Cardioactive compounds from the Australian plant genus, Eremophila (Myoporaceae).

Abstract

For over 40 000 years, the Australian Aboriginal people relied on native plants as a source of medicinal agents. Although they employed a wide range of species for this purpose, some of the most commonly used were Eremophila species (Myoporaceae). In particular, E. alternifolia was considered the 'number one medicine'. Reportedly, infusions of the leaves were used both internally and externally as an analgesic, decongestant and expectorant. This was believed to be useful in the treatment of colds, influenza, fevers and headaches, as well as for sterilising septic wounds and for promoting general well being.A methanolic extract of E. alternifolia leaves was tested on Langendorff rat hearts and was shown to mediate significant increases in heart rate (chronotropism), contractile force (inotropism) and coronary perfusion rate (CPR). With similar responses to those induced by adrenaline, it seemed likely that the active constituents of E. alternifolia leaves may have acted through adrenergic receptors. Challenging the extract with alpha- and beta- receptor antagonists did not, however, significantly reduce the size of responses. The active compound acted through a different mechanism.The identity of the active constituent in E. alternifolia leaves was revealed and shown to be a known phenylethanoid glycoside called verbascoside. Also known as acteoside, this compound's identity was confirmed by comparison of its spectral parameters with those described in the literature and by comparative tlc behaviour with that of standard samples. Its effects on the Langendorff rat heart were similar to those induced by the methanolic extract, but were more pronounced and did not act through adrenergic receptors or slow calcium channels . Repeatedly, 1 ml of 1 mM verbascoside dose-dependently increased chronotropism, inotropism and CPR in Langendorff rat hearts by increasing intracellular levels of the second messenger, cyclic, 3',5'-adenosine monophosphate (cAMP). The increase in cAMP production occurred in response to an increase in prostacyclin. Significant increases in this hormone-like compound were detected in hearts treated w verbascoside. The calcium channel blocker, verapamil, did not significantly diminish the effects of verbascoside.Another of the highly prized medicinal agents employed by the Aboriginal people was E. longifolia, a plant of sacred and mystical significance. Infusions made from the leaves were prepared for eye washes, as counter-irritants, for treating headaches and for skin and body washes. Pharmacological testing of the methanolic extract of leaves indicated that one or more active compounds with a biphasic effect on the Langendorff rat heart were responsible. The major active constituent was identified as an iridoid glucoside called geniposidic acid. One ml of 1 mM geniposidic acid significantly inhibit chronotropism, inotropism and CPR. The compound did not, however, induce biphasic effect. This was later rationalised by the small amounts of verbascoside that co-occur in the extract.Four similar iridoid glucosides that had been isolated from three other Eremophila species were tested for their effects on Langendorff rat hearts. Melampyroside (from E. pantonii), verminoside (E. ionantha), ferruloylajugol (E. pantonii) and catalpol (E. maculata subsp brevifolia) all significantly altered myocardial activity in the isolated rat heart preparations. Melampyroside and verminoside were predominantly stimulatory, while ferruloylajugol was biphasic and catalpol only inhibitory. The effects of these iridoids is discussed in comparison with geniposidic acid and other known cardioactive iridoid glucosides. The results suggest that the effects exhibited by these compounds is more common phenomenon than was previously realised.