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Mechanisms and molecular targets of the Yu-Ping-Feng powder for allergic rhinitis, based on network pharmacology.

ABSTRACT:

Abstract

In traditional Chinese medicine (TCM), Yu-Ping-Feng powder (YPFP) has been used to treat allergic rhinitis (AR) for centuries. However, the mechanisms underlying its effects or its molecular targets in AR treatment are yet to be elucidated. Therefore, the active compounds of YPFP and their targets were collected and identified from the Traditional Chinese Medicine Systems Pharmacology database. Moreover, AR-associated targets were acquired from the GeneCards and Online Mendelian Inheritance in Man database. Proteins interactions network of YPFP presumed targets and AR-associated targets were examined and merged to reveal the candidate YPFP targets against AR.Cytoscape software and BisoGenet Database were employed to perform the Visualization and Integrated Discovery (Cluster Profiler R package, version: 3.8.1). Kyoto Encyclopedia of Genes and Genomes and genome pathway analyses. To identify the key target genes, a gene-pathway network has been constructed.We identified 44 effective active compounds and 622 YPFP targets. Also 1324 target genes related to AR were identified. Twenty pathways, including those of AGE-RAGE signaling, fluid shear stress, atherosclerosis, PI3K-Akt signaling, and tumor necrosis factor signaling was enriched significantly. MAPK1 was identified as the core gene, while others including RELA, AKT1, NFKBIA, IL6, and JUN, were also important in the gene-pathway network. Clearly, network pharmacology can be applied in revealing the molecular targets and mechanisms of action of complex herbal preparations.These findings suggested that YPFP could treat AR by regulating immunological functions, diminishing inflammation, and improving immunity through different pathways.

SUBMITTER: Yang S

PROVIDER: S-EPMC8415986 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe potential treatment effects and safety of Yu ping feng san (YPFS) for pediatric allergic rhinitis (PAR) patients have yet to be studied systematically.ObjectivesTo assess the effects and safety of YPFS for treat pediatric patients, allergic rhinitis.MethodsWe systematically searched PubMed, EMBASE (Excerpta Medical Database), Cochrane library, Chinese Cochrane Centre's Controlled Trials Register platform, Wanfang Chinese Digital Periodical and Conference Database, China National Knowledge Infrastructure Database, and VIP Chinese Science, from inception dates to November 1, 2019. Randomized controlled trials (RCTs) were included. The risk of bias in the trials was assessed in accordance with the Cochrane Handbook, version 5.1.0. RevMan 5.3 software was used to perform a meta-analysis. Grading of Recommendations Assessment, Development and Evaluation methodology was applied to evaluate the evidence quality for each outcome. The quality of evidence for each outcome measurement was low for 4 outcomes and very low for 5 outcomes.ResultsA total of 10 RCTs involving 1069 participants (3-15 years old) fulfilled the inclusion criteria. After exclusion, 8 RCTs were pooled for efficacy assessment. The overall efficacy evaluation result did not show benefit for the experimental group (relative risk 0.32, CI 95% 0.24-0.45; P = .98;) Investigation of variation of serum IgA, immunoglobulin E, IgG in three studies in 2 groups returned no statistical significance. YPFS gave relatively better safety (relative risk 0.29, CI 95% 0.14-0.58; P = .0005; Fig. S8, http://links.lww.com/MD/F751) and lower recurrence rates than did Western medical therapy.ConclusionsCurrent evidence cannot support the routine use of YPFS for treatment of PAR. This may be due to poor-quality study-design limitations of the included YPFS studies. Our data showed that the use of YPFS for PAR is relatively safe compared to Western medical therapy, but a conclusion could not be drawn because only 5 studies were analyzed. Every study suffered from some methodological limitation. Therefore, further large, rigorously-designed studies are necessary to determine conclusively the utility of YPFS in PAR.

