Effect of Haoqin Qingdan Tang on influenza A virus through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway.

OBJECTIVE: Influenza, a viral respiratory illness, leads to seasonal epidemics and occasional pandemics. Given the rising resistance and adverse reactions associated with anti-influenza drugs, Traditional Chinese Medicine (TCM) emerges as a promising approach to counteract the influenza virus. Specifically, Haoqin Qingdan Tang (HQQDT), a TCM formula, has been employed as an adjuvant treatment for influenza in China. However, the active compounds and underlying mechanisms of HQQDT remain unknown. AIM: The aim of this study was to investigate HQQDT's antiviral and anti-inflammatory activities in both in vivo and in vitro, and further reveal its active ingredients and mechanism. METHODS: In vivo and in vitro experiments were conducted to verify the antiviral and anti-inflammatory activities of HQQDT. Subsequently, the active ingredients and mechanism of HQQDT were explored through combining high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) analysis and network pharmacology. Finally, the examinations of cell cytokines and signaling pathways aimed to elucidate the predicted mechanisms. RESULTS: The results indicated that HQQDT exhibited inhibitory effects on influenza viruses A/PR/8/34 (H1N1), A/HK/1/68 (H3N2), and A/California/4/2009 (H1N1) in vitro. Furthermore, HQQDT enhanced the survival rate of influenza-infected mice, reduced the lung index and lung virus titer, and mitigated lung tissue damage in vivo. The proinflammatory cytokine expression levels upon influenza virus infection in PR8-induced A549 cells or mice were suppressed by HQQDT, including IL-6, IL-1ß, CCL2, CCL4, IP-10, interferon ß1 (IFN-ß1), the interferon regulatory factor 3 (IRF3), and hemagglutinin (HA). Twenty-two active components of HQQDT against influenza were identified using HPLC-Q-TOF-MS analysis. Based on network pharmacological predictions, the JAK/STAT signaling pathway is considered the most relevant for HQQDT's action against influenza. Finally, western blot assays revealed that HQQDT regulated the protein level of the JAK/STAT signaling pathway in PR8-infected A549 cells and lung tissue. CONCLUSION: These findings verified the antiviral and anti-inflammatory effects of HQQDT through JAK-STAT signaling pathway in influenza infections, laying the foundation for its further development.

Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy.

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.

Sangbaipi decoction exerted in vitro and in vivo anti-influenza effect through inhibiting viral proteins.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Sangbaipi Decoction (SBPD) is an effective treatment for lung diseases caused by phlegm-heat obstruction according to Jingyue Quanshu, and soothes panting by purging the lung meridian. It is composed of anti-pyretic herbs (e.g., Scutellaria baicalensis Georgi and Coptis chinensis Franch.) and antitussive herbs (e.g., Cortex Mori and Armeniacae Semen Amarum). Therefore, we hypothesized that SBPD has therapeutic effects on lung injury caused by influenza virus. AIM OF THE STUDY: This study aimed to explore anti-influenza activity, active components, and mechanisms of SBPD. MATERIALS AND METHODS: The anti-influenza activities of SBPD were determined in 48 h drug-treated MDCK cell model using CPE and plaque reduction assays, and 24 h drug-treated A549 cells using qRT-PCR. The in vivo efficacy of SBPD (1.0 g/kg/day and 0.5 g/kg/day) was evaluated in PR8 infected BALB/c mice. The chemical component was assessed through HPLC-Q-TOF MS/MS analysis. Network pharmacology was built via TCMSP, GeneCards, DisgeNet, OMIM, DrugBank databases, and Cytoscape software. Additionally, TOA, HI and NAI assays were employed to investigate impact on the virus replication cycle with different concentrations of SBPD (2.5 mg/mL, 1.25 mg/mL, or 0.625 mg/mL). RESULTS: In MDCK infected with viruses A/PR/8/34, A/Hong Kong/1/68, or A/California/4/2009, the IC50 values of SBPD were 0.80 mg/mL, 1.20 mg/mL, and 1.25 mg/mL. In A549 cells, SBPD treatment reduced cytokine expression (e.g., TNF-α, IL-6, IL-1ß) (p < 0.05). In PR8 infected BALB/c mice, SBPD improved the survival rate of infected mice, reduced lung index (p < 0.05), protected lung tissue from pathological damage, and regulated cytokine overexpression (p < 0.05). 29 components of SBPD were identified in SBPD treated mouse serum including some phytochemicals targeting influenza proteins. HI and NAI assays suggested the potential antiviral mechanism of SBPD through inhibition of HA and NA. CONCLUSION: This study is the first to demonstrate the anti-influenza and the anti-inflammatory effects of SBPD in vitro and in vivo. Its major anti-influenza phytochemicals were explored and its inhibitory effects on HA and NA protein were proved. It provides more options for anti-influenza drug discovery.

