Coriolus versicolor and its bioactive molecule are potential immunomodulators against cancer cell metastasis via inactivation of MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor (CV) has been used in traditional Chinese medicine for over 2000 years as a premium medicine for enhancing good health and longevity. The immunomodulatory and anti-cancer effects of polysaccharopeptides (PSP) from cultured CV have been extensively studied; however, the effect and the mechanism of action of other small molecules from CV remain unknown. AIM OF THE STUDY: we aim to examine the immunomodulatory and anti-cancer effects of the small molecules from CV (SMCV) and identify the active compounds that are responsible for the biological effects against glioblastoma multiforme cells. MATERIALS AND METHODS: The effects of SMCV/active compound on cytokine and MMP mRNA expressions and productions were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. An active compound from SMCV was identified with a bioassay-guided fractionation scheme. The potential mode of action of the active compound was further investigated by identifying the cell signaling pathway. The protein expressions of phospho-ERK, phospho-JNK and phospho-p38 MAPKs were measured by Western Blotting. The anti-invasive effect of SMCV/bioactive compound against T98G, lung carcinoma (A549), and breast adenocarcinoma (MDA-MB-231) cells were determined using invasion assay. RESULTS: Our results showed that SMCV had strong immunomodulatory effect by suppressing LPS-induced TNF-α production, whereas increasing poly I:C-induced IFN-ß level in PBMac. SMCV not only possessed indirect anti-cancer effect by suppressing TNF-α-induced MMP-3 production in glioblastoma T98G cells, but also directly reduced the invasion ability of malignant cells including T98G, A549 and MDA-MB-231. Using bioassay-guided fractionation scheme, we isolated 9-KODE methyl ester (compound AM) that was responsible for the bioactivity of SMCV. This compound suppressed TNF-α-induced MMP-3 production in T98G cells and the suppression may be correlated with the inactivation of p38 mitogen-activated protein kinase (MAPK) pathway. Moreover, compound AM also directly reduced T98G cell invasion. CONCLUSION: Results of our present study provides scientific evidence that SMCV possesses immunomodulatory and anti-cancer effects. Its bioactive compound, compound AM, is a potential new drug candidate against the invasion and metastasis of glioblastoma cells.

Seroprevalence of SARS-CoV-2 among adults in three regions of France following the lockdown and associated risk factors: a multicohort study.

Aim To estimate the seroprevalence of SARS-CoV-2 infection in May-June 2020 after the lockdown in adults living in three regions in France and to identify the associated risk factors. Methods Participants in a survey on COVID-19 from an existing consortium of three general adult population cohorts living in the Ile-de-France (IDF) or Grand Est (GE), two regions with high rate of COVID-19, or in the Nouvelle-Aquitaine (NA), with a low rate, were asked to take a dried-blood spot (DBS) for anti-SARS-CoV-2 antibodies assessment. The primary outcome was a positive anti-SARS-CoV-2 ELISA IgG result against the spike protein of the virus (ELISA-S). The secondary outcomes were a positive ELISA IgG against the nucleocapsid protein (ELISA-NP), anti-SARS-CoV-2 neutralizing antibodies titers >=40 (SN), and predicted positivity obtained from a multiple imputation model (MI). Prevalence estimates were adjusted using sampling weights and post-stratification methods. Findings Between May 4, 2020 and June 23, 2020, 16,000 participants were asked to provide DBS, and 14,628 were included in the analysis, 983 with a positive ELISA-S, 511 with a positive ELISA-NP, 424 with SN>=40 and 941 (Standard Deviation=31) with a positive MI. Adjusted estimates of seroprevalence (positive ELISA-S) were 10.0% (95%CI 9.1%;10.9%) in IDF, 9.0% (95%CI 7.7%; 10.2%) in GE and 3.1% (95%CI 2.4%; 3.7%), in NA. The adjusted prevalence of positive ELISA-NP, SN and MI were 5.7%, 5.0% and 10.0% in IDF, 6.0%, 4.3% and 8.6% in GE, and 0.6%, 1.3% and 2.5% in NA, respectively. A higher seroprevalence was observed in younger participants and when at least one child or adolescent lived in the same household. A lower seroprevalence was observed in smokers compared to non-smokers. Interpretation At the end of the lockdown the prevalence of anti-SARS-CoV-2 IgG or neutralizing antibodies remained low in the French adult population, even in regions with high reported rates of COVID-19.

