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: Chunmei Lin, Jung-Min Yon, Jin Tae Hong, Jong Kwon Lee, Jayoung Jeong, In-Jeoung Baek, Beom Jun Lee, Young Won Yun, Sang-Yoon Nam
• Journal: Birth defects research. Part B, Developmental and reproductive toxicology (Birth Defects Res B Dev Reprod Toxicol) Vol. 101 Issue 2 Pg. 125-34 (Apr 2014) ISSN: 1542-9741 [Electronic] United States
• PMID: 24692394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• 4-O-methylhonokiol
• Biphenyl Compounds
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Interleukin-1beta
• Lignans
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Nicotine
• Phospholipid Hydroperoxide Glutathione Peroxidase
• Glutathione Peroxidase
• Superoxide Dismutase
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Biphenyl Compounds (pharmacology)
• Caspase 3 (genetics, metabolism)
• Embryo Culture Techniques
• Female
• Glutathione Peroxidase (genetics, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Inflammation (chemically induced, pathology)
• Interleukin-1beta (genetics, metabolism)
• Lignans (pharmacology)
• Lipid Peroxidation (drug effects)
• Lymphoma, B-Cell (genetics, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Nicotine (adverse effects)
• Organogenesis (drug effects)
• Oxidative Stress (drug effects)
• Phospholipid Hydroperoxide Glutathione Peroxidase
• Pregnancy
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)