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer.

Ferroptosis is a type of iron-dependent programmed cell death characterized by the dysregulation of iron metabolism and the accumulation of lipid peroxides. This nonapoptotic mode of cell death is implicated in various physiological and pathological processes. Recent findings have underscored its potential as an innovative strategy for cancer treatment, particularly against recalcitrant malignancies that are resistant to conventional therapies. This article focuses on ferroptosis-based therapeutic strategies for precision cancer treatment, covering the molecular mechanisms of ferroptosis, four major types of ferroptosis inducers and their inhibitory effects on diverse carcinomas, the detection of ferroptosis by fluorescent probes, and their implementation in image-guided therapy. These state-of-the-art tactics have manifested enhanced selectivity and efficacy against malignant carcinomas. Given that the administration of ferroptosis in cancer therapy is still at a burgeoning stage, some major challenges and future perspectives are discussed for the clinical translation of ferroptosis into precision cancer treatment.

Design, Synthesis and Anti-cancer Evaluation of Nitrogen-containing Derivatives of 30-Carboxyl of Gambogic Acid.

BACKGROUND: Gambogic acid (GA) is a natural product from the resin of the Garcinia species, which showed significant activity in the induction of apoptosis. It can be one promising lead compound for the design and synthesis of new anticancer drugs. OBJECTIVE: The objective of the current study is to design novel nitrogen-contained GA derivatives with better anti-cancer activities and study the effect of the introduction of different nitrogen-contained groups on the activity of GA. METHODS: The designed 15 derivatives were synthesized via esterification or amidation of 30-carboxylate. The synthetic compounds were characterized via different spectroscopic techniques, including X-ray single crystal diffraction, MS and NMR. The cytotoxic activity of the designed derivatives was evaluated in vitro against A549, HepG-2, and MCF-7 cell lines using methyl thiazolyl tetrazolium (MTT) test. RESULTS: 15 nitrogen-contained GA derivatives were successfully synthesized and established. Based on the IC50 values, compounds 9, 10, 11 and 13 showed stronger inhibitory effects on A549, HepG-2, MCF-7 cell lines than GA, while 9 is the most active compound with IC50 value of 0.64-1.49 µM. Most derivatives of GA with esterification of C-30 including cyano-benzene ring were generally weaker than those of pyrimidinyl-substituted derivatives. In addition, length of alkyl linkers between C-30 of GA and nitrogen-contained group produced different effects on A549, HepG-2 and MCF-7 cell lines. CONCLUSION: The structure-activity relationship results show that aromatic substituent and linker length play important roles to improve the anticancer activities, while compound 9 with pyrimidine substituent and C-C-C linkers is the most active derivative against tested cell lines, and is a promising anti-cancer agent for further development.

Recent advances towards natural plants as potential inhibitors of SARS-Cov-2 targets.

