title: Proanthocyanidins improves lead-induced cognitive impairments by blocking endoplasmic reticulum stress and nuclear factor-κB-mediated inflammatory pathways in rats.
abstract: Proanthocyanidins (PCs), a class of naturally occurring flavonoids, had been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor and anti-inflammatory. In this study, we examined the protective effect of PCs against lead-induced inflammatory response in the rat brain and explored the potential mechanism of its action. The results showed that PCs administration significantly improved behavioral performance of lead-exposed rats. One of the potential mechanisms was that PCs decreased reactive oxygen species production and increased the total antioxidant capacity in the brains of lead-exposed rats. Furthermore, the results also showed that PCs significantly decreased the levels of tumor necrosis factor-α, interleukin 1β and cyclooxygenase-2 in the brains of lead-exposed rats. Moreover, PCs significantly decreased the levels of beta amyloid and phosphorylated tau in the brains of lead-treated rats, which in turn inhibited endoplasmic reticulum (ER) stress. PCs also decreased the phosphorylation of protein kinase RNA-like ER kinase, eukaryotic translation initiation factor-2, inositol-requiring protein-1, c-Jun N-terminal kinase, p38 and inhibited nuclear factor-κB nuclear translocation in the brains of lead-exposed rats. In conclusion, these results suggested that PCs could improve cognitive impairments by inhibiting brain oxidative stress and inflammatory response.
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China. Electronic address: lcm9009@126.com.
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, Xuyuan Road, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Liu
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Gui-Hong
authors.initials: GH
authors.lastname: Zheng
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Feng
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Sun
mesh_terms: D000284:Administration, Oral; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D053583:Interleukin-1beta; D008565:Membrane Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D007854:Lead; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C486557:Ern2 protein, rat; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Beta amyloid; Brain inflammation; Endoplasmic reticulum stress; Lead; Oxidative stress; Proanthocyanidins