EXPERIMENTAL METHOD AND ANIMAL

Effects of Magnolol on Sodium Salicylate-Induced Pregnancy Damage of Pregnant Mice

  • FAN Qiwen ,
  • CHEN Fang ,
  • ZHANG Wei ,
  • GUO Wanzheng ,
  • HUANG Shaowen ,
  • ZHAO Na ,
  • DU Encun ,
  • WEI Jintao
Expand
  • Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Institute of Animal Science and Veterinary Medicine, Hubei Academy of Agricultural Sciences, Wuhan 430064, China

Received date: 2020-11-10

  Online published: 2021-06-10

Abstract

This study was conducted to explore the effects of magnolol on sodium salicylate-induced pregnancy damage of pregnant mice and its mechanism. A total of 96 pregnant mice were randomly divided into 4 groups, namely the control group, the model group (group Ⅰ) and the repair groups (groups Ⅱ and Ⅲ), with 6 replicates in each group and 4 mice per replicate. The control group was given by distilled water (1% dimethylsulfoxide) and gavage normal saline. Groups Ⅰ, Ⅱ, and Ⅲ were given by distilled water (1% dimethylsulfoxide) with 0, 80 and 800 μmol/L magnolol and gavage 280 mg/kg sodium salicylate per day. The test lasted for 9 days and gavage test was carried out from the first day of pregnancy (GD1) to GD4. The results showed that compared with the control group, in group Ⅰ, the gravid uterus weight and fetus number were significantly reduced (P<0.05), and the relative expression level of NAD(P)H dehydrogenase 1 (NQO1) was significantly decreased (P<0.05), while the relative expression level of leukemia inhibitory factor receptor (LIFR) was significantly increased (P<0.05) in the endometrium on GD4. The serum superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), endometrial relative expression levels of E-cadherin (CDH1) and nuclear factor E2 related factor 2 (NRF2) were significantly reduced (P<0.05), while the relative expression levels of heme oxygenase-1 (HO-1) and homeobox gene A10 (HOXA10) were significantly up-regulated (P<0.05) on GD9 in group Ⅰ. Compared with group Ⅰ, the gravid uterus weight and fetus number in group Ⅲ were significantly up-regulated (P<0.05), and the serum SOD activity and T-AOC in pregnant mice on GD9 were significantly up-regulated (P<0.05). In addition, compared with group Ⅰ, the relative expression level of LIFR on GD4 in endometrium in group Ⅲ was significantly down-regulated (P<0.05), and the relative expression levels of CDH1 and NRF2 were significantly up-regulated on GD9 (P<0.05), the relative expression levels of HO-1 and HOXA10 were significantly decreased on GD9 (P<0.05). In summary, these results indicate that magnolol can alleviate pregnancy damage and embryo loss caused by high concentration of sodium salicylate. These effects may be related to the adaptive regulation of magnolol on the endometrium during embryo implantation and mid-gestation.

Cite this article

FAN Qiwen , CHEN Fang , ZHANG Wei , GUO Wanzheng , HUANG Shaowen , ZHAO Na , DU Encun , WEI Jintao . Effects of Magnolol on Sodium Salicylate-Induced Pregnancy Damage of Pregnant Mice[J]. Chinese Journal of Animal Nutrition, 2021 , 33(6) : 3507 -3514 . DOI: 10.3969/j.issn.1006-267x.2021.06.052

