Anti-HIV-1 integrase activity of Mimusops elengi leaf extracts.

CONTEXT: Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes that, together with a reverse transcriptase and protease, allow the virus to reproduce itself after infecting the host cells. Any new knowledge on inhibitors of this enzyme could provide essential clues for the development of anti-HIV drugs. OBJECTIVE: To evaluate the anti-HIV-1 IN activity of some Thai medicinal plant extracts, and to isolate the active compounds from the extract that possessed the strongest anti-HIV-1 IN activity. MATERIALS AND METHODS: Ethanol extracts of eight Thai medicinal plants (10-100 µg/mL) were evaluated for their inhibitory effect against HIV-1 IN. An extract of Mimusops elengi L. (Sapotaceae) leaves that possessed the strongest anti-HIV-1 IN activity was fractionated to isolate the active compounds by an anti-HIV-1 IN assay-guided isolation process. RESULTS AND DISCUSSION: The leaf extract from M. elengi had the strongest anti-HIV-1 IN activity with an IC50 value of 62.1 µg/mL. A bioassay-guided isolation of the active compounds from M. elengi leaf extract resulted in the isolation of active compounds, identified as a mixture of gallocatechin and epigallocatechin. This mixture of gallocatechin and epigallocatechin showed satisfactory anti-HIV-1 IN activity with an IC50 value of 35.0 µM. A flavanol glycoside, mearnsitrin was also isolated but was inactive at a concentration of 100 µM.

Anti-inflammatory principles from Heritiera littoralis bark.

Compounds from the hexane, dichloromethane and acetone extracts of Heritiera littoralis bark were investigated for their nitric oxide (NO) inhibitory effects using RAW264.7 macrophage cells. The result indicated that ergosterol peroxide (13) exhibited the highest activity against NO release with an IC(50) value of 2.5 microM, followed by 6-alpha-hydroxystigmast-4-en-3-one (11, IC(50)=9.5 microM) and stigmast-4-en-3-one (9, IC(50)=15.9 microM), whereas other compounds showed moderate and mild effects (25.4- > 100 microM). Ergosterol peroxide (13) and 6-alpha-hydroxystigmast-4-en-3-one (11) were also tested against prostaglandin E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha) releases. It was found that ergosterol peroxide (13) possessed marked activity against PGE(2) release with an IC(50) value of 28.7 microM, while 6-alpha-hydroxystigmast-4-en-3-one (11) was 86.7 microM. However, these two compounds were inactive towards TNF-alpha release (IC(50) > 100 microM). The mechanism in transcriptional level of ergosterol peroxide (13) was found to down regulate mRNA expressions of iNOS and COX-2 in dose-dependent manners.