Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities

• Published in: Food and chemical toxicology 2013-08, Vol.58, p.355-361
• Main Authors: Cho, Namki, Lee, Ki Yong, Huh, Jungmoo, Choi, Ji Hoon, Yang, Heejung, Jeong, Eun Ju, Kim, Hong Pyo, Sung, Sang Hyun
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Anti-neuroinflammation; antioxidants; Antioxidants - pharmacology; bark; binding proteins; Biological and medical sciences; brain; Chromatography, High Pressure Liquid; cognition; Cognition - drug effects; Cognitive-enhancing activity; CREB–BDNF signaling; ethyl acetate; Flavonoids; Flavonoids - pharmacology; glutathione peroxidase; glutathione-disulfide reductase; inducible nitric oxide synthase; lipopolysaccharides; Male; Medical sciences; memory; Mice; Mice, Inbred ICR; Nerve Tissue Proteins - metabolism; neurons; Neuroprotective Agents - pharmacology; neuroprotective effect; neurotoxicity; Oxidative Stress - drug effects; Plant Bark - chemistry; Plant Extracts - pharmacology; prostaglandin synthase; rats; Rhus; Rhus - chemistry; Rhus verniciflua bark; scopolamine; Scopolamine Hydrobromide - pharmacology; superoxide dismutase; Toxicodendron vernicifluum; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.05.007

[Display omitted] •PREF showed neuroprotective effects in vitro and cognitive enhancing effects in vivo.•Fisetin and butein attenuates LPS-induced proinflammatory mediators such as iNOS, COX-2, ERK and JNK phosphorylation.•Fisetin enhanced memory deficit induced by scopolamine by the activation of the CREB–BDNF pathway. The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)–brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers.