Characterization and isolation of anti-HIV and latency reversal agents for the development of a herbal mixture of Gnidia sericocephala, Senna italica, Sclerocarya birrea and Pentanisia prunelloides

Abstract

Two non-daphnane diterpenoids were isolated as biomarkers and later identified using one and two dimensional nuclear magnetic resonance (1D and 2D NMR) as lasioerin and lasiocephalin. The preparative purification of the active fractions resulted in isolation of five daphnane diterpenoids (yuanhuacine A, yuanhuacine, a cis 2′′/3′′ isomer of gnididin, yuanhuajine and gniditrin) with viral inhibition properties as well as latency reversal activity. The compound yuanhuacine A and the mixture of yuanhuacine and the cis 2′′/3′′ isomer of gnididin showed in vitro HIV replication inhibition by > 80% at 0.08 μg/ml. Furthermore, yuanhuacine A inhibited a subtype C virus replication in peripheral blood mononuclear cells (PBMC) with a half maximal effective concentration (EC50) of 0.03 μM without cytotoxicity. The mixture of compounds, yuanhuacine and the cis 2′′/3′′ isomer of gnididin in an in vitro assay also reversed HIV latency by 16.7-fold lower concentrations than the control prostratin and also reversed HIV latency in primary helper T cells (CD4+ T cells) from combinatory anti- retroviral therapy (cART)-suppressed donors with HIV similar to the protein kinase C (PKC) activator prostratin but at 6.7-fold lower concentrations. These results suggests that G. sericocephala, yuanhuacine A and the mixture of yuanhuacine and a cis 2′′/3′′ isomer of gnididin act as anti-HIV agents to improve cART efficacy and support HIV cure efforts in resource-limited regions.