CONTEXT: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still ongoing and currently the most striking epidemic disease. With the rapid global spread of SARS-CoV-2 variants, new antivirals are urgently needed to avert a more serious crisis. Inhibitors from traditional medicines or natural plants have shown promising results to fight COVID-19 with different mechanisms of action. OBJECTIVES: To provide comprehensive and promising approaches to the medical community in the fight against this epidemic by reviewing potential plant-derived anti-SARS-CoV-2 inhibitors. METHODS: Structural databases such as TCMSP (http://lsp.nwu.edu.cn/tcmsp.php), TCM Database @ Taiwan (http://tcm.cmu.edu.tw/), BATMAN-TCM (http://bionet.ncpsb.org/batman-tcm/) and TCMID (http://www.megabionet.org/tcmid/), as well as PubMed, Sci Finder, Research Gate, Science Direct, CNKI, Web of Science and Google Scholar were searched for relevant articles on TCMs and natural products against SARS-CoV-2. RESULTS: Seven traditional Chinese medicines formulas have unique advantages in regulating the immune system for treating COVID-19. The plant-derived natural compounds as anti-SARS-CoV-2 inhibitors were identified based on 5 SARS-CoV-2 key proteins, namely, angiotensin-converting enzyme 2 (ACE2), 3 C-like protease (3CLpro), papain-like protease (PLpro), spike (S) protein, and nucleocapsid (N) protein. CONCLUSIONS: A variety of natural products, such as flavonoids, terpenoids, phenols, and alkaloids, were identified, which could be used as potential SASR-Cov-2 inhibitors. These shed new light on the efficient discovery of SASR-Cov-2 inhibitors from natural products.

Drug induced mitochondria dysfunction to enhance photodynamic therapy of hypoxic tumors.

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer. To synergize their pharmacological behaviors, Ce6 and IVM are encapsulated into stable Pluronic F127 micelles. The micelles are uniform in size and seem well-suited for the co-delivery of Ce6 and IVM. The micelles could passively target the drugs into tumors and enhance their cellular internalization. Most importantly, through mitochondrial dysfunction, the micelles reduce the oxygen consumption (making the tumor less hypoxic). Consequently, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.

Network pharmacology associated anti-influenza mechanism research of Qingjie-Tuire Granule via STAT1/3 signaling pathway.

Qingjie-Tuire (QT) granule was approved for clinical use and its combination was reported to treat influenza infection. To explore its active component and mechanism, the components of QT granule were retrieved from UPLC-UC-Q-TOF/MS analysis. The genes corresponding to the targets were retrieved using GeneCards and TTD database. The herb-compound-target network was constructed by Cytoscape. The target protein-protein interaction network was built using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of QT granule to IAV were performed for further study. The regulation to different signaling transduction events and cytokine/chemokine expression of QT granule was evaluated using Western blotting and real-time qPCR. Totally, 47 compounds were identified and effect of QT granule on cell STAT1/3 signaling pathways was confirmed by A549 cell model. The efficiency of QT granule on host cell contributes to its clinical application and mechanism research.

Self-delivery biomedicine for enhanced photodynamic therapy by feedback promotion of tumor autophagy.

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. STATEMENT OF SIGNIFICANCE: Autophagy is a "double-edged sword" in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.

Three new phenanthrenes from Pholidota chinensis Lindl. and their antibacterial activity.

Three new phenanthrenes were isolated from Pholidota chinensis Lindl. Their structures were elucidated on the basis of spectroscopic techniques and comparison of their data to the values reported in the literature. From the 95% EtOH extract, three new compounds, namely 9, 10-dihydro-2, 4, 6-trihydroxy-7-methoxyphenanthrene (1), 11-methoxyflaccidin (2), and 2-methoxy-3,7-dihydroxy-5H phenanthro[4,5-bcd] pyran (3), were identified. Compound 3 showed an MIC50 of 68.39 µM against Staphylococcus aureus subsp. Aureus.

Bisabolane-type sesquiterpenoids from Curcuma longa L. exert anti-influenza and anti-inflammatory activities through NF-κB/MAPK and RIG-1/STAT1/2 signaling pathways.

