Background: Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet.Methods: We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP.Results: Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment.Conclusion: Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.

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 multicompounds and multitargets characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of the pharmacological mechanisms and broader clinical application.

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.

Background: Baihu Jia Renshen Decoction (BJRD) is used for diabetes mellitus (DM) management in clinics. Objective: To elucidate the potential mechanism of BJRD in treating type 1 DM (T1DM). Methods: T1DM models were established via intraperitoneal injection of streptozotocin (STZ). Rats were subsequently randomly divided into the normal control (NC), model (MOD), insulin (INS), INS + BJRD-medium dose (MID), and INS + BJRD-high dose (HIGH) groups. The rats’ body weight was measured. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs) in the muscle and adipose tissues. Quantitative real-time polymerase chain reaction was utilized to verify the DEG levels. Results: Body weights of MOD, INS, MID, and HIGH groups were significantly reduced as compared to those of NC group. Compared with NC group, MOD group showed significant Hspa1b and Notch3 downregulation and Camkk2 level elevation. Compared with MOD group, INS group showed further downregulation of the Hspa1b level, whereas MID group exhibited an increase. The Camkk2 levels in INS, MID, and HIGH groups were further reduced. The Notch3 levels did not significantly change in INS and MID groups, whereas that of HIGH group increased. Additionally, compared with NC group, MOD group demonstrated upregulation of the Myl1, Mylpf, Acacb, and Pygm levels and downregulation of Fasn level. Compared with MOD group, Myl1, Mylpf, and Pygm levels in INS, MID, and HIGH groups were down-regulated, whereas Fasn and Acacb levels were up-regulated. Conclusion: BJRD may influence pancreatic β-cell function, thereby enhancing the function of the skeletal muscle and adipose tissues in a T1DM rat model.

Background: Baihu Jia Renshen Decoction (BJRD) applied to diabetes mellitus (DM). We explored the metabolic regulatory pathways and mechanisms of BJRD in Type 1 DM (T1DM). Methods: T1DM rat model was established with STZ induction and then continuously treated with insulin and different concentrations of BJRD for 2 weeks. The therapeutic effect of BJRD was evaluated by detecting the levels of fasting blood glucose and insulin in the blood and observing the ultrastructure of pancreatic tissues by transmission electron microscopy and immunofluorescent staining. Metabolomics analysis on rat serum was performed. Results: Compared with the diabetes model (DC) group, the high‐concentration BJRD treatment (BJRD‐H) group reduced fasting blood glucose, increased insulin levels, and increased the quantity of β‐cells in the pancreatic tissues in rats. And rat pancreatic islet β‐cells in the DC group had lost their nuclear membranes, had abnormal mitochondrial morphology, and had significantly reduced secretory granules, whereas rat pancreatic islet β‐cells in the BJRD‐H group had moderately increased secretory granules, and the structure of the nucleus was apparently normal. Moreover, the metabolic profile expression pattern of rats in the BJRD‐H group was closer to that of normal rats, suggesting that a high concentration of BJRD combined with insulin treatment was more effective. And differentially expressed metabolites were predominantly enriched in amino acid metabolism, including amino acids, glycine, serine, and threonine metabolism. Conclusion: BJRD facilitated the therapeutic effect of insulin in T1DM rats and resulted in a significant improvement in their metabolic profiles, expanding the application of traditional Chinese medicine’s alternative therapies in T1DM.

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 analysis were carried out on the Metascape web platform. Molecular docking was utilized AutoDock Vina and PyMOL software. Result 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 nine key targets. 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 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 multi-compounds and multi-targets characteristics of LDP in DN treatment. Furthermore, this study provides valuable evidence for further scientific research of pharmacological mechanisms and broader clinical application.