Antiviral effect of forsythoside A from Forsythia suspensa (Thunb.) Vahl fruit against influenza A virus through reduction of viral M1 protein.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinqiaosan is a classical traditional Chinese medicine formula, which has been used to treat respiratory diseases since ancient China. It consists of nine herbs and among them, Forsythia suspensa (Thunb.) Vahl fruit is one of the major herbal components. Despite the long history of Yinqiaosan, the active compounds and the mechanisms of action of this formula remain elusive. AIM OF THE STUDY: The present study aimed to examine the suppressive effect of Yinqiaosan on influenza virus and to identify the active components in the formula targeting influenza. MATERIALS AND METHODS: Anti-influenza virus effect of Yinqiaosan was assessed by tissue culture infective dose assay, and was also tested in an in vivo mouse model. Active compound from the formula was identified with a bioactivity-guided fractionation scheme. The potential mode of action of the compound was further investigated by identifying the host cell signaling pathways and viral protein production using in vitro cell culture models. RESULTS: Our results showed that forsythoside A from Forsythia suspensa (Thunb.) Vahl fruit, a major herbal component in Yinqiaosan, reduced the viral titers of different influenza virus subtypes in cell cultures and increased the survival rate of the mice in an in vivo influenza virus infection model. Further experiments on the mode of action of forsythoside A showed that it reduced the influenza M1 protein, which in turn intervened the budding process of the newly formed virions and eventually limited the virus spread. CONCLUSION: Results of our present study provides scientific evidence to support to the application of a traditional herbal formula. We also identify novel candidate compound for future drug development against influenza virus.

Differential effects of Radix Paeoniae Rubra (Chishao) on cytokine and chemokine expression inducible by mycobacteria.

BACKGROUND: Upon initial infection with mycobacteria, macrophages secrete multiple cytokines and chemokines, including interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α), to mediate host immune responses against the pathogen. Mycobacteria also induce the production of IL-10 via PKR activation in primary human monocytes and macrophages. As an anti-inflammatory cytokine, over-expression of IL-10 may contribute to mycobacterial evasion of the host immunity. Radix Paeoniae Rubra (RPR, Chishao), a Chinese medicinal herb with potentials of anti-inflammatory, hepatoprotective and neuroprotective effects, is used to treat tuberculosis. This study investigates the immunoregulatory effects of RPR on primary human blood macrophages (PBMac) during mycobacterial infection. METHODS: The interaction of Bacillus Calmette-Guerin (BCG) with PBMac was used as an experimental model. A series of procedures involving solvent extraction and fractionation were used to isolate bioactive constituents in RPR. RPR-EA-S1, a fraction with potent immunoregulatory effects was obtained with a bioactivity guided fractionation scheme. PBMac were treated with crude RPR extracts or RPR-EA-S1 before BCG stimulation. The expression levels of IL-6, IL-8, IL-10 and TNF-α were measured by qPCR and ELISA. Western blotting was used to determine the effects of RPR-EA-S1 on signaling kinases and transcriptional factors in the BCG-activated PBMac. RESULTS: In BCG-stimulated macrophages, crude RPR extracts and fraction RPR-EA-S1 specifically inhibited IL-10 production while enhanced IL-8 expression at both mRNA and protein levels without affecting the expressions of IL-6 and TNF-α. Inhibition of BCG-induced IL-10 expression by RPR-EA-S1 occurred in a dose- and time-dependent manner. RPR-EA-S1 did not affect the phosphorylation of cellular protein kinases including MAPK, Akt and GSK3ß. Instead, it suppressed the degradation of IκBα in the cytoplasm and inhibited the translocation of transcription factor NF-κB1 p50 to the nucleus. CONCLUSION: RPR crude extracts and its fraction RPR-EA-S1 inhibited anti-inflammatory cytokine IL-10 and enhanced pro-inflammatory chemokine IL-8 expression in BCG-activated PBMac. The inhibitory effects of RPR-EA-S1 on IL-10 expression in BCG-activated PBMac may be due to the reduced nuclear translocation of NF-κB1 p50.