title: Alleviation of kainic acid-induced brain barrier dysfunction by 4-o-methylhonokiol in in vitro and in vivo models.
abstract: This experiment was designed to investigate whether 4-O-methylhonokiol (MH), a principal ingredient of Magnolia (M.) officinalis bark, alleviated acute intraperitoneal (i.p.) kainic acid- (KA-) induced brain blood barrier dysfunction (BBBD) via pathological examination and cytological analyses of the brain tissues of mice. KA (10-30 mg/kg) time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy. However, pretreatment with MH (5 and 20 mg/kg, i.p.) significantly reduced the water content of the brain compared to that observed in the KA control group. Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan's blue dye (EBD) staining and malondialdehyde (MDA) levels that were induced by KA (10 mg/kg, i.p.). MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p.) in mice in a manner similar to scavengers such as DMTU and trolox. Additionally, MH significantly scavenged intracellular ROS and Ca2+ within hippocampal cells. The tight junction seals mediated by claudin (Cld-5) were also found to be modulated by MH. MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50, 52.4 mM) and •OH with an electron spin resonance (ESR) signal rate constant of 4×10(9) M(-1)·S(-1), which is close to the reactivity of the vitamin E analog trolox. Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.
authors: Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Jin-Yi
authors: JY
authors: Han
authors: Lee's Biotech Co., Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-606, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Ahn
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Jae Hyeon
authors: JH
authors: Yoo
authors: College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Sang-Yoon
authors: SY
authors: Nam
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Jin Tae
authors: JT
authors: Hong
authors: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Ki-Wan
authors: KW
authors: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology*; D001927:Brain Diseases / Q000139:chemically induced*; D002199:Capillary Permeability; D007608:Kainic Acid / Q000633:toxicity*; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C542058:4-O-methylhonokiol; D000975:Antioxidants; D001713:Biphenyl Compounds; D017705:Lignans; D007608:Kainic Acid