Journal of Traditional Chinese Medicine >
Qigu capsule (芪骨胶囊) alleviates dexamethasone-induced muscle dysfunction through mitochondrial biogenesis
Received date: 2024-01-15
Accepted date: 2024-04-06
Online published: 2025-07-25
Supported by
Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases(20MC1920600);Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901);Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"(Letter of the People's Education of Traditional Chinese Medicine (2019) No. 62);Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team(No. 3 of Shanghai Education Commission (2022));"Extension Plan for the Inheritance of Shanghai Style Traditional Chinese Medicine Schools", "Construction of TCM Specialty Alliance for Muscle and Bone Injury in East China Region and City Level"(ZY(2021-2023)-0302);Program for Shanghai High-Level Local University Innovation Team(SZY20220315);Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan(SHDC2020CR3090B)
OBJECTIVE: To explore the potential molecular mechanism of Qigu capsule (芪骨胶囊,QGC) improve the functional performance of skeletal muscle.
METHODS: The primary components of QGC were analyzed using high-performance liquid chromatography (HPLC). Muscle dysfunction was established in male C57BL/6 mice treated with dexamethasone (1 mg/kg body weight, i.p., six weeks). Rotarod test, mitochondrial ultrastructure, respiratory chain complex V activity, succinate dehydrogenase (SDH) activity, adenosine triphosphate (ATP) content, and reactive oxygen species (ROS) levels were assessed. The mitochondrial biogenesis-related protein expressions were analyzed using Western blot or polymerase chain reaction (PCR).
RESULTS: QGC treatment enhanced Rotarod test performance. Additionally, QGC significantly alleviated dexamethasone-induced mitochondrial damage, reduced mitochondrial swelling, increased respiratory chain complex enzyme activity, SDH activity, ATP content, and decreased ROS levels. PCR and western blot results revealed that QGC enhanced mitochondrial biogenesis via adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC-1α) signaling pathway.
CONCLUSIONS: QGC ameliorates dexamethasone-induced skeletal muscle dysfunction by activating AMPK/ PGC-1α, which might be developed as a therapeutic agent for treating age-related muscle weakness.
Jinyu SHI , Haiya GE , Zongrui YANG , Hongsheng ZHAN . Qigu capsule (芪骨胶囊) alleviates dexamethasone-induced muscle dysfunction through mitochondrial biogenesis[J]. Journal of Traditional Chinese Medicine, 2025 , 45(4) : 739 -746 . DOI: 10.19852/j.cnki.jtcm.2025.04.004
| 1. | Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr 1997; 127: 990S-1S. |
| 2. | Morley JE, Anker SD, von Haehling S. Prevalence, incidence, and clinical impact of sarcopenia: facts, numbers, and epidemiology-update 2014. J Cachexia Sarcopenia Muscle 2014; 5: 253-9. |
| 3. | Cosquéric G, Sebag A, Ducolombier C, Thomas C, Piette F, Weill-Engerer S. Sarcopenia is predictive of nosocomial infection in care of the elderly. Br J Nutr 2006; 96: 895-901. |
| 4. | Landi F, Cruz-Jentoft AJ, Liperoti R, et al. Sarcopenia and mortality risk in frail older persons aged 80 years and older: results from ilSIRENTE study. Age Ageing 2013; 42: 203-9. |
| 5. | Yalcin A, Aras S, Atmis V, et al. Sarcopenia and mortality in older people living in a nursing home in Turkey. Geriatr Gerontol Int 2017; 17: 1118-24. |
| 6. | Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int 2010; 21: 543-59. |
| 7. | Rolland Y, Czerwinski S, Abellan VKG, et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging 2008; 12: 433-50. |
