Highly potent anti-HIV-1 activity isolated from fermented Polygonum tinctorium Aiton

Zhong, Yu; Yoshinaka, Yoshiyuki; Takeda, Tadahiro; Shimizu, Noriko; Yoshizaki, Sayaka; Inagaki, Yoshio; Matsuda, Shinobu; Honda, Gisho; Fujii, Nobutaka; Yamamoto, Naoki

A water-soluble extract of fermented Polygonum tinctorium Aiton (Polygonaceae) called Sukumo, exhibited a potent inhibitory activity against HIV type 1 in vitro. The extract potently suppressed acute HIV-1 (III(B)) infection in MT-4 cells with EC(50) values of 0.5 μg/ml but exhibited low cytotoxicity to MT-4 cells even at a high concentration (CC(50) > 1000 μg/ml). It also inhibited giant cell formation in co-cultures of HIV-infected cells and uninfected Molt-4 cells. Sukumo extract was found to interact with both the viral envelope glycoprotein and cellular receptors, thus blocking virus-cell binding and virus-induced syncytium formation. There was a good correlation between the extract's anti-HIV-1 activity and its inhibitory effects on HIV-1 binding. It also suppressed replication of herpes simplex virus type 1 in Vero cells with an EC(50) of 11.56 μg/ml. On the other hand, there was no appreciable activity against influenza A virus, poliovirus or SARS corona virus when tested at concentrations ranging from 3.2–400 μg/ml as shown by microscopic image analysis for cytopathic effect (CPE). Physico-chemical studies revealed that the anti-HIV activity in the extract was essentially maintained after boiling at 100 °C in 1N HCl or 1N NaOH, and after treatment with 100 mM NaIO(4). The inhibitory activity of the extract was also not reduced after pronase digestion. The active factor in the extract is likely to be a novel compound(s) having a polyanionic substructure and a molecular weight of 10,000–50,000.