Search

Background. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been widely used to treat a variety of disorders, including renal diseases. Despite being well-established in clinical practice, the mechanisms behind the therapeutic effects of DSS on diabetic nephropathy (DN) remain elusive. Methods. To explore the therapeutic mechanism, we explored the action mechanism of DSS on DN using network pharmacology strategies. All ingredients were selected from the relevant databases, and active ingredients were chosen on the basis of their oral bioavailability prediction and drug-likeness evaluation. The putative proteins of DSS were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas the potential genes of DN were obtained from the GeneCards and OMIM databases. Enrichment analysis using gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) was performed to discover possible hub targets and gene-related pathways. Afterwards, the underlying molecular mechanisms of DSS against DN were validated experimentally in vivo against db/db mice. Results. We identified 91 phytochemicals using the comprehensive network pharmacology technique, 51 of which were chosen as bioactive components. There were 40 proteins and 20 pathways in the target-pathway network. The experimental validation results demonstrated that DSS may reduce the expression of TNF-α, IL-6, and ICAM-1, as well as extracellular matrix deposition, by blocking the JNK pathway activation, which protects against kidney injury. Conclusion. This study discovered the putative molecular mechanisms of action of DSS against diabetic kidney damage through a network pharmacology approach and experimental validation. [ABSTRACT FROM AUTHOR]

Purpose: As a formula of traditional Chinese medicine (TCM), Huoxue Jiangtang Decoction (HJD) has positive effects on diabetes mellitus (DM) through improving of the metabolism of glycolipid and the function of β-cell. Hence, this research aims to explore the potential therapeutic effects of HJD on diabetes and reveal its underlying mechanisms. Methods: Diabetic rat models induced by high-fat diet (HFD) and streptozotocin (STZ) were included in this study. Following successful modeling, diabetic rats were treated with HJD, and then its therapeutic effects in eight weeks were evaluated. In addition to biochemical indicators, two-bottle preference tests were carried out to examine the rats' preferences for fat and sugar, and 16S rRNA gene sequencing was performed to disclose the differences of oral microbiota among groups. Finally, Pearson correlation coefficient was used to explore the correlation between oral microbiota and the preferences for fat and sugar. Results: It was found that HJD significantly improved the levels of fasting blood glucose (FBG), glucose tolerance, and dyslipidemia. Additionally, HJD contributed to decreasing preferences for fat and sugar in diabetic rats, which plays an important role in food intake. Furthermore, HJD regulated the abundance, distribution, and structure of oral microbiota in diabetic rats, serving as one of the underlying mechanisms of its antidiabetic effects. Conclusion: Taken with other formulas, HJD functions to improve the metabolism of glycolipid and the function of β-cell by inhibiting preferences for fat and sugar, as well as regulating the oral microbiota of diabetic rats. Furthermore, a potential correlation between the oral micro-environment and preferences for fat and sugar in STZ-induced diabetic rats is likely to exist. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is characterized by chronic inflammation. Baishao (radix paeoniae alba, RPA), classified as a top-grade herbal medicine in TCM, has anti-inflammatory, immune adjustment, and anti-oxidative activities. RPA has been used to treat PCOS in clinical practice, but its potential mechanism of action is unclear. This study aimed at exploring the potential mechanism of RPA in PCOS treatment and to investigate the anti-inflammatory constituents of RPA. Methods: The TCMSP database was used to screen the potential active compounds of RPA. On the other hand, the possible target genes of PCOS were collected from the TTD, DrugBank, GeneCard, OMIM, and PharmGKB databases. The PPI network of RPA–PCOS target genes was established by STRING, and the visual network among RPA, ingredients, disease and potential target genes was constructed in Cytoscape. The bioactivity and potential mechanism of RPA in PCOS treatment were analyzed by GO and KEGG enrichment approaches. Furthermore, molecular docking was utilized to indicate the best compounds of RPA binding with TNF-α. Results: Fifty-four potential target genes were filtered and gathered from RPA and PCOS. Visual network indicated that 8 ingredients in RPA, β-sitosterol, (+)-catechin, palbinone, sitosterol, mairin, kaempferol, paeoniflorigenone, and paeoniflorin, were closely correlated with 54 possible therapeutic target genes. The possible pathways relating the treatment of PCOS by RPA mainly contained the TNF, lipid atherosclerosis, C-type lectin receptor, and AGE-RAGE signal pathways. Paeoniflorigenone was the optimal anti-inflammatory compound of RPA to bind with TNF-α in molecular docking analysis. Conclusion: This study manifested that the most effective anti-inflammation compound of RPA was paeoniflorigenone and provided a potential therapeutic strategy for PCOS treatment. [ABSTRACT FROM AUTHOR]

