Alkaloids from Isopyrum thalictroides L.

Three new bisbenzylisoquinoline alkaloids, isopyruthaldine, isopythaldine and isothalmidine, containing new type of bridges were isolated from roots and rhizomes of Isopyrum thalictroides. The known isoquinoline alkaloids, reticuline, isocorydine. columbamine and palmatine, obtained from the aerial parts, are new for the genus Isopyrum. All structures were elucidated by spectroscopic analysis.

Phytochemical study and cytotoxic activity of alkaloids from Uvaria chamae P. Beauv.

Phytochemical study of leaves of Uvaria chamae resulted in the isolation for the first time for the genus Uvaria of benzylisoquinoline alkaloids (+)-armepavine (1) and racem. O,O-dimethylcoclaurine (2). The aporphines nornantenine (3), nantenine (4) and corydine (7) are new for the species. The alkaloids were found to express cytotoxic activity against L 929 transformed cells. The highest activity was shown by 1, 3, and 5. At a concentration corresponding to their IC50 against L929 cells, they were nontoxic against mouse thymocytes.

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

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 Itl and It3 depended on the concentration of Ca2+ and Mg2+ 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.

Complement-mediated antiinflammatory effect of bisbenzylisoquinoline alkaloid fangchinoline.

Complement-mediated mode of action of bisbenzylisoquinoline alkaloid fangchinoline was investigated in vivo and in vitro. The application of fangchinoline intraperitoneally (i.p.) to complement normal mice, strain ICR, inhibited the complement activity in serum and peritoneal exudate. The substance activated serum complement of C5-deficient DBA/2 mice. Fangchinoline was able to provoke local inflammatory reaction in both strains after subcutaneous (s.c.) injection. The alkaloid suppressed paw swelling induced by live Candida albicans in ICR and DBA/2 mice. Its effect depended on the dose and time of injection prior to inflammatory reaction. The in vitro experiments proved the interference of fangchinoline action with post-C5 reactions. The substance augmented C5-convertase formation and functional activity. These results are in correspondence with our previous investigations, proving the complement-mediated action of fangchinoline. The antiinflammatory effect could be a consequence of the caused complement exhaustion.

Phytochemical study and antiinflammatory properties of Lobelia laxiflora L.

Three new piperidine alkaloids were isolated from stems, leaves and flowers of Lobelia laxiflora L. (Campanulaceae). The structures of racem. cis-8,10-diethyl-3,4-dehydrolobelidiol (1), racem. trans-8-ethyl-10-phenyl-3,4-dehydrolobelidiol (2) and racem. cis-8-ethyl-10-phenyl-3, 4-dehydrolobelidiol (3) were established by spectral analyses. The residues obtained from the ethanol extracts from stems (S), leaves (L), and flowers (F) were applied in carrageenan (Car)- and cobra venom (CV)-induced acute inflammation in mice. A suppression of paw edema formation at a dose of 100 mg kg-1 was established. In this study the antiinflammatory potential of Lobelia l. was regarded in connection with the complement system. The sequential activation and assembly into functional units of complement components can proceed via two different pathways, named classical (CP) and alternative (AP). The ability of the residues, nonalkaloid fractions, alkaloid fractions and the three alkaloids at a concentration from 0.125 to 1.0 mg ml-1 to inhibit complement activation and thus to prevent inflammatory process was estimated in vitro in human serum via both pathways. All of them inhibited complement activity with a predominant action on CP.

Antimicrobial and immunological activity of ethanol extracts and fractions from Isopyrum thalictroides.

The antimicrobial and immunological properties of ethanol extracts, non-alkaloid, tertiary alkaloid and quaternary alkaloid fractions, obtained from roots and aerial parts of Isopyrum thalictroides were examined. The non-alkaloid fraction from aerial parts inhibited the growth of seven test microorganisms and was the most effective suppressor of classical pathway (CP) complement activity in normal human serum (NHS) and guinea pig serum (GPS). The alkaloid fractions, containing quaternary alkaloids expressed suppressive effect on mitogen-induced splenocyte proliferation. The in vitro antibody response against sheep red blood cells (anti-SRBC) was inhibited by ethanol extracts and quaternary alkaloid fraction. The intraperitoneal (i.p.) application of ethanol extract and tertiary alkaloid fraction from aerial parts showed that they possess in vivo effect on alternative pathway (AP) complement activity, anti-SRBC response and delayed type hypersensitivity (DTH).