Inhibitory effects of Egyptian folk medicines on human immunodeficiency virus (HIV) reverse transcriptase

Abstract

Extracts of 41 medicinal plants used in Egyptian folk medicine were screened for their inhibitory effects on human immunodeficiency virus-1 reverse transcriptase. The extracts of fruits of Phyllanthus emblica, Quercus pedunculata, Rumex cyprius, Terminalia bellerica, Terminalia chebula and Terminalia horrida showed significant inhibitory activity with IC50 < or = 50 micrograms/ml. Through a bioassay guided-fractionation of the methanol extract of the fruit of P. emblica, putranjivain A (1) was isolated as a potent inhibitory substance with IC50 = 3.9 microM, together with 1,6-di-O-galloyl-beta-D-glucose (2), 1-O-galloyl-beta-D-glucose (3), kaempferol-3-O-beta-D-glucoside (4), quercetin-3-O-beta-D-glucoside (5) and digallic acid (6). The inhibitory mode of action by 1, 2 and 6 was non-competitive with respect to the substrate but competitive with respect to a template-primer. Furthermore, the stereochemistry of 1 was established in this paper by nuclear magnetic resonance spectroscopy.

PIP: The fundamental role played by reverse transcriptase (RT) in the replication of retroviruses has made this enzyme a key target in the chemotherapy of HIV infection. Since the replicative cycle of HIV is interrupted by RT inhibitors, the inhibition of HIV RT is currently considered as a useful approach in the prophylaxis and intervention of AIDS. The MeOH and water extracts of 41 medicinal plants used in Egyptian folk medicine were evaluated for their HIV-1 RT inhibitory effects, and inhibitory substances were identified from the fruit of Phyllanthus emblica that showed a potent inhibitory activity to HIV-1-RT. The enzyme activity was determined by the amount of tritium labeled-substrate incorporation into a polymer fraction in the presence of a template-primer. Of the plant materials tested, the fruits of Phyllanthus emblica L. (MeOH extract), Quercus pedunculata (MeOH and water extracts), Rumex cyprius (MeOH and water extracts), Terminalia bellerica (MeOH and water extracts), Terminalia chebula (MeOH and water extracts), and Terminalia horrida (MeOH extract) showed significant inhibitory activity with IC50 of 2-49 mcg/ml. However, in the presence of bovine serum albumin (BSA), the inhibitory potency of most of the extracts, except for P. emblica (MeOH extract) and T. chebula (water extract), was appreciably reduced by nonspecific binding of their ingredients with BSA. Through a bioassay guided-fractionation of the methanol extract of the fruit of P. emblica, putranjivain A (1) was isolated as a potent inhibitory substance with IC50 = 3.9 mcM, together with 1,6-di-O-galloyl-beta-D-glucose (2), 1-O-galloyl-beta-D-glucose (3), kaempferol-3-O-beta-D-glucoside (4), quercetin-3-O-beta-D-glucoside (5), and digallic acid (6). The inhibitory mode of action by 1, 2, and 6 was noncompetitive with respect to the substrate but competitive with respect to a template-primer. Furthermore, the stereochemistry of 1 was established in this paper by nuclear magnetic resonance spectroscopy.