Context. Zishen Jiangtang Pill (ZJP) is a Chinese herbal compound, which has a positive therapeutic effect on diabetic osteoporosis (DOP) by regulating glucose metabolism and bone metabolism. However, its regulatory role and mechanism are still unclear. Objective. To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. Materials and Methods. After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). Results. Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. Conclusion. ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP. [ABSTRACT FROM AUTHOR]

Background. Diabetic nephropathy (DN) is a common and serious complication of diabetes, but without a satisfactory treatment strategy till now. Liuwei Dihuang pills (LDP), an effective Chinese medicinal formula, has been used to treat DN for more than 1000 years. However, its underlying mechanism of action is still vague. Methods. Active compounds and corresponding targets of LDP were predicted from the TCMSP database. DN disease targets were extracted from the OMIM, GeneCards, TTD, DisGeNET, and DrugBank databases. Subsequently, the "herbal-compound-target" network and protein-protein interaction (PPI) network were constructed and analyzed via the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Molecular docking utilized AutoDock Vina and PyMOL software. Results. 41 active components and 186 corresponding targets of LDP were screened out. 131 common targets of LDP and DN were acquired. Quercetin, kaempferol, beta-sitosterol, diosgenin, and stigmasterol could be defined as five crucial compounds. JUN, MAPK8, AKT1, EGF, TP53, VEGFA, MMP9, MAPK1, and TNF might be the nine key targets. The enrichment analysis showed that common targets were mainly associated with inflammation reaction, oxidative stress, immune regulation, and cell apoptosis. AGE-RAGE and IL-17 were the suggested two significant signal pathways. Molecular docking revealed that the nine key targets could closely bind to their corresponding active compounds. Conclusion. The present study fully reveals the multicompound's and multitarget's characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application. [ABSTRACT FROM AUTHOR]

Eight nonaromatic acylphloroglucinol-terpenoid adducts including 7 new compounds were isolated from H. japonicum. Among them, compounds 1 – 4 showed significant PXR agonistic activity. [Display omitted] • Seven novel nonaromatic acylphloroglucinol-terpenoid adducts were isolated. • Compounds 1 − 4 showed significant PXR agonistic activity in dual-luciferase reporter gene model. • Compounds 1 − 4 can upregulate the expression of PXR-targeted gene in mice primary hepatocyte model. • Compounds 1 − 4 efficiently promoted PXR nuclear translocation at 10 μM. • The binding models of active compounds and PXR were elucidated. Pregnane X receptor (PXR) has been considered as a promising therapeutic target for cholestasis due to its crucial regulation in bile acid biosynthesis and metabolism. To search promising natural PXR agonists, the PXR agonistic activities of five traditional Chinese medicines (TCMs) with hepatoprotective efficacy were assayed, and Hypericum japonicum as the most active one was selected for subsequent phytochemical investigation, which led to the isolation of eight nonaromatic acylphloroglucinol-terpenoid adducts including seven new compounds (1 − 4 , 5a , 5b and 6). Their structures including absolute configurations were determined by comprehensive spectroscopic, computational and X-ray diffraction analysis. Meanwhile, the PXR agonistic activities of aplenty compounds were evaluated via dual-luciferase reporter assay, RT-qPCR and immunofluorescence. Among them, compounds 1 − 4 showed more potent activity than the positive drug rifampicin. Furthermore, the molecular docking revealed that 1 − 4 were docked well on the PXR ligand binding domain and formed hydrogen bonds with amino acid residues Gln285, Ser247 and His409. This investigation revealed that H. japonicum may serve as a rich source of natural PXR agonists. [ABSTRACT FROM AUTHOR]