| 8. | Ferri E, Marzetti E, Calvani R, Picca A, Cesari M, Arosio B. Role of age-related mitochondrial dysfunction in sarcopenia. Int J Mol Sci 2020; 21: 5236. |
| 9. | Leduc-Gaudet JP, Hussain S, Barreiro E, Gouspillou G. Mitochondrial dynamics and mitophagy in skeletal muscle health and aging. Int J Mol Sci 2021; 22: 8179. |
| 10. | Johnson ML, Robinson MM, Nair KS. Skeletal muscle aging and the mitochondrion. Trends Endocrinol Metab 2013; 24: 247-56. |
| 11. | Romanello V. The interplay between mitochondrial morphology and myomitokines in aging sarcopenia. Int J Mol Sci 2020; 22: 91. |
| 12. | Favaro G, Romanello V, Varanita T, et al. DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass. Nat Commun 2019; 10: 2576. |
| 13. | Liu D, Fan YB, Tao XH, et al. Mitochondrial quality control in sarcopenia: updated overview of mechanisms and interventions. Aging Dis 2021; 12: 2016-30. |
| 14. | Terman A, Kurz T, Navratil M, Arriaga EA, Brunk UT. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid Redox Signal 2010; 12: 503-35. |
| 15. | Stuart JA, Maddalena LA, Merilovich M, Robb EL. A midlife crisis for the mitochondrial free radical theory of aging. Longev Healthspan 2014; 3: 4. |
| 16. | Jang YC, Lustgarten MS, Liu Y, et al. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. Faseb J 2010; 24: 1376-90. |
| 17. | Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 2012; 13: 251-62. |
| 18. | Arad M, Seidman CE, Seidman JG. AMP-activated protein kinase in the heart: role during health and disease. Circ Res 2007; 100: 474-88. |
| 19. | Hardie DG, Hawley SA, Scott JW. AMP-activated protein kinase--development of the energy sensor concept. J Physiol 2006; 574: 7-15. |
| 20. | Day EA, Ford RJ, Steinberg GR. AMPK as a therapeutic target for treating metabolic diseases. Trends Endocrinol Metab 2017; 28: 545-60. |
| 21. | Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 2018; 19: 121-35. |
| 22. | Zheng Y, Wang X, Zhang Z, et al. Bushen Yijing fang reduces fall risk in late postmenopausal women with osteopenia: a randomized double-blind and placebo-controlled trial. Sci Rep 2019; 9: 2089. |
| 23. | Huang YF, Ou GC, Ma SH, Liu MW, Deng W. Effect of icariin on the H(2)O(2)-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis. Int J Immunopathol Pharmacol 2023; 37: 1200371611. |
| 24. | Yu LM, Dong X, Xu YL, et al. Icariin attenuates excessive alcohol consumption-induced susceptibility to atrial fibrillation through SIRT 3 signaling. Biochim Biophys Acta Mol Basis Dis 2022; 1868: 166483. |
| 25. | Shaito A, Al-Mansoob M, Ahmad S, et al. Resveratrol-mediated regulation of mitochondria biogenesis-associated pathways in neurodegenerative diseases: molecular insights and potential therapeutic applications. Curr Neuropharmacol 2023; 21: 1184-201. |
| 26. | Chen KG, Kang RR, Sun Q, et al. Resveratrol ameliorates disorders of mitochondrial biogenesis and mitophagy in rats continuously exposed to benzo(a)pyrene from embryonic development through adolescence. Toxicology 2020; 442: 152532. |
| 27. | Yu LM, Dong X, Xue XD, et al. Naringenin improves mitochondrial function and reduces cardiac damage following ischemia-reperfusion injury: the role of the AMPK-SIRT3 signaling pathway. Food Funct 2019; 10: 2752-65. |
| 28. | Zhou L, Yao M, Tian Z, et al. Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission. Free Radic Biol Med 2020; 152: 697-714. |
