antiviral

Phytoterapy: a glimmer of hope in the prevention of recurrent respiratory tract infections in children.: Minerva Pediatr. 2007 Aug;59(4):389-395 Authors: Miniello VL, Brunetti L, Cafagna R, Lieggi MS, Lippolis P, Natile M, Francavilla R, Armenio L

Evidence on the efficacy of standardised phytoterapic extracts for the prevention of recurrent respiratory tract infections (RRTIs) in children is reviewed. Echinacea extracts are widely used in European countries and in the United States as immune-stimulating agents. However, further prospective, appropriately powered clinical studies are required to confirm their benefits in reducing duration and severity of RRTIs.

PMID: 17947844 [PubMed - as supplied by publisher]

Tea catechins as a potential alternative anti-infectious agent.: Expert Rev Anti Infect Ther. 2007 Jun;5(3):497-506 Authors: Song JM, Seong BL

Besides well-known health benefits, green tea catechins exert antimicrobial and antiviral activities against a variety of infectious agents. Although the detailed mechanism of the antimicrobial activity of tea catechins remains to be explored, the broad-spectrum activity of catechins may involve common target(s), such as the cell membrane, in addition to specific targets for each pathogen. This extends to antiviral activities, where many pronounced activities were reported for enveloped viruses. Yet, the effectiveness of tea catechins as antimicrobials is compromised by relative chemical instability and poor bioavailability. Whether tea catechins will emerge as a viable option as alternative medicine or as a synergistic combination therapy with pre-existing antivirals or antibiotics must therefore depend on a method of delivery that ensures its stability and bioavailability. However, green tea may provide an option for mitigating the health and economic burdens associated with emerging and re-emerging infectious diseases, especially considering the paucity of effective control measures. Considering the zoonotic nature of newly arising infectious diseases, the dual use of green tea components in both humans and livestock may reduce animal-human transmission, which would complement the current management of infectious diseases.

PMID: 17547513 [PubMed - indexed for MEDLINE]

Structure determination of inonotsuoxides A and B and in vivo anti-tumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus.: Bioorg Med Chem. 2007 Jan 1;15(1):257-64 Authors: Nakata T, Yamada T, Taji S, Ohishi H, Wada S, Tokuda H, Sakuma K, Tanaka R

Two new lanostane-type triterpenoids, inonotsuoxides A (1) and B (2) along with three known lanostane-type triterpenoids, inotodiol (3), trametenolic acid (4), and lanosterol (5), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanakake) (Russian name: Chaga). Their structures were determined to be 22R,25-epoxylanost-8-ene-3beta,24S-diol (1) and 22S,25-epoxylanost-8-ene-3beta,24S-diol (2) on the basis of spectral data including single crystal X-ray analysis. These compounds except for 2 were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. The most abundant triterpene, inotodiol (3), was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compound 3 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.

Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects.: Clin Infect Dis. 2006 Oct 15;43(8):1052-9 Authors: Lee LS, Andrade AS, Flexner C

Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained.

In vitro and in vivo anti-retroviral activity of the substance purified from the aqueous extract of Chelidonium majus L.: Antiviral Res. 2006 Nov;72(2):153-6 Authors: Gerencer M, Turecek PL, Kistner O, Mitterer A, Savidis-Dacho H, Barrett NP

We have isolated a substance with anti-retroviral activity from the freshly prepared crude extract of Chelidonium majus L. (greater celandine) by 9-aminoacridine precipitation method and ion exchange chromatography using Dowex-50W/H+ resin followed by the gel filtration on Sephadex-75 column. Elemental and phenol/sulfuric acid method analyses as well as the mass spectrometry of the purified substance indicated that it may represent a low-sulfated poly-glycosaminoglycan moiety with molecular weight of approximately 3800 Da. The substance prevented infection of human CD4+ T-cell lines AA2 and H9 with HIV-1 at concentration of 25 microg/mL as well as the cell-to-cell virus spread in H9 cells continuously infected with HIV-1, as determined by the measurement of reverse transcriptase activity and p24 content in cell cultures. Furthermore, we have shown in a murine AIDS model that the treatment with purified substance significantly prevented splenomegaly and the enlargement of cervical lymph nodes in C57Bl/6 mice chronically infected with the pool of murine leukemia retroviruses. The mechanism(s) of anti-retroviral activity of this substance have to be elucidated.

Year-and-a-half old, dried Echinacea roots retain cytokine-modulating capabilities in an in vitro human older adult model of influenza vaccination.: Planta Med. 2006 Oct;72(13):1207-15 Authors: Senchina DS, Wu L, Flinn GN, Konopka del N, McCoy JA, Widrelechner MP, Wurtele ES, Kohut ML

