Journal of Traditional Chinese Medicine >
Protective mechanisms of Tuina therapy against lipopolysaccharide-induced fever in young rabbits based on untargeted metabolomics analysis
Received date: 2022-07-22
Accepted date: 2022-11-15
Online published: 2023-07-03
Supported by
National Natural Science Foundation of China: to Explore the Antipyretic Effects and Mechanism of the “Reducing Fever Six Methods” Technique on Infant Rabbits with Fever from the Peripheral TLR4/NF-kB Signaling Pathway to the Central Positive and Negative Mediators(81873392)
OBJECTIVE: To investigate the effect of Tuina on the plasma metabolites of lipopolysaccharide-induced febrile in infant rabbits.
METHODS: Twenty-four infant New Zealand rabbits were selected and randomly divided into three groups: saline, model, and Tuina. The fever model was established by injecting LPS intravenously through the ear margin vein in the model group and Tuina group, respectively. The modeling was considered successful when the anal temperature increased by 0.5℃ or above within 1 h. In the Tuina group, six Tuina techniques (i.e., opening Tianmen / the heaven gate, pushing Kangong / the superciliary arch, kneading Taiyang and the prominent bone behind the ears, clearing Tianheshui, spine pinching) that alleviate fever were performed on the young rabbits 1 h after the modeling, whereas the model and saline groups were not given Tuina treatment, with the real-time anal temperature monitored during the experiment. The plasma was taken 3 h after the modeling for liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics study.
RESULTS: Our results showed a fever-reducing effects of Tuina therapy on lipopolysaccharide-induced fever in young rabbits, as indicated by a significantly lower anal temperature, maximum rise in body temperature, and body response index at 2 and 3 h after modeling in the Tuina group compared to the model group, with reductions in the PGE2 expression observed in the blood and hypothalamus. The differential metabolites including riboflavin, nicotinamide N-oxide, porphobilinogen, 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, and lysoPC (16:1 (9Z)/0:0) were found following the Tuina intervention. Tuina primarily involves glycine-serine-threonine, arginine-proline, porphyrin-chlorophyll, pyrimidine, primary bile acid biosynthesis, and cyanoamino acid metabolic pathways.
CONCLUSION: Tuina therapy has proven to be effective in reducing body temperature and down-regulating PGE2 expression in LPS-induced febrile young rabbits, with its mechanism of fever-reducing action possibly associated with the changes in plasma metabolites and metabolic pathways.
Di LIU , Yingqi ZHANG , Tianyuan YU , Zhifeng LIU , Yi JIAO , Hourong WANG , Yajing XU , Qian GUAN , Lulu CHEN , Hui HU . Protective mechanisms of Tuina therapy against lipopolysaccharide-induced fever in young rabbits based on untargeted metabolomics analysis[J]. Journal of Traditional Chinese Medicine, 2023 , 43(4) : 725 -733 . DOI: 10.19852/j.cnki.jtcm.2023.04.007
| 1. | Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 2015; 15: 335-49. |
| 2. | Urbane UN, Likopa Z, Gardovska D, et al. Beliefs, practices and health care seeking behavior of parents regarding fver in children. Medicina (Kaunas) 2019; 55: 398. |
| 3. | Li HP, Chen ZG, Liu GP, et al. Clinical efficacy of Lingnan characteristic Tuina in treating 60 cases of pediatric exogenous fever. Sichuan Zhong Yi 2020; 38: 211-4. |
| 4. | Wei LZ, Xu L. Central inhibitory effect of Qingtianheshui on endotoxic fever in infant rabbits and its related clinical application. Xin Zhong Yi 2020; 52: 148-51. |
| 5. | Geng C, Guo Y, Wang C, et al. Comprehensive evaluation of lipopolysaccharide-induced changes in rats based on metabolomics. J Inflamm Res 2020; 13: 477-86. |
| 6. | Liu HY, Zhang L, Zhao BS, et al. Hypothalamus metabolomic profiling to elucidate the tissue-targeted biochemical basis of febrile response in yeast-induced pyrexia rats. Chem Biol Interact 2015; 231: 61-70. |
