A COMPONENT OF THE MEDICINAL HERB EPHEDRA BLOCKS ACTIVATION IN THE CLASSICAL AND ALTERNATIVE PATHWAYS OF COMPLEMENT

Extracts of the herb Ephedra sinica have long been used in traditional Chinese medicine for the treatment of, among other conditions, acute nephritis. In preliminary studies it was shown that extracts of ephedr a caused inhibition of complement in vitro. We thus set out to isolate the active component(s) of this herb, to examine the complement-inhib iting capacity in sera from different species, and to characterize the mechanism(s) by which it inhibits complement, Aqueous extraction of t he herb followed by fractionation using thin layer chromatography (TLC ) demonstrated that complement-inhibiting activity resided within a si ngle band, hereafter termed the complement-inhibiting component (CIC), which represents an as yet uncharacterized polyanionic carbohydrate m olecule. TLC-purified CIC inhibited the classical complement pathway i n all species tested (human, pig, guinea pig, rat and rabbit). Using e rythrocyte intermediates and sera specifically depleted of individual components it was apparent that CIC inhibited C2. This finding was con firmed using purified human C2, CIC causing a dose-dependent loss of C 2 haemolytic activity, At much higher doses, CIC also showed some inhi biting effect in the terminal pathway, and this was shown to be due to inhibition of C9. In the alternative pathway CIC also showed inhibito ry activity, although its site of action in this pathway remains unres olved. In Chinese medicine the herb is taken orally, though no studies of complement levels in patients taking the herb have been reported. Preliminary data indicate that oral administration in rats causes a pa rtial inhibition of serum complement activity. Given the current enthu siasm for complement inhibition as a therapy for inflammatory diseases , this non-toxic, naturally occurring agent might be of therapeutic va lue.