Sanhuang Xiexin Decoction (SXD) is commonly used to treat type 2 diabetes mellitus (T2DM) in clinical practice of traditional Chinese medicine (TCM). In order to elucidate the specific analysis mechanisms of SXD for T2DM, the method of network pharmacology was applied to this article. First, the effective ingredients of SXD were obtained and their targets were identified based on the TCMSP database. The T2DM‐related targets screened from the GEO database were also collected by comparing the differential expressed genes between T2DM patients and healthy individuals. Then, the common targets in SXD‐treated T2DM were obtained by intersecting the putative targets of SXD and the differential expressed genes of T2DM. And the protein–protein interaction (PPI) network was established using the above common targets to screen key genes through protein interactions. Meanwhile, these common targets were used for GO and KEGG analyses to further elucidate how they exert antidiabetic effects. Finally, a gene pathway network was established to capture the core one in common targets enriched in the major pathways to further illustrate the role of specific genes. Based on the data obtained, a total of 67 active compounds and 906 targets of SXD were identified. Four thousand one hundred and seventy‐six differentially expressed genes with a P value < 0.005 and ∣log2(fold change) | >0.5 were determined between T2DM patients and control groups. After further screening, thirty‐seven common targets related to T2DM in SXD were finally identified. Through protein interactions, the top 5 genes (YWHAZ, HNRNPA1, HSPA8, HSP90AA1, and HSPA5) were identified. It was found that the functional annotations of target genes were associated with oxygen levels, protein kinase regulator, mitochondria, and so on. The top 20 pathways including the PI3K‐Akt signaling pathway, cancers, HIF‐1 signaling pathway, and JAK‐STAT signaling pathway were significantly enriched. CDKN1A was shown to be the core gene in the gene‐pathway network, and other several genes such as CCND1, ERBB2, RAF1, EGF, and VEGFA were the key genes for SXD against T2DM. Based on the network pharmacology approach, we identified key genes and pathways related to the prognosis and pathogenesis of T2DM and also provided a feasible method for further studying the chemical basis and pharmacology of SXD.

Background: We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. Methods: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin. Results: The AUC (p < 0.01) and C_max (p < 0.01) could be significantly decreased in the berberine-induced group in vivo, and the metabolic activity of HepG2 cell ccould be increased by berberine induction in vitro. The metabolism parameters of lovastatin such as CL, V_max and K_m were increased after the induction of berberine. From the pharmacokinetic study of lovastatin induced with berberine, we obtained pharmacokinetic parameters which are compliance with the metabolic parameters of lovastatin in HepG2 cells with berberine induction in vitro. Conclusions: From the in vivo pharmacokinetics study and the HepG2 cell metabolism study in vitro, berberine could be an inducer for the metabolism of lovastatin according to our previous research on berberine induction effects on HepG2 cells, which may be relevant to the fact that berberine possesses induction effects through the CYP 450 3A4 enzyme.

Objective: Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and anti-bacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. This study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology. Materials and methods: Compound-related information was obtained from the PubChem database. Potential target genes were identified using STITCH, SwissTargetPrediction, BATMAN-TCM, and CTD. Genes involved in atherosclerosis were obtained from DisGeNet and compared to AG target genes to obtain an overlapping set. Protein-protein interactions were determined by STRING. Gene ontology (GO) analysis was performed at WebGestalt, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was analysed using Metascape. The final network showing the relationship between compounds, targets, and pathways was constructed using Cytoscape. After that, oxLDL-induced RAW264.7 cells were used to further validate a part of the network pharmacology results. Result: 81 potential AG target genes were identified. PPI, GO, and KEGG enrichment revealed genes closely related to tumour progression, lipid transport, inflammation, and related pathways. AG improves the reverse cholesterol transport (RCT) through NF-κB/CEBPB/PPARG signalling in oxLDL-induced RAW264.7 cells. Conclusion: We successfully predict AG's potential targets and pathways in atherosclerosis and illustrate the mechanism of action. AG may regulate NF-κB/CEBPB/PPARG signalling to alleviate atherosclerosis.

Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood–brain barrier (BBB) and balance of the fibrinolytic system. A VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay. KJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells. KJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system.

The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin‑5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague‑Dawley rats were provided with a high‑fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin‑5f islet cell line were also evaluated. The effects on Rin‑5f cell proliferation and cell cycle, glucose‑stimulated insulin release test (GSIS), the anti‑apoptotic effects caused by fat induction, and protein expression levels of poly ADP‑ribose polymerase (PARP‑1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting β‑cell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin‑5F cells, it was found that the Rin‑5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP‑1 were altered and improved, which may have protected pancreatic islet β‑cells by improving islet β‑cell proliferation and the protein expression of PARP‑1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet β‑cells via improving islet β‑cell proliferation and the protein expression of PARP‑1.