Kuo-Chih Wang

Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan

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Publications (11)26.98 Total impact

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    ABSTRACT: Human respiratory syncytial virus (HRSV) infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata) is a common ingredient of Ge-Gen-Tang (Kakkon-to) and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to), which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2) and lower (A549) respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001) against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001) by inhibiting viral attachment (p < 0.0001) and penetration (p < 0.0001). However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.
    The Kaohsiung journal of medical sciences 12/2013; 29(12):651-7. · 0.50 Impact Factor
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    ABSTRACT: Paeonia lactiflora Pallas (P. lactiflora, Ranunculaceae) is a common ingredient of Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) and Ge-Gen-Tang (GGT; kakkon-to). SMGGT and GGT are different prescriptions of traditional Chinese medicine with different ingredients designed for airway symptoms. Both SMGGT and GGT have anti-viral activity against human respiratory syncytial virus (HRSV). Therefore, P. lactiflora was hypothesized to be the effective ingredient of both SMGGT and GGT against HRSV. However, P. lactiflora does not have any proven antiviral activity. This study used both human upper (Human larynx epidermoid carcinoma cell line, HEp-2) and lower (human lung carcinoma cell line, A549) respiratory tract cells to test the hypothesis that a hot water extract of P. lactiflora could effectively inhibit plaque formation induced by HRSV infection. The ability of P. lactiflora to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that P. lactiflora was time-dependently and dose-dependently effective against HRSV in HEp-2 and A549 cells, particularly supplemented before viral inoculation (p < 0.0001). 10 μg/ml P. lactiflora had a comparable anti-HRSV activity with 10 μg/ml ribavirin, a broad-spectrum antiviral agent. P. lactiflora was dose-dependently effective against viral attachment (p < 0.0001), with a better effect on A549 cells (p < 0.0001). P. lactiflora was time-dependently (p < 0.0001) and dose-dependently (p < 0.0001) effective against viral penetration. Moreover, P. lactiflora stimulated IFN-β secretion without any effect on TNF-α secretion. Therefore, P. lactiflora could be beneficial at preventing HRSV infection by inhibiting viral attachment, internalization, and stimulating IFN secretion.
    The American Journal of Chinese Medicine 01/2013; 41(3):585-599. · 2.28 Impact Factor
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    ABSTRACT: Human respiratory syncytial virus (RSV) causes serious infection of the lower respiratory tract in children and an effective antiviral therapy against the viral pathogen remains unavailable. We previously demonstrated that the oriental medicinal plant, Cimicifuga foetida L. (C. foetida), possessed inhibitory activity against RSV. Since cimicifugin is a major constituent of C. foetida, we sought to examine in this study its anti-RSV effect on both the human upper (HEp-2) and lower (A549) respiratory tract cell lines. Results revealed that cimicifugin dose-dependently inhibited RSV-induced plaque formation in both HEp-2 and A549 cells (p < 0.0001), with a superior effect in the latter cell type (p < 0.0001). The antiviral activity of cimicifugin was time-dependent (p < 0.0001) and was most effective when cells were treated with the compound before viral inoculation. Additional experiments demonstrated that cimicifugin could inhibit viral attachment (p < 0.0001) and viral internalization (p < 0.0001). Furthermore, the drug could potentiate heparin's effect against attachment of RSV, particularly in A549 cells. Enzyme-linked immunosorbent assay (ELISA) analysis of antiviral cytokines induction revealed that cimicifugin could also stimulate epithelial cells to secrete IFN-β to counteract viral infection. Taken together, these results indicate that cimicifugin is an efficient antiviral agent against RSV infection. We suggest that cimicifugin might be useful for the management of RSV pathogenesis.
    The American Journal of Chinese Medicine 01/2012; 40(5):1033-45. · 2.28 Impact Factor
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    ABSTRACT: Sheng-Ma-Ge-Gen-Tang (SMGGT; Shoma-kakkon-to) has been used against pediatric viral infection for thousands of year in ancient China. However, it is unknown whether SMGGT is effective against human respiratory syncytial virus (HRSV). HRSV is a major pediatric viral pathogen of low respiratory tract infection without effective management. This study tested the hypothesis that SMGGT effectively inhibited cytopathy induced by HRSV. Effect of the crude extract of SMGGT on HRSV was tested by plaque reduction assay in both human upper (HEp-2) and low (A549) respiratory tract cell lines. Ability of SMGGT to stimulate anti-viral cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA). Crude extract of SMGGT dose-dependently inhibited HRSV-induced plaque formation. The crude extract was more effective when given before viral infection (p<0.0001). It inhibited viral attachment dose-dependently (p<0.0001) and could increase heparin effect on viral attachment. Furthermore, it was synergistic with very low-dose heparin on viral attachment. In addition, the crude extract time-dependently and dose-dependently (p<0.0001) inhibited HRSV internalization into HEp-2 cells. Epithelial cells secrete IFN-β and TNF-α to counteract viral infection. The crude extract could stimulate epithelial cells to secrete these cytokines beforehand and become resistant to viral infection. It also stimulated IFN-β to defense HRSV after viral inoculation. Sheng-Ma-Ge-Gen-Tang could be effective to manage HRSV infection in young children.
