Experiments Validated the Development of Zebrafish Embryos and Toxicological Mechanism of Borneols in Perinatal Period


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Abstract

Background:Studies have confirmed that high dose borneol has perinatal toxicity and has a certain effect on embryonic development. However, there is little about the effect of borneol on the development of zebrafish embryos. Therefore, we compared the effects of D-borneol, L-borneol and synthetic borneol on the growth and development of zebrafish embryos, and predicted the possible mechanism of perinatal toxicity.

Methods:The embryonic mortality rate, hatching rate, and heart rate of each group were recorded at 48 hpf to compare the effects of borneols on the development of zebrafish embryos. Network pharmacology and molecular docking technology were used to predict the possible mechanism of perinatal toxicity.

Results:We found that borneols increased the mortality at 24 and 48 hpf, inhibited the autonomous movement behavior at 24 hpf, and affected the hatching rate and heart rate at 48 hpf. Network pharmacology analysis showed that borneols had the same toxic targets in the perinatal period and were involved in regulating perinatal toxicity by regulating pathways in cancer, chemical carcinogenesis-receptor activation, PI3K-Akt and others. Molecular docking showed that the binding activity of the active ingredients and the core target was at a medium level, and the binding activity of the borneols active ingredients and the core target was not much different.

Conclusion:Three kinds of borneol on the development of zebrafish embryos were different. The toxicity of L-borneol was the lowest. The mechanisms of perinatal toxicity were related to inflammation, apoptosis, cell cycle and growth, differentiation and reproduction.

About the authors

Qian Xie

School of Medicine, Foshan University

Email: info@benthamscience.net

Danni Lu

School of Chinese Medicine, Shaanxi Institute of International Trade and Commerce

