Two new triterpenes from the Rhizome of Dryopteris crassirhizoma, and inhibitory activities of its constituents on human immunodeficiency virus-1 protease.

Two new hopane type triterpenes, named dryopteric acids A (1) and B (2), were isolated from the Rhizome of Dryopteris crassirhizoma (Aspiadaceae) together with sixteen known compounds (3-18). Of isolated compounds, ursolic acid (15), and dryopteric acid A (1) and B (2) showed potent inhibitory activities against HIV-1 protease with IC50 values of 8.9-44.5 microM. In addition, acetylated compounds 1 and 2 appreciably increased inhibitory activities with their IC50 values of 1.7 and 10.8 microM, respectively.

Effects of triterpenoids and flavonoids isolated from Alnus firma on HIV-1 viral enzymes.

Triterpenoids and flavonoids isolated from Alnus firma S. Z. were found to inhibit HIV-1 virus replication and controlled its essential enzymes. In this study, the inhibition of HIV-1 viral replication and its essential enzymes, such as reverse transcriptase, protease and alpha-glucosidase, were observed using 18 Korean plant extracts. Among the extracts, the methanol extract of Alnus firma leaves showed potent inhibition against the HIV-1 induced cytopathic effect (CPE) in MT-4 cells on microscopic observation (the minimum concentration for complete inhibition of HIV-1 induced CPE, IC=50 microg/mL). Thus, 14 compounds were isolated and identified from the methanol extract of Alnus firma leaves. Of these compounds, the alnustic acid methyl ester exhibited inhibition against HIV-1 protease, with an IC50 of 15.8 microM, and quercetin, quercitrin and myricetin 3-O-beta-D-galactopyranoside displayed inhibition against HIV-1 reverse transcriptase, all with IC50 values of 60 microM. Based on these results, the viral replication inhibition of the methanol extract of Alnus firma leaves was adjudged to be acutely related to the protease inhibition activation of the alnustic acid methyl ester as well as the reverse transcriptase inhibition activation of flavonoids.

Anti-HIV protease activity from rosa family plant extracts and rosamultin from Rosa rugosa.

To identify substances with anti-human immunodeficiency virus (HIV) activity from plant sources, 12 extracts of Rosa family plants were screened for their inhibitory effects against HIV-1 protease. Of the extracts tested, the strongest inhibitory effects were observed in the root of Rosa rugosa and the leaves of Prunus sargentii, at a concentration of 100 microg/mL. Rosamultin isolated from the root of R. rugosa inhibited HIV-1 protease by 53% at a concentration of 100 microM.

Anti-complement activity of constituents from the stem-bark of Juglans mandshurica.

Four known flavonoids and two galloyl glucoses isolated from the stem-bark of Juglans mandshurica (Juglandaceae), namely taxifolin (1), afzelin (2), quercitrin (3), myricitrin (4), 1,2,6-trigalloylglucose (5), and 1,2,3,6-tetragalloylglucose (6), were evaluated for their anti-complement activity against complement system. Afzelin (2) and quercitrin (3) showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) values of 258 and 440 microM. 1,2,6-Trigalloylglucose (5) and 1,2,3,6-tetragalloylglucose (6) exhibited anti-complement activity with IC(50) values of 136 and 34 microM. In terms of the evaluation of the structure-activity relationship of 3,5,7-trihydroxyflavone, compounds 2, 3, and 4 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (4a) as their aglycones, and these were also tested for their anti-complement activity. Of the three aglycones, kaempferol (2a) exhibited weak anti-complement activity with an IC(50) value of 730 microM, while quercetin (3a) and myricetin (4a) were inactive in this assay system. Among the compounds tested, 1,2,3,6-tetragalloylglucose (6) showed the most potent anticomplement activity (IC(50), 34 microM).

HIV-1 integrase inhibitory substances from Coleus parvifolius.

