptom-based flexible application by doctors, it is currently commonly used in the treatment of diabetic nephropathy， constipation， chronic renal failure, and other diseases.
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Objective::To define the clinical efficacy of modified Taohe Chengqitang combined with colon hydrotherapy in patients with severe nonalcoholic fatty liver disease (NAFLD) accompanied by phlegm-heat stagnation syndrome and its mechanism. Method::Totally 100 patients with severe NAFLD by phlegm-heat stagnation syndrome were enrolled in the study.They were all given Shanzha Xiaozhi capsule.According to the random number table, the patients were randomly divided into the observation group (50 patients, colon hydrotherapy combined with traditional Chinese medicine) and the control group (50 patients, Shanzha Xiaozhi capsule alone). The observation period was 4 weeks.The therapeutic effect of colon hydrotherapy was verified through determinations of the liver function, blood lipid, insulin resistance index (IRI), controlled attenuation parameter (CAP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) before and after treatment.The mechanism of colon hydrotherapy combined with modified Taohe Chengqitang was preliminarily analyzed based on changes of IR, TNF-α and IL-6. Result::Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), total cholesterol (TCH), triglyceride (TG), fasting plasma glucose (FPG), fasting insulins (FINS), IRI, CAP, TNF-αand IL-6 of NAFLD patients in both of two groups were significantly lower than those before treatment (P<0.01). ALT, AST, γ-GT, TCH, TG, FPG, IRI, CAP, TNF-α and IL-6 in observation group were significantly lower than those in the control group after treatment (P<0.01). FINS in observation group was significantly lower than that in the control group (P<0.05). Conclusion::Colon hydrotherapy combined with modified Taohe Chengqitang is an effective method for treating NAFLD accompanied by phlegm-heat stagnation syndrome.Its mechanism may be mainly correlated with the reduction of IRI, serum TNF-α and IL-6.The course of colon hydrotherapy, the therapeutic mechanism and the long-term efficacy need to be further studied in the future.
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Objective:To explore the effect of different effective parts of Taohe Chengqitang on the synthesis and degradation of extracellular matrix in human kideny-2（HK-2） cells induced by transforming growth factor-β1（TGF-β1）. Method:Petroleum ether extract, ethyl acetate extract, n-butanol extract, raffinate and polysaccharide extract, mirabilite extract were extracted with 70% ethanol by systematic solvent method. The HK-2 cell fibrosis model induced by TGF-β1 was built to intervene the cells in different parts of Taohe Chengqitang with different concentrations (0, 50, 100, 200, 400, 800 mg·L-1). Enzyme-linked immunosorbent assay（ELISA）kit assay was used to detect collagen（Col）-Ⅰα1 and fibronectin （FN）in supernatant to screen out the main active parts. Cell counting kit-8 （CCK-8）method was used to determine the best concentration of intervention site of bioactive components. Western blot analysis was used to detect the expression levels of Col-Ⅰ, Col-Ⅲ, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase inhibitor2 (TIMP2), and connective tissue growth factor (CTGF). Immunofluorescence assay was used to detect the expression of α-smooth muscle actin（α-SMA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） analysis was used to detect the mRNA expression of plasminogen activator inhibitor-1（PAI-1）. Result:ELISA kit assay demonstrated that compared with the model group, ethyl acetate extract, n-butanol extract and chloroform extract significantly reduced the Col-Ⅰα1 and FN content at the concentrations of 200 and 400 mg·L-1 (P<0.05, P<0.01). CCK-8 assay showed that the cells viability was significantly inhibited with drug intervention at the concentrations of 400 and 800 mg·L-1 (P<0.01). Western blot demonstrated that compared with the model group, ethyl acetate extract, n-butanol extract and chloroform extract decreased the expression levels of Col-Ⅰ, Col-Ⅲ, TIMP2 and CTGF in HK-2 cells induced by TGF-β1, and increased the expression of MMP-2 (P<0.05), with more significant effect in n-butanol extract (P<0.01). The results of immunofluorescence showed that ethyl acetate extract, n-butanol extract and chloroform extract could inhibit the expression of α-SMA (P<0.05), with more significant effect in n-butanol extract (P<0.01). The results of Real-time PCR showed that ethyl acetate extract and chloroform extract inhibited mRNA expression of PAI-1 (P<0.05), with more significant effect in n-butanol extract (P<0.01). Conclusion:The extracts of ethyl acetate, n-butanol and chloroform are the active parts of Taohe Chengqitang with the anti-renal fibrosis effect, with n-butanol extract as the most active part. The mechanism on anti-renal fibrosis may be related to its regulation of extracellular matrix (ECM) synthesis and degradation.
