| This research project has focused on the further study of the antiviral constituents from a traditional Chinese herbal medicine, Prunella vulgaris (Xia-Ku-Cao).; In vivo anti-HSV-1 and -2 results showed the polysaccharide (PVP) from P. vulgaris has strong inhibition effects on HSV-1 infections in guinea pigs and therapeutic effects on HSV-2 infections in mice at 5–15% (w/w) concentrations.; PPS-2b showed a significant reduction in anti-HSV-1 activity by periodate oxidation but not by protease treatment. It is another evidence that the anti-HSV-1 activity of PPS-2b is not due to protein. Results suggested that the active constituent PPS-2b has the properties of a lignin-carbohydrate complex.; Molecular weights of PPS-2a and PPS-2b were estimated to be 930 kDa and 8.5 kDa, respectively. Results of elemental analysis showed that the components contain minor or no proteins. Sulfur percentage was lower than 3%. Chemical analysis indicated that PPS-2b comprised lignin moieties in its molecule besides carbohydrate moieties. PPS-2a was found to be composed completely of carbohydrates. PPS-2b was found to comprise arabinose, xylose, rhamnose, mannose, galactose, glucose and galacturonic acid in its carbohydrate moieties in a molar ratio of 0.1:0.3:0.3:0.7:1.0:3.4:0.5. In contrast, PPS-2a comprised arabinose, xylose, rhamnose, galactose, glucose and galacturonic acid in a molar ratio of 4.0:11.1:0.1:1.0:4.0:1.1.; Mechanism study showed that PPS-2b inactivate HSV-1 directly by inhibition of 86% virus yield and has an obvious blocking effect on the HSV-1 attachment to Vero cells. PPS-2b had the significant inhibition effect on the penetration of HSV-1 into Vero cells. The binding ability of PPS-2b to viral glycoproteins was determined with 35S-labeled HSV-1 proteins through an affinity chromatography process in comparison with heparin as a control. PPS-2b showed a tendency to bind gC of HSV-1, similar to heparin. PPS-2b also showed the tendency to bind gD of HSV-1 through the results of immunoprecipitation. It is therefore concluded that the binding of PPS-2b to viral glycoproteins may competently inhibit the virus binding to the cells. The mechanism of PPS-2b was to inhibit mainly on the early stage of viral infection, exhibiting a different mechanism to ACV. However, the complex interactions between several viral and cellular proteins and the influence of PPS-2b to the interactions are still awaiting further investigation.; Antiviral activities of PPS-2b for anti-RSV anti-PIV-3, anti-DHBV and anti-HIV integrase were also screened in this study. PPS-2b showed potent dose-dependent inhibitory effects on RSV, DHBV and HIV integrase through in vitro screening. Other fractions and compounds showed these activities in different extent.; As a conclusion, the anti-HSV properties of the polysaccharide fraction (PVP) from the hot water extract of the fruitspikes of P. vulgaris were confirmed in both in vitro and in vivo experiments. PPS-2b was demonstrated to be the main antiviral constituent in P. vulgaris. There is a good potential for the application of PVP and PPS-2b in HSV therapy. Clinical trial will help determine their therapeutic values. (Abstract shortened by UMI.)... |
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