Inhibitory Effects of Phylligenin on the Proliferation of Cultured Rat Neural Progenitor Cells

Abstract

-Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer’s disease model

“…FF contains lignans, lignan glycosides, and flavonoids, whereas its major components are phylligenin, betulinic acid, oleanolic acid-3-acetate, arctiin, isorengyol, and matairesinoside (Lee et al. 2010 ). The effects of FF on the prevention of neuronal cell death have not been studied in Alzheimer’s disease-induced animals.…”

“…FF, including phylligenin, reduced the productions of reactive oxygen species (ROS) and nitric oxide (NO) in rat glial cells in vitro (Lee et al. 2010 ). On the other hand, CS contains anthraquinones such as chrysophanol, emodin, physcion, obtusifolin, aloe-emodin, alaternin, and aurantio-obtusin (Guo et al.…”