Project description:Chinese herbal medicine formula Yu ping feng san (YPFS) is commonly used for allergic rhinitis (AR). Previous review had summarized the effectiveness and safety of YPFS, however without any subgroup analysis performed to provide detailed evidence for guiding clinical practice. YPFS was recommended for the management of AR by Chinese medicine clinical practice guideline, but the treatment duration of YPFS was also not specified. The aim of this study is to evaluate the effectiveness and safety of YPFS in treating adult AR with the most recent evidence, and attempt to specify the duration of utilisation through subgroup meta-analyses.Seven databases were searched from their inceptions to September 2017. Randomized controlled trials (RCTs) evaluating YPFS for adult AR were included. Methodological quality of studies was assessed using the Cochrane risk of bias tool. Meta-analysis and subgroup meta-analyses were conducted for evaluating the effectiveness of YPFS. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence.Twenty-two RCTs involving 23 comparisons were included in this review. YPFS was compared to placebo, pharmacotherapy, and used as an add-on treatment compared to pharmacotherapy. Meta-analyses were feasible for the outcomes of four individual nasal symptom scores and "effective rate". Four individual nasal symptom scores decreased after YPFS' combination treatment: itchy nose (MD-0.46, 95% CI[-0.50, -0.42]), sneezing (MD-0.41, 95% CI[-0.47, -0.35]), blocked nose (MD-0.46, 95% CI[-0.54, -0.39]) and runny nose (MD-0.42, 95% CI[-0.58, -0.26]). Based on "effective rate", meta-analysis showed that YPFS did not achieve better effect than pharmacotherapy (RR1.07, 95%CI [0.94, 1.22), but its combination with pharmacotherapy seemed more effective than pharmacotherapy alone (RR1.27, 95%CI [1.19, 1.34]) (low quality). Subgroup analysis suggested that YPFS was not superior to the second-generation antihistamine (RR1.04, 95%CI [0.90, 1.19]) (low quality). Further, YPFS' combination treatment seemed more beneficial when it was used for more than three weeks (RR1.15, 95%CI [1.01, 1.32]). In addition, YPFS was well-tolerated for treating adult AR.Chinese herbal medicine formula YPFS seems beneficial for adult AR. This potential benefit need to be further evaluated by more rigorous RCTs.

Project description:The incidence of asthma has increased in recent decades. Although corticosteroids and bronchodilators are used in clinical practice, the control of asthma remains a challenge. Allergic asthma is characterized airway inflammation mediated by type 2 immune response. Group 2 innate lymphoid cells (ILC2s) are an important source of type 2 cytokines IL-5 and IL-13, which contribute to the progress of asthma. Jia-Wei-Yu-Ping-Feng-San (JWYPFS), a traditional Chinese medicine, has been widely used to treat asthma in China. In this study we investigated the mechanisms of JWYPFS in the treatment of asthma, especially the effect on ILC2s important in airway inflammation. Female C57BL/6 mice were sensitized and challenged with OVA to establish a model of allergic asthma. Airway hyperresponsiveness was examined by direct airway resistance analysis. Inflammatory cell counts were determined in bronchoalveolar lavage fluid (BALF). Inflammatory cell infiltration and mucus hypersecretion in lung tissue sections was observed by HE and PAS staining, respectively. The numbers and proportions of ILC2s as well as the ILC2s-related transcription factors GATA3, IRF4, and type 2 cytokines were measured in lung tissue samples. Additionally, ILC2s were collected from mouse lung; ILC2s-related cytokines and GATA3 and IRF4 were evaluated after IL-33-induced activation of ILC2s in vitro. Elevated inflammatory cells, mucus secretion, airway hyperresponsiveness and type 2 cytokines in the OVA-treated asthma group indicated that an allergic asthma model had been established. JWYPFS treatment attenuated airway resistance and reduced inflammatory cells including eosinophils, and inhibited mucus production and type 2 cytokines in these asthmatic mice. Moreover, JWYPFS treatment dramatically decreased the numbers and proportions of ILC2s and the mRNA levels of GATA3 and IRF4. In an in vitro experiment JWYPFS significantly suppressed GATA3, IRF4 and type 2 cytokine expression, including IL-5 and IL-13 in IL-33-stimulated ILC2s. JWYPFS alleviates ILC2s-mediated airway inflammation, suggesting that JWYPFS might be an effective agent to treat allergic asthma.

