6-Gingerol Improves In Vitro Porcine Embryo Development by Reducing Oxidative Stress

6-Gingerol, the main active ingredient in ginger, exhibits a variety of biological activities, such as antioxidant, anti-inflammatory, and anticancer activities, and can affect cell development. However, the effects of 6-gingerol on mammalian reproductive processes, especially early embryonic development, are unclear. This study explored whether 6-gingerol can be used to improve the quality of in vitro-cultured porcine embryos. The results showed that 5 μM 6-gingerol significantly increased the blastocyst formation rates of porcine early embryos. 6-Gingerol attenuated intracellular reactive oxygen species accumulation and autophagy, increased intracellular glutathione levels, and increased mitochondrial activity. In addition, 6-gingerol upregulated NANOG, SRY-box transcription factor 2, cytochrome c oxidase subunit II, mechanistic target of rapamycin kinase, and RPTOR independent companion of MTOR complex 2 while downregulating Caspase 3, baculoviral IAP repeat containing 5, autophagy related 12, and Beclin 1. Most importantly, 6-gingerol significantly increased the levels of p-extracellular regulated protein kinase 1/2 while reducing the levels of p-c-Jun N-terminal kinase 1/2/3 and p-p38. These results indicate that 6-gingerol can promote the development of porcine early embryos in vitro.

[1]  Jing Wang,et al.  Oroxin A reduces oxidative stress, apoptosis, and autophagy and improves the developmental competence of porcine embryos in vitro. , 2022, Reproduction in domestic animals = Zuchthygiene.

[2]  S. Liang,et al.  Schisanhenol improves early porcine embryo development by regulating the phosphorylation level of MAPK. , 2021, Theriogenology.

[3]  A. Efeyan,et al.  The mTOR–Autophagy Axis and the Control of Metabolism , 2021, Frontiers in Cell and Developmental Biology.

[4]  T. Spencer,et al.  NANOG is required to form the epiblast and maintain pluripotency in the bovine embryo , 2019, Molecular reproduction and development.

[5]  Yingbo Ma,et al.  Autophagy: A novel mechanism of chemoresistance in cancers. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  S. Makpol,et al.  Ginger (Zingiber officinale Roscoe) in the Prevention of Ageing and Degenerative Diseases: Review of Current Evidence , 2019, Evidence-based complementary and alternative medicine : eCAM.

[7]  Chunyang Kang,et al.  6-Gingerols (6G) reduces hypoxia-induced PC-12 cells apoptosis and autophagy through regulation of miR-103/BNIP3 , 2019, Artificial cells, nanomedicine, and biotechnology.

[8]  Wenli Sun,et al.  Clinical aspects and health benefits of ginger (Zingiber officinale) in both traditional Chinese medicine and modern industry , 2019, Acta Agriculturae Scandinavica, Section B — Soil & Plant Science.

[9]  Feng Li,et al.  6-Gingerol Attenuates Ischemia-Reperfusion-Induced Cell Apoptosis in Human AC16 Cardiomyocytes through HMGB2-JNK1/2-NF-κB Pathway , 2019, Evidence-based complementary and alternative medicine : eCAM.

[10]  Yuhao Li,et al.  6‐gingerol ameliorates age‐related hepatic steatosis: Association with regulating lipogenesis, fatty acid oxidation, oxidative stress and mitochondrial dysfunction , 2019, Toxicology and applied pharmacology.

[11]  Hongbing Zhang,et al.  Regulation of Autophagy by mTOR Signaling Pathway. , 2019, Advances in experimental medicine and biology.

[12]  Z. Qin,et al.  Beclin 1, Bcl-2 and Autophagy. , 2019, Advances in experimental medicine and biology.

[13]  D. Griffin,et al.  The production of pig preimplantation embryos in vitro: Current progress and future prospects. , 2018, Reproductive biology.

[14]  Ying-Jie Niu,et al.  The toxic effect of aflatoxin B1 on early porcine embryonic development. , 2018, Theriogenology.

[15]  J. Qiao,et al.  Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial , 2018, Reproductive Biology and Endocrinology.

[16]  D. Gardner,et al.  Antioxidants improve IVF outcome and subsequent embryo development in the mouse , 2017, Human reproduction.

