patchouli-alcohol and Orthomyxoviridae-Infections

Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects.. In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining.. The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir.. Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.

Topics: Administration, Intranasal; Animals; Antiviral Agents; Disease Models, Animal; Influenza A virus; Lung; Mice; Orthomyxoviridae Infections; Sesquiterpenes; Signal Transduction; Survival Analysis; Treatment Outcome

Seasonal influenza A infection results in considerable morbidity and mortality. The limited efficacy of available therapeutic strategies stresses the need for development and study of new molecules against influenza virus (IFV). Patchouli alcohol (PA), the major chemical constituent of Pogostemonis Herba, was previously found to strongly inhibit influenza H1N1 replication in vitro. In the present study, the in vivo anti-IFV effect of PA was investigated. In a mouse model infected with lethal levels of FM1, oral administration of PA (20 mg/kg to 80 mg/kg) for 7 d post IFV infection significantly increased the survival rate and survival time. For IFV infection at nonlethal levels, the quantity of IFV in the lungs 5 d after infection was significantly reduced after PA (20 mg/kg to 80 mg/kg) administration. Anti-IFV IgA, IgM, and IgG titers in serum on day 6 were significantly higher in the PA-treated group than the IFV-control group. Anti-IFV immune response augmentation was further confirmed by the elevated production of CD3+, CD4+, and CD8+ T cell levels in blood. Furthermore, the levels of inflammatory cytokines, including TNF-alpha, IL-10 and IFN-gamma in serum of mice, were regulated. Lung inflammation was reduced significantly after PA administration, and the effect may be mediated, at least in part, by regulating the lung levels of inflammatory cytokines. Thus, oral administration of PA appears to be able to augment protection against IFV infection in mice via enhancement of host immune responses, and attenuation of systemic and pulmonary inflammatory responses.

Topics: Administration, Oral; Alphainfluenzavirus; Animals; Antibodies, Viral; Cytokines; Drugs, Chinese Herbal; Female; Lamiaceae; Lung; Male; Mice; Orthomyxoviridae Infections; Phytotherapy; RNA, Viral; Sesquiterpenes

In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico. The CC₅₀ of patchouli alcohol was above 20 µM. Patchouli alcohol could inhibit influenza virus with an IC₅₀ of 4.03 ± 0.23 µM. MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell. In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day. Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of -40.38 kcal mol⁻¹. The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process. Based on spatial and energetic criteria, patchouli alcohol interfered with the NA functions. Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.

Topics: Administration, Oral; Animals; Antiviral Agents; Binding Sites; Cell Line; Cell Survival; Dogs; Influenza A Virus, H2N2 Subtype; Inhibitory Concentration 50; Mice; Mice, Inbred Strains; Molecular Dynamics Simulation; Neuraminidase; Orthomyxoviridae Infections; Oseltamivir; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Sesquiterpenes; Survival Rate; Thermodynamics; Virus Replication