Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
권호 표지
DOI QR코드

DOI QR Code

Possibility of liver inflammatory response and endoplasmic reticulum stress recovery through electroacupuncture in a model of circadian disruption caused by chronic constant light

광자극에 의한 일주기 교란 모델에서 전침의 간 염증 반응과 소포체 스트레스 회복 가능성

  • Young Ju Do (Department of Oriental Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Sang Eun Han (Department of Oriental Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Su Yeon Seo (Department of Oriental Medicine Research Division, Korea Institute of Oriental Medicine)
  • 도영주 (한국한의학연구원 한의과학연구부) ;
  • 한상은 (한국한의학연구원 한의과학연구부) ;
  • 서수연 (한국한의학연구원 한의과학연구부)
  • Received : 2024.10.23
  • Accepted : 2024.11.11
  • Published : 2024.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: Oriental medicine emphasizes circadian rhythm for maintaining health by balancing yin and yang energy. This study aims to investigate whether acupuncture treatment can recover liver dysfunction and inflammation-related indicators disrupted by photostimulation. Methods and Results: Continuous exposure to 150 Lux of light for 4 weeks extended the circadian rhythm of experimental animals from 23.95 hours to 26.6 hours. Zeitgeber 9 (ZT9) and ZT21 were selected as representative times of day and night, and blood was collected for analysis. Results showed that White Blood Cell(WBC) and lymphocyte counts decreased at ZT21 compared to ZT9, and these changes were restored after 3 weeks of acupuncture treatment at ZT21. In liver tissue, chemokines RANTES and CXCL7, altered by constant light exposure(CCL), were also restored by acupuncture treatment at HT7 and ST36. Additionally, pro-inflammatory cytokines IL-6 and IL-1β were increased in the CCL group, but immune and inflammatory responses improved after acupuncture treatment at HT7 and ST36. As for endoplasmic reticulum stress, which regulates inflammatory cytokine expression, the expression of Bip, a protein that increases with protein folding abnormalities, was elevated in the CCL group but restored to ZT21 levels by acupuncture treatment. However, while proteins involved in apoptosis showed a decreasing trend in the CCL group, recovery through acupuncture treatment was not statistically confirmed. Conclusions: This study concludes that electroacupuncture at HT7 and ST36 can regulate blood and liver inflammation, as well as endoplasmic reticulum stress, in circadian rhythm disruption caused by photostimulation. It highlights a non-pharmacological approach to recovery.

Keywords

Acknowledgement

This work was supported a grant from the Korea Institute of Oriental Medicine, Korea (No. KSN20233304) and supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (No. 2021R1A2C1093712).