Alcohol tinctures prepared from aged Echinacea roots are typically taken for preventing or treating upper respiratory infections, as they are purported to stimulate immunity in this context. The effects of long-term (> 1 year) dry storage on the capabilities of Echinacea spp. roots from mature individuals to modulate cytokine production are unknown. Using an older human adult model of influenza vaccination, we collected peripheral blood mononuclear cells from subjects 6 months post-vaccination and stimulated them in vitro with the two Type A influenza viruses contained in the trivalent 2004-2005 vaccine with a 50 % alcohol tincture prepared from the roots of one of seven Echinacea species: E. angustifolia, E. pallida, E. paradoxa, E. purpurea, E. sanguinea, E. simulata, and E. tennesseensis. Before being processed into extracts, all roots had been stored under dry conditions for sixteen months. Cells were cultured for 48 hours; following incubation, supernatants were collected and assayed for interleukin-2, interleukin-10, and interferon-gamma production, cytokines important in the immune response to viral infection. Four species ( E. angustifolia, E. purpurea, E. simulata, E. tennesseensis) augmented IL-10 production, diminished IL-2 production, and had no effect on IFN-gamma production. Echinacea pallida suppressed production of all cytokines; E. paradoxa and E. sanguinea behaved similarly, although to a lesser extent. The results from these in vitro bioactivity assays indicate that dried Echinacea roots stored for sixteen months maintain cytokine-modulating capacities. Our data support and extend previous research and indicate that tinctures from different Echinacea species have different patterns of immune modulation; further, they indicate that certain species may be efficacious in the immune response to viral infection.

Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells.: Phytother Res. 2006 Jan 27;20(2):147-152 Authors: Sharma M, Arnason JT, Burt A, Hudson JB

Extracts of Echinacea purpurea are among the most widely used herbal medicines throughout Europe and North America for the prevention or treatment of common cold, coughs, bronchitis and other upper respiratory infections. Popular preparations include expressed juice from the aerial parts of the plant (which contain polysaccharides) and alcoholic tinctures from roots (containing caffeic acid derivatives and alkylamides).Since immune modulation has been reported for similar extracts, cytokine antibody arrays were used to investigate the changes in the pro-inflammatory cytokines and chemokines released from a cultured line of human bronchial epithelial cells exposed to Rhinovirus 14 and two different chemically characterized Echinacea extracts. Virus infection stimulated the release of at least 31 cytokine-related molecules, including several important chemokines known to attract inflammatory cells. Most of these effects were reversed by simultaneous exposure to either of the two Echinacea extracts, although the patterns of response were different for the two extracts. These results could explain the antiinflammatory properties of Echinacea extracts.Furthermore, a number of these cytokines were stimulated by the same Echinacea preparations in uninfected cells. These observations therefore provide support for the alleged benecial uses of Echinacea extracts. Copyright (c) 2006 John Wiley & Sons, Ltd.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

Background: Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. Methods: We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results: Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusions: These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system.: Antiviral Res. 2005 Nov;68(2):75-83 Authors: Romero MR, Efferth T, Serrano MA, Castaño B, Macias RI, Briz O, Marin JJ

The antiviral effect against hepatitis B virus (HBV) of artemisinin, its derivative artesunate and other compounds highly purified from traditional Chinese medicine remedies, were investigated. HBV production by permanently transfected HepG2 2.2.15 cells was determined by measuring the release of surface protein (HBsAg) and HBV-DNA after drug exposure (0.01-100 microM) for 21 days. The forms of HBV-DNA released were investigated by Southern-blotting. Neutral Red retention test was used to evaluate drug-induced toxicity on host cells. The compounds were classified according to their potential interest as follows: (i) none: they had no effect on viral production (daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin); (ii) low: they were able to markedly reduce viral production, but also induced toxicity on host cells (berberine and tannic acid) or they had no toxic effect on host cells but only had a moderate ability to reduce viral production (curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin); (iii) high: they induced strong inhibition of viral production at concentrations at which host cell viability was not affected (artemisinin and artesunate). Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection.

Antiviral activities of extracts and selected pure constituents of Ocimum basilicum.: Clin Exp Pharmacol Physiol. 2005 Oct;32(10):811-6 Authors: Chiang LC, Ng LT, Cheng PW, Chiang W, Lin CC

1. Ocimum basilicum (OB), also known as sweet basil, is a well known medicinal herb in traditional Chinese medicine preparations. In the present study, extracts and purified components of OB were used to identify possible antiviral activities against DNA viruses (herpes viruses (HSV), adenoviruses (ADV) and hepatitis B virus) and RNA viruses (coxsackievirus B1 (CVB1) and enterovirus 71 (EV71)). 2. The results show that crude aqueous and ethanolic extracts of OB and selected purified components, namely apigenin, linalool and ursolic acid, exhibit a broad spectrum of antiviral activity. Of these compounds, ursolic acid showed the strongest activity against HSV-1 (EC50 = 6.6 mg/L; selectivity index (SI) = 15.2), ADV-8 (EC50 = 4.2 mg/L; SI = 23.8), CVB1 (EC50 = 0.4 mg/L; SI = 251.3) and EV71 (EC50 = 0.5 mg/L; SI = 201), whereas apigenin showed the highest activity against HSV-2 (EC50 = 9.7 mg/L; SI = 6.2), ADV-3 (EC50 = 11.1 mg/L; SI = 5.4), hepatitis B surface antigen (EC50 = 7.1 mg/L; SI = 2.3) and hepatitis B e antigen (EC50 = 12.8 mg/L; SI = 1.3) and linalool showed strongest activity against AVD-II (EC50 = 16.9 mg/L; SI = 10.5). 3. No activity was noted for carvone, cineole, beta-caryophyllene, farnesol, fenchone, geraniol, beta-myrcene and alpha-thujone. 4. The action of ursolic acid against CVB1 and EV71 was found to occur during the infection process and the replication phase. 5. With SI values greater than 200, the potential use of ursolic acid for treating infection with CVB1 and EV71 merits further investigation.