ABSTRACT
The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human immunodeficiency virus [HIV (HTLV-III/LAV)]. In this report, we synthesized sulfated plant polyphenols such as tannic acid sulfate, rutin sulfate, ellagic acid sulfate, (-)-epicatechin sulfate, and (-)-epigallocatechin 3-gallate sulfate, and examined the in vitro inhibitory effect on HIV infection using human T-cell lymphotropic virus type-I-carrying MT-4 cells, which are extremely susceptible to HIV infection. Of the compounds tested, tannic acid sulfate was the most effective and had low cytotoxicity. Tannic acid sulfate completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at the concentration of 6 micrograms/ml. In addition, this sulfate inhibited giant cell formation in coculture at the concentration of 5 micrograms/ml.
Subject(s)
Flavonoids , HIV/drug effects , Hydrolyzable Tannins/pharmacology , Sulfates/pharmacology , Cell Line , Cytopathogenic Effect, Viral/drug effects , Giant Cells/drug effects , HIV/pathogenicity , HIV Antigens/biosynthesis , Humans , Hydrolyzable Tannins/chemistry , Molecular Structure , Phenols/pharmacology , Polymers/pharmacology , PolyphenolsABSTRACT
Two sulfated polyphenols, NF-86II-S-13.3 and NF-86II-S-6.2, were synthesized from NF-86II without sulfur their inhibitory effect on human immunodeficiency virus (HIV) infection in vitro was examined, using cytopathic effect and an antigen expression assay system in MT-4 cells. NF-86II-S-13.3 (sulfur content, 13.3%) completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at concentrations of more than 6.3 micrograms/ml. The effect of NF-86II-S-6.2 (sulfur content, 6.2%) was much weaker than that of NF-86IIS-13.3. On the other hand, NF-86II without sulfur did not show any activity at all.
Subject(s)
5'-Nucleotidase/antagonists & inhibitors , Benzenesulfonates/pharmacology , Biopolymers , HIV/drug effects , Polymers/pharmacology , Benzenesulfonates/chemical synthesis , Cell Division/drug effects , Cell Line , Cytopathogenic Effect, Viral/drug effects , HIV/physiology , HIV Antigens/analysis , Humans , Phenols/chemistry , Polymers/chemical synthesis , Polymers/chemistryABSTRACT
New 5'-nucleotidase inhibitors designated as NPF-88BU-IA, NPF-88BU-IB, NPF-88BU-IIA and NPF-88BU-IIB, respectively, were isolated from the seeds and skin of the wine grape "Koshu". They were purified by solvent extraction, dialysis, and reversed-phase high performance liquid chromatography (HPLC). Their physico-chemical properties revealed these compounds to be polyphenolic substances. The average relative molecular masses of the four were estimated by gel permeation chromatography (GPC) analysis to be 7850, 5950, 11900, and 11300, respectively. They strongly inhibited 5'-nucleotidase activities from snake venom and rat liver membrane, and displayed significant therapeutic activity against Ehrlich ascites carcinoma. They also showed inhibitory effects on the growth of Streptococcus mutans MT8148(c), a primary cariogenic bacterium. Furthermore, these 5'-nucleotidase inhibitors inhibited the glucan formation from sucrose. These results suggest that the 5'-nucleotidase inhibitors can prevent the cause of caries of tooth.
Subject(s)
5'-Nucleotidase/antagonists & inhibitors , Fruit/chemistry , Phenols/pharmacology , Animals , Bacteria/drug effects , Glucans/biosynthesis , Mice , Mice, Inbred ICR , Phenols/isolation & purification , Skin/enzymology , Streptococcus mutans/drug effects , Streptococcus mutans/metabolism , Tumor Cells, Cultured/enzymologyABSTRACT
New 5'-nucleotidase inhibitors named NF-86I, NF-86II were recently isolated from the seeds of Areca catechu L. NF-86I and NF86II showed inhibitory effects on the growth of Streptococcus mutans MT8148(c) and Streptococcus mutans MT6715(g), respectively. In addition, these inhibitors could inhibit insoluble glucan formation from sucrose. NF-86I and NF-86II were found to be polyphenolic substances. Some polyphenols such as tannic acid bind non-specifically to proteins (tannic activity). The 5'-nucleotidase inhibitors that we isolated did not show any such activity. However, the growth inhibitory activity and the inhibitory effect on water-insoluble glucan production were equal to tannic acid. It is therefore considered that these inhibitors bind specifically to the bacterial cell surface. Our findings suggest that the 5'-nucleotidase inhibitors NF-86I and NF-86II may be useful anti-plaque preventing agents.
Subject(s)
5'-Nucleotidase/antagonists & inhibitors , Areca/chemistry , Flavonoids , Plants, Medicinal , Streptococcus mutans/growth & development , Phenols/pharmacology , Polymers/pharmacology , Polyphenols , Streptococcus mutans/drug effects , Streptococcus mutans/enzymologyABSTRACT
New 5'-nucleotidase-inhibitory polyphenols named NPF-86IA, NPF-86IB, NPF-86IIA and NPF-86IIB were isolated from the seeds of Areca catechu L. The ability of the inhibitors to precipitate gelatin was investigated by microturbidimetry. These inhibitors produced weak turbidity. As 5'-nucleotidase is a kind of phosphatase, we examined the effects of these inhibitors on alkaline and acidic phosphatases. While they showed moderate inhibitory effects on the activity of acidic phosphatases, they did not have any significant effect on the activity of alkaline phosphatase. Therefore, they showed a higher inhibitory effect on the 5'-nucleotidase than the other phosphatases, Murine macrophages were directly stimulated by the 5'-nucleotidase inhibitors.
