Ivy Leaf (Hedera helix) and Menstrual cramps: evidence and sources

Hederacoside C, alpha-hederin, and hederagenin are saponins of dry extracts obtained from the leaves of ivy (Hedera helix L.). Internalization of beta(2)-adrenergic receptor-GFP fusion proteins after stimulation with 1 microM terbutaline was inhibited by preincubation of stably transfected HEK293 cells with 1 microM alpha-hederin for 24 h, whereas neither hederacoside C nor hederagenin (1 microM each) influenced this receptor regulation. After incubation of A549 cells with 5 nM Alexa532-NA, two different diffusion time constants were found for beta(2)AR-Alexa532-NA complexes by fluorescence correlation spectroscopy. Evaluation of the autocorrelation curve revealed diffusion time constants: tau(bound1) = 1.4 +/- 1.1 ms (n = 6) found for receptor-ligand complexes with unrestricted lateral mobility, and tau(bound2) = 34.7 +/- 14.1 ms (n = 6) for receptor-ligand complexes with hindered mobility. The distribution of diffusion time constants was 24.3 +/- 2.5% for tau(bound1) and 8.7 +/- 4.3% for tau(bound2) (n = 6). A549 cells pretreated with 1 microM alpha-hederin for 24 h showed dose-dependent alterations in this distribution with 37.1 +/- 5.5% for tau(bound1) and 4.1 +/- 1.1% for tau(bound2). Simultaneously, the level of Alexa532-NA binding was significantly increased from 33.0 +/- 6.8 to 41.2 +/- 4.6%. In saturation experiments, alpha-hederin did not influence the beta(2)-adrenergic receptor density (B(max)), whereas the K(D) value for Alexa532-NA binding decreased from 36.1 +/- 9.2 to 24.3 +/- 11.1 nM. Pretreatment of HASM cells with alpha-hederin (1 microM, 24 h) revealed an increased intracellular cAMP level of 13.5 +/- 7.0% under stimulating conditions. Remarkably, structure-related saponins like hederacoside C and hederagenin did not influence either the binding behavior of beta(2)AR or the intracellular cAMP level.

Commercial dry extract of Hedera helix L. is used for the treatment of disorders of the respiratory tract; it is standardized towards papaverine (papaverine equivalent value, PE, activity of 1 g test substance equivalent to the activity of x mg papaverine) by in vitro antispasmodic activity on isolated guinea-pig ileum with acetylcholine as spasmogen. In order to determine the phytochemical basis for the antispasmodic activity, bioassay guided fractionation and subsequent isolation of phenolic compounds (flavonols, caffeoylquinic acids) and saponins (hederacoside C, alpha-hederin, hederagenin) was carried out. Fractions and isolates obtained were investigated for antispasmodic activity and their contribution to the activity of the extract was calculated. Significant activity was found for both saponins and phenolic compounds, the PE values being approx. 55 and 49 for alpha-hederin and hederagenin, 54 and 143 for quercetin and kaempferol, and 22 for 3,5-dicaffeoylquinic acid, respectively. In view of their relative high concentration the saponins contribute most to the anti-spasmodic activity, followed by dicaffeoylquinic acids and the flavonol derivatives. The results indicate that the summed PE value of the compounds mentioned is an acceptable agreement with the PE value of the whole extract determined biologically.

Ethnopharmacological relevance The long tradition of using the dry extract of Hedera helix (common ivy) leaves in traditional and contemporary alternative medicine caused that many biological and pharmacological studies have been aimed at evaluating the effects of ivy. Some of the results suggest that Hedera helix extract possesses bronchodilatatory and antispasmodic activity. On the other hand, the symptoms of ivy intoxication in human and animals, as well as adverse-reactions observed during the therapy with ivy-based pharmaceuticals, indicate rather stimulant effect of the plant on smooth muscle. Thus, the aim of this study was to evaluate the effect of two main active substances extracted from the plant (α-hederin and hederacoside C) and the whole dry extract of Hedera helix on the gut motility. Materials and methods The experiments were carried out on isolated stomach corpus and fundus strips. The tissues were isolated from rats. The experiments were performed in isotonic conditions. The results are expressed as the percent of the reaction caused by a reference contractile substance, acetylcholine. Results and conclusions The obtained results revealed that α-hederin applied in the concentration ranged from 25 to 320μM significantly changed the spontaneous motoric activity of rat stomach smooth muscle. The observed reaction had always the same character, a contraction, and its force was concentration dependent. The second tested saponin, hederacoside C, did not alter the motility of rat isolated stomach corpus and fundus strips when administered in the concentration up to 100 μM, however, if applied in the concentration of 350 μM it induced a remarkable concentration of smooth muscle. Eventually, the whole extract of Hedera helix in a dose containing 60 μM of hederacoside C produced a strong contraction which strength was comparable with the reaction generated by acetylcholine. According to the results, it is very likely that α-hederin, but not hederacoside C contributes to the contractile response of isolated stomach corpus and fundus strips to the application of Hedera helix leaves' extract.