CYTOTOXIC PROPERTIES OF TRITERPENE SAPONIN TAUROSID SX1 AND ITS EFFECT ON HUMAN IMMUNODEFICIENCY VIRUS AND INFLUENZA VIRUS INFECTION IN MICE.

Triterpene saponin Taurosid Sx1 purified from leaves of the plant Crimean Ivy Hedera taurica Carr. (Araliaceae) was evaluated for its cytotoxic activity against lymphoblastoid cell lines MT-4, Jurkat-tat, U937, and human peripheral blood monocytes. The ability of saponin to influence HIV-1 replication was studied as well. In addition, the ability of Taurosid Sx1 to increase survival of mice infected with influenza virus А/WSN/1/33(H1N1) and its capacity for strengthening the immune responses in mice immunized with the influenza vaccine Grippol® have been studied. Taurosid Sx1 has been shown to inhibit MT-4 cell line at 25 µg ml-1 concentration, IC50 33,3 µmol l-1 (MTT assay). The saponin concentration of 5 µg ml-1 was non-toxic for all the cell lines studied and demonstrated a moderate inhibitory effect on HIV p24 production in Jurkat-tat cells. In the lower concentrations Taurosid Sx1 did not stimulate HIV p24 production. It was shown that oral administration of 200 µg Taurosid Sx1 to the influenza virus infected mice caused 1.5-fold increase in their survival. Taurosid Sx1 given orally amplified immunopotentiating ability of an intramusculary administered subunit influenza vaccine. Antibody production was significantly higher in animals fed Taurosid Sx1 after primary or secondary immunizatuion. In mice given 2 doses of vaccine, from 1 to 3 weeks apart, feeding 200 µg saponin resulted in 2 to 10-fold enhancement in production of anti-H1, anti-H3, and anti-inluenza type B hemagglutinin antibodies. Thus, Taurosid Sx1 can be considered as low-toxic promising immunopotentiating agent uncapable of enhancing HIV-1 replication.

Study of the adjuvant activity of new MDP derivatives and purified saponins and their influence on HIV-1 replication in vitro.

Muramyl dipeptide (MDP), eight new lipophilic MDP derivatives (MDPs) and three purified saponins were evaluated for their ability to induce immune responses in mice immunized with HIV-1 envelope protein rgp160 and for their ability to influence the HIV-1 replication in vitro. Three of nine new synthetic MDP derivatives (beta-butyl-MDP, MTPO-26 and beta-cholesteryl-MDP) and one saponin (Taurosid I) have been shown to induce strong humoral immune responses to HIV-1 envelope glycoproteins rgp160 and rgp120. Three substances (beta-butyl-MDP, MDP-cholyl and beta-G27-MDP) induced high levels of T-cell stimulation to HIV-1 rgp160. beta-butyl-MDP induced the strongest B- and T-cell responses to HIV-1 glycoproteins. Two substances (beta-butyl-MDP and Taurosid I) did not induce an enhancement of HIV-1 replication in vitro and can be considered as promising adjuvants.