Large-conductance calcium-dependent potassium (maxi-K) channels play an important role in regulating the tone of airway smooth muscle and the release of bronchoconstrictive substances from nerves in the lung. Crude extracts of Desmodium adscendens, a medicinal herb used in Ghana as a treatment for asthma, inhibit binding of monoiodotyrosine charybdotoxin (125I-ChTX) to receptor sites in bovine tracheal smooth muscle membranes that have been shown to be associated with maxi-K channels. Using this assay, three active components have been purified and identified by NMR and MS. Comparison with authentic samples revealed the three active components as the known triterpenoid glycosides dehydrosoyasaponin I (DHS-I), soyasaponin I, and soyasaponin III. The most potent of these compounds, DHS-I, is a partial inhibitor of 125I-ChTX binding (Ki = 120 nM, 62% maximum inhibition). Inhibition of 125I-ChTX binding is primarily due to a decrease in the observed maximum number of binding sites, with a smaller decrease in affinity. DHS-I increases the rate of toxin dissociation from its receptor, suggesting that modulation of ChTX binding occurs through an allosteric mechanism. DHS-I reversibly increases the open probability of maxi-K channels from bovine tracheal smooth muscle incorporated into planar lipid bilayers when applied to the intracellular, but not the extracellular, side of the membrane at concentrations as low as 10 nM. In contrast, DHS-I had no effect on several other types of potassium channels or membrane transporters. This natural product is the first example of a high-affinity activator of calcium-dependent potassium channels and is the most potent known potassium channel opener.

Seven female hypertensive subjects, being treated with an aqueous extract of Adenia cissampeloides, ('Adenia'), and seven weight-, age-and sex-matched hypertensive subjects about to begin treatment, were used to evaluate the therapeutic and possible toxic effects of this herbal preparation which is used at the Centre for Scientific Research into Plant Medicine (CSRPM), to control hypertension. Measurements of systolic and diastolic blood pressures were recorded, and serum levels of a-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were determined to give an indication of the effectiveness of 'Adenia' as an anti-hypertensive agent. Serum levels of y-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, proteins and cholesterol were used to indicate possible liver damage, and blood urea nitrogen (BUN), serum creatinine and creatinine clearance rate were determined for the assessment of possible nephrotoxicity. Systolic blood pressure was significantly lower in subjects on 'Adenia' compared to the control subjects not on 'Adenia'. (p < 0.01). HBDH and CK, were lower in the patients on 'Adenia', but the differences were not statistically significant. Levels of total and conjugated bilirubin were significantly lower in the subjects on 'Adenia', (p < 0.05). The plant preparation appears not to have hepatotoxic or nephrotoxic effects.

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Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.

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