    Journal of ethnopharmacology 04/2011; 135(2):538-44. · 2.32 Impact Factor
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    ABSTRACT: Human infection by enterovirus type 71 (EV71) can cause life-threatening meningo-encephalitis. Currently, there is no effective anti-EV71 therapy available. Since EV71 infection commonly involves skin lesions, we tested our hypothesis that water extract of Glycyrrhiza uralensis (G. uralensis) could inhibit the cytopathic effects of EV71 in a human foreskin cell line by using an XTT-based method. Our results showed that the water extract of G. uralensis at 3,000 microg/ml has only 30% cytotoxicity on host cells, and furthermore, that the water extract of G. uralensis at 0.1 microg/ml could effectively protect host cells against EV71 infection (p < 0.0001). The half maximal inhibitory concentration (IC(50)) was 0.056 microg/ml with a selective index greater than 50,000. The water extract of G. uralensis exerted its effects not only by preventing viral attachment (p < 0.0001), but also by inhibiting the penetration of the virus (p < 0.0001). EV71 infection caused cells to produce significant amounts of IFN-beta (p = 0.0003). However, the anti-EV71 activity of the water extract of G. uralensis was not mediated by IFN. In conclusion, the water extract of G. uralensis possesses potent anti-EV71 effects with less cytotoxicity. Its low IC(50) and high 50% cytotoxic concentration (CC(50)) values suggest that it is a promising anti-EV71 agent.
    The American Journal of Chinese Medicine 01/2009; 37(2):383-94. · 2.28 Impact Factor
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    ABSTRACT: Enterovirus 71 (EV71) can cause brain encephalitis and mortality. However, effective vaccines or chemotherapeutic agents are not yet available. We tested the hypothesis that Pueraria lobata could inhibit the cytotoxic effect of EV71 in a human foreskin fibroblast cell line by the XTT method. Our results showed that the water extract of P. lobata could inhibit cytopathy induced by EV71 when given before (p < 0.0001), simultaneously with (p < 0.0001), or after viral infection (p < 0.0001). Water extract of P. lobata was effective and its minimal concentration that inhibited 50% of the cytopathic effect (IC50) was 0.028 microg/mL. P. lobata was also safe with a selectivity index greater than 107,000. Water extract of P. lobata appeared to inhibit viral attachment (p < 0.0001) and penetration (p < 0.0001). The anti-EV71 activity of the water extract of P. lobata was not mediated by interferons. In conclusion, the water extract of P. lobata was effective in the management of the disease induced by EV71 infection.
    The Kaohsiung journal of medical sciences 10/2008; 24(10):523-30. · 0.50 Impact Factor
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    ABSTRACT: To search for an effective antiviral agent, this study tested the hypothesis that sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins possess the activity directly against HBV and could affect the expressions of viral antigens, HBeAg and HBsAg, in HepG(2) 2.2.15 cell model. The viral amount and viral antigens in the suspension were estimated by quantitative real time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that sho-saiko-to could inhibit the production of HBV (p < 0.0001), 20 microg/ml sho-saiko-to was efficacious at day-3 of treatment and 10 microg/ml at day-6. The calculated IC(50) and CC(50) of sho-saiko-to were 55.76 microg/ml and 372 microg/ml, respectively, with a selectivity index of 6.67. Crude saponin of B. chinense could also inhibit the replication of HBV (p < 0.0001). Owing to the anti-neoplastic activity of sho-saiko-to and saikosaponin, their calculated CC(50) and selectivity index might be under-estimated. Sho-saiko-to also decreased the expression of HBeAg with the minimal effective concentration of 20 microg/ml. Sho-saiko-to contained too little saikosaponin. Therefore, the anti-HBV activity of sho-saiko-to might not be mediated by saikosaponin. Sho-saiko-to could be supplementary to nucleotide analogues to minimize the recurrence of viremia after its discontinuation.
