Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice

Kurokawa, Mineo; Ochiai, Hiroshi; Nagasaka, Kazuhiko; Neki, Minoru; Xu, Hong‐Xi; Kadota, Shigetoshi; Sutardjo, Supriyatna; Matsumoto, Takao; Namba, Tsuneo; Shiraki, Kimíyasu

doi:10.1016/0166-3542(93)90094-y

Cited by 129 publications

(106 citation statements)

References 19 publications

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“…Traditional medicines utilizing natural products have been shown to contain antiviral compounds. [5][6][7][8][9] The screening of plants as a possible source of antiviral has led to the discovery of potent inhibitors of in vitro viral growth and the use of the ethnopharmacological approach enhances the probability of identifying new bioactive plant compounds. 10) Our interest has focused on the treatments for respiratory viral infections.…”

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confidence: 99%

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Wei

et al. 2003

Chem. Pharm. Bull.

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Viruses are the leading cause of respiratory infections in children and adults and are a major cause of morbidity and mortality worldwide. Respiratory viral infections contribute to be leading cause of morbidity, mortality, and economic loss throughout the world.1) Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants, in children, and even in adults.2) Ribavirin and immunoglobulin preparations with high titers of RSV-specific neutralizing antibodies are currently approved for use to treat and prevent RSV infections. However, neither of these is cost-effective and simple to administer.3) Parainfluenza type 3 virus (PIV 3) is another respiratory virus caused infections in children. No chemotherapy agents and vaccine have been used to treat PIV 3 infections. 4) Therefore, the development of new antiviral agents with different mechanisms is most desirable. Traditional medicines utilizing natural products have been shown to contain antiviral compounds. [5][6][7][8][9] The screening of plants as a possible source of antiviral has led to the discovery of potent inhibitors of in vitro viral growth and the use of the ethnopharmacological approach enhances the probability of identifying new bioactive plant compounds. 10)Our interest has focused on the treatments for respiratory viral infections. In order to find more potent inhibitors of RSV and PIV 3, we have been looking for some inhibitory substances from natural sources. 11-17)Selaginella uncinata SPRING is a Chinese herb medicine widely distributed in south China, which has been used to treat infectious diseases and tumors. Previous phytochemical studies on the constituents of genus Selaginella led to the discovery of many compounds, including flavonoids and lignans. 18,19) As part of our continuous searching for novel antivial agents from medicinal plants, ethanol extract of the whole plants of S. uncinata was found to show significant inhibitory activities against RSV. The active extract led to the isolation and characterization of two new compounds, named uncinoside A (1) and uncinoside B (2) 20) together with three known compounds. Here we report the isolation and structure elucidation of the two new chromone glycosides and their antiviral activities against RSV, PIV 3, and influenza type A virus (Flu A). Results and DiscussionAn EtOH extract of the whole plant of S. uncinata was concentrated and partitioned with CHCl 3 and EtOAc. The CHCl 3 fraction was separated by silica gel column chromatography to yield two new chromone glycosides uncinoside A (1) and uncinoside B (2), and one known 5,7-dihydroxy-2,6-8-trimethylchromone (8-methyleugenitol) (3). The EtOAc fraction was separated by silica gel and polyamide column chromatography and prepared thin-layer chromatography (TLC) to afford two known biflavonoids: amentoflavone (4) 11,21) and hinokiflavone (5) 21,22) (Chart 1). The structure of the compound 3 was determined by the Xray diffraction analysis and spectral data. The structures of the other two known biflavonoids were...

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confidence: 99%

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Wei

et al. 2003

Chem. Pharm. Bull.

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“…The cytotoxicity of compounds was determined as the inhibition of Vero cell growth. 13) Briefly, Vero cells were seeded at a density of 5ϫ10 4 cells/well in 24-well plates and incubated at 37°C for 2 d. The culture medium was replaced with fresh medium containing test compounds at various concentrations, and the cells were further incubated for 2 d. The cells were lysed with trypsin and the number of viable cells was determined by Trypan blue exclusion. The concentrations of test compounds that reduced cell viability by 50% (CC 50 ) were determined from a curve relating % cell viability to the TDB concentration.…”