| 7. | Cao H, Zhang A, Zhang H, et al. The application of metabolomics in Traditional Chinese Medicine opens up a dialogue between Chinese and Western medicine. Phytother Res 2015; 29: 159-66. |
| 8. | Yang GJ, Chen XL, Shao P, et al. Study on the endotoxin method of rabbit fever animal model and its standardization. Zhong Guo Shi Yan Dong Wu Xue Bao 2001; 9: 57-60. |
| 9. | Wu XL. Study on the time-effect relationship of Qingtianheshui on the reduction of fever in pediatric exogenous fever. Chengdu: Chengdu university of Traditional Chinese Medicine, 2015: 16. |
| 10. | Jiao Y, Liu ZF, Yu TY, et al. Effect of “Six Methods of Antipyretic” on TLR4/NF-κB and inflammatory factors LPS-induced fever rabbits. Huan Qiu Zhong Yi Yao 2022; 15, 7-12. |
| 11. | Milton AS, Wendlandt S. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol 1971; 218: 325-36. |
| 12. | Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol 2016; 17: 451-9. |
| 13. | Liang WS, Liu YL, Li ZY, et al. Study on antipyretic effect and mechanism of Ban-lian Bai-du Oral-liquid (BBQ). Dong Wu Yi Xue Jin Zhan 2019; 40: 74-8. |
| 14. | Yang JZ. The great compendium of acupuncture and moxibustion. Tianjin: scientific and technical publishers, 2017: 175. |
| 15. | Yao X. The Effect on the rabbits’body temperature by pushing down or up Ji (spine). Jinan: Shandong university of Traditional Chinese Medicine, 2001: 7. |
| 16. | Oren R, Farnham AE, Saito K, et al. Metabolic patterns in three types of phagocytizing cells. J Cell Biol 1963; 17: 487-501. |
| 17. | Toyosawa T, Suzuki M, Kodama K, et al. Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice. Eur J Pharmacol 2004; 492: 273-80. |
| 18. | Korbecki J, Bajdak-Rusinek K. The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms. Inflamm Res 2019; 68: 915-32. |
| 19. | Liu J, Zong ZY, Zhang WH, et al. Nicotinamide mononucleotide alleviates LPS-induced inflammation and oxidative stress via decreasing COX-2 expression in macrophages. Front Mol Biosci 2021; 8: 702107. |
| 20. | Yien YY, Ringel AR, Paw BH. Mitochondrial transport of protoporphyrinogen IX in erythroid cells. Oncotarget 2015; 6: 20742-3. |
| 21. | Dutra FF, Alves LS, Rodrigues D, et al. Hemolysis-induced lethality involves inflammasome activation by heme. Proc Natl Acad Sci USA 2014; 111: E4110-8. |
| 22. | Zhang C, He J, Wang X, et al. Dietary gamma-aminobutyric acid (GABA) improves non-specific immunity and alleviates lipopolysaccharide (LPS)-induced immune overresponse in juvenile Chinese mitten crab (Eriocheir sinensis). Fish Shellfish Immunol 2022; 124: 480-9. |
| 23. | Mota CMD, Rodrigues-Santos C, Fernández RAR, et al. Central serotonin attenuates LPS-induced systemic inflammation. Brain Behav Immun 2017; 66: 372-81. |
| 24. | Zhong Z, Wheeler MD, Li X, et al. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care 2003; 6: 229-40. |
| 25. | Zhang Y, Ma X, Jiang D, et al. Glycine attenuates lipopolysaccharide-induced acute lung injury by regulating NLRP3 inflammasome and NRF2 signaling. Nutrients 2020; 12: 611. |
| 26. | Zhang YQ, Liu ZF, Yu TY, et al. Effects of six antipyretic methods of Tuina on COX-2/PGE2 expression in peripheral of LPS-induced infant rabbits. Huan Qiu Zhong Yi Yao 2022; 15: 211-16. |
| 27. | Cheng ZX, Guo C, Chen ZG, et al. Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing. Nat Commun 2019; 10: 3325. |
| 28. | Xiao N, Nie M, Pang H, et al. Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications. Nat Commun 2021; 12: 1618. |
| 29. | Qiu Y, Yang X, Wang L, et al. L-arginine inhibited inflammatory response and oxidative stress induced by lipopolysaccharide via arginase-1 signaling in IPEC-J2 cells. Int J Mol Sci 2019; 20: 1800. |
| 30. | Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005; 5: 641-54. |
| 31. | Rath M, Müller I, Kropf P, et al. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol 2014; 5: 532. |
/
| 〈 |
|
〉 |