[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Prevention and treatment of natural products from Traditional Chinese Medicine in depression: Potential targets and mechanisms of action.

The molecular pathology involved in the development of depression is complex. Many signaling pathways and transcription factors have been demonstrated to display crucial roles in the process of depression occurrence and development. The multi-components and multi-targets of Traditional Chinese Medicine (TCM) are uniquely advantageous in the prevention and treatment of chronic diseases. This review summarizes the pharmacological regulations of natural products from TCM in the prevention and treatment of depression from the aspects of transcription factors (CREB, NF-κB, Nrf2) and molecular signaling pathways (BDNF-TrkB, MAPK, GSK-3ß, TLR-4).

[Prediction of anti-liver fibrosis effect of Piperis Longi Fructus based on network pharmacology].

Network pharmacology and liver fibrosis(LF) model in vitro were used to analyze the underly mechanism of anti-liver fibrosis effect that induced by Piperis Longi Fructus and its major active compounds. TCMSP and TCMIP were used to search for the chemical constituents of Piperis Longi Fructus, as well as the oral bioavailability(OB), drug-likeness(DL), intercellular permeability of intestinal epithelial cells(Caco-2) and Drug-likeness grading were set as limiting conditions. The related target genes of Piperis Longi Fructus were queried by TCMSP database, while related targets of LF were screened by GeneCards databases. Interaction network was constructed using Cytoscape 3.7.1. These above data were imported into STRING database for PPI network analysis. Enrichment of gene ontology(GO) and pathway analysis(KEGG) within Bioconductor database were utilized to note functions of related targets of Piperis Longi Fructus. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The effects of piperlongumine(PL), the major active component of Piperis Longi Fructus, on proliferation of rat liver stellate cells(HSC-T6) and expression of α smooth muscle actin(α-SMA) and collagen Ⅰ were investigated. The major factors TNF-α of tumor necrosis factor(TNF) pathway and NF-κB p65, IL-6 protein expressions of LF process were examined. A total of 12 active compounds such as PL were obtained by analyzing the bioavailability and drug-like properties, which inferred to 48 targets. The functional enrichment analysis of GO obtained 1 240 GO items, mainly involving in process of biology and molecular function. A total of 99 signaling pathways were enriched in the KEGG pathway enrichment analysis, including TNF signaling pathway, cGMP-PKG signaling pathway, calcium signaling pathways. CCK-8 assay showed that PL inhibited proliferation of HSC-T6 induced by transforming growth factor-ß1(TGF-ß1). Western blot analysis found that treated with PL suppressed the protein expressions of α-SMA, collagen Ⅰ, TNF-α and p65 in HSC-T6. Enzyme linked immunosorbent assay(ELISA) showed that PL inhibited the expressions of TNF-α and IL-6 in the cluture supertant of HSC-T6 cells. In conclusion, PL could play an anti-liver fibrosis role by regulating TNF/NF-κB signaling pathway. This study provided the mechanism basis of anti-LF effects induced by Piperis Longi Fructus and its major active compounds, which might help for the further study of the mechanism and key targets of Piperis Longi Fructus.

Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy.

BACKGROUND: Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. METHODS: To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. RESULTS: Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. CONCLUSION: Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1.

Pharmacological targets and clinical application of traditional Chinese medicine and active components in the prevention and treatment for depression / 中国临床药理学与治疗学

The pathological mechanism for depression is complicated due to the involvement of types of transcriptional factors and signaling pathways in the occurrence and development of depression. Traditional Chinese medicine (TCM) characterized with multi-components and multi-targets exert unique advantage in the prevention and treatment of depression. This review summarized the pharmacological action of TCM and active components on transcriptional factors (CREB, NF-κB, Nrf2) and signaling pathways (BDNF-TrkB, MAPK, GSK-3β, TLR-4-NLRP3-IL-1β) as well as elucidated the clinical application of TCM formula in the prevention and treatment for depression based on relevant literatures from home and abroad.