Section: Viruses and Cellsmentioning

confidence: 99%

“…We propagated wild type 7401H HSV-1, 13) thymidine kinase-deficient (TK Ϫ ) HSV-1 (B2006) 14) and acyclovir (ACV) and phosphonoacetic acid (PAA)-resistant AP r HSV-1 15,16) in Vero E6 cells. The infected cultures were frozen and thawed three times, centrifuged at 1650ϫg for 15 min and then supernatants were stored at Ϫ80°C.…”

Section: Viruses and Cellsmentioning

confidence: 99%

Antiviral Activity of the Marine Alga Symphyocladia latiuscula against Herpes Simplex Virus (HSV-1) in Vitro and Its Therapeutic Efficacy against HSV-1 Infection in Mice

Park

Kurokawa

Shiraki

et al. 2005

Biological & Pharmaceutical Bulletin

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“…Traditional medicines utilizing natural products have been shown to contain antiviral compounds. [3][4][5][6][7] We screened for such compounds from natural products. In this paper, we report the isolation of active compounds from the whole herb of Selaginella sinensis (Selaginellaceae) and the content determination of amentoflavone in nine different species of Selaginella.…”

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Antiviral Amentoflavone from Selaginella sinensis

But

Ooi

et al. 2001

Biological & Pharmaceutical Bulletin

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Upper respiratory infection, especially in infants and children, is a common disease worldwide. Respiratory syncytial virus (RSV) has been recognized as a major cause of such infections.1) The nucleoside analog ribavirin has been used widely for treating RSV infections in healthcare settings such as hospitals and nursing homes. However, the treatment protocol, the potentially severe side effects and the emergence of drug-resistant mutants during long-term medication with this drug have often limited its administration to patients. 2)Therefore, the development of new antiviral agents with different mechanisms is most desirable. Traditional medicines utilizing natural products have been shown to contain antiviral compounds. [3][4][5][6][7] We screened for such compounds from natural products. In this paper, we report the isolation of active compounds from the whole herb of Selaginella sinensis (Selaginellaceae) and the content determination of amentoflavone in nine different species of Selaginella. Antiviral Assays The antiviral activity of test sample against RSV was measured by the plaque reduction assay. 8,9) Briefly, two-days old confluent monolayers of Hep 2 cells were infected with RSV at 100 plaque-forming units (PFU) per well in 0.5 ml maintenance medium . The inoculated cultures were incubated at 37°C in a CO 2 incubator with gentle agitation at 10-15 intervals to ensure uniform virus adsorption. Following 1 h virus adsorption, the inoculum was removed and 1.5 ml of agarose overlay medium containing 0.6% agarose in DMEM and 2% FBS were added to each well. When the agarose overlay became well-solidified, 1.5 ml of diluted test samples in maintenance medium were added to each well. A minimum of three different concentrations of each test sample was tested. One well per plate was added with 1.5 ml of maintenance medium without the test sample as control. The culture plates were incubated in the humidified CO 2 incubator for 4-5 d. The cultures were then fixed with 10% formalin in PBS and subsequently stained with 1% crystal violet in 20% ethanol upon removal of the agarose overlay. The number of plaques per well was enumerated macroscopically. The 50% inhibitory concentration (IC 50 ) was determined as the concentration of the test sample that reduced 50% of the plaque formation in the control wells. MATERIALS AND METHODS MaterialsExtraction and Isolation of Main Compound from the Herb of S. sinensis Air dried herb (5.0 kg) was extracted by refluxing with 90 l ethanol for three times, each time for 2 h. The ethanol solution was filtered and evaporated under reduced pressure to give a brownish ethanol extract (660 g). The ethanol extract was dissolved in water containing 0.5 N HCl and filtered. The precipitate was dissolved in water containing 0.5 N NaOH and filtered. The basic solution was adjusted to pH 1-3 with HCl, stayed overnight and filtered. The precipitate was washed with water to give a yellowish powder (195 g). Then this yellowish powder was extracted with chloroform, ethyl acetate and methanol by ...

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Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice

Cited by 129 publications

References 19 publications

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Uncinoside A and B, Two New Antiviral Chromone Glycosides from <i>Selaginella uncinata</i>

Antiviral Activity of the Marine Alga Symphyocladia latiuscula against Herpes Simplex Virus (HSV-1) in Vitro and Its Therapeutic Efficacy against HSV-1 Infection in Mice

Antiviral Amentoflavone from Selaginella sinensis

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