Anti-HIV-1 activity and safety profile of a polyherbal gel formulation as a candidate microbicide

Abstract

Microbicides represent one of the promising options for the prevention of sexually transmitted HIV infection. Medicinal plants have a long history of use to provide treatment against many diseases. In this regard, polyherbal aqueous gel formulation comprising 50% ethanolic extract prepared from the heart wood of Acacia catechu, leaves of Lagerstroemia speciosa, fruits of Aegle marmelos, Phyllanthus emblica and Terminalia chebula using carbopol 974 P NF polymer has been prepared. The gel formulation showed significant anti-HIV-1 activity against both CXCR4 tropic (HIV-1NL4.3) and CCR5 tropic (HIV-1NLAD8) viruses with IC50 values of 58.17 ± 4.4 and 63.54 ± 6.8 μg/ml respectively. It also showed significant inhibition of HIV-1 reverse transcriptase (p = 0.004), protease (p = 0.014), and integrase (p = 0.018) enzymes activity as compared to gel base. The gel formulation did not show any adverse effect on the viability of the vaginal lactobacilli, human vaginal keratinocytes (Vk2/E6E7), and the monolayer formed by Caco-2 cells. Furthermore, no significant changes in the secretion of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF from the gel formulation treated Vk2/E6E7 cells were observed as compared to cells treated with gal base or medium control. Gel formulation did not show any significant increase in mutagenic index using Salmonella typhimurium. Gel formulation stored at either 30 ± 2 °C or 40 ± 2 °C was stable for 6 months for anti-HIV-1 activity. In conclusion, the polyherbal gel formulation reported herein having potent anti-HIV-1 activity and with limited safety profile may be a promising candidate as an herbal microbicide.