Influenza is a viral respiratory illness that causes seasonal epidemics and occasional pandemics. Disease severity may be contributed by influenza virus-induced cytokine dysregulation. The study was designed to investigate the isolation and identification of bisabolane-type sesquiterpenoids from Curcuma longa L., their antiviral and anti-inflammatory activities against H1N1 and their potential role in regulating host immune response in vitro. A pair of new bisabolane-type sesquiterpenoids, (6S,7S)-3-hydroxy-3-hydroxymethylbisabola-1,10-diene-9-one (18) together with seventeen known analogs (1-17), was isolated and elucidated from Curcuma longa L. Compounds 2, 11 and 14 could significantly inhibit A/PR/8/34 (H1N1) replication in MDCK cells, and compound 2 could significantly inhibit A/PR/8/34 (H1N1) replication in A549 cells. Compounds 4, 8, 9, 13 and 17 could markedly reduce pro-inflammatory cytokine (TNF-α, IL-6, IL-8 and IP-10) production at the mRNA and protein levels in A549 cells. Compound 4 regulated the levels of steroid biosynthesis, oxidative phosphorylation and protein processing in the endoplasmic reticulum, thereby inhibiting immune responses by proteomics analysis. Furthermore, compound 4 could inhibit the expression of p-NF-κB p65, NF-κB p65, IκBα, p-p38 MAPK, p-IκBα, RIG-1, STAT-1/2 and p-STAT-1/2 in the signaling pathways. These findings indicate that bisabolane-type sesquiterpenoids of C. longa could inhibit the expression of inflammatory cytokines induced by the virus and regulate the activity of NF-κB/MAPK and RIG-1/STAT-1/2 signaling pathways in vitro.

Progress of Plant Medicine Derived Extracts and Alkaloids on Modulating Viral Infections and Inflammation.

Viral infectious diseases are serious threats to human health in both developing and developed countries. Although there is the continued development of new drugs from synthetic sources as antiviral agents, medicinal plants continue to provide the basic raw materials for some of the most important antiviral drugs. Alkaloids are a class of pharmacologically active plant compounds that are usually alkaline in nature. In this review, we tried to summarize recent progress in herb-based antiviral research, the advantages of using active plant compounds as antiviral agents, and the inflammatory responses initiated by alkaloids, based on the literature from 2009 to 2019, for the treatment of conditions, including influenza, human immunodeficiency virus, herpes simplex virus, hepatitis, and coxsackievirus infections. Articles are retrieved from PubMed, Google Scholar, and Web of Science using relevant keywords. In particular, the alkaloids from medicinal plants responsible for the molecular mechanisms of anti-inflammatory actions are identified and discussed. This review can provide a theoretical basis and approaches for using various alkaloids as antiviral treatments. More research is needed to develop alkaloidal compounds as antiviral therapeutic agents and potential regulators of the anti-inflammatory response.

Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines.

Alkyl carboxylic acids as well as primary amines are ubiquitous in all facets of biological science, pharmaceutical science, chemical science and materials science. By chemical conversion to redox-active esters (RAE) and Katritzky's N-alkylpyridinium salts, respectively, alkyl carboxylic acids and primary amines serve as ideal starting materials to forge new connections. In this work, a Mn-mediated reductive decarboxylative/deaminative functionalization of activated aliphatic acids and primary amines is disclosed. A series of C-X (X = S, Se, Te, H, P) and C-C bonds are efficiently constructed under simple and mild reaction conditions. The protocol is applicable to the late-stage modification of some structurally complex natural products or drugs. Preliminary mechanistic studies suggest the involvement of radicals in the reaction pathway.

Phytochemical Profiles and their Anti-inflammatory Responses Against Influenza from Traditional Chinese Medicine or Herbs.

Traditional Chinese medicine (TCM) or herbs are widely used in the prevention and treatment of viral infectious diseases. However, the underlying mechanisms of TCMs remain largely obscure due to complicated material basis and multi-target therapeutics. TCMs have been reported to display anti-influenza activity associated with immunoregulatory mechanisms by enhancing host antiinfluenza immune responses. Previous studies have helped us understand the direct harm caused by the virus itself. In this review, we have tried to summarize recent progress in TCM-based anti-influenza research on the indirect harmful immune responses caused by influenza viruses. In particular, the phytochemicals from TCMs responsible for molecular mechanisms of action belonging to different classes, including phenolic compounds, flavonoids, alkaloids and polysaccharides, have been identified and demonstrated. In addition, this review focuses on the pharmacological mechanism, e.g., inflammatory responses and the interferon (IFN) signaling pathway, which can provide a theoretical basis and approaches for TCM based anti-influenza treatment.

