Interaction with aromatase
There is strong evidence that nettle extract interferes with the conversion of testosterone into oestrogens. The ethanolic nettle root extract WS1031 (DER 8–13:1, solvent 60% ethanol) inhibited aromatisation of androstenedione in vitro (IC50 338 μg/ml). This effect was increased by adding saw palmetto extract (Koch, 1995). The active principle was found in an heptane fraction, suggesting that lipophilic compounds are responsible for the action (Koch, 1995). The heptane fraction was more effective than a single component – 9-hydroxy-10,12-octadecadienoic acid. Semimaximal inhibitory concentrations were higher than those of Sabal extracts (solvents ethanol 90%, hexane) but the combination of Sabal and Urtica extracts showed a clear additive effect. In a similar test procedure, a comparable aromatase inhibition of ethanolic nettle extract LI 166 (60% ethanol, DER 8–12:1) and a synthetic aromatase inhibitor was achieved, however at a concentration 250 fold higher than that of the synthetic (Morgenstern and Ziska, 1999). Likewise, the dose-dependent inhibitory effect of a methanolic extract (DER 10:1, solvent 30% methanol) on aromatase was increased by concomittant administration of a Pygeum extract (Hartmann et al., 1996).
Besides common fatty acids, (10E,12Z)-9-hydroxy-10,12-octadecadienoic acid was identified as co-active component (Kraus et al., 1991). Later, other lignans, e.g. secoisolariciresinol, oleanolic and ursolic acid, (9Z,11E)-13-hydroxy-9,11-octadecadienoic acid and 14-octacosanol, were identified as weak to moderate inhibitors of the aromatase (Gansser and Spiteller, 1995b). Nettle root extracts of various producers were found to inhibit the aromatase, as did isolated 9-hydroxy-10-trans-12-cis-ocadecadienoic acid or its derivative 9-oxo-10-trans-12-cis-ocadecadienoic acid (Bartsch and Kühne, 1992). However, nettle root contains only low quantities of these components and the active principle for a clinical relevant aromatase inhibition needs still to be defined. However, the aqueous nettle extract BNO 1250 (DER 10:1, 0.75 and 7.5 mg/ml) also inhibited oestradiol formation in a time and dose-dependent manner (a cytotoxic effect could be excluded). Jarry et al. (1999) suggested that besides the inhibition of the enzyme activity, inhibition of aromatase gene expression may be involved in the nettle root effect.
Interaction with androgen receptor binding
There is no evidence that the nettle root extract BAZ (DER 5:1, solvent 20% methanol) interacts with the binding of radioactively labelled DHT to rat prostatic androgen receptors (Rhodes et al., 1993) nor that this nettle root extract affected microsomal 5α-reductase activity (Rausch et al., 1992).
Interaction with 5α-reductase
Only high doses of a methanolic extract (DER 10:1, solvent 30% methanol) inhibited 5α-reductase (ED50 14.7 mg/ml; Hartmann et al., 1996). The effect was very low when compared with the synthetic 5α-reductase inhibitor finasteride (Rhodes et al., 1993). Likewise, the ethanolic extract WS1031 had no impact on the conversion of testosterone into DHT (Koch and Biber, 1994).