title: 4-O-methylhonokiol inhibits serious embryo anomalies caused by nicotine via modulations of oxidative stress, apoptosis, and inflammation.
abstract: BACKGROUND
  Since the increasing smoking rate among women has resulted in higher rates of embryonic malformations, it is important to search for an efficient and inexpensive agent that can help reduce the rate of serious fetal anomalies caused by maternal cigarette smoking. In this study, the bioavailability of 4-O-methylhonokiol isolated from Magnolia officinalis was first demonstrated in the mouse embryos exposed to nicotine using a whole embryo culture system.
  
  
  METHODS
  Mouse embryos on embryonic day 8.5 were cultured with 1 mM nicotine and/or 4-O-methylhonokiol (1 × 10(-4) or 1 × 10(-3) μM) for 48 hr and were analyzed on the viewpoints of embryo developmental changes, oxidative damages, and apoptotic and inflammatory changes.
  
  
  RESULTS
  Embryos exposed to 1 mM nicotine developed not only severe morphological anomalies, increased expressions of tumor necrosis factor-α, interleukin-1β, and caspase 3 mRNAs; and elevated levels of lipid peroxidation, but also decreased levels of cytoplasmic superoxide dismutase, cytosolic glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, hypoxia inducible factor-1α, and B-cell lymphoma-extra large mRNAs, and reduced superoxide dismutase activity. However, these parameters were significantly improved when embryos exposed to the nicotine were concurrently treated with 4-O-methylhonokiol (1 × 10(-4) or 1 × 10(-3) μM).
  
  
  CONCLUSIONS
  These findings indicate that 4-O-methylhonokiol reduces serious embryo anomalies caused by nicotine in mouse embryos via the modulations of oxidative stress, apoptosis, and inflammation, suggesting that 4-O-methylhonokiol may be a preventive and therapeutic agent against the dysmorphology induced by maternal smoking during pregnancy.
authors.affiliation: College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Lin
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Yon
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Jong Kwon
authors.initials: JK
authors.lastname: Lee
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
authors.forename: In-Jeoung
authors.initials: IJ
authors.lastname: Baek
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Lee
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Nam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D046149:Embryo Culture Techniques; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000009:adverse effects*; D038081:Organogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C542058:4-O-methylhonokiol; D001713:Biphenyl Compounds; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053583:Interleukin-1beta; D017705:Lignans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: 4-O-methylhonokiol; anti-inflammation; antiapoptosis; antioxidant; dysmorphology; nicotine