Huanglian-Hongqu herb pair improves nonalcoholic fatty liver disease via NF-κB/NLRP3 pathway in mice: network pharmacology, molecular docking and experimental validation.

The Huanglian-Hongqu herb pair (HH) is a carefully crafted traditional Chinese herbal compound designed to address disorders related to glucose and lipid metabolism. Its primary application lies in treating hyperlipidemia and fatty liver conditions. This study explored the potential mechanism of HH in treating non-alcoholic fatty liver disease (NAFLD) through network pharmacology, molecular docking, and in vivo animal experiments. Ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UPLC-Q-TOF-MS) was employed to identify the chemical composition of HH. Network pharmacology was used to analyze the related signaling pathways affected by HH. Subsequently, the prediction was verified by animal experiment. Finally, we identified 29 components within HH. Network pharmacology unveiled interactions between HH and 153 NAFLD-related targets, highlighting HH's potential to alleviate NAFLD through NF-κB signaling pathway. Molecular docking analyses illuminated the binding interactions between HH components and key regulatory proteins, including NF-κB, NLRP3, ASC, and Caspase-1. In vivo experiments demonstrated that HH alleviated NAFLD by reducing serum and liver lipid levels, improving liver function, and lowering inflammatory cytokine levels in the serum. Moreover, HH administration downregulated mRNA and protein levels of the NF-κB/NLRP3 pathway. In conclusion, our findings demonstrated that HH has potential therapeutic benefits in ameliorating NAFLD by targeting the NF-κB/NLRP3 pathway, facilitating the broader application of HH in the field of NAFLD.

[Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway].

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

Identification of potential targets of triptolide in regulating the tumor microenvironment of stomach adenocarcinoma patients using bioinformatics.

This study aimed to identify potential pharmacological targets of triptolide regulating the tumor microenvironment (TME) of stomach adenocarcinoma (STAD) patients. A total of 343 STAD cases from The Cancer Genome Atlas (TCGA) were assigned into high- or low-score groups applying Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE). Hub genes were identified from differentially expressed genes (DEGs) shared by stromal- and immune-related components in the TME of STAD patients using R software. Cox regression analysis was used to identify genes significantly correlated with STAD patient survival. Triptolide target genes were predicted from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Top 30 genes filtered by Cytohubba from 734 DEGs were screened as hub genes. Forty-two genes were found to be at high risk for STAD prognosis. Thirty-four targets of triptolide were predicted using the TCMSP database. Importantly, C-X-C chemokine receptor type 4 (CXCR4) was identified as a potential target of triptolide associated with the TME in STAD. Analysis of survival highlighted the association between CXCR4 upregulation with STAD progression and poor prognosis. Gene Set Enrichment Analysis (GSEA) confirmed that genes in the CXCR4- upregulated group had significant enrichment in immune-linked pathways. Additionally, triptolide targets were found to be significantly enriched in CXCR4-related chemokine and cancer-related p53 signaling pathways. Molecular docking demonstrated a high affinity between triptolide and CXCR4. In conclusion, CXCR4 may be a therapeutic target of triptolide in the treatment of STAD patients by modulating the TME.

Efficacy and safety of Zuojin Pill for chronic gastritis: Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Chronic gastritis (CG), as the highest incidence of gastrointestinal diseases, has been gradually increasing around globally. With the obvious disadvantages of standard treatment, more and more people ask the traditional Chinese medicine for help in the treatment of CG. As a traditional Chinese medicine compound, Zuojin Pill (ZJP) has a long history of clinical application in the treatment of digestive system diseases. Whereas, neither systematic nor meta-analysis of randomized controlled trials explain the efficacy and safety of ZJP in treating CG. Thus, we provide a protocol to evaluate the efficacy and safety of ZJP for CG. METHODS: From the beginning to December 2019, the following electronic databases will be searched for studies in English or Chinese: the Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, and the Wanfang Database. Clinical efficiency, helicobacter pylori infection clearance rate, quality of life and symptom scores will be measured as primary outcomes. Meta-analysis will be performed using the Stata 15. OUTCOMES: This study will provide the current evidence of CG treated with ZJP from the several aspects including clinical efficiency, helicobacter pylori infection clearance rate, quality of life, symptom scores, the 1-year recurrent rate, efficacy under endoscopy and number of reported adverse events associated with the use of ZJP. CONCLUSION: The outcomes of this review will be served as a proof to evaluate if ZJP is effective in the treatment of CG. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020155036.