For the purpose of discovering anti-HIV-1 agents from natural sources, water and EtOH extracts of 50 Thai plants were screened for their inhibitory activity against HIV-1 integrase (IN), an enzyme essential for viral replication. Of these plants, an EtOH extract of Coleus parvifolius Benth. (aerial parts) showed potent activity against HIV-1 IN with an IC50 value of 9.2 microg/mL. From this extract, 11 compounds were isolated and identified as luteolin 5-O-beta-d-glucopyranoside (1), luteolin (2), luteolin 7-methyl ether (3), luteolin 5-O-beta-d-glucuronide (4), 5-O-beta-d-glucopyranosyl-luteolin 7-methyl ether (5), rosmarinic acid (6), rosmarinic acid methyl ester (7), daucosterol (8), a mixture of alpha- and beta-amyrin (9, 10) and phytol (11). Of these compounds, rosmarinic acid methyl ester (7), rosmarinic acid (6), luteolin (2) and luteolin 7-methyl ether (3) exhibited inhibitory activities against HIV-1 IN with IC50 values of 3.1, 5.0, 11.0 and 11.0 microM, respectively. Among rosmarinic acid derivatives, the HIV-1 IN inhibitory activity increased in turn for a dimer (IC50 = 5.0 microM), a trimer (IC50 = 1.4 microM), and a tetramer (IC50 = 1.0 microM).

Inhibitory effects of Korean medicinal plants and camelliatannin H from Camellia japonica on human immunodeficiency virus type 1 protease.

To identify substances with anti-human immunodeficiency virus (HIV) activity in traditional medicines, 101 extracts of Korean medicinal plants were screened for their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was determined by HPLC. Of the extracts tested, strong inhibitory effects were observed in the acetone extracts of the pericarp and leaves of Camellia japonica, the water extract of the leaves of Sageretia theezans and the methanol extract of the aerial part of Sophora flavescens. Camelliatannin H from the pericarp of C. japonica, showed a potent inhibitory activity on HIV-1 PR with IC(50) of 0.9 microM.

Screening of Chinese and Mongolian herbal drugs for anti-human immunodeficiency virus type 1 (HIV-1) activity.

Water and methanol extracts of 30 Chinese and Mongolian medicinal plants were tested for their human immunodeficiency virus type-1 (HIV-1) inhibitory activity. Of the 60 extracts, 23 showed anti-HIV activity. Bioassay-guided fractionation of one of the most active extracts, the methanol extract of the root tuber of Stephania cepharantha, led to the isolation of two alkaloids, aromoline and FK-3000 as potent inhibitory substances. They completely inhibited the cytopathic effects of HIV-1 on MT-4 cells at 31.3 and 7.8 microg/mL, respectively.

Inhibitory effects of quinones on RNase H activity associated with HIV-1 reverse transcriptase.

In an effort to develop new drugs preventing the growth of human immunodeficiency virus (HIV), we developed an in vitro assay method of ribonuclease H (RNase H) activity associated with reverse transcriptase (RT) from HIV-1. Some naphthoquinones, such as 1,4-naphthoquinone (1), vitamin K(3) (2), juglone (3) and plumbagin (6), moderately inhibited RNase H activity, and others, including naphthazarin (5) and shikonins (8-9, 18-23), showed weak inhibition. Diterpenoid quinones, tanshinones (24-28), had also moderate inhibition against RNase H activity. Of these quinones, compound 1 showed the most potent inhibition on RNase H activity with a 50% inhibitory concentration (IC(50)) of 9.5 microM, together with moderate inhibition against RNA-dependent and DNA-dependent DNA polymerase (RDDP and DDDP) activities with IC(50) values of 69 and 36 microM, respectively. Compounds 3 and 5 showed significant inhibition against RDDP (IC(50) = 8 and 10 microM, respectively) and DDDP (IC(50) = 5 and 7 microM, respectively) activities. The structure-activity relationship of the naphthoquinones suggested that non-hydroxylated naphthoquinones (1 and 2) showed significant inhibition of RNase H activity, whereas 5-hydroxylated naphthoquinones (3 and 5) showed potent inhibition against RDDP and DDDP activities.