Neurodifferentiating potential of 8-prenylnaringenin and related compounds in neural precursor cells and correlation with estrogen-like activity

Neurodegenerative diseases are an increasing burden for our ageing societies; there is an as yet unmet need for the development of effective therapies. Neurogenesis, i.e., the generation of new neurons in the adult brain from neural stem cells, has received increasing attention since it offers the potential for endogenous brain repair and functional regeneration. Adult neurogenesis is partially under the control of sex hormones such as estradiol, and boosting neurogenesis with estradiol in animals correlates with cognitive improvement. 8-Prenylnaringenin imitates as highly potent phytoestrogen the effects of estradiol. Here, we studied the potential of 8-prenylnaringenin, 6-prenylnaringenin, and related compounds on differentiation induction in vitro using neural precursor cells transiently transfected with a doublecortin promoter luciferase construct, which was recently shown to indicate neuronal fate and differentiation. The flavanones 8-prenylnaringenin and 6-prenylnaringenin showed slight activity in this assay but significant activity by immunostaining. Although the estrogen-like activities of 8-prenylnaringenin and 6-prenylnaringenin are very different, the activity in differentiation induction is similar. Interestingly, also some prenylflavonoids with extended prenyl groups, e.g., a geranyl group, showed increased differentiation activity, while estrogen-like activity is decreased. This allows the conclusion that estrogen-like activity of prenylflavanones does not correlate directly with the activity of differentiation induction in neural precursor cells.