Neuroregenerative Potential of Prenyl- and Pyranochalcones: A Structure-Activity Study

Loss of neuronal tissue is a hallmark of age-related neurodegenerative diseases. Since adult neurogenesis has been confirmed in the human brain, great interest has arisen in substances stimulating the endogenous neuronal regeneration mechanism based on adult neural stem cells. Medicinal plants are a valuable source of neuroactive small molecules. In the structure-activity study presented here, the activities of prenyl- and pyranochalcones were compared to each other, using a differentiation assay based on the doublecortin promoter sequences. The latter revealed that the pyrano ring is a crucial structural element for the induction of neuronal differentiation of adult neural stem cells, while compounds with a prenyl group show significantly lower activities. Furthermore, a decrease of pro-differentiation activity was observed following structural modifications, such as substitutions on the pyrano ring and on the B-ring of the chalcone. We also initiated the elucidation of the structural characteristics of the newly discovered lead substance xanthohumol C, which correlated with the activation of the doublecortin promoter during neuronal differentiation.

Automated summary

Loss of neuronal tissue is a hallmark of age-related neurodegenerative diseases. Adult neurogenesis in the human brain has sparked interest in substances stimulating the endogenous neuronal regeneration mechanism. Medicinal plants are valuable sources of neuroactive small molecules. The pyrano ring is crucial for inducing neuronal differentiation of adult neural stem cells, while compounds with a prenyl group show lower activities.