In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

Cinzia Sanna; Arianna Marengo; Stefano Acquadro; Alessia Caredda; Roberta Lai; Angela Corona; Enzo Tramontano; Patrizia Rubiolo; Francesca Esposito

doi:10.3390/plants10102124

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

Plants (Basel). 2021 Oct 7;10(10):2124. doi: 10.3390/plants10102124.

Authors

Cinzia Sanna¹, Arianna Marengo², Stefano Acquadro², Alessia Caredda³, Roberta Lai¹, Angela Corona³, Enzo Tramontano³, Patrizia Rubiolo², Francesca Esposito³

Affiliations

¹ Laboratory of Pharmaceutical Botany, Department of Life and Environmental Sciences, University of Cagliari, Via S. Ignazio da Laconi 13, 09123 Cagliari, Italy.
² Department of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, Italy.
³ Laboratory of Molecular Virology, Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, ss554, km 4500, Monserrato, 09042 Cagliari, Italy.

Abstract

In a search for natural compounds with anti-HIV-1 activity, we studied the effect of the ethanolic extract obtained from leaves, bark, and peels of Punica granatum L. for the inhibition of the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) and integrase (IN) LEDGF-dependent activities. The chemical analyses led to the detection of compounds belonging mainly to the phenolic and flavonoid chemical classes. Ellagic acid, flavones, and triterpenoid molecules were identified in leaves. The bark and peels were characterized by the presence of hydrolyzable tannins, such as punicalins and punicalagins, together with ellagic acid. Among the isolated compounds, the hydrolyzable tannins and ellagic acid showed a very high inhibition (IC₅₀ values ranging from 0.12 to 1.4 µM and 0.065 to 0.09 µM of the RNase H and IN activities, respectively). Of the flavonoids, luteolin and apigenin were found to be able to inhibit RNase H and IN functions (IC₅₀ values in the 3.7-22 μM range), whereas luteolin 7-O-glucoside showed selective activity for HIV-1 IN. In contrast, betulinic acid, ursolic acid, and oleanolic acid were selective for the HIV-1 RNase H activity. Our results strongly support the potential of non-edible P. granatum organs as a valuable source of anti-HIV-1 compounds.

Keywords: HIV-1 integrase; HIV-1 reverse transcriptase; Punica granatum; bark; ellagic acid; hydrolyzable tannins; leaves; peel; pomegranate; triterpenoids.