ISSN: 2008-2258
Vol 16, No 1 (2023): Winter
Protective effects of crocin and Gallic acid on the liver damage induced by methylglyoxal: the role of inflammatory factors Crocin, Gallic acid and hepatoprotective
Gastroenterology and Hepatology from Bed to Bench,
,
https://doi.org/10.22037/ghfbb.v16i1.2620
Abstract
Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver.
Background: MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. GA and Cr can reduce inflammation.
Methods: In this study, 50 NMRI mice were divided into 5 groups (n=10): Control, MG (600 mg/Kg/d, p.o.), MG+GA (30 mg/kg/day, p.o.), MG+Cr (60 mg/kg/day, p.o.), MG+MT (150 mg/kg/day, p.o.). Our study was conducted at five weeks. After diabetes induction (forth weeks), GA, Cr, and MT were administered. Biochemical and histologic evaluations were assessed after plasma collection and tissue samples preparation.
Results: Ga and Cr receiving groups significantly reduced FBG, total cholesterol, triglyceride levels, and elevate insulin sensitivity. Administration of MG exerted marked increase in the levels of hepatic enzymes. Treatment with GA, Cr, and MT significantly decreased them. Inflammatory factors increased in MG group. GA, Cr, and MT significantly improved these variables. High levels of steatosis and RBCs accumulation in MG group, markedly recovered in other treated mice.
Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice can be effectively attenuated by the use of GA and Cr.
Keywords:
- Methylglyoxal, Gallic acid, Crocin, TNF-α, Liver
How to Cite
Radmehr, V., Mojadami , S., Ahangarpour, A., & Mard, S. A. (2022). Protective effects of crocin and Gallic acid on the liver damage induced by methylglyoxal: the role of inflammatory factors: Crocin, Gallic acid and hepatoprotective. Gastroenterology and Hepatology from Bed to Bench, 16(1). https://doi.org/10.22037/ghfbb.v16i1.2620
References
References
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2. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.
3. Lee B-H, Hsu W-H, Chang Y-Y, Kuo H-F, Hsu Y-W, Pan T-M. Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med. 2012;53(11):2008–16.
4. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020;21(17):6275.
5. Saki K, Mansouri V, Abdi S, Fathi M, Razzaghi Z, Haghazali M. Assessment of common and differentially expressed proteins between diabetes mellitus and fatty liver disease: a network analysis. Gastroenterol Hepatol From Bed to Bench. 2021;14(Suppl1):S94.
6. Zhang J, Zhang L, Zhang S, Yu Q, Xiong F, Huang K, et al. HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol. 2017;454:103–11.
7. Tang D, Kang R, Livesey KM, Cheh C-W, Farkas A, Loughran P, et al. Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010;190(5):881–92.
8. Yang L, Zhou L, Wang X, Wang W, Wang J. Inhibition of HMGB1 involved in the protective of salidroside on liver injury in diabetes mice. Int Immunopharmacol. 2020;89:106987.
9. Chen M, Huang W, Wang C, Nie H, Li G, Sun T, et al. High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice. Clin Immunol. 2014;153(1):56–63.
10. Römermann D, Ansari N, Schultz‐Moreira AR, Michael A, Marhenke S, Hardtke‐Wolenski M, et al. Absence of Atg7 in the liver disturbed hepatic regeneration after liver injury. Liver Int. 2020;40(5):1225–38.
11. Qian H, Chao X, Williams J, Fulte S, Li T, Yang L, et al. Autophagy in liver diseases: A review. Mol Aspects Med. 2021;100973.
12. Horiuchi T, Sakata N, Narumi Y, Kimura T, Hayashi T, Nagano K, et al. Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity. J Biol Chem. 2017;292(20):8436–46.
13. Silvares RR, Pereira ENG da S, Flores EEI, Estato V, Reis PA, Silva IJ da, et al. Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high‐fat diet‐/streptozotocin‐induced diabetes. Int J Exp Pathol. 2016;97(3):266–77.
14. Yin H, Huang L, Ouyang T, Chen L. Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway. Int Immunopharmacol. 2018;55:55–62.
