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Methionine enkephalin, the endogenous opioid peptide, has a diversity of effects on the immune system. Although the biological effects of the pentapeptide have been well documented, little is known about the intracellular events involved in the effects of opioids on human immunodeficiency virus (HIV) infected immune cells. In the present investigation, the possible mechanism of apoptosis alleviated by exposure of methionine enkephalin at 1 μmol/l to CEM×174 cells, the hybrid lymphocytes, infected with simian immunodeficiency virus (SIV) in vitro is elucidated. Apoptosis and cell cycle analysis is carried out by flow cytometry, the phosphorylation of mitogen-activated protein kinases (MAPK) ERK1 and ERK2 is detected by Western blotting assay, and changes of calcium concentration were analyzed using the calcium-sensitive dye Fluo-3 AM. The results exhibit that methionine enkephalin at the concentrations of 1 μmol/l increase remarkably the proportion of vital cells and decrease the apoptotic cells based on annexin V binding assay. In response to the treatment with methionine enkephalin, SIV-infected cells display a prolonged survival and are accumulated in G1 phase. Methionine enkephalin increase obviously the content of intracellular calcium in normal cells within 1–2 min and maintains a high level within monitoring time. However, the intracellular calcium reaches the highest level at 1 min and subsequently decline to background in SIV infected group. In addition, methionine enkephalin also elevates the levels of protein kinase C (PKC) activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2. It is proposed that calcium–PKC–MAPK cascade is involved in methionine enkephalin-prolonged survival of SIV-infected cells in the early stages of virus infection. The results provide a further evidence for potential use of methionine enkephalin on the therapy of Acquired Immunodeficiency Syndrome (AIDS). [Copyright &y& Elsevier]

Ethnopharmacological relevance Ligustrum purpurascens Y.C. Yang (Oleaceae) is traditionally recorded as “Ku Ding Cha”, a kind of functional tea in southern China for about two thousand years, which has been reported with sore throat alleviating and pathogenic heat expelling effects. However, there are no scientific studies demonstrating its antiviral activity. The aim of the study This study is aimed at investigating the anti-influenza virus effects of phenylethanoid glycosides isolated from L. purpurascens (LPG) as well as its corresponding mechanisms. Materials and methods In vitro , hemagglutination assay was employed to detect the influenza virus titer; In vivo , C57BL/6J mice were given oral administration of LPG (100 mg/kg, 300 mg/kg, 900 mg/kg) or ribavirin (100 mg/kg) once daily for 5 successive days. Meanwhile, on the second day, mice were infected intranasally (i.n.) with A/FM/1/47 H1N1 virus. Mice survival rate and other clinical index were monitored for 15 days. Infected mice were sacrificed to measure the lung lesion and stained with hematoxylin–eosin. Flow cytometry analyses spleen lymphocytes and interferon-γ (IFN-γ) level. The IFN-γ knockout mice (IFN-γ −/− mice, C57BL/6J) which had been verified lacking IFN-γ through Western Blot, were applied in the death-protection test to identify the role of IFN-γ played in LPG antiviral effect. Results In vitro , LPG at 0.5 mg/ml inhibited Influenza A Virus H1N1 type (H1N1) infection of MDCK cells. In vivo , LPG at 300 and 900 mg/kg significantly decreased the mouse lung index ( p <0.05), alleviated influenza-induced lethality and clinical symptoms, and therefore enhanced mouse survival ( p <0.05). More detailed experiments demonstrated that antiviral cytokine IFN-γ was involved in the antiviral effect of LPG. Flow cytometric analysis revealed that LPG (900 mg/kg) significantly induced secretion of IFN-γ by splenic CD4 + and CD8 + cells ( p <0.05). Moreover, LPG (900 mg/kg) protected wild-type C57BL/6J mice from H1N1 injury, whereas LPG-mediated survival protection disappeared in IFN-γ −/− mice. Conclusion These results suggest that up-regulating endogenous IFN-γ by LPG may represent a novel therapeutic approach for H1N1 infection. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance In traditional Chinese medicine, the root of Ilex asprella (Hook. & Arn.) Champ. ex Benth. (IA) has been widely used to treat influenza, lung abscess and other diseases in South China for many years. The present study is aimed at investigating the treatment effect of IA on acute respiratory distress syndrome (ARDS) induced by the H1N1 virus in mice. Materials and methods After being inoculated with several viral doses of influenza A/FM/1/47 H1N1 virus, mice were given oral administration of IA extract (500 mg/kg or 125 mg/kg per day) for five or 10 consecutive days, respectively. Mice survival rate and clinical condition were observed for 15 days after inoculation. Lung weight, pathological analysis and arterial blood gas analysis were assessed. Lung viral load was quantified by RT-PCR. Moreover, immunological analysis was measured by leukocyte counts and the levels of inflammatory cytokines, including IL-6, IL-10, TNF-α, IFN-γ, MCP-1 and IL-12p70 in serum of mice. Results We found that the extract of Ilex asprella at dosages of 500 mg/kg could effectively diminish mortality rate, and ameliorate lung edema and inflammation. Administration of IA extract significantly depressed the expression of IL-6, TNF-α and MCP-1, and significantly increased the expression of IL-10 and IFN-γ in serum. Simultaneously, the extract was also found to reduce the lung viral load and improve pulmonary ventilation. Conclusion The present study shows that the extract of IA has the potential to treat ARDS, due to its abilities of attenuation of systemic and pulmonary inflammatory responses and inhibition of viral replication. [ABSTRACT FROM AUTHOR]

Abstract: 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 (20mg/kg to 80mg/kg) for 7d post IFV infection significantly increased the survival rate and survival time. For IFV infection at nonlethal levels, the quantity of IFV in the lungs 5d after infection was significantly reduced after PA (20mg/kg to 80mg/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. [Copyright &y& Elsevier]

Abstract: A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. The most active anti-HBV compound 6a showed high activities against the secretion of HBV surface antigen (IC50 =0.024mM), HBV e antigen (IC50 =0.028mM) and remarkable selective indices (SIHBsAg >108, SIHBeAg >93), which was selected for further evaluation as a novel HBV inhibitor. [Copyright &y& Elsevier]

Abstract: Two new alkaloids, hypserpanines A and B (1, 11), together with eleven known compounds, phenolbetain (2), acutumine (3), acutumidine (4), dechloroacutumine (5), dauricumine (6), dauricumidine (7), pronuciferine (8), glaziovine (9), S-reticuline (10), magnoflorine (12) and laurifoline(13), were isolated from Hypserpa nitida Miers. (Menispermaceae) and chemically elucidated through spectral analyses. All the isolated alkaloids were evaluated for their anti-HBV activities in vitro using the HBV transfected Hep G2.2.15 cell line. The most active compound, dauricumidine (7), exhibited an IC50 value of 0.450mM (SI=4.13) on hepatitis B virus (HBV) surface antigen (HBsAg) secretion of the Hep G2.2.15 cell line. [Copyright &y& Elsevier]

Abstract: A series of 4-aryl-6-chloro-quinolin-2-ones and 5-aryl-7-chloro-1,4-benzodiazepine were synthesized and assayed for their in vitro anti-hepatitis B virus activities and cytotoxicities for the first time. Some of the tested compounds were active against HBsAg and HBeAg secretion in Hep G2.2.15 cells. Compound 5c showed IC50 of 0.074 and 0.449mM on HBsAg and HBeAg secretions, respectively, which were 10 times higher than that of its analog 4c and led to better selective index (SI) values (SI=23.2 and 3.4, respectively). [Copyright &y& Elsevier]