Prenylflavonoids from hops induce neural differentiation independent from an estrogen-like activity

8Prenylnaringenin was identified as potent phytoestrogen which imitates most of the effects of estradiol [1]. Endogenous hormones such as estradiol promote neurogenesis, the differentiation of neural stem cells to neurons. Estradiol is furthermore known to ameliorate general behavior in neurodegenerative processes like Parkinson's or Alzheimer's and lowers the risk of inefficient regeneration after cerebral infarction in vitro and in vivo in women [summarized in 2]. In this study it was of interest to investigate whether 8-prenylnaringenin, which is also used in hormone replacement therapy, imitates the differentiation-inducing effect of estradiol on neural adult stem cells. Furthermore, it was of interest to determine if other hop prenylflavonoids e.g. 6prenylnaringenin with almost no estrogen-like activity show a different potential to induce differentiation in vitro. Therefore an assay based on neural precursor cells transiently transfected with a doublecortin promoter construct was used, which was recently shown to indicate neuronal fate and differentiation [3]. Isomers 8prenylnaringenin (1) and 6prenylnaringenin (2) (Figure 1) showed a similar potential in differentiation induction. Furthermore, isomers seem to be less potent than positive control (retinoic and valproic acid), which was also substantiated by immunocytochemistry (Figure 2; c = 10µM). Side-chain elongation (e.g. 8-geranylnaringenin) mediated an improved differentiation activity, although estrogen-like activity was reduced. These results allow the conclusion that the neuro-differentiation activity, measured in the DCX-assay, does not correlate with the estrogen-like activity of the tested prenylflavonoids.

Keywords: Humulus lupulus L., differentiation, 8-prenylnaringenin, estrogen-like activity

References:

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