| 29. | Wang YH, Xuan ZH, Tian S, Du GH. Echinacoside protects against 6-hydroxydopamine-induced mitochondrial dysfunction and inflammatory responses in PC12 cells via reducing ROS production. Evid Based Complement Alternat Med 2015; 2015: 189239. |
| 30. | Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7: 27-31. |
| 31. | Zeng L, Maruyama S, Nakamura K, et al. The injury-induced myokine insulin-like 6 is protective in experimental autoimmune myositis. Skelet Muscle 2014; 4: 16. |
| 32. | Boal F, Roumegoux J, Alfarano C, et al. Apelin regulates FoxO 3 translocation to mediate cardioprotective responses to myocardial injury and obesity. Sci Rep 2015; 5: 16104. |
| 33. | Wang YY, Li J, Wu ZR, et al. Insights into the molecular mechanisms of polygonum multiflorum thunb-induced liver injury: a computational systems toxicology approach. Acta Pharmacol Sin 2017; 38: 719-32. |
| 34. | Nalika N, Waseem M, Kaushik P, Salman M, Andrabi SS, Parvez S. Role of melatonin and quercetin as countermeasures to the mitochondrial dysfunction induced by titanium dioxide nanoparticles. Life Sci 2023: 121403. |
| 35. | Diolez P, Bourdel-Marchasson I, Calmettes G, et al. Hypothesis on skeletal muscle aging: mitochondrial adenine nucleotide translocator decreases reactive oxygen species production while preserving coupling efficiency. Front Physiol 2015; 6: 369. |
| 36. | Moylan JS, Reid MB. Oxidative stress, chronic disease, and muscle wasting. Muscle Nerve 2007; 35: 411-29. |
| 37. | Kim S, Kim K, Park J, Jun W. Curcuma longa L. water extract improves dexamethasone-induced sarcopenia by modulating the muscle-related gene and oxidative stress in mice. Antioxidants (Basel) 2021; 10: 1000. |
| 38. | Clay ML, Deng JJ, Bai Y. Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics 2009; 36: 125-31. |
| 39. | Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: an undiagnosed condition in older adults. current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 2011; 12: 249-56. |
| 40. | Ma J, Ye M, Li Y, et al. Zhuanggu Zhitong capsule alleviates osteosarcopenia in rats by up-regulating PI3K/Akt/Bcl 2 signaling pathway. Biomed Pharmacother 2021; 142: 111939. |
| 41. | Shang Y, Kuang M, Wang Z, et al. An Ultrashort peptide-based supramolecular hydrogel mimicking IGF-1 to alleviate glucocorticoid-induced sarcopenia. Acs Appl Mater Interfaces 2020; 12: 34678-88. |
| 42. | Xie WQ, He M, Yu DJ, et al. Mouse models of sarcopenia: classification and evaluation. J Cachexia Sarcopenia Muscle 2021; 12: 538-54. |
| 43. | Kaasik P, Umnova M, Pehme A, et al. Ageing and dexamethasone associated sarcopenia: peculiarities of regeneration. J Steroid Biochem Mol Biol 2007; 105: 85-90. |
| 44. | Shen S, Liao Q, Liu J, Pan R, Lee SMY, Lin L. Myricanol rescues dexamethasone-induced muscle dysfunction via a sirtuin 1-dependent mechanism. J Cachexia Sarcopenia Muscle 2019; 10: 429-44. |
| 45. | Huang Y, Chen K, Ren Q, et al. Dihydromyricetin attenuates dexamethasone-induced muscle atrophy by improving mitochondrial function via the PGC-1α pathway. Cell Physiol Biochem 2018; 49: 758-79. |
| 46. | Santanasto AJ, Glynn NW, Jubrias SA, et al. Skeletal muscle mitochondrial function and fatigability in older adults. J Gerontol a Biol Sci Med Sci 2015; 70: 1379-85. |
| 47. | Gonzalez-Freire M, Scalzo P, D'Agostino J, et al. Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: the baltimore longitudinal study of aging. Aging Cell 2018; 17. |
| 48. | Meng H, Yamashita C, Shiba-Fukushima K, et al. Loss of parkinson's disease-associated protein CHCHD 2 affects mitochondrial crista structure and destabilizes cytochrome c. Nat Commun 2017; 8: 15500. |
