title: Effect of hesperetin against oxidative stress via ER- and TrkA-mediated actions in PC12 cells.
abstract: Hesperetin is known to activate estrogen receptors (ERs). Estrogen-mediated neuroprotection could be via both ER and tyrosine kinase receptor (Trk) signaling. This study tested whether hesperetin protected PC12 cells from hydrogen peroxide induced oxidative damage via ER- and/or TrkA-mediated actions. Hesperetin (0.1, 1, and 50 μM) inhibited cell viability decreases and reactive oxygen species, intracellular calcium level, and caspase-3 activity increases in H(2)O(2)-induced PC12 cells. Such actions were significantly (p < 0.05) suppressed by ICI 182,780 (an ER antagonist) or K252a (a TrkA antagonist) at low concentrations (0.1 or 1 μM) only. Hesperetin also stimulated the activation of Akt, ERK, and CREB as well as induced brain-derived neurotrophic factor, PPARγ coactivator 1α (PGC-1α), and seladin-1 (selective Alzheimer's disease indicator-1) via both ER and TrkA in the cells. This study demonstrates that the neuroprotective effects of hesperetin, at low concentrations, are attributed to its stimulation on receptor signaling. Moreover, ER and TrkA are known to be expressed in most Alzheimer's disease (AD) vulnerable brain regions. This study thus suggests that hesperetin might have potential for intervention in neurodegenerative disorders, particularly for AD.
authors.affiliation: Food Industry Research and Development Institute, Hsinchu, Taiwan.
authors.forename: Sam-Long
authors.initials: SL
authors.lastname: Hwang
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000818:Animals; D006569:Hesperidin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D006861:Hydrogen Peroxide; D006569:Hesperidin; D020794:Receptor Protein-Tyrosine Kinases; C013015:hesperetin