Sinapic acid attenuates muscle atrophy in streptozotocin-induced diabetic mice

Document Type : Original Article

Authors

1 Institute of Physical Culture, Hunan University of Arts and Science, 415000 Changde, China

2 Faculty of Science, College of Furong, Hunan University of Arts and Science, 415000 Changde, China

3 The First Affiliated Hospital of Hunan University of Chinese Medicine, 410021 Changsha, China

Abstract

Objective(s): Diabetes is fundamentally connected with the inability of skeletal muscle. Sinapic acid (SA) has multiple biologic functions and is diffusely utilized in diabetic complications. The purpose of this study was to explore the potential improvement effect and mechanisms of SA in streptozotocin (STZ)-induced diabetic muscle atrophy.
Materials and Methods: The model of diabetic mice was established by intraperitoneal STZ (200 mg/kg) to evaluate the treatment effect of SA (40 mg/kg/d for 8 weeks) on muscle atrophy. Muscle fiber size was assessed by Hematoxylin and Eosin (HE) staining. Muscle force was measured by a dynamometer. Biochemical parameters were tested by using corresponding commercial kits. The expressions of Atrogin-1, MuRF-1, nuclear respiratory factor 1 (NRF-1), peroxisome proliferative activated receptor gamma coactivator 1 alpha (PGC-1α), CHOP, GRP-78, BAX, and BCL-2 were detected by Western blot.
Results: Our data demonstrated that SA increased fiber size and weight of gastrocnemius, and enhanced grip strength to alleviate diabetes-induced muscle atrophy. In serum, SA restrained creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor (TNF-a), and interleukin 6 (IL-6) levels, while enhancing total anti-oxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) levels to improve muscle injury. In gastrocnemius, SA promoted NRF-1, PGC-1α, and BCL-2 expressions, while inhibiting Atrogin-1, MuRF-1, CHOP, GRP-87, and BAX expressions.
Conclusion: SA protected against diabetes-induced gastrocnemius injury via improvement of mitochondrial function, endoplasmic reticulum (ER) stress, and apoptosis, and could be developed to prevent and treat diabetic muscle atrophy.

