Buzhong Yiqi decoction attenuates acquired myasthenia by regulating the JAK2/STAT3/AKT signaling pathway, inhibiting inflammation, and improving mitochondrial function
Main Article Content
Keywords
acquired myasthenia, Buzhong Yiqi decoction, Dysfunction, mitochondrial inflammation, JAK2/STAT3/AKT
Abstract
Acquired myasthenia (AM), a debilitating autoimmune disease, is typically characterized by skeletal muscle fatigue and weakness. Despite advances in myasthenia gravis treatment, current approaches remain unsatisfactory and many result in unexpected side effects. Traditional Chinese medicine has shown great potential in the treatment of myasthenia gravis, including relieving myasthenic symptoms, improving patients' quality of life, and reducing Western medicine side effects. This study investigates the protective effects and mechanism of BZYQD in mice with acquired myasthenia. BZYQD alleviates the reduced grip strength and increased expression of MAFbx and MuRF-1 in mice with acquired myasthenia. It also reduces levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α in the mouse serum. In addition, BZYQD reduces ROS accumulation and the mitochondrial ROS production rate, while increasing ATP levels and mitochondrial membrane potential in mice with acquired myasthenia. Moreover, BZYQD decreases the expression of p-JAK2, p-STAT3, and p-AKT in the skeletal muscle of mice with acquired myasthenia. In summary, BZYQD reduces inflammation, enhances mitochondrial function, and regulates the JAK2/STAT3/AKT signaling pathway to treat acquired myasthenia.
References
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2. Zanders L, Kny M, Hahn A, Schmidt S, Wundersitz S, Todiras M, et al. Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting. J Cachexia Sarcopenia Muscle. 2022;13(1):713–27. 10.1002/jcsm.12867
3. Li Z, Zhang Q, Zhang P, Sun R, Jiang H, Wan J, et al. Prevalence and risk factors for intensive care unit acquired weakness: A protocol for a systematic review and meta--analysis. Medicine. 2020;99(36):e22013. 10.1097/MD.0000000000022013
4. Klawitter F, Ehler J, Bajorat R, Patejdl R. Mitochondrial dysfunction in intensive care unit-acquired weakness and critical illness myopathy: a narrative review. Int J Mol Sci. 2023;24(6). 10.3390/ijms24065516
5. Zong G, Liu S, Chen Z, Hu Y. Efficacy and safety of Buzhong Yiqi decoction combined with western medicine in the treatment of myasthenia gravis: A protocol for systematic review and meta-analysis. Medicine. 2021;100(11):e24807. 10.1097/MD.0000000000024807
6. Zhu SJ, Wang RT, Yu ZY, Zheng RX, Liang CH, Zheng YY, et al. Chinese herbal medicine for myasthenia gravis: A systematic review and meta-analysis of randomized clinical trials. Integr Med Res. 2022;11(2):100806. 10.1016/j.imr.2021.100806
7. Yuan H, Ma Q, Cui H, Liu G, Zhao X, Li W, et al. How can synergism of traditional medicines benefit from network pharmacology? Molecules. 2017;22(7). 10.3390/molecules22071135
8. Chen Y, Shergis JL, Wu L, Yu X, Zeng Q, Xu Y, et al. A systematic review and meta-analysis of the herbal formula Buzhong Yiqi Tang for stable chronic obstructive pulmonary disease. Complement Ther Med. 2016;29:94–108. 10.1016/j.ctim.2016.09.017
9. Li Q, Cao M, Wei Z, Mei J, Zhang Y, Li M, et al. The protective effect of Buzhong Yiqi decoction on ischemic stroke mice and the mechanism of gut microbiota. Front Neurosci. 2022;16:956620. 10.3389/fnins.2022.956620
10. Ju WJ, Zhao ZK, Chen SL, Zhou DD, Yang WN, Wen XP, et al. Buzhongyiqi decoction protects against loperamide-induced constipation by regulating the arachidonic acid pathway in rats. Front Pharmacol. 2020;11:423. 10.3389/fphar.2020.00423
11. Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab. 2014;307(6):E469–84. 10.1152/ajpendo.00204.2014
12. Amin S, Aung M, Gandhi FR, Pena Escobar JA, Gulraiz A, Malik BH. Myasthenia gravis and its association with thyroid diseases. Cureus. 2020;12(9):e10248. 10.7759/cureus.10248
13. Jiang X, Chen G, Huang J, Xie L, Shen D, Jiang K, et al. Modified Buzhong Yiqi decoction for myasthenia gravis: A systematic review protocol. Medicine. 2018;97(50):e13677. 10.1097/MD.0000000000013677
14. Li J, Qi G, Liu Y. Effect of Buzhong Yiqi decoction on anti-acetylcholine receptor antibody and clinical status in juvenile ocular myasthenia gravis. Medicine. 2021;100(44):e27688. 10.1097/MD.0000000000027688
15. Zhao M, Liu L, Liu F, Liu L, Liu Z, Gao Y, et al. Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host. Front Microbiol. 2022;13:1082565. 10.3389/fmicb.2022.1082565
16. Vankrunkelsven W, Derde S, Gunst J, Vander Perre S, Declerck E, Pauwels L, et al. Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin. J Cachexia Sarcopenia Muscle. 2022;13(1):418–33. 10.1002/jcsm.12904
17. Leduc-Gaudet JP, Mayaki D, Reynaud O, Broering FE, Chaffer TJ, Hussain SNA, et al. Parkin overexpression attenuates sepsis--induced muscle wasting. Cells. 2020;9(6). 10.3390/cells9061454
18. Hua Z, Dai S, Li S, Wang J, Peng H, Rong Y, et al. Deciphering the protective effect of Buzhong Yiqi Decoction on osteoporotic fracture through network pharmacology and experimental validation. J Orthop Surg Res. 2023;18(1):86. 10.1186/s13018-023-03545-7
19. Hood DA, Memme JM, Oliveira AN, Triolo M. Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu Rev Physiol. 2019;81:19–41. 10.1146/annurev-physiol-020518-114310
20. Wang W, Chen S, Xu S, Liao G, Li W, Yang X, et al. Jianpi Shengqing Huazhuo Formula improves abnormal glucose and lipid metabolism in obesity by regulating mitochondrial biogenesis. J Ethnopharmacol. 2024;319(Pt 1):117102. 10.1016/j.jep.2023.117102
21. Babon JJ, Kershaw NJ, Murphy JM, Varghese LN, Laktyushin A, Young SN, et al. Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity. 2012;36(2):239–50. 10.1016/j.immuni.2011.12.015
22. Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012;303(3):E410–21. 10.1152/ajpendo.00039.2012
23. Pena G, Cai B, Deitch EA, Ulloa L. JAK2 inhibition prevents innate immune responses and rescues animals from sepsis. J Mol Med. 2010;88(8):851–9. 10.1007/s00109-010-0628-z
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Sep 1, 2024
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Zeng, Y., Zeng, H., Liu, X., & Fan, T. (2024). Buzhong Yiqi decoction attenuates acquired myasthenia by regulating the JAK2/STAT3/AKT signaling pathway, inhibiting inflammation, and improving mitochondrial function. Allergologia Et Immunopathologia, 52(5), 59-64. https://doi.org/10.15586/aei.v52i5.1147
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How to Cite
Zeng, Y., Zeng, H., Liu, X., & Fan, T. (2024). Buzhong Yiqi decoction attenuates acquired myasthenia by regulating the JAK2/STAT3/AKT signaling pathway, inhibiting inflammation, and improving mitochondrial function. Allergologia Et Immunopathologia, 52(5), 59-64. https://doi.org/10.15586/aei.v52i5.1147