Email: info@benthamscience.net

Rong Ma

School of Medicine, Foshan University

Author for correspondence.
Email: info@benthamscience.net

Xuxin Zeng

School of Medicine, Foshan University

Author for correspondence.
Email: info@benthamscience.net

Jialiang Guo

School of Medicine, Foshan University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Su J. Newly Revised Materia Medica. Anhui Science and Technology Publishing House 2004.
  2. Wang J, Zhang B. Clinical Chinese Materia Medica. China Publishing House of Traditional Chinese Medicine 2004.
  3. Wu Y, Zhu Z, Chen J, et al. Research progress on pharmacological effects of borneol and borneol ester. J Pharm Res 2020; 39(4): 217-24.
  4. Zhao Y, Guo Y, Huang S, et al. Advances in research on the pharmacological effects and molecular mechanisms of borneol guiding action. J Nanjing Univ Trad Chin Med 2021; 37(1): 150-5.
  5. Zhang Y, Wang J, Dong T, et al. Research progress on the mechanism of borneol on blood-brain barrier permeability. Zhongchengyao 2020; 42(12): 3236-40.
  6. Huang C, Wang J, Wen J, et al. Research process and the pregnancy-contraindicated mechanism of borneol. Zhongyao Yu Linchuang 2015; 6(4): 54-7.
  7. Chen Y, Pu Y, Yan H, et al. Safety evaluation of borneol in the development of zebrafish embryos. China Pharmacy 2014; 25(19): 1733-7.
  8. Ma R, Lu D, Wang J, Xie Q, Guo J. Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol. Biomed Pharmacother 2023; 164: 114668. doi: 10.1016/j.biopha.2023.114668 PMID: 37321057
  9. Hu L, Jiang M, Ling S, et al. General reproductive toxicity of natural borneol versus synthetic borneol in mice. J Toxicol 2006; 20(4): 275-6.
  10. Liu Y, Hu L, Li Y, et al. Comparative study of mutagenicity between natural borneol and synthetic borneol from a new source. Zhongyao Xinyao Yu Linchuang Yaoli 2004; (4): 232-5.
  11. Bambino K, Chu J. Zebrafish in toxicology and environmental health. Curr Top Dev Biol 2017; 124: 331-67. doi: 10.1016/bs.ctdb.2016.10.007 PMID: 28335863
  12. Rosa JGS, Lima C, Lopes-Ferreira M. Zebrafish larvae behavior models as a tool for drug screenings and pre-clinical trials: A review. Int J Mol Sci 2022; 23(12): 6647. doi: 10.3390/ijms23126647 PMID: 35743088
  13. Lu D, Ma R, Xie Q, et al. Application and advantages of zebrafish model in the study of neurovascular unit. Eur J Pharmacol 2021; 910: 174483. doi: 10.1016/j.ejphar.2021.174483 PMID: 34481878
  14. Fan H, He S, Yang J, et al. Evaluation on the development and acute toxicity of rhodioside to zebrafish. Chin J Ethnomed Ethnopharm 2021; 30(19): 18-21.
  15. Westerfield M. The Zebrafish Book: A Guide for the Laboratory use of Zebrafish. University of Oregon Press 2000.
  16. Fan L, Zhang X, Hou L. Developmental toxicity of Thallium nitrate to zebrafish embryos. Hunan Nongye Kexue 2021; (9): 32-7.
  17. Zhou F, He Y, Xiong L, et al. Toxicity of motherwort (Leonurus japonicus) essential oil on embryo development of zebrafish. J Chengdu Univ Trad Chin Med 2019; 42(4): 24-8.
  18. Liu J, Zhang C, Zhang D, et al. Comparative study on toxicity of aristolochic acid and aristololactam to zebrafish embryos. J Hubei Polytech Univ 2018; 34(6): 58-63.
  19. Li C, Zhu C, Zhang J, et al. Safety evaluation of water extract from leaves of Three Gorges Yangju based on zebrafish model. Yaowu Pingjia Yanjiu 2021; 44(8): 1607-13.
  20. Gu J, Du J, Zhao T, et al. Potential mechanism of Meicha tea in prevention and treatment of coronavirus disease 2019 by acting on angiotensin-converting enzyme 2 based on network pharmacology. Hunan J Trad Chin Med 2022; 38(4): 139-46.
  21. Wang B. Pharmacology and Clinical Practice of Modern Chinese Medicine. Tianjin Science and Technology Translation Press 2004.
  22. Wang X, Shen Y, Wang S, et al. PharmMapper 2017 update: A web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res 2017; 45(W1): W356-60. doi: 10.1093/nar/gkx374 PMID: 28472422
  23. Liu X, Ouyang S, Yu B, et al. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res 2010; 38(Web Server issue): W609-14.
  24. Liu X, Qin Z, Guo B, et al. Mechanism of Zhizichi decoction in treatment of depression, anxiety and insomnia based on network pharmacology. Drugs Clin 2022; 37(4): 719-28.
  25. Liu X, Liu S, Liao Y, et al. Network pharmacology of dendrobium alkaloids against cerebral ischemia-reperfusion injury. Chin J Pharmacovigil 2022; 19(3): 252-8.