Keywords

References

1. Desai S, Deshmukh A. Mapping of type 1 diabetes mellitus. Curr Diabetes Rev 2020; 16: 438-441. 
2. Zamfirov K, Philippe J. Musculoskeletal complications in diabetes mellitus. Rev Med Suisse 2017; 13: 917-921.
3. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The growing epidemic of diabetes mellitus. Curr Vasc Pharmacol 2020; 18: 104-109. 
4. Madhavi YV, Gaikwad N, Yerra VG, Kalvala AK, Nanduri S, Kumar A. Targeting AMPK in diabetes and diabetic complications: energy homeostasis, autophagy and mitochondrial health. Curr Med Chem 2019; 26: 5207-5229. 
5. Demirtas L, Guclu A, Erdur FM, Akbas EM, Ozcicek A, Onk D, Turkmen K. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res 2016; 144: 515-524. 
6. Kitajima Y, Yoshioka K, Suzuki N. The ubiquitin-proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders. J Physiol Sci 2020; 70: 40-51.
7. Khalil R. Ubiquitin-proteasome pathway and muscle atrophy. Adv Exp Med Biol 2018; 1088: 235-248. 
8. Rusbana TB, Agista AZ, Saputra WD, Ohsaki Y, Watanabe, K, Ardiansyah, A, Budijanto, S, Koseki, T, Aso, H, Komai, M, & Shirakawa, H. Supplementation with fermented rice bran attenuates muscle atrophy in a diabetic rat model. Nutrients 2020; 12: 2409-2422. 
9. Ono T, Takada S, Kinugawa S, Tsutsui H. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination. Exp Physiol 2015; 100: 1052-1063.
10. Pandi A, Kalappan VM. Pharmacological and therapeutic applications of Sinapic acid-an updated review. Mol Biol Rep 2021; 48: 3733-3745. 
11. Menezes JC, Kamat SP, Cavaleiro JA, Gaspar A, Garrido J, Borges F. Synthesis and anti-oxidant activity of long chain alkyl hydroxycinnamates. Eur J Med Chem 2011; 46: 773-777. 
12. Altındağ F, Rağbetli MÇ, Özdek U, Koyun N, Ismael Alhalboosi JK, Elasan S. Combined treatment of sinapic acid and ellagic acid attenuates hyperglycemia in streptozotocin-induced diabetic rats. Food Chem Toxicol 2021; 156: 112443. 
13. Cherng YG, Tsai CC, Chung HH, Lai YW, Kuo SC, Cheng JT. Antihyperglycemic action of sinapic acid in diabetic rats. J Agric Food Chem 2013; 61: 12053-12059. 
14. Alaofi AL. Sinapic acid ameliorates the progression of streptozotocin (STZ)-induced diabetic nephropathy in rats via nrf2/ho-1 mediated pathways. Front Pharmacol 2020; 11: 1119.
15. Zych M, Wojnar W, Borymski S, Szałabska K, Bramora P, Kaczmarczyk-Sedlak I. Effect of rosmarinic acid and sinapic acid on oxidative stress parameters in the cardiac tissue and serum of type 2 diabetic female rats. Antioxidants (Basel) 2019; 8: 579-601. 
16. Han Y, Qiu H, Pei X, Fan Y, Tian H, Geng J. Low-dose sinapic acid abates the pyroptosis of macrophages by downregulation of lncRNA-MALAT1 in rats with diabetic atherosclerosis. J Cardiovasc Pharmacol 2018; 71: 104-112. 
17. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012; 8: 457-465. 
18. Lee JH, Jun HS. Role of myokines in regulating skeletal muscle mass and function. Front Physiol 2019; 10: 42-50. 
19. Monaco CMF, Perry CGR, Hawke TJ. Diabetic myopathy: current molecular understanding of this novel neuromuscular disorder. Curr Opin Neurol 2017; 30: 545-552. 
20. Hernández-Ochoa EO, Llanos P, Lanner JT. The underlying mechanisms of diabetic myopathy. J Diabetes Res 2017; 2017: 7485738. 
21. Guo S, Chen Q, Sun Y, Chen J. Nicotinamide protects against skeletal muscle atrophy in streptozotocin-induced diabetic mice. Arch Physiol Biochem 2019; 125: 470-477. 
22. He N, Ye H. Exercise and muscle atrophy. Adv Exp Med Biol 2020; 1228: 255-267. 
23. Yin L, Li N, Jia W, Wang N, Liang M, Yang X, Du G.  Skeletal muscle atrophy: From mechanisms to treatments. Pharmacol Res 2021; 172: 105807.
24. Attaix D, Ventadour S, Codran A, Béchet D, Taillandier D, Combaret L. The ubiquitin-proteasome system and skeletal muscle wasting. Essays Biochem 2005; 41: 173-186. 
25. Ishida T, Iizuka M, Ou Y, Morisawa S, Hirata A, Yagi Y, Jobu K, Morita Y, Miyamura M. Juzentaihoto suppresses muscle atrophy in streptozotocin-induced diabetic mice. Biol Pharm Bull 2019; 42: 1128-1133. 
26. Kramer A. An overview of the beneficial effects of exercise on health and performance. Adv Exp Med Biol 2020; 1228: 3-22. 
27. Wada J, Nakatsuka A. Mitochondrial dynamics and mitochondrial dysfunction in diabetes. Acta Med Okayama 2016; 70: 151-158. 
28. Wu MY, Yiang GT, Lai TT, Li CJ. The oxidative stress and mitochondrial dysfunction during the pathogenesis of diabetic retinopathy. Oxid Med Cell Longev 2018; 2018: 3420187. 
29. Wang D, Sun H, Song G, Yang Y, Zou X, Han P, Li S. Resveratrol improves muscle atrophy by modulating mitochondrial quality control in STZ-induced diabetic mice. Mol Nutr Food Res 2018; 62: e1700941. 
30. Hyatt H, Deminice R, Yoshihara T, Powers SK. Mitochondrial dysfunction induces muscle atrophy during prolonged inactivity: A review of the causes and effects. Arch Biochem Biophys 2019; 662: 49-60.
31. Stanely Mainzen Prince P, Dey P, Roy SJ. Sinapic acid safeguards cardiac mitochondria from damage in isoproterenol-induced myocardial infarcted rats. J Biochem Mol Toxicol 2020; 34: e22556. 
32. Cao ZH, Wu Z, Hu C, Zhang M, Wang WZ, Hu XB. Endoplasmic reticulum stress and destruction of pancreatic β cells in type 1 diabetes. Chin Med J (Engl) 2020; 133: 68-73.
33. Reddy SS, Shruthi K, Joy D, Reddy GB. 4-PBA prevents diabetic muscle atrophy in rats by modulating ER stress response and ubiquitin-proteasome system. Chem Biol Interact 2019; 306: 70-77. 
34. Bohnert KR, McMillan JD, Kumar A. Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease. J Cell Physiol 2018; 233: 67-78. 
35. Gallot YS, Bohnert KR. Confounding Roles of ER stress and the unfolded protein response in skeletal muscle atrophy. Int J Mol Sci 2021; 22: 2567-2584. 
36. Afroze D, Kumar A. ER stress in skeletal muscle remodeling and myopathies. FEBS J 2019; 286: 379-398. 
37. Tungalag T, Yang DK. Sinapic acid protects SH-SY5Y human neuroblastoma cells against 6-Hydroxydopamine-induced neurotoxicity. Biomedicines 2021; 9: 295-310. 
38. Turkmen K. Inflammation, oxidative stress, apoptosis, and autophagy in diabetes mellitus and diabetic kidney disease: the Four Horsemen of the Apocalypse. Int Urol Nephrol 2017; 49: 837-844. 
39. Dupont-Versteegden EE. Apoptosis in skeletal muscle and its relevance to atrophy. World J Gastroenterol 2006; 12: 7463-7466. 
40. Fan J, Yang X, Li J, Shu Z, Dai J, Liu X, Li B, Jia S, Kou X, Yang Y, Chen N. Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget 2017; 8: 17475-17490. 
41. Edlich F. BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem Biophys Res Commun 2018; 500: 26-34.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 12
December 2021
Pages 1695-1701

Files

Share

How to cite

Statistics