Ferulic acid alleviates Aβ25-35- and lipopolysaccharide-induced PC12 cellular damage: a potential role in Alzheimer's disease by PDE inhibition.

Abstract

OBJECTIVE:

Phosphodiesterase (PDE) plays an important role in the pathogenesis of Alzheimer's disease (AD). Ferulic acid (FA) has a therapeutic benefit in the treatment of AD. We investigated whether this therapeutic effect is based on the modulation of the PDE/cyclic adenosine monophosphate (cAMP) pathway. In the present study, we investigated whether FA could abrogate Aβ25-35- and lipopolysaccharide-induced cellular damage.

MATERIALS AND METHODS:

Cell viability, superoxide production, and the levels of inflammatory factors were investigated. We further investigated the intracellular levels of cAMP and Ca2+, both of which are associated with PDE activity. Furthermore, molecular docking was used to identify the binding mode between phosphodiesterase 4B2 (PDE4B2) and FA.

RESULTS:

Pretreatment with FA significantly maintained cell viability, increased the levels of superoxide dismutase, and inhibited production of TNF-α and IL-1β induced by Aβ25-35. Moreover, pretreatment with FA increased the intracellular levels of cAMP and decreased the intracellular levels of Ca2+. The docking results also showed that FA has the potential to inhibit PDE4B2 activity.

CONCLUSIONS:

Taken together, our results suggested that one of the therapeutic effects of FA on AD was potentially mediated by modulating the PDE/cAMP pathway.

• Authors: Hao Huang, Zeng-Chun Ma, Yu-Guang Wang, Qian Hong, Hong-Ling Tan, Cheng-Rong Xiao, Qian-De Liang, Xiang-Lin Tang, Yue Gao
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 53 Issue 10 Pg. 828-37 (Oct 2015) ISSN: 0946-1965 [Print] Germany
• PMID: 26308168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Coumaric Acids
• Interleukin-1beta
• Lipopolysaccharides
• Peptide Fragments
• Phosphodiesterase Inhibitors
• Tumor Necrosis Factor-alpha
• amyloid beta-protein (25-35)
• ferulic acid
• Cyclic AMP
• Superoxide Dismutase
• Cyclic Nucleotide Phosphodiesterases, Type 4
• PDE4B protein, rat
• Calcium

Topics

• Alzheimer Disease (drug therapy)
• Amyloid beta-Peptides (toxicity)
• Animals
• Calcium (metabolism)
• Cell Survival (drug effects)
• Coumaric Acids (pharmacology, therapeutic use)
• Cyclic AMP (analysis)
• Cyclic Nucleotide Phosphodiesterases, Type 4 (physiology)
• Interleukin-1beta (antagonists & inhibitors)
• Lipopolysaccharides (toxicity)
• Molecular Docking Simulation
• PC12 Cells
• Peptide Fragments (toxicity)
• Phosphodiesterase Inhibitors (pharmacology)
• Rats
• Superoxide Dismutase (biosynthesis)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)