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<b>Objective::To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic gastroparesis by regulating relative genes and signaling pathways based on network pharmacology. <b>Method::Target genes of modified Taohe Chengqitang were obtained from Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM) database, and target genes of diabetic gastroparesis were obtained from Comparative Toxicogenomics Database (CTD) database. The target genes of modified Taohe Chengqitang-diabetic gastroparesis intersection protein were obtained through the integration of two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. Cytospace software ClueGO, CluePedia plug-in were used for gene ontology (GO) analysis and enrichment analysis of KEGG pathway of modified Taohe Chengqitang-diabetic gastroparesis target genes intersection, and results were visualized. Finally, CTD database and literatures were used to obtain intersection genes in the treatment of diabetic gastroparesis. <b>Result::Among 621 target genes in modified Taohe Chengqitang, 25 were related to diabetic gastroparesis. By regulating expressions of MLNR, SST, PTGS1, HRH2, HTR3A, HTR4, HTR7, NOS3 and other intersection genes, Taohe Chengqitang could improve the gastrointestinal hormone levels, affected the combination of serotonin and its receptors, activated adenylate cyclase (AC), and induced cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), so as to activiate AC/cAMP/PKA signaling pathway, regulate Ca<sup>2+</sup> /K<sup>+</sup> channel, control ion balance, promote the adaptability of gastric smooth muscle, and contract gastric smooth muscle to regulate gastric volume. At the same time, gastric acid secretion was improved to protect gastric mucosa, which may help improve vasoconstriction and hemodynamics. <b>Conclusion::Based on the network pharmacology, modified Taohe Chengqitang has multiple mechanisms in the prevention and treatment of diabetic gastroparesis. This study explored relevant signaling pathways, advantages and research directions of modified Taohe Chengqitang in treatment of diabetic gastroparesis.
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Objective: To study the potential therapeutic targets of modified Taohe Chengqitang for type 2 diabetes mellitus based on network pharmacology. Method: Based on TCMSP database and Uniprot database, the active constituents and target genes of flavored modified Taohe Chengqitang were screened.Target genes of type 2 diabetes were screened by gene cards database and OMIM database, and Cytoscape software was used to construct " active component-target" interaction network diagram.The active component targets and disease targets were uploaded to the STRING database, the protein interaction network map (PPI) was constructed, and the characteristic values were calculated, and core genes were screened by using R language.Finally, R language was used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment of key targets. Result: The 155 active components and 106 effective targets of modified Taohe Chengqitangin the treatment of type 2 diabetes were predicted.Quercetin, kaempferol and isorhamnetin were the most effective components, while estrogen receptor alpha (ESR1), peroxidosomal hyperplasia activates receptor gamma (PPARG) and androgen receptor (AR) were the most effective components.Core genes in PPI network areepidermal growth factor receptor (EGFR)and ESR1, etc.GO enrichment analysis shows that it can affect gene transcription, nuclear receptor activity, hormone receptor binding, neurotransmitter, etc.Enrichment analysis of KEGG pathway showed that fluid shear stress and atherosclerosis pathways were the most significant pathways, followed by advanced glycation end products-receptor for AGE (AGE-RAGE) pathway. Conclusion: Predicted by the method of network pharmacology modified Taohe Chengqitang key targets for prevention and treatment of type 2 diabetes and related pathways, results suggest the recipe has multiple targets, multiple pathways, such as complex mechanism, not only show that modified Taohe Chengqitang has hypoglycemic effect, but it also has anti-inflammatory, improve insulin resistance, regulate lipid metabolism, and biological functions.
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Objective: To study the mechanism of modified Taohe Chengqitang in preventing and treating diabetic nephropathy by means of network pharmacology. Method: Target genes of modified Taohe Chengqitang were obtained from BAT-MAN database, while target genes of diabetic nephropathy were obtained from CTD database. The target genes of disease-drug protein were obtained by crossing two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The key genes were screened out through the computational analysis algorithm of network structure and weighted relatedness between nodes. With DAVID online tools, gene ontology (GO) analysis of Disease-Drug Intersection Target Genes and enrichment analysis of kyoto encyclopedia of genes and genomes(KEGG) pathway were conducted. Finally, CTD database and literature study were used to obtain the key genes in the treatment of diabetic nephropathy. Result: Among 621 compounds in modified Taohe Chengqitang, 581 of them were related to diabetic nephropathy. NOS3, OAT, NT5C2, ACACB, AGXT, PDE3B and other key genes mainly regulated nerve tissue transmission, cholinergic synaptic pathway, calcium channel, metabolic pathway, purine metabolic pathway, angiotensin-neurosynaptic pathway, cyclic guanosine monophosphate/cGMP-dependent protein kinase G (cGMP/PKG) signaling pathway and cyclic adenosine phosphate signaling pathway, with effect in molecular reactions, such as plasma membrane, postsynaptic membrane and mitochondria. Conclusion: The network pharmacology predicts the key targets of modified Taohe Chengqitang in the prevention and treatment of diabetic nephropathy and the related pathways involved, suggesting a multi-target, multi-channel and multi-choice complex mechanism, and which is mostly related to anti-inflammation, oxidative phosphorylation and purine metabolism.