[17]  V. Negrón-Pérez,et al.  Single-cell gene expression of the bovine blastocyst. , 2017, Reproduction.

[18]  Qi Zhang,et al.  Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[19]  N. Blüthgen,et al.  A compendium of ERK targets , 2017, FEBS letters.

[20]  E. Farombi,et al.  Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. , 2017, Chemico-biological interactions.

[21]  H. Khodaei,et al.  The effects of 6-Gingerol on reproductive improvement, liver functioning and Cyclooxygenase-2 gene expression in estradiol valerate - Induced polycystic ovary syndrome in Wistar rats. , 2017, Biochemical and biophysical research communications.

[22]  M. Khazaei,et al.  Reactive Oxygen Species Generation and Use of Antioxidants during In Vitro Maturation of Oocytes , 2017, International journal of fertility & sterility.

[23]  Shaohui Zong,et al.  The Role of 6-Gingerol on Inhibiting Amyloid β Protein-Induced Apoptosis in PC12 Cells. , 2015, Rejuvenation research.

[24]  A. Ghasemzadeh,et al.  Optimization protocol for the extraction of 6-gingerol and 6-shogaol from Zingiber officinale var. rubrum Theilade and improving antioxidant and anticancer activity using response surface methodology , 2015, BMC Complementary and Alternative Medicine.

[25]  Fan Wang,et al.  Protective Effects of Astaxanthin on ConA-Induced Autoimmune Hepatitis by the JNK/p-JNK Pathway-Mediated Inhibition of Autophagy and Apoptosis , 2015, PloS one.

[26]  E. Soniya,et al.  [6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling , 2014, PloS one.

[27]  Shaopeng Wang,et al.  Biological Properties of 6-Gingerol: A Brief Review , 2014, Natural product communications.

[28]  S. Sollott,et al.  Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. , 2014, Physiological reviews.

[29]  Dongfeng Chen,et al.  Protective Effect Against Hydroxyl Radical-induced DNA Damage and Antioxidant Mechanism of [6]-gingerol: A Chemical Study , 2014 .

[30]  C. Grupen The evolution of porcine embryo in vitro production. , 2014, Theriogenology.

[31]  Wei-Kang Wu,et al.  Higenamine Combined with [6]-Gingerol Suppresses Doxorubicin-Triggered Oxidative Stress and Apoptosis in Cardiomyocytes via Upregulation of PI3K/Akt Pathway , 2013, Evidence-based complementary and alternative medicine : eCAM.

[32]  H. Mukhtar,et al.  Modulation of signaling pathways in prostate cancer by green tea polyphenols. , 2013, Biochemical pharmacology.

[33]  K. Bishayee,et al.  Lycopodine triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: signaling cascade and drug-DNA interaction. , 2013, European journal of pharmacology.

[34]  De Cheng,et al.  Vitamin C enhances the in vitro development of porcine pre-implantation embryos by reducing oxidative stress. , 2012, Reproduction in domestic animals = Zuchthygiene.

[35]  Yuan Cheng,et al.  Promotion of Human Early Embryonic Development and Blastocyst Outgrowth In Vitro Using Autocrine/Paracrine Growth Factors , 2012, PloS one.

[36]  K. Gupta,et al.  Green tea polyphenols causes cell cycle arrest and apoptosis in prostate cancer cells by suppressing class I histone deacetylases. , 2012, Carcinogenesis.

[37]  A. Thorburn,et al.  Autophagy and apoptosis: what is the connection? , 2011, Trends in cell biology.

[38]  Gyu Hwan Park,et al.  [6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[39]  Eunsong Lee,et al.  Anthocyanin stimulates in vitro development of cloned pig embryos by increasing the intracellular glutathione level and inhibiting reactive oxygen species. , 2010, Theriogenology.

[40]  K. Singletary Ginger: An Overview of Health Benefits , 2010 .

[41]  J. Roca,et al.  Advances in swine in vitro embryo production technologies. , 2010, Reproduction in domestic animals = Zuchthygiene.

[42]  W. A. King,et al.  Thyroid hormone supplementation improves bovine embryo development in vitro. , 2010, Human reproduction.

