Complement modulatory activity of bisbenzylisoquinoline alkaloids isolated from Isopyrum thalictroides—I : Influence on classical pathway in human serum

Abstract

Eleven bisbenzylisoquinoline alkaloids (BBI) were isolated from the plant Isopyrum thalictroides (L.). Treatment of normal human serum (NHS) with BBI resulted in a diminution of the haemolytic activity of the classical pathway (CP). The mode of action of the main alkaloids isopyruthaline (It1), fangchinoline (It2) and isotalictrine (It3) on CP activation was investigated in vitro. The inhibition was time- and temperature-related and for It1 and It3 depended on the concentration of Ca 2+ and Mg 2+ ions. It was established that the substances reduced C1 haemolytic activity. It2 and It3 enhanced the complement consumption caused by heat aggregated human IgG (HAGG). The BBI prevented the formation of C3 convertase of the classical pathway. The loss of haemolytic activity was partially restored by the addition of C142 reagent (zymosan-treated guinea pig serum) to alkaloids-treated NHS. The addition of the late components C3–9 (EDTA-treated rat sera) recovered to some extent the haemolytic activity of It1-treated NHS, but not of It2- and It3-treated NHS.