No abstract

With the emergence of drug-resistant strains of influenza A viruses (IAV), new antivirals are needed to supplement the existing counter measures against IAV infection. We have previously shown that brevilin A, a sesquiterpene lactone isolated from C. minima, suppresses the infection of influenza A/PR/8/34 (H1N1) in vitro. Here, we further investigate the antiviral activity and mode of action of brevilin A against different IAV subtypes. Brevilin A inhibited the replication of influenza A H1N1, H3N2, and H9N2 viruses in vitro. The suppression effect of brevilin A was observed as early as 4–8 hours post infection (hpi). Furthermore, we determined that brevilin A inhibited viral replication in three aspects, including viral RNA (vRNA) synthesis, expression of viral mRNA, and protein encoded from the M and NS segments, and nuclear export of viral ribonucleoproteins (vRNPs). The anti-IAV activity of brevilin A was further confirmed in mice. A delayed time-to-death with 50% surviving up to 14 days post infection was obtained with brevilin A (at a dose of 25 mg/kg) treated animals compared to the control cohorts. Together, these results are encouraging for the exploration of sesquiterpene lactones with similar structure to brevilin A as potential anti-influenza therapies.

Illicium verum Hook.f. (Chinese star anise), a known Chinese traditional spice, is commonly applied in Chinese cuisine and cooking in Southeast Asia. As a kind of medicinal and edible resource, the fruit of I. verum has attracted great attention for its chemical constituents and physiological activities. In this work, the phytochemical study of the fruits of I. verum led to the isolation and identification of 20 compounds, including 6 new lignans and phenylpropanoids (1–6) and 14 known ones (7–20). Their structures were characterized by extensive analysis of spectroscopic data (IR, UV, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional (1D) and two-dimensional (1D) NMR), electronic circular dichroism (ECD) calculation, and by comparison with literature data. Meanwhile, all compounds (1–20) were evaluated for their antiviral and antioxidant activities. Especially, compound 7 [(−)-bornyl p-coumarate] showed strong antiviral activities against influenza virus A/Puerto Rico/8/34 H1N1 (PR8) with an IC50 value of 1.74 ± 0.47 μM, which is much better than those of Tamiflu (IC50 = 10.01 ± 0.92 μM) and ribavirin (IC50 = 10.76 ± 1.60 μM). The antiviral activity against PR8 of compound 7 was reported for the first time, which was sufficiently confirmed by cell counting kit 8 (CCK-8), cytopathic effect (CPE) reduction, and immunofluorescence assays. In this study, the discovery of antiviral and antioxidant components from the fruits of I. verum could benefit the further development and utilization of this plant.

BackgroundThe objective of this study is to observe whether cyclosporine A (CsA) inhibits the expression of dectin-1 in human corneal epithelial cells infected with Aspergillus fumigatus (A. fumigatus) and to investigate the molecular mechanisms of the inhibition.MethodsImmortalized human corneal epithelial cells (HCECs) were pretreated with 1,25(OH)2D3 and VDR inhibitor for 1 h, and then they were pretreated with CsA for 12h. After these pretreatments, the HCECs were stimulated with A. fumigatus and curdlan respectively, and the expression of dectin-1 and proinflammatory cytokines (IL-1β and TNF-α) were detected by RT-PCR, western blot and ELISA.ResultsDectin-1 mRNA and dectin-1 protein expression increased when HCECs were stimulated with A. fumigatus or curdlan, and CsA inhibited the dectin-1 expression both in mRNA and protein levels specifically. Dectin-1 and proinflammatory cytokine expression levels were higher when HCECs were pretreated with VDR inhibitor and CsA compared to pretreatment with CsA alone, while dectin-1 and proinflammatory cytokine levels were lower when HCECs were pretreated with 1,25(OH)2D3 and CsA compared to pretreatment with CsA alone.ConclusionsThese data provide evidence that CsA can inhibit the expression of dectin-1 and proinflammatory cytokines through dectin-1 when HCECs are stimulated by A. fumigatus or curdlan. The active form of vitamin D, 1,25(OH)2D3, and VDR signaling pathway regulate the inhibition of CsA. The inhibition is enhanced by 1,25(OH)2D3, and the VDR inhibitor suppresses the inhibition.