Anti-asthmatic activity of alkaloid compounds from Pericarpium Citri Reticulatae (Citrus reticulata 'Chachi').

Pericarpium Citri Reticulatae (PCR, Citrus reticulata 'Chachi', Guangchenpi in Chinese) is one of the most famous Chinese citrus herbal medicines. The in vivo anti-asthmatic activity of 'Chachi' PCR was investigated using a histamine-induced experimental asthma model in Guinea pigs. Two alkaloid-type compounds, synephrine and stachydrine, were analyzed and identified in the 'Chachi' PCR alkaloid fraction. The alkaloid fraction and synephrine protected Guinea pigs against histamine-induced experimental asthma in a dose-dependent manner. The respective application of high, middle, and low doses of the 'Chachi' PCR alkaloid fraction significantly increased specific airway resistance by 284%, 328%, and 355%, and decreased dynamic compliance by 57%, 67%, and 75%. A similar change was observed for synephrine. The expression of eosinophils in bronchoalveolar lavage fluid (BALF) and serum IgE, IL-4, and IL-5 levels in histamine-induced experimental asthmatic Guinea pigs were significantly downregulated by the 'Chachi' PCR alkaloid fraction and synephrine compared to the control group, whereas stachydrine did not impart a statistically significant effect on the expression of tested inflammatory cells (leucocytes, eosinophils, neutrophils, and lymphocytes), immunoglobulin (IgE), or cytokines (IL-4 and IL-5). Pathological changes in lung tissues in each treatment group included the infiltration of inflammatory cells around the bronchia.

Targeted Treatments for Chronic Obstructive Pulmonary Disease (COPD) Using Low-Molecular-Weight Drugs (LMWDs).

Chronic obstructive pulmonary disease (COPD) is a very common and frequently fatal airway disease. Current therapies for COPD depend mainly on long-acting bronchodilators, which cannot target the pathogenic mechanisms of chronic inflammation in COPD. New pharmaceutical therapies for the inflammatory processes of COPD are urgently needed. Several anti-inflammatory targets have been identified based on increased understanding of the pathogenesis of COPD, which raises new hopes for targeted treatment of this fatal respiratory disease. In this review, we discuss the recent advances in bioactive low-molecular-weight drugs (LMWDs) for the treatment of COPD and, in addition to the first-line drug bronchodilators, focus particularly on low-molecular-weight anti-inflammatory agents, including modulators of inflammatory mediators, inflammasome inhibitors, protease inhibitors, antioxidants, PDE4 inhibitors, kinase inhibitors, and other agents. We also provide new insights into targeted COPD treatments using LMWDs, particularly small-molecule agents.

A novel icariin type flavonoid from Epimedium pseudowushanense.

A novel icariin type flavonoid glycoside with a malonaldehydic acid intramolecular ester and two known flavonoid glycosides were isolated from Epimedium pseudowushanense. Their structures were elucidated on the basis of spectroscopic analysis and comparison of their data to the values reported in the literatures. The anti-inflammatory activities of these compounds icariin 3'''-O-malonaldehydic acid intramolecular 1'''', 2''' ester (1), icariin (2) and epimedin C (3) were tested. The results indicated that compounds 1, 2 and 3 showed maximal inhibitory ratio of 27.91, 44.80 and 46.61%, respectively in in vitro anti-inflammatory activity on LPS-induced TNF-α secretion in RAW264.7 cells. Compounds icariin (2) and epimedin C (3) were found to inhibit the secretion of TNF-α to a comparable degree as quercetin.

