Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.

Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.

To explore the effect of kaempferol on non-small cell lung cancer based on network pharmacology and molecular docking.

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.

Research progress of natural products for the treatment of ischemic stroke.

Stroke is a leading cause of death and disability world-widely. The incidence rate of stroke has been increasing due to the aging population and lifestyle changes. At present, the only drug approved by the US Food and Drug Administration (FDA) for the treatment of ischemic stroke is tissue plasminogen activator (t-PA), but its clinical application is greatly limited because of its narrow time window and bleeding risk. Natural products have a long history of being used in traditional medicine with good safety, making them an important resource for the development of new drugs. Indeed, some natural products can target a variety of pathophysiological processes related to stroke, including oxidative stress, inflammation and neuronal apoptosis. Therefore, the development of high-efficiency, low-toxicity, safe and cheap active substances from natural products is of great significance for improving the treatment alternatives of patients with stroke. This article reviews the neuroprotective effects of 33 natural compounds by searching recent related literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), and resveratrol have great potential in the clinical treatment of ischemic stroke. This review will provide a powerful reference for screening natural compounds with potential clinical application value in ischemic stroke or synthesizing new neuroprotective agents with natural compounds as lead compounds.