Research Articles

Dark red tongue color formation caused by hyperglycemia is attributed to decreased blood flow of tongue tissue partially due to nuclear factor-kappa B pathway activation

  • Shenyi JIN ,
  • Yahua LIU ,
  • Xu HAN ,
  • Mengjie CAI ,
  • Jiatuo XU ,
  • Hao LU ,
  • Qingguang CHEN
Expand
  • 1 Department of Endocrinology, Diabetes Institute, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2 Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received date: 2022-09-22

  Accepted date: 2022-12-16

  Online published: 2023-11-01

Supported by

Exploring the Biological Basis of Tongue Color in Diabetic Rats Based on Nuclear Factor-Kappa B Pathway-Mediated Microcirculation Disorders(81503552);Shanghai Key Laboratory of Chinese Medicine Clinical Medicine(20DZ2272200);New Traditional Chinese Medicine Intelligent Series Tongue Diagnosis Research and Development(2017YFC1703301);Investigating the Mechanism Which Berberine Improved Cognitive Dysfunction Based on the Phosphoinositide 3-Kinase/Protein Kinase B Pathway(2018D01C024)

Abstract

OBJECTIVE: To investigate the potential mechanisms underlying the dark red tongue color formation induced by hyperglycemia.
METHODS: A high-fat diet and intraperitoneal injection of streptozotocin were used to establish a diabetes model. The color and blood flow of tongues were analyzed by the Tongue Diagnosis Analysis System and laser Doppler flowmetry, respectively. Inflammatory factors and adhesion factors were measured in the circulation and tongue tissue by an enzyme-linked immunosorbent assay. Western blotting was employed to evaluate nuclear factor-kappa B (NF-κB) p50 and inhibitor of kappa B kinase protein expression levels in the tongue. Then, the NF-κB inhibitor, pyrrolidine dithiocarbamic acid ammonium salt was utilized to repress NF-κB pathway activation to validate that the NF-κB pathway plays a key role in blood flow and dark red tongue color formation.
RESULTS: The diabetic rats displayed a dark red tongue color that was accompanied by NF-κB pathway activation and decreased blood flow in the tongue. These effects could be reversed by the NF-κB inhibitor.
CONCLUSIONS: Our investigation demonstrated that hyperglycemia led to dark red tongue color formation by decreasing blood flow in the tongue, which was partly due to NF-κB pathway activation.

Cite this article

Shenyi JIN , Yahua LIU , Xu HAN , Mengjie CAI , Jiatuo XU , Hao LU , Qingguang CHEN . Dark red tongue color formation caused by hyperglycemia is attributed to decreased blood flow of tongue tissue partially due to nuclear factor-kappa B pathway activation[J]. Journal of Traditional Chinese Medicine, 2023 , 43(6) : 1118 -1125 . DOI: 10.19852/j.cnki.jtcm.20231018.003