15. Kim JK, Shin KK, Kim H, Hong YH, Choi W, Kwak Y-S, et al. Korean red ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice. J Ginseng Res. 2021;
16. Mojadami S, Ahangarpour A, Mard SA, Khorsandi L. Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1–Nrf2 in male mice. Arch Physiol Biochem. 2021;1–8.
17. Kahkeshani N, Farzaei F, Fotouhi M, Alavi SS, Bahramsoltani R, Naseri R, et al. Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran J Basic Med Sci. 2019;22(3):225.
18. Latief U, Husain H, Mukherjee D, Ahmad R. Hepatoprotective efficacy of gallic acid during Nitrosodiethylamine-induced liver inflammation in Wistar rats. J Basic Appl Zool. 2016;76:31–41.
19. de Oliveira LS, Thomé GR, Lopes TF, Reichert KP, de Oliveira JS, da Silva Pereira A, et al. Effects of gallic acid on delta–aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Biomed Pharmacother. 2016;84:1291–9.
20. Bashar SM, Elhadidy MG, Mostafa AF, Hamed B, Helmy S, Abd-Elmoniem HA. Hepatoprotective effect of gallic acid against type 2-induced diabetic liver injury in male rats through modulation of fetuin-A and GLP-1 with involvement of ERK1/2/NF-κB and Wnt1/β-catenin signaling pathways. Gen Physiol Biophys. 2021;40(3):221–34.
21. Pashirzad M, Shafiee M, Avan A, Ryzhikov M, Fiuji H, Bahreyni A, et al. Therapeutic potency of crocin in the treatment of inflammatory diseases: Current status and perspective. J Cell Physiol. 2019;234(9):14601–11.
22. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333–7.
23. Chhimwal J, Sharma S, Kulurkar P, Patial V. Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats. Hum Exp Toxicol. 2020;39(12):1639–49.
24. Kalantar M, Kalantari H, Goudarzi M, Khorsandi L, Bakhit S, Kalantar H. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacol Reports. 2019;71(4):746–52.
25. Topsakal S, Ozmen O, Cicek E, Comlekci S. The ameliorative effect of gallic acid on pancreas lesions induced by 2.45 GHz electromagnetic radiation (Wi-Fi) in young rats. J Radiat Res Appl Sci. 2017;10(3):233–40.
26. Vakili A, Einali MR, Bandegi AR. Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23(1):106–13.
27. Qi SS, Zheng HX, Jiang H, Yuan LP, Dong LC. Protective effects of chromium picolinate against diabetic-induced renal dysfunction and renal fibrosis in streptozotocin-induced diabetic rats. Biomolecules. 2020;10(3):398.
28. Sharma R, Tiwari S. Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes. World J Diabetes. 2021;12(5):556.
29. Schalkwijk CG, Stehouwer CDA. Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol Rev. 2020;100(1):407–61.
30. Hanssen NMJ, Stehouwer CDA, Schalkwijk CG. Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease. Curr Opin Nephrol Hypertens. 2019;28(1):26–33.
31. Biddinger SB, Hernandez-Ono A, Rask-Madsen C, Haas JT, Alemán JO, Suzuki R, et al. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab. 2008;7(2):125–34.
32. Shirali S, Zahra Bathaie S, Nakhjavani M. Effect of crocin on the insulin resistance and lipid profile of streptozotocin‐induced diabetic rats. Phyther Res. 2013;27(7):1042–7.
33. Hewedy WA. Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice. Brazilian J Pharm Sci. 2021;56.
34. Sun L, Wen S, Li Q, Lai X, Chen R, Zhang Z, et al. L-theanine relieves acute alcoholic liver injury by regulating the TNF-α/NF-κB signaling pathway in C57BL/6J mice. J Funct Foods. 2021;86:104699.
35. Fouad D, Badr A, Attia HA. Hepatoprotective activity of raspberry ketone is mediated via inhibition of the NF-κB/TNF-α/caspase axis and mitochondrial apoptosis in chemically induced acute liver injury. Toxicol Res (Camb). 2019;8(5):663–76.
36. Ramos V, Kowaltowski A, Kakimoto P. Autophagy in hepatic steatosis: A structured review. Front cell Dev Biol. 2021;9:801.
