Ferulic Acid exerts concentration-dependent anti-apoptotic and neuronal differentiation-inducing effects in PC12 and mouse neural stem cells.

Ferulic Acid (FA) is a phenolic compound with anti-apoptotic and anti-oxidative properties. There are reports regarding its neuro-protective, neuro-proliferative and neuro-differentiative effects. However, effect of FA on neuronal differentiation and its effective neuro-protective and neuro-differentiative concentrations are unknown. Also the role of sirtuin molecules in neuroprotective effects of FA were not reported. We used PC12 and mouse neural stem cells (mNSCs) in our experiments. Intact and apoptotic (H2O2-exposed) cells were treated with different concentrations of FA, and then they were evaluated by MTT, quantitative real-time RT-PCR and immunostaining assays. FA treatment at low concentrations (50 µg/ml) significantly reduced apoptosis in H2O2-treated PC12 cells. Real-time RT-PCR and western blot assays confirmed that FA induced this effect through stabilization and degradation of P53 by increasing the expression rate of SIRT1, SIRT7 and MDM2 but down-regulation of USP7. Beside this anti-apoptotic effect, treatments of PC12 cells and mNSCs with higher concentrations of FA (250-800 µg/ml on PC12 cells and 100-500 µg/ml on mNSCs) increased the rate of neuronal differentiation. Immunocytochemical staining for ß-tubulin III and Map2 verified the presence of mature neurons, and western blot assay showed that FA-treated PC12 cells had a stepwise rise of phosphorylated-ERK1/2 with increasing concentrations of FA. Our findings showed that FA at low concentrations has neuroprotective effect through up-regulation of SIRT1, SIRT7 and MDM2, and at higher concentrations can promote neural differentiation and neurite outgrowth.

Effects of Oleo Gum Resin of Ferula assa-foetida L. on Senescence in Human Dermal Fibroblasts: - Asafoetida reverses senescence in fibroblasts.

OBJECTIVES: Based on data from Chinese and Indian traditional herbal medicines, gum resin of Ferula assa-foetida (sometimes referred to asafetida or asafoetida) has several therapeutic applications. The authors of various studies have claimed that asafetida has cytotoxic, antiulcer, anti-neoplasm, anti-cancer, and anti-oxidative effects. In present study, the anti-aging effect of asafetida on senescent human dermal fibroblasts was evaluated. METHODS: Senescence was induced in in vitro cultured human dermal fibroblasts (HDFs) through exposure to H2O2, and the incidence of senescence was recognized by using cytochemical staining for the activity of ß-galactosidase. Then, treatment with oleo gum resin of asafetida was started to evaluate its rejuvenating effect. The survival rate of fibroblasts was evaluated by using methyl tetrazolium bromide (MTT) assays. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot assays were performed to evaluate the expressions of apoptotic and anti-apoptotic markers. RESULTS: Our experiments show that asafetida in concentrations ranging from 5 × 10-8 to 10-7 g/mL has revitalizing effects on senescent fibroblasts and significantly reduces the ß-galactosidase activity in these cells (P < 0.05). Likewise, treatment at these concentrations increases the proliferation rate of normal fibroblasts (P < 0.05). However, at concentrations higher than 5 × 10-7 g/mL, asafetida is toxic for cells and induces cell death. CONCLUSION: The results of this study indicate that asafetida at low concentrations has a rejuvenating effect on senescent fibroblasts whereas at higher concentrations, it has the opposite effect of facilitating cellular apoptosis and death.