  26. Bardou P, Mariette J, Escudié F, Djemiel C, Klopp C. Jvenn: An interactive Venn diagram viewer. BMC Bioinformatics 2014; 15(1): 293. doi: 10.1186/1471-2105-15-293 PMID: 25176396
  27. Li Y, Zeng Y, Liu W. Molecular mechanism of Lanqin oral solution in the treatment of COVID-19 based on network pharmacology. J Hainan Med Univ 2021; 32(7): 821-6.
  28. Lv H, Wang S. To explore the mechanism of Erzhi pill in the treatment of vitiligo based on network pharmacology. Shanxi J Tradit Chin Med 2022; 38(4): 63-6.
  29. Tang X, Zhou H, Liu X, et al. Mechanism of Bushen Zhuyun prescrption in treatment od LPD by reducing apoptotic levels of ovary based on network pharmcology and animal experiment. Inf Trad Chin Med 2022; 39(4): 1-9.
  30. Niu W, Liu P, Wang J. Mechanism of Huangqi-Danggui on diabetic foot based on network pharmacology. Chin J Surg Integr Tradit West Med 2022; 28(2): 252-7.
  31. Wang F, Jin Y. Discussion on the treatment of viral respiratory tract infection by folium isatidis based on network pharmacology study on mechanism of action and material basis. Asian J Tradit Med 2022; 18(5): 159-66.
  32. Zhang Q, Ruan J, Shang H, et al. Study on the mechanism of Lidan Huatan Huoxue decoction for the treatment of metabolic syndrome based on network pharmacology and molecular docking. Mod Trad Chin Med Materia Medica-World Sci Technol 2022; 24(1): 328-37.
  33. Tao H. Mingyi Bielu. People’s Medical Publishing House 1986.
  34. Xu L, Tao J, Feng Y. Study on antifertility effect and dosage form of borneol. Zhongchengyao 1986; (3): 1-2.
  35. Rubinstein AL. Zebrafish assays for drug toxicity screening. Expert Opin Drug Metab Toxicol 2006; 2(2): 231-40. doi: 10.1517/17425255.2.2.231 PMID: 16866609
  36. Li YF, Cheng YB, Tian ZL, Liu NG. Research progress of zebrafish model in toxicology and its application prospects in forensic science. Fa Yi Xue Za Zhi 2021; 37(6): 867-72. PMID: 35243854
  37. Fan T, Chen X, Yang F, et al. A network pharmacology and bioinformatics exploration of the possible molecular mechanisms of Fuzheng Xiaoliu Granule for the treatment of hepatocellular carcinoma. J Clin Transl Res 2023; 9(3): 182-94. PMID: 37275579
  38. Yang HY, Liu ML, Luo P, Yao XS, Zhou H. Network pharmacology provides a systematic approach to understanding the treatment of ischemic heart diseases with traditional Chinese medicine. Phytomedicine 2022; 104: 154268. doi: 10.1016/j.phymed.2022.154268 PMID: 35777118
  39. Wang X, Wang ZY, Zheng JH, Li S. TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches. Chin J Nat Med 2021; 19(1): 1-11. doi: 10.1016/S1875-5364(21)60001-8 PMID: 33516447
  40. Jiashuo WU, Fangqing Z, Zhuangzhuang LI, et al. Integration strategy of network pharmacology in traditional Chinese medicine: A narrative review. J Tradit Chin Med 2022; 42(3): 479-86.
  41. Zhang P, Zhang D, Zhou W, et al. Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine. Brief Bioinform 2023; 25(1): bbad518. doi: 10.1093/bib/bbad518 PMID: 38197310
  42. Zhao L, Zhang H, Li N, et al. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J Ethnopharmacol 2023; 309: 116306. doi: 10.1016/j.jep.2023.116306 PMID: 36858276
  43. Jiang L, Lei F, Qin Y. The role of retinoic acid receptor and its signal pathway in the renal disease. J Clin Pediatr 2016; 34(3): 227-31.
  44. Yang J, Zhang X. Research progress on retinoic acid receptor and its mechanism of action. J Diagn Ther Dermato-venereol 2014; 21(5): 423-6.
  45. Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol 2014; 10(10): 582-91. doi: 10.1038/nrendo.2014.143 PMID: 25135573
  46. Salas-Lucia F, Stan MN, James H, et al. Effect of the fetal THRB genotype on the placenta. J Clin Endocrinol Metab 2023; 108(10): e944-8. doi: 10.1210/clinem/dgad243 PMID: 37149816
  47. Zhao L, Yang C, Chen B, et al. Gegen decoction reverses cisplatin resistance in COC1/DDP cells by down-regulating THRB expression. Zhongchengyao 2021; 43(11): 3186-90.
  48. Zhang C, Zhu W, Xu J. Expressions of the vitamin D receptor protein and its mRNA in mucosa epithelium of human fallopian tubes. J Jinan Univ (Natural Science & Medicine Edition) 2009; 30(2): 170-5.
  49. Pu X, Tian X, Gu C, et al. Effects of Astragalus polysaccharides on proliferation inhibition and Bax, Caspase-3, VDR, CYP24A and CYP27B protein expression of MC-3T3-E1 osteoblasts induced by dexamethasone. Lishizhen Med Materia Medica Res 2020; 31(12): 2850-3.
