Send to

Choose Destination
Mech Ageing Dev. 2019 Apr 10;180:70-81. doi: 10.1016/j.mad.2019.04.002. [Epub ahead of print]

Astragaloside IV and ferulic acid synergistically promote neurite outgrowth through Nrf2 activation.

Author information

The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
The Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China. Electronic address:


Recently, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) have nuclear localization and nuclear exclusion signals and shuttle between the cytoplasm and the nucleus. Thus, we hypothesised that astragaloside IV (AS-IV) induction nuclear import of Nrf2 and ferulic acid (FA) inhibition nuclear export of Nrf2 contribute to synergistic antioxidant effects of combination of FA and AS-IV (FA/AS-IV). Here, we have demonstrated that FA/AS-IV enhances neurite outgrowth of PC12 cells challenged with lead acetate (PbAc) via antioxidant properties in a synergistic manner. Concomitantly, FA/AS-IV significantly promotes Nrf2 activation and induces "phase-II'' enzymes during PbAc toxicity, compared with either FA or AS-IV alone. Interestingly, FA but not AS-IV activates the extracellular signal-regulated kinases 1 and 2 (ERK1/2), leading to an increase in both de novo synthesis of Nrf2 and nuclear import of Nrf2. Simultaneously, AS-IV but not FA suppresses Fyn phosphorylation via Akt-mediated inhibition of GSK-3β, which inhibited nuclear export of Nrf2. Importantly, dual activation of both ERK1/2 and Akt by FA/AS-IV in PC12 cells challenged with PbAc is mediated by independent mechanisms, which are supported by pharmacological inhibitors. Collectively, these results support the notion that the FA/AS-IV may be promising in therapy for lead developmental neurotoxicity. This combination deserves further study in vivo.


Astragaloside IV; Ferulic acid; Lead developmental neurotoxicity; Nuclear factor erythroid 2-related factor 2; Synergism


Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center