    The American Journal of Chinese Medicine 01/2007; 35(2):341-51. · 2.28 Impact Factor
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    ABSTRACT: Chronic hepatitis B virus (HBV) infection is endemic in Asia and its consequences are among the major public health problems in the world. Unfortunately, the therapeutic efficacies of present strategies are still unsatisfactory with a major concern about viral mutation. In search of effective antiviral agent, we examined the efficacy of extracts of Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum) against HBV in HepG2 2.2.15 cells by quantitative real time polymerase chain reaction. The expressions of viral antigens, HBeAg and HBsAg, were also determined by enzyme linked immunosorbent assay. The ethanol extract of P. cuspidatum could inhibit dose-dependently the production of HBV (p<0.0001) with an effective minimal dosage of 10 microg/ml. The water extract of P. cuspidatum might also inhibit the production of HBV at a higher dosage. The expression of HBsAg was significantly increased by both ethanol extract and water extract of P. cuspidatum dose-dependently (p<0.0001) and time-dependently (p<0.0001). Higher dose of water extract of P. cuspidatum (30 microg/ml) could inhibit the expression of HBeAg (p<0.05). The extract of P. cuspidatum might contain compounds that would contribute to the control of HBV infection in the future. However, its promoting effect on the expression of HBsAg and its cytotoxicity should be monitored. Further purification of the active compounds, identification and modification of their structures to improve the efficacy and decrease the cytotoxicity are required.
    Antiviral Research 04/2005; 66(1):29-34. · 3.93 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the in vitro antiviral properties of pterocarnin A, extracted from the bark of Pterocarya stenoptera (Juylandaceae). Results showed that pterocarnin A exhibited anti-herpes simplex virus (HSV) activity. It had a low selectivity index (SI) value and only possessed some level of cell cytotoxic effect at high antiviral concentrations. Mechanism studies demonstrated that pterocarnin A inhibited herpes simplex virus type 2 (HSV-2) from attaching and penetrating into cells. It also actively suppressed HSV-2 multiplication in Vero cells even when added 12 h after infection. This observation indicated that pterocarnin A affected the late stage(s) of HSV-2 infection cycle. Pterocarnin A also significantly reduced viral infectivity at high concentrations. From these observations, it was concluded that pterocarnin A suppressed both early and late in the replication cycle of HSV-2. The various modes of action of pterocarnin A in interfering with certain steps of viral infection thus merit further investigation.
    Microbes and Infection 08/2004; 6(8):738-44. · 2.92 Impact Factor
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    ABSTRACT: To investigate the in vitro antiviral properties of putranjivain A, isolated from the whole plant of Euphorbia jolkini Bioss (Euphorbiaceae). Herpes simplex virus (HSV)-2 strain 196-infected Vero cells were used. It was shown that putranjivain A exhibited antiviral activity with an IC50 of 7.9 +/- 1.2 micro M using the XTT assay, with the IC50 value increasing with increasing multiplicity of infection. Using the plaque reduction assay, the IC50 and IC90 were 6.3 +/- 0.8 and 14.5 +/- 3.1 micro M, respectively. Putranjivain A showed no cytotoxic effect on cell multiplication at concentrations that achieved antiviral activity. The 50% cell cytotoxic concentration (CC50) was 80.3 +/- 14.7 microM, and the selectivity index (SI) (ratio of CC50 to IC50) for the XTT and plaque reduction assays was 10.2 and 12.7, respectively. When tested for virucidal activity, putranjivain A significantly reduced viral infectivity at concentrations of 75 and 100 micro M, but not at 50 microM or below. The results of the time-of-addition studies suggested that putranjivain A affected the late stage of HSV-2 replication at 25 microM. Interestingly, putranjivain A also showed inhibition of viral attachment and cell penetration. The combination of putranjivain A and aciclovir produced no interaction. Putranjivain A possesses antiviral activity, inhibiting viral attachment and penetration, and also interfering with the late stage of viral replication.
    Journal of Antimicrobial Chemotherapy 05/2004; 53(4):577-83. · 5.34 Impact Factor
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    ABSTRACT: In this study, the in vitro antiviral properties of prodelphinidin B-2 3,3'-di- O-gallate (PB233'OG) isolated from the bark of Myrica rubra (Myricaceae) was investigated. Results showed that PB233'OG exhibited anti-herpes simplex virus type 2 (HSV-2) activity with IC (50) values of 5.3 +/- 0.1 and 0.4 +/- 0.04 microM for XTT and plaque reduction assays, respectively. The IC (50) value increased with increasing MOI (multiplicity of infection). PB233'OG did not show a cellular cytotoxic effect at concentrations that possessed antiviral activity. Mechanistic studies demonstrated that PB233'OG inhibited HSV-2 attachment to the Vero cell, interfered with the penetration of HSV-2 into the Vero cell, affected the late stage(s) of the HSV-2 infection cycle, and also reduced the viral infectivity at high concentrations. It is concluded that PB233'OG exhibits various modes of action in its anti-HSV-2 effects.
    Planta Medica 11/2003; 69(10):953-6. · 2.35 Impact Factor