References

1. International Diabetes Federation. IDF Diabetes Atlas, 10th ed. Brussels, Belgium: International Diabetes Federation 2021; 172: 108630.
2. Ogurtsova K, Guariguata L, Barengo NC, et al. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract 2022; 183: 109118.
3. Li J, Yuan P, Hu X, et al. A tongue features fusion approach to predicting prediabetes and diabetes with machine learning. J Biomed Inform 2021; 115: 103693.
4. Hu M, Lan K, Fang W, et al. Automated tongue diagnosis on the smartphone and its applications. Comput Methods Programs Biomed 2019; 174: 51-64.
5. Jiao W, Hu X, Tu LP, et al. Tongue color clustering and visual application based on 2D information. Int J Comput Assist Radiol Surg 2020; 15: 203-12.
6. Kanawong R, Obafemi-Ajayi T, Liu D, Zhang M, Xu D, Duan Y. Tongue image analysis and its mobile app development for health diagnosis. Adv Exp Med Biol 2017; 1005: 99-121.
7. Li J, Yuan P, Hu X, et al. A tongue features fusion approach to predicting prediabetes and diabetes with machine learning. J Biomed Inform 2021; 115: 103693.
8. Tania MH, Lwin K, Hossain MA. Advances in automated tongue diagnosis techniques. Integr Med Res 2019; 8: 42-56.
9. Chen QG, Gao Y, Cai MJ, et al. A study on the objective characteristics of tongue images in the elderly with different glucose metabolism. Geriatr Health Care 2020; 26: 383-6.
10. Hsu PC, Wu HK, Huang YC, et al. The tongue features associated with type 2 diabetes mellitus. Medicine (Baltimore) 2019; 98: e15567.
11. Hsu PC, Huang YC, Chiang JY, Chang HH, Liao PY, Lo LC. The association between arterial stiffness and tongue manifestations of blood stasis in patients with type 2diabetes. BMC Complement Altern Med 2016; 16: 324.
12. Park YJ, Yang DH, Lee JM, Park YB. Development of a valid and reliable blood stasis questionnaire and its relationship to heart rate variability. Complement Ther Med 2013; 21: 633-40.
13. Zheng XY. Guiding principle of clinical research on new drugs of Chinese medicine. Beijing: Chinese Medical Science and Technology Press, 2002: 29-31.
14. Xu M, Chen H, Shi ZX, et al. Pathological observation of blood stasis syndrome in non-diabetic peripheral neuropathies: a retrospective analysis based on nerve biopsy. Chin J Integr Med 2020; 26: 776-82.
15. Liu WL, Zhang HY, Che NC, Tang ZQ, Gao LY. Changes of color and blood flow of the tongue in the mini-swine of immune hepatic injury. J Tradit Chin Med 2010; 30: 265-71.
16. Wang ZC, Zhang SP, Yuen PC, et al. Intra-rater and inter-rater reliability of tongue coating diagnosis in Traditional Chinese Medicine using smartphones: quasi-Delphi study. JMIR Mhealth Uhealth 2020; 8: e16018.
17. López-Díez R, Shen X, Daffu G, et al. Ager deletion enhances ischemic muscle inflammation, angiogenesis, and blood flow recovery in diabetic mice. Arterioscler Thromb Vasc Biol 2017; 37: 1536-47.
18. Liu M, Li F, Liang M, Rao X. Effects of aldose reductase inhibitors on renal blood flow parameters in patients with early diabetic nephropathy. J Diabetes Complications 2020; 34: 107620.
19. Nagaoka T, Sato E, Takahashi A, Yokota H, Sogawa K, Yoshida A. Impaired retinal circulation in patients with type 2 diabetes mellitus: retinal laser Doppler velocimetry study. Invest Ophthalmol Vis Sci 2010; 51: 6729-34.
20. Betsy BD. The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids. Diabetes Spectr 2008; 21: 160-5.
21. Jansen JF, van Bussel FC, van de Haar HJ, et al. Cerebral blood flow, blood supply, and cognition in type 2 diabetes mellitus. Sci Rep 2016; 6: 10.
22. Shin YK, Hsieh YS, Kwon S, Lee HS, Seol GH. Linalyl acetate restores endothelial dysfunction and hemodynamic alterations in diabetic rats exposed to chronic immobilization stress. J Appl Physiol (1985) 2018; 124: 1274-83.
23. Li H, Shi Y, Wang X, et al. Piceatannol alleviates inflammation and oxidative stress via modulation of the Nrf2/HO-1 and NF-κB pathways in diabetic cardiomyopathy. Chem Biol Interact 2019; 310: 108754.
24. Fernández J, Clària J, Amorós A, et al. Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis. Gastroenterology 2019; 157: 149-62.
25. Yao L, Bhatta A, Xu Z, et al. Obesity-induced vascular inflammation involves elevated arginase activity. Am J Physiol Regul Integr Comp Physiol 2017; 313: R560-71.
26. Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB. Trends Cell Biol 2017; 27: 417-29.
27. Patel S, Santani D. Role of NF-κB in the pathogenesis of diabetes and its associated complications. Pharmacol. Rep 2009; 61: 595-603.
28. Hu R, Wang MQ, Ni SH, et al. Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP 3 signaling pathway in AGEs-induced HUVECs. Eur J Pharmacol 2020; 867: 172797.
29. Liu R, Jiang LJ, Yang Y, et al. Study on syndrome differentiation strategy of phlegm and blood stasis syndromes of coronary heart disease based on expert consultation on medical cases. Ann Palliat Med 2021; 10: 9940-52.
30. Cvijanovic N, Feinle-Bisset C, Young RL, Little TJ. Oral and intestinal sweet and fat tasting: impact of receptor polymorphisms and dietary modulation for metabolic disease. Nutr Rev 2015; 73: 318-34.
31. Ponte E, Tabaj D, Maglione M, Melato M. Diabetes mellitus and oral disease. Acta Diabetol 2001; 38: 57-62.
32. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J 2013; 34: 2436-43.
33. Hartge MM, Unger T, Kintscher U. The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res 2007; 4: 84-8.
34. Jaap AJ, Pym CA, Seamark C, Shore AC, Tooke JE. Microvascular function in type 2 (non-insulin-dependent) diabetes: improved vasodilation after one year of good glycaemic control. Diabet Med 1995; 12: 1086-91.
35. Muller WA. New mechanisms and pathways for monocyte recruitment. J Exp Med 2001; 194: F47-51.
36. Niu J, Kolattukudy PE. Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Sci (Lond) 2009; 117: 95-109.
37. Yang J, Park Y, Zhang H, et al. Role of MCP-1 in tumor necrosis factor-alpha-induced endothelial dysfunction in type 2 diabetic mice. Am J Physiol Heart Circ Physiol 2009;297: H1208-16.
38. Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: the role of cytokines. Ann N Y Acad Sci 2006; 1084: 89-117.
39. Peiró C, Lorenzo ó, Carraro R, Sánchez-Ferrer CF. IL-1β inhibition in cardiovascular complications associated to diabetes mellitus. Front Pharmacol 2017; 8: 363.
40. Fischer TA. Pharmacological therapy of age-related macular degeneration based on etiopathogenesis. Orv Hetil 2015; 156: 1847-58.
41. Bilsborough W, O'Driscoll G, Stanton K, et al. Effect of lowering tumour necrosis factor-alpha on vascular endothelial function in Type Ⅱ diabetes. Clin Sci (Lond) 2002; 103: 163-9.
42. Kracht M, Müller-Ladner U, Schmitz ML. Mutual regulation of metabolic processes and proinflammatory NF-κB signaling. J Allergy Clin Immunol 2020; 146: 694-705.
43. Catrysse L, van Loo G. Inflammation and the metabolic syndrome: the tissue-specific functions of NF-κB. Trends Cell Biol 2017; 27: 417-29.
44. Sun SC. The non-canonical NF-κB pathway in immunity and inflammation. Nat Rev Immunol 2017; 17: 545-58.
45. Zhang Q, Lenardo MJ, Baltimore D. 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell 2017; 168: 37-57.
46. Bao L, Li J, Zha D, et al. Chlorogenic acid prevents diabetic nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-?B pathways. Int Immunopharmacol 2018; 54: 245-53.
47. Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007; 2007: 95103.
Outlines

/