[43]  Hen-Hong Chang,et al.  6-Gingerol inhibits ROS and iNOS through the suppression of PKC-alpha and NF-kappaB pathways in lipopolysaccharide-stimulated mouse macrophages. , 2009, Biochemical and biophysical research communications.

[44]  L. Magnani,et al.  In vitro and in vivo derived porcine embryos possess similar, but not identical, patterns of Oct4, Nanog, and Sox2 mRNA expression during cleavage development , 2008, Molecular reproduction and development.

[45]  P. Dennery Effects of oxidative stress on embryonic development. , 2007, Birth defects research. Part C, Embryo today : reviews.

[46]  Y. Surh,et al.  [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo , 2007, Free radical research.

[47]  X. Cui,et al.  Increase in DNA fragmentation and apoptosis-related gene expression in frozen-thawed bovine blastocysts. , 2006, Zygote.

[48]  B. Huppertz,et al.  Regulation of proliferation and apoptosis during development of the preimplantation embryo and the placenta. , 2005, Birth defects research. Part C, Embryo today : reviews.

[49]  B. H. Shah,et al.  Roles of LPA3 and COX-2 in implantation , 2005, Trends in Endocrinology & Metabolism.

[50]  P. Robson,et al.  Transcriptional Regulation of Nanog by OCT4 and SOX2* , 2005, Journal of Biological Chemistry.

[51]  P. Holm,et al.  The effect of oxygen tension on porcine embryonic development is dependent on embryo type. , 2005, Theriogenology.

[52]  M. Tada,et al.  Octamer and Sox Elements Are Required for Transcriptional cis Regulation of Nanog Gene Expression , 2005, Molecular and Cellular Biology.

[53]  Robert S. Balaban,et al.  Mitochondria, Oxidants, and Aging , 2005, Cell.

[54]  Tomomasa Watanabe,et al.  Effects of oxygen concentration and antioxidants on the in vitro developmental ability, production of reactive oxygen species (ROS), and DNA fragmentation in porcine embryos. , 2004, Theriogenology.

[55]  M. Murakami,et al.  mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem Cells , 2004, Molecular and Cellular Biology.

[56]  R. Prather,et al.  In vitro development of preimplantation porcine nuclear transfer embryos cultured in different media and gas atmospheres. , 2004, Theriogenology.

[57]  B. Bjerregaard,et al.  Expression of Nucleolar-Related Proteins in Porcine Preimplantation Embryos Produced In Vivo and In Vitro1 , 2004, Biology of reproduction.

[58]  N. Tsuji,et al.  Survivin Enhances Fas Ligand Expression via Up-Regulation of Specificity Protein 1-Mediated Gene Transcription in Colon Cancer Cells , 2004, The Journal of Immunology.

[59]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[60]  N. Seeram,et al.  Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells. , 2003, Cancer letters.

[61]  H. Rodríguez-Martínez,et al.  Parthenogenetic activation and subsequent development of porcine oocytes activated by a combined electric pulse and butyrolactone I treatment. , 2003, The Journal of reproduction and development.

[62]  A. Lisowski,et al.  Expression of cyclooxygenase-2 in embryonic and fetal tissues during organogenesis and late pregnancy. , 2003, Birth defects research. Part A, Clinical and molecular teratology.

[63]  G. Johnson,et al.  Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases , 2002, Science.

[64]  T. Kondo,et al.  Effects of EDTA saturated with Ca2+ (Ca-EDTA) on pig, bovine and mouse oocytes at the germinal vesicle stage during maturation culture and the involvement of chelation of Zn2+ in pronuclear formation induction by Ca-EDTA. , 2002, Reproduction.

[65]  L. R. Abeydeera In vitro fertilization and embryo development in pigs. , 2020, Reproduction (Cambridge, England) Supplement.

[66]  Y. Menezo,et al.  Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. , 2001, Human reproduction update.

[67]  E. Wolf,et al.  Activation of ribosomal RNA genes in preimplantation cattle and swine embryos. , 2000, Animal reproduction science.

[68]  A. Yajima,et al.  Growth hormone improves mouse embryo development in vitro, and the effect is neutralized by growth hormone receptor antibody. , 1998, The Tohoku journal of experimental medicine.

[69]  B. Ames,et al.  Oxidative damage and mitochondrial decay in aging. , 1994, Proceedings of the National Academy of Sciences of the United States of America.