References

  1. Mukherji A, Bailey SM, Staels B, Baumert TF. The circadian clock and liver function in health and disease. Journal of hepatology. 2019; 71: 200-11. https://doi.org/10.1016/j.jhep.2019.03.020
  2. Castanon-Cervantes O, Wu M, Ehlen JC, Paul K, Gamble KL, Johnson RL et al. Dysregulation of inflammatory responses by chronic circadian disruption. The Journal of Immunology. 2010; 185: 5796-805. https://doi.org/10.4049/jimmunol.1001026
  3. Colombini B, Dinu M, Murgo E, Lotti S, Tarquini R, Sofi F et al. Ageing and low-level chronic inflammation: the role of the biological clock. Antioxidants. 2022; 11: 2228. https://doi.org/10.3390/antiox11112228
  4. Oosterman JE, Wopereis S, Kalsbeek A. The circadian clock, shift work, and tissue-specific insulin resistance. Endocrinology. 2020; 161: bqaa180. https://doi.org/10.1210/endocr/bqaa180
  5. Shetty A, Hsu JW, Manka PP, Syn W-K. Role of the circadian clock in the metabolic syndrome and nonalcoholic fatty liver disease. Digestive diseases and sciences. 2018; 63: 3187-206. https://doi.org/10.1007/s10620-018-5242-x
  6. Zeng Z-H, Zeng M-H, Huang X-K, Chen R, Yu H. Effect of electroacupuncture stimulation of back-shu points on expression of TNF-alpha and lipid peroxidation reaction in the liver tissue in non-alcoholic fatty liver disease rats. Zhen ci yan jiu= Acupuncture Research. 2014; 39: 288-92.
  7. Li B, Fang L. Research progress on the mechanism of acupuncture treatment for nonalcoholic fatty liver disease. Gastroenterology Research and Practice. 2022; 2022: 5259088. https://doi.org/10.1155/2022/5259088
  8. Ji L, Li Q, He Y, Zhang X, Zhou Z, Gao Y et al. Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD: A promising drug Potentilla discolor Bunge. Acta Pharmaceutica Sinica B. 2022; 12: 3529-47. https://doi.org/10.1016/j.apsb.2022.05.001
  9. Yuan J, Wang H, Chen U, Lei Y, Wan Z, Zhao Y et al. Effect of low frequency repetitive magnetic stimulation at Shenmen (HT7) on sleep quality in patients with chronic insomnia. Medicine. 2020; 99: e21292. https://doi.org/10.1097/MD.0000000000021292
  10. Seo SY, Ryu Y. Electroacupuncture stimulation of HT7 alleviates sleep disruption following acute caffeine exposure by regulating BDNF-mediated endoplasmic reticulum stress in the rat medial septum. Biomedicine & Pharmacotherapy. 2022;155: 113724. https://doi.org/10.1016/j.biopha.2022.113724
  11. Eshkevari L, Permaul E, Mulroney SE. Acupuncture blocks cold stress-induced increases in the hypothalamus–pituitary–adrenal axis in the rat. Journal of Endocrinology. 2013; 217: 95-104. https://doi.org/10.1530/JOE-12-0404
  12. Cheng J, Wang X, Guo J, Yang Y, Zhang W, Xie B et al. Effects of electroacupuncture on the daily rhythmicity of intestinal movement and circadian rhythmicity of colonic Per2 expression in rats with spinal cord injury. BioMed Research International. 2016; 2016: 9860281. https://doi.org/10.1155/2016/9860281
  13. Oh J-E, Kim S-N. Anti-inflammatory effects of acupuncture at ST36 point: a literature review in animal studies. Frontiers in Immunology. 2022; 12: 813748. https://doi.org/10.3389/fimmu.2021.813748
  14. Silva S, Bicker J, Falcão A, Fortuna A. Antidepressants and circadian rhythm: exploring their bidirectional interaction for the treatment of depression. Pharmaceutics. 2021; 13: 1975. https://doi.org/10.3390/pharmaceutics13111975
  15. Bering T, Hertz H, Rath MF. The circadian oscillator of the cerebellum: triiodothyronine regulates clock gene expression in granule cells in vitro and in the cerebellum of neonatal rats in vivo. Frontiers in Physiology. 2021; 12: 706433. https://doi.org/10.3389/fphys.2021.706433
  16. Ferreira LL, Cervantes M, Froufe HJ, Egas C, Cunha-Oliveira T, Sassone-Corsi P et al. Doxorubicin persistently rewires cardiac circadian homeostasis in mice. Archives of Toxicology. 2020; 94: 257-71. https://doi.org/10.1007/s00204-019-02626-z
  17. Patiño MAL, Rodríguez-Illamola A, Conde-Sieira M, Soengas JL, Míguez JM. Daily rhythmic expression patterns of clock1a, bmal1, and per1 genes in retina and hypothalamus of the rainbow trout, Oncorhynchus mykiss. Chronobiology international. 2011; 28: 381-9. https://doi.org/10.3109/07420528.2011.566398
  18. Tsutsumi S, Gotoh T, Tomisato W, Mima S, Hoshino T, Hwang H et al. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death & Differentiation. 2004; 11: 1009-16. https://doi.org/10.1038/sj.cdd.4401436
  19. Lee S-H, Moon H-J, Lee Y-S, Kang C-D, Kim S-H. Potentiation of TRAIL-induced cell death by nonsteroidal anti-inflammatory drug in human hepatocellular carcinoma cells through the ER stress-dependent autophagy pathway. Oncology reports. 2020; 44: 1136-48. https://doi.org/10.3892/or.2020.7662
  20. Ketelauri P, Scharov K, von Gall C, Johann S. Acute circadian disruption due to constant light promotes Caspase 1 activation in the mouse hippocampus. Cells. 2023; 12: 1836. https://doi.org/10.3390/cells12141836
  21. Suzuki S, Toyabe S-i, Moroda T, Tada T, Tsukahara A, Iiai T et al. Circadian rhythm of leucocytes and lymphocyte subsets and its possible correlation with the function of the autonomic nervous system. Clinical & Experimental Immunology. 1997; 110: 500-8. https://doi.org/10.1046/j.1365-2249.1997.4411460.x
  22. Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Annals of the New York Academy of Sciences. 2010; 1193: 48-59. https://doi.org/10.1111/j.1749-6632.2009.05300.x
  23. Akbulut H, Icli F, Büyükcelik A, Akbulut KG, Demirci S. The role of granulocyte‐macrophage‐colony stimulating factor, cortisol, and melatonin in the regulation of the circadian rhythms of peripheral blood cells in healthy volunteers and patients with breast cancer. Journal of pineal research. 1999; 26: 1-8. https://doi.org/10.1111/j.1600-079X.1999.tb00560.x
  24. Esquifino AI, Pandi-Perumal S, Cardinali DP. Circadian organization of the immune response: a role for melatonin. Clinical and Applied Immunology Reviews. 2004; 4: 423-33. https://doi.org/10.1016/j.cair.2004.08.002
  25. Oishi K, Ohkura N, Kadota K, Kasamatsu M, Shibusawa K, Matsuda J et al. Clock mutation affects circadian regulation of circulating blood cells. Journal of circadian rhythms. 2006; 4: 1-7. https://doi.org/10.1186/1740-3391-4-1
  26. Zijlstra FJ, van den Berg-de Lange I, Huygen FJ, Klein J. Anti‐inflammatory actions of acupuncture. Mediators of inflammation. 2003; 12: 59-69. https://doi.org/10.1080/0962935031000114943
  27. Zhao X, Zhang G, Wu L, Tang Y, Guo C. Inhibition of ER stress-activated JNK pathway attenuates TNF-α-induced inflammatory response in bone marrow mesenchymal stem cells. Biochemical and Biophysical Research Communications. 2021; 541: 8-14. https://doi.org/10.1016/j.bbrc.2020.12.101
  28. Kim S, Joe Y, Kim HJ, Kim Y-S, Jeong SO, Pae H-O et al. Endoplasmic reticulum stress–induced IRE1α activation mediates cross-talk of GSK-3β and XBP-1 to regulate inflammatory cytokine production. The Journal of Immunology. 2015; 194: 4498-506. https://doi.org/10.4049/jimmunol.1401399
  29. Sun X, Liu H, Sun Z, Zhang B, Wang X, Liu T et al. Acupuncture protects against cerebral ischemia–reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis. Molecular Medicine. 2020; 26: 1-14. https://doi.org/10.1186/s10020-020-00236-5