Project description:Yu-Ping-Feng (YPF) formula is a classical prescription used for enhancing the body's immunity function in traditional Chinese medicine (TCM). In clinical practice, the YPF formula has been reported to exhibit antilung cancer and immunomodulatory effect. However, the relationship between them remains unclear. The present study aimed to investigate the antilung cancer effect of the YPF formula and its immune-related mechanisms. The C57BL/6 tumor-bearing mice model was established and randomly divided into the YPF group and the control group. Tumor volume, spleen weight, and survival in both groups were measured and evaluated during 28 days of consecutive intervention. Flow cytometry was used to detect the proportion of immune cell subsets. Myeloid-derived suppressor cells (MDSCs) were induced in vitro from bone marrow cells. After intervention by the YPF formula, CCK-8 and flow cytometry analyses were performed to detect proliferation and apoptosis of MDSCs. A coculture system containing T cells and MDSCs was established to further study the role of MDSCs in the regulation of T-cell subsets proportion by the YPF formula. The expressions of MDSCs-related genes and proteins were detected by RT-PCR and Western blotting. The results showed the YPF formula inhibited tumor growth, reduced spleen weight, and prolonged the survival of mice. Besides, the proportions of MDSCs subsets and Regulatory T (Treg) in the YPF group decreased, whereas those of CD4 +T and CD8 +T increased both in vitro and in vivo. CCK-8 and flow cytometry demonstrated that the YPF formula could inhibit proliferation and promote apoptosis of MDSCs. The coculture experiments further confirmed that MDSCs served a critical role in regulating the tumor microenvironment by the YPF formula. RT-PCR and Western blotting indicated that the levels of MDSCs' activation and proliferation-related proteins and genes were downregulated in the YPF group. Therefore, our results demonstrated that the YPF formula could promote apoptosis and inhibit the proliferation of MDSCs. As a result, the negative regulatory effect on the positive immune cells induced by MDSCs was weakened, thus achieving the antilung cancer effect by remodeling the tumor microenvironment.

Project description:BackgroundClinically, Yu ping feng san (YPFS) has been extensively used as a medication for treating immune deficiency, and YPFS is combined with chemotherapy drugs to treat cancer, including hepatocellular carcinoma (HCC), lung cancer, and pancreatic cancer. Previous research has shown that YPFS has a therapeutic effect on HCC by improving the immunosuppressive state of the liver cancer microenvironment. The present study aimed to investigate the effect of YPFS on angiogenesis of HCC.MethodsHigh-performance liquid chromatography (HPLC) was used to certify the composition of YPFS. An orthotopic transplanted model of murine HCC was entrenched. Immunohistochemistry was used to observe the changes of the microvessel density (MVD). The MTT assay was used to detect the cell viability. ELISA was performed to analyze the expression of related factors. Western blot was used to analyze the protein expression. Tube formation assay was used to analyze the anti-angiogenic efficiency.ResultsYPFS significantly reduced the tumor volume and weight, thus exerted the growth inhibitory effect. The level of MVD and VEGF was obviously decreased in YPFS-treated HCC-bearing mice, and the YPFS treatment also reduced the VEGF level in Hepa1-6 cells. Further study revealed that the expression of TSLP/TSLPR and p-STAT3/STAT3 was decreased by YPFS. The level of MVD and VEGF and the expression of TSLP/TSLPR and p-STAT3/STAT3 in tumor tissue and Hepa1-6 cells were suppressed by incubation with the anti-TSLP antibody, whereas treatment with the anti-TSLP antibody in YPFS-treated cells did not cause further significant inhibition compared with the cells treated only with YPFS. More importantly, YPFS inhibited proliferation, expression of p-STAT3/STAT3, and tube formation of HUVECs induced by TSLP.ConclusionsThese results indicated that YPFS attenuated the activation of the TSLP-STAT3 signaling pathway by inhibiting the immune-related factor-TSLP, thereby inhibiting the formation of hepatic microvessels and exerting an anti-HCC effect.

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Mechanisms and molecular targets of the Yu-Ping-Feng powder for allergic rhinitis, based on network pharmacology.

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