Effects of Podophyllum peltatum compounds in various preparations and dilutions on human neutrophil functions in vitro

Human blood neutrophil granulocytes (neutrophils) treated with Podophyllum peltatum L.-derived compounds exhibited an enhanced oxidative response to subsequent challenge with bacterial formyl peptides. This priming effect was concerned with superoxide anion (O2-) release (respiratory burst). The phenomenon was observed with a potentized preparation containing, among other things, podophyllum extract (Podophyllum compositum), with Podophyllum 4x (final concentration of active principle about 0.025 pg/ml), whereas enhancement of 0 2release was not caused by homoeopathic Podophyllum 12x or other components of the complex homoeopathic preparation. Purified podophyllotoxin had the same effect at doses of 0.1-10 pg/ml, whereas doses higher than 100 pg/ml of podophyllotoxin inhibited the respiratory burst, so that pure toxin showed a typical bi-phasic dose-response curve. Similar effects were obtained with purified colchicine (1-1000 pg/ml), a microtubule-disrupting agent. No priming by a Podophyllum-derived compound was observed on neutrophils stimulated with 50 ng/ml phorbol ester. Further, both potentized podophyllum-derived compounds and pure podophyllotoxin-inhibited cellular adhesion to the serum-coated surface of culture microplates. These results show that low potencies of a drug extract have specific stimulating effects on the activation of neutrophil metabolism. The same stimulating effects are also caused by low doses of the active principle of the drug, which is an inhibitor when used at high doses. KEVWORDS: Leukocyte function; Superoxide anion; Adhesion; Podophyllum peltatum L.; Podophyllotoxin; Colchicine; Hormesis. Introduction Podophyllum belongs to a series of purgative drugs derived from the Berberidaceae (Podophyllum peltatum L.). Podophyllin, the raw extract containing the active principle podophyllotoxin, is drawn from the rhizome. Podophyllum has proved an irritant on patch testing 1 and a mixture of natural and semisynthetic (modified) lignan from Podophyllum emodi (proreside) has been used for many years in the treatment of rheumatoid arthritis, but its use was hampered by gastrointestinal side-effects. 2 In addition podophyllum and podophyl lotoxin have been used in *Institute of Clinical Chemistry and Microscopy, University of Verona; **Institute of Pharmacology, University of Verona; ***Biologische Heilmittel Heel GmbH, Baden Baden. dermatological conditions such as condylomata acuminata.3.4 Podophyllotoxin and its chemical derivatives like epipodophyl lo toxins (teniposide) affect cell division. As they interact with microtubules or with associated protein or modify tubulin GTP binding and also affect DNA, they have been widely investigated as anti-cancer drugs. 5, 6 The action ofpodophyllum derivatives on leukocytes has been studied principally as regards the effect of its main component, the podophyllotoxin and its derivatives. Its action is to inhibit lymphocyte proliferation, 7 probably because it affects microtubule dynamics 8 and DNA topoisomerases. 9 Podophyllotoxin molecular action could be ascribed to its chemical resemblance to colchicine and vinca alkaloids. These compounds have a significant effect on microtubule function.