Sheng Jiang San, a traditional multi-herb formulation, exerts anti-influenza effects in vitro and in vivo via neuraminidase inhibition and immune regulation.

BACKGROUND: Sheng Jiang San (SJS), a multi-herb formulation, is used in treating high fever, thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza nowadays. However, there is no evidence-based investigation and mechanism research to support the anti-influenza efficacy of SJS. This study aims at evaluating the anti-influenza effect of SJS and investigating its possible mechanism. METHODS: The inhibitory effect of SJS against different influenza virus strains on MDCK cells was examined. Influenza virus infected BALB/c mice were employed to evaluate the efficacy as in vivo model. Mice challenged with A/PR/8/34 (H1N1) were orally administrated 1 g/kg/day of SJS for seven days and monitored for 14 days. The survival rate, body weight changes, lung index, lung viral load, histopathologic changes and immune regulation of the mice were measured. The underlying anti-influenza virus mechanism of SJS was studied by a series of biological assays to determine if hemagglutinin, ribonucleoprotein complex or neuraminidase were targets of SJS. RESULTS: Results showed SJS exerted a broad-spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner. IC50 of SJS against A/WSN/33 (H1N1) was lower than 35 µg/ml. SJS also protected 50% of mice from A/PR/8/34 (H1N1) infection. The lung index and the lung viral load of SJS treated mice were significantly decreased compared with untreated mice. Meanwhile, SJS targeted on neuraminidase of influenza virus as SJS at 2 mg/ml inhibited 80% of neuraminidase enzymatic activity. SJS also significantly down-regulated TNF-α and up-regulated IL-2 of influenza virus induced mice. CONCLUSIONS: Thus, SJS is a useful formulation for treating influenza virus infection.

Anti-inflammatory neolignans from Epimedium pseudowushanese.

One new 8-O-4' neolignan has been isolated from Epimedium pseudowushanese B. L. Guo, together with nine other known neolignans. The structures of these neolignans were elucidated using spectroscopic and chemical techniques, and their anti-inflammatory activities were also evaluated. The results of these experiments revealed that compound 6 was the most potent of the 10 different compounds tested in the current study, with a maximal inhibitory ratio of 79% for its in vitro anti-inflammatory activity towards lipopolysaccharide-induced tumour necrosis factor alpha secretion in RAW264.7 cells. The other nine compounds exhibited only moderate inhibitory effects.

Inhibition of influenza virus via a sesquiterpene fraction isolated from Laggera pterodonta by targeting the NF-κB and p38 pathways.

BACKGROUND: Influenza virus poses serious threats to human health, especially human infection with avian influenza virus. Laggera pterodonta (DC.) Benth is a medicinal plant that is widely used in Traditional Chinese Medicine, especially in Yunnan province, and has been used to treat influenza, pharyngolaryngitis, and bronchitis. However, the compound(s) responsible for the activity and their mechanisms of action against the influenza virus remain to be elucidated. METHODS: L. pterodonta extract was fractionated, and the active fraction was identified as Fraction 14 (Fr 14). Fr 14 was further analysed and characterized by ultra-high-performance liquid chromatography hyphenated with quadrupole-time of flight mass spectrometry (UHPLC/Q-TOF-MS). The inhibitory effect against influenza virus was evaluated using a cytotoxicity assay. Then, cytokines and chemokines were detected by qRT-PCR and a bio-plex assay. Signalling pathways that inhibited the influenza virus were identified using a western blotting assay. RESULTS: The active fr 14 showed a wide spectrum of anti-influenza virus activity. The pharmacological mechanisms showed that Fr 14 acts on the early stage of virus replication (0-6 h). It inhibited the p38/MAPK pathway and then inhibited the NF-κB pathway and COX-2. Fr 14 also prevented the increased expression of cytokines and chemokines. CONCLUSION: This study demonstrated the preliminary mechanisms of fr 14 against the influenza virus. Fr 14 possessed antiviral and anti-inflammatory effects. L. pterodonta can be used to develop innovative antiviral drugs, and further studies will be performed to illustrate the detailed mechanisms.