References

[1] ZHANG J H,CHEN Z X,HUANG X H,et al.Insights on the multifunctional activities of magnolol[J].Biomed Research International,2019,2019:1847130.
[2] HUANG S H,CHEN Y,TUNG P Y,et al.Mechanisms for the magnolol-induced cell death of CGTH W-2 thyroid carcinoma cells[J].Journal of Cellular Biochemistry,2007,101(4):1011-1022.  
[3] KIM G D,OH J,PARK H J,et al.Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells[J].International Journal of Oncology,2013,43(2):600-610.  
[4] TSE A K W,WAN C K,ZHU G Y,et al.Magnolol suppresses NF-κB activation and NF-κB regulated gene expression through inhibition of IkappaB kinase activation[J].Molecular Immunology,2007,44(10):2647-2658.  
[5] ZHANG H T,XU X,CHEN L L,et al.Molecular determinants of magnolol targeting both RXRα and PPARγ[J].PLoS One,2011,6(11):e28253.
[6] DREIER D,LATKOLIK S,RYCEK L,et al.Linked magnolol dimer as a selective PPARγ agonist-structure-based rational design,synthesis,and bioactivity evaluation[J].Scientific Reports,2017,7(1):13002.
[7] KUMAR S,GURU S K,PATHANIA A S,et al.Autophagy triggered by magnolol derivative negatively regulates angiogenesis[J].Cell Death & Disease,2013,4(10):e889.
[8] LI H B,YI X,GAO J M,et al.Magnolol-induced H460 cells death via autophagy but not apoptosis[J].Archives of Pharmacal Research,2007,30(12):1566-1574.  
[9] 高厚明,刘志承,石巧玲,等.厚朴酚改善LPS诱导的小鼠抑郁行为和大脑细胞因子的研究[J].中医药通报,2016,15(2):56-58. GAO H M,LIU Z C,SHI Q L,et al.Study on magnolol in improving depression behavior and brain cytokines in mice induced by LPS[J].Traditional Chinese Medicine Journal,2016,15(2):56-58.(in Chinese)
[10] LU Y C,CHEN H H,KO C H,et al.The mechanism of honokiol-induced and magnolol-induced inhibition on muscle contraction and Ca2+ mobilization in rat uterus[J].Naunyn-Schmiedeberg's Archives of Pharmacology,2003,368(4):262-269.  
[11] FOULON O,JAUSSELY C,REPETTO M,et al.Postnatal evolution of supernumerary ribs in rats after a single administration of sodium salicylate[J].Journal of Applied Toxicology,2000,20(3):205-209.  
[12] WÉRY N,FOULON O,BLACKER A,et al.Vertebral malformations induced by sodium salicylate correlate with shifts in expression domains of Hox genes[J].Reproductive Toxicology,2005,20(1):39-45.  
[13] ZHANG Q Q,YE X F,WANG L Z,et al.Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats[J].Regulatory Toxicology and Pharmacology,2016,74:117-122.
[14] BERGMAN K,CEKAN E,SLANINA P,et al.Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat[J].Toxicology,1990,61(2):135-146.  
[15] DAVIS D P,DASTON G P,ODIO M R,et al.Maternal reproductive effects of oral salicylic acid in Sprague-Dawley rats[J].Toxicology Letters,1996,84(3):135-141.  
[16] WANG W,CHEN S R,ZHOU Z P,et al.Aspirin suppresses neuronal apoptosis,reduces tissue inflammation,and restrains astrocyte activation by activating the Nrf2/HO-1 signaling pathway[J].Neuroreport,2018,29(7):524-531.  
[17] MONG M C,YIN M C.Nuclear factor κB-dependent anti-inflammatory effects of s-allyl cysteine and s-propyl cysteine in kidney of diabetic mice[J].Journal of Agricultural and Food Chemistry,2012,60(12):3158-3165.  
[18] LU S Y,SU W,LI H H,et al.Abscisic acid improves drought tolerance of triploid bermudagrass and involves H2O2-and NO-induced antioxidant enzyme activities[J].Plant Physiology and Biochemistry,2009,47(2):132-138.  
[19] GIARDINA C,INAN M S.Nonsteroidal anti-inflammatory drugs,short-chain fatty acids,and reactive oxygen metabolism in human colorectal cancer cells[J].Biochimica et Biophysica Acta:Molecular Cell Research,1998,1401(3):277-288.  
[20] SARKAR S,BUHA D.Effect of ripe fruit pulp extract of Cucurbita pepo Linn.in aspirin induced gastric and duodenal ulcer in rats[J].Indian Journal of Experimental Biology,2008,46(9):639-645.
[21] PAIVA P,MENKHORST E,SALAMONSEN L,et al.Leukemia inhibitory factor and interleukin-11:critical regulators in the establishment of pregnancy[J].Cytokine & Growth Factor Reviews,2009,20(4):319-328.  
[22] WANG X J,QIAO Y,XIAO M M,et al.Opposing roles of acetylation and phosphorylation in LIFR-dependent self-renewal growth signaling in mouse embryonic stem cells[J].Cell Reports,2017,18(4):933-946.  
[23] YOO I,CHAE S,HAN J,et al.Leukemia inhibitory factor and its receptor:expression and regulation in the porcine endometrium throughout the estrous cycle and pregnancy[J].Asian-Australasian Journal of Animal Sciences,2019,32(2):192-200.  
[24] GOTTARDI C J,WONG E,GUMBINER B M.E-cadherin suppresses cellular transformation by inhibiting β-catenin signaling in an adhesion-independent manner[J].The Journal of Cell Biology,2001,153(5):1049-1060.  
[25] ORSULIC S,HUBER O,ABERLE H,et al.E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation[J].Journal of Cell Science,1999,112(8):1237-1245.  
[26] YIANNAKOPOULOU E.Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents-implications for cancer treatment and chemoprevention[J].Cellular Oncology,2014,37(3):167-178.  
[27] TAHARA T,SHIBATA T,NAKAMURA M,et al.Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa[J].Digestive Diseases and Sciences,2010,55(1):54-59.  
[28] TAYLOR S H,HEUVEL G B V,IGARASHI P.A conserved Hox axis in the mouse and human female reproductive system:late establishment and persistent adult expression of the Hoxa cluster genes[J].Biology of Reproduction,1997,57(6):1338-1345.  
Outlines

/