  50. Roskoski R Jr. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol Res 2015; 94: 9-25. doi: 10.1016/j.phrs.2015.01.003 PMID: 25662515
  51. Bagnato G, Leopizzi M, Urciuoli E, Peruzzi B. Nuclear functions of the tyrosine kinase Src. Int J Mol Sci 2020; 21(8): 2675. doi: 10.3390/ijms21082675 PMID: 32290470
  52. Matsubara T, Yasuda K, Mizuta K, Kawaue H, Kokabu S. Tyrosine kinase Src is a regulatory factor of bone homeostasis. Int J Mol Sci 2022; 23(10): 5508. doi: 10.3390/ijms23105508 PMID: 35628319
  53. Kato G. Regulatory roles of the N-terminal intrinsically disordered region of modular Src. Int J Mol Sci 2022; 23(4): 2241. doi: 10.3390/ijms23042241 PMID: 35216357
  54. Qiu H, Qian T, Wu T, Gao T, Xing Q, Wang L. Src family kinases inhibition ameliorates hypoxic-ischemic brain injury in immature rats. Front Cell Neurosci 2021; 15: 746130. doi: 10.3389/fncel.2021.746130 PMID: 34992524
  55. Li B, Yu W, Kong L, et al. Mechanism of Yishen Chuanning decoction regulating TCR signaling pathway protein Lck and CD4 on asthma with kidney Qi deficiency. China J Trad Chin Med Pharm 2021; 36(03): 1402-5.
  56. Yang T, Wu B. MAPK14 in the radioresistance of gastric cancer. China J Cancer Prev Treat 2019; 26(21): 1599-605.
  57. Li Z, Xu L, Wang Q. Integrative analysis of MAPK14 as a potential biomarker for cardioembolic stroke. BioMed Res Int 2020; 2020: 1-15. doi: 10.1155/2020/9502820 PMID: 32879891
  58. Zhang J, Cai H, Gao H, et al. The expression and significance of KI-67, P53, C23, EGFR protein in different ovarian tumor tissues. Shandong Yiyao 2016; 56(19): 67-9.
  59. Liu X, Chen J, Hao D, et al. Research process of Angelica sinensis and its active components on cancer chemopreventive mechanism. Glob Trad Chin Med 2021; 14(11): 2102-8.
  60. Wang X, Chen Z, Li L, et al. Effect of Zhenwu decoction on cardiomyocyte apoptosis and the PIth congestive heart failure3K-AKT pathway in rats wi. Chin J Comp Med 2022; 32(7): 27-33.
  61. Shi J, Guo Y, Chang J. Effects of Osthole on proliferation, apoptosis, migration and invasion of ovarian cancer cells by regulating PI3K/AKT/MAPK signal pathway. Zhongguo Yousheng Yu Yichuan Zazhi 2022; 30(7): 1115-9.
  62. Pei Z, Wang G, Dong X, et al. Protective effect of Yiqi Tongluo decoction medicated serum on oxidative stress and activating PI3K/Akt pathway. Liaoning Zhongyiyao Daxue Xuebao 2023; 25(2): 36-41.
  63. Qian J, Meng L. Study on the mechanism of Ang-II activated P38MAPK signaling pathway in small intestine injury induced by NSAID in rats. China Modern Doctor 2022; 60(19): 1-5.
  64. Li Y. Plant resources of natural borneol. Chin Herb Med 1992; (6): 9-12.
  65. Song X, Lu Y, Wen R, et al. In situ and in vivo study of nasal absorption of borneol in rats. Pharmazie 2012; 67(10): 848-51. PMID: 23136719
  66. Song X, Du S, Lu Y, et al. Study on rat nasal absorption in situ of borneol based on single pass perfusion method. Zhongguo Zhongyao Zazhi 2011; 36(18): 2489-92. PMID: 22256751
  67. Yang H, Li Z, Yu N, et al. Effect of borneol on the permeability of the blood-eye barrier. Int J Ophthalmol 2008; (8): 1576-8.
  68. Zhao J-Y, Du S-Y, Lu Y, Wu HC, Li HY. Study on tissue distribution of borneol in mice by intravenous and intranasal administrations. Zhongguo Zhongyao Zazhi 2013; 38(7): 1071-4. PMID: 23847960
  69. Gibson DE, Moore GP, Pfaff JA. Camphor ingestion. Am J Emerg Med 1989; 7(1): 41-3. doi: 10.1016/0735-6757(89)90083-1 PMID: 2643959
  70. Siegel E, Wason S. Camphor toxicity. Pediatr Clin North Am 1986; 33(2): 375-9. doi: 10.1016/S0031-3955(16)35008-8 PMID: 3515302
  71. Quintaneiro C, Teixeira B, Benedé JL, Chisvert A, Soares AMVM, Monteiro MS. Toxicity effects of the organic UV-filter 4-Methylbenzylidene camphor in zebrafish embryos. Chemosphere 2019; 218: 273-81. doi: 10.1016/j.chemosphere.2018.11.096 PMID: 30472611
  72. Dosoky NS, Setzer WN. Maternal reproductive toxicity of some essential oils and their constituents. Int J Mol Sci 2021; 22(5): 2380. doi: 10.3390/ijms22052380 PMID: 33673548
  73. Wei G, Lin S, Fang Y, et al. The quality of borneol was detected by GC-MS method. Zhongchengyao 2005; (3): 109-10.
  74. Jiang X, Zou J, Yuan Y, et al. Preliminary study: Biotransformation of borneol to camphor in mice, rats and rabbits. Modern Trad Chin Med Materia Medica-World Sci Technol 2008; (3): 27-36.

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