| 49. | Hu C, Shu L, Huang X, et al. OPA1 and MICOS regulate mitochondrial crista dynamics and formation. Cell Death Dis 2020; 11: 940. |
| 50. | Perier C, Bové J, Wu DC, et al. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental parkinson's disease. Proc Natl Acad Sci USA 2007; 104: 8161-6. |
| 51. | Ross JM. Visualization of mitochondrial respiratory function using cytochrome c oxidase/succinate dehydrogenase (COX/SDH) double-labeling histochemistry. J Vis Exp 2011: e3266. |
| 52. | Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014; 94: 909-50. |
| 53. | Soleimanpour-Lichaei HR, Kühl I, Gaisne M, et al. mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol Cell 2007; 27: 745-57. |
| 54. | Valero T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des 2014; 20: 5507-9. |
| 55. | Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 2008; 88: 611-38. |
| 56. | Westerblad H, Bruton JD, Katz A. Skeletal muscle: energy metabolism, fiber types, fatigue and adaptability. Exp Cell Res 2010; 316: 3093-9. |
| 57. | Wang Y, Liu Z, Han Y, Xu J, Huang W, Li Z. Medium chain triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism. Plos One 2018; 13: e191182. |
| 58. | Wei Y, Jia J, Jin X, Tong W, Tian H. Resveratrol ameliorates inflammatory damage and protects against osteoarthritis in a rat model of osteoarthritis. Mol Med Rep 2018; 17: 1493-8. |
| 59. | Park S, Ahmad F, Philp A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by Inhibiting cAMP phosphodiesterases. Cell 2012; 148: 421-33. |
| 60. | Price NL, Gomes AP, Ling AJ, et al. SIRT 1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 2012; 15: 675-90. |
| 61. | Ma S, Feng J, Zhang R, et al. SIRT 1 activation by resveratrol alleviates cardiac dysfunction via mitochondrial regulation in diabetic cardiomyopathy mice. Oxid Med Cell Longev 2017; 2017: 4602715. |
| 62. | Huang Y, Zhu X, Chen K, et al. Resveratrol prevents sarcopenic obesity by reversing mitochondrial dysfunction and oxidative stress via the PKA/LKB1/AMPK pathway. Aging (Albany NY) 2019; 11: 2217-40. |
| 63. | Hua W, Li S, Luo R, et al. Icariin protects human nucleus pulposus cells from hydrogen peroxide-induced mitochondria-mediated apoptosis by activating nuclear factor erythroid 2-related factor 2. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165575. |
| 64. | Yang Y, Wu Y, Zou J, et al. Naringenin attenuates non-alcoholic fatty liver disease by enhancing energy expenditure and regulating autophagy via AMPK. Front Pharmacol 2021; 12: 687095. |
| 65. | Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 2005; 37: 822-34. |
| 66. | Rebelo AP, Dillon LM, Moraes CT. Mitochondrial DNA transcription regulation and nucleoid organization. J Inherit Metab Dis 2011; 34: 941-51. |
| 67. | Hu K, Gong X, Ai Q, et al. Endogenous AMPK acts as a detrimental factor in fulminant hepatitis via potentiating JNK-dependent hepatocyte apoptosis. Cell Death Dis 2017; 8: e2637. |
| 68. | Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 2008; 79: 208-17. |
| 69. | J?ger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 2007; 104: 12017-22. |
| 70. | Kiyama T, Chen C, Zhang A, Mao C. Differential susceptibility of retinal neurons to the loss of mitochondrial biogenesis factor Nrf1. Cells 2022; 11: 2203. |
| 71. | Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol Metab 2012; 23: 459-66. |
| 72. | Alam TI, Kanki T, Muta T, et al. Human mitochondrial DNA is packaged with TFAM. Nucleic Acids Res 2003; 31: 1640-5. |
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