37. Hosny S, Sahyon H, Youssef M, Negm A. Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis. Anti-Cancer Agents Med Chem (Formerly Curr Med Chem Agents). 2021;21(5):621–9.
1. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Baltimore). 2019;47(1):22–7.
2. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.
3. Lee B-H, Hsu W-H, Chang Y-Y, Kuo H-F, Hsu Y-W, Pan T-M. Ankaflavin: a natural novel PPARγ agonist upregulates Nrf2 to attenuate methylglyoxal-induced diabetes in vivo. Free Radic Biol Med. 2012;53(11):2008–16.
4. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020;21(17):6275.
5. Saki K, Mansouri V, Abdi S, Fathi M, Razzaghi Z, Haghazali M. Assessment of common and differentially expressed proteins between diabetes mellitus and fatty liver disease: a network analysis. Gastroenterol Hepatol From Bed to Bench. 2021;14(Suppl1):S94.
6. Zhang J, Zhang L, Zhang S, Yu Q, Xiong F, Huang K, et al. HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity. Mol Cell Endocrinol. 2017;454:103–11.
7. Tang D, Kang R, Livesey KM, Cheh C-W, Farkas A, Loughran P, et al. Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010;190(5):881–92.
8. Yang L, Zhou L, Wang X, Wang W, Wang J. Inhibition of HMGB1 involved in the protective of salidroside on liver injury in diabetes mice. Int Immunopharmacol. 2020;89:106987.
9. Chen M, Huang W, Wang C, Nie H, Li G, Sun T, et al. High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice. Clin Immunol. 2014;153(1):56–63.
10. Römermann D, Ansari N, Schultz‐Moreira AR, Michael A, Marhenke S, Hardtke‐Wolenski M, et al. Absence of Atg7 in the liver disturbed hepatic regeneration after liver injury. Liver Int. 2020;40(5):1225–38.
11. Qian H, Chao X, Williams J, Fulte S, Li T, Yang L, et al. Autophagy in liver diseases: A review. Mol Aspects Med. 2021;100973.
12. Horiuchi T, Sakata N, Narumi Y, Kimura T, Hayashi T, Nagano K, et al. Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity. J Biol Chem. 2017;292(20):8436–46.
13. Silvares RR, Pereira ENG da S, Flores EEI, Estato V, Reis PA, Silva IJ da, et al. Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high‐fat diet‐/streptozotocin‐induced diabetes. Int J Exp Pathol. 2016;97(3):266–77.
14. Yin H, Huang L, Ouyang T, Chen L. Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway. Int Immunopharmacol. 2018;55:55–62.
15. Kim JK, Shin KK, Kim H, Hong YH, Choi W, Kwak Y-S, et al. Korean red ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice. J Ginseng Res. 2021;
16. Mojadami S, Ahangarpour A, Mard SA, Khorsandi L. Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1–Nrf2 in male mice. Arch Physiol Biochem. 2021;1–8.
17. Kahkeshani N, Farzaei F, Fotouhi M, Alavi SS, Bahramsoltani R, Naseri R, et al. Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran J Basic Med Sci. 2019;22(3):225.
18. Latief U, Husain H, Mukherjee D, Ahmad R. Hepatoprotective efficacy of gallic acid during Nitrosodiethylamine-induced liver inflammation in Wistar rats. J Basic Appl Zool. 2016;76:31–41.
19. de Oliveira LS, Thomé GR, Lopes TF, Reichert KP, de Oliveira JS, da Silva Pereira A, et al. Effects of gallic acid on delta–aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Biomed Pharmacother. 2016;84:1291–9.
20. Bashar SM, Elhadidy MG, Mostafa AF, Hamed B, Helmy S, Abd-Elmoniem HA. Hepatoprotective effect of gallic acid against type 2-induced diabetic liver injury in male rats through modulation of fetuin-A and GLP-1 with involvement of ERK1/2/NF-κB and Wnt1/β-catenin signaling pathways. Gen Physiol Biophys. 2021;40(3):221–34.
21. Pashirzad M, Shafiee M, Avan A, Ryzhikov M, Fiuji H, Bahreyni A, et al. Therapeutic potency of crocin in the treatment of inflammatory diseases: Current status and perspective. J Cell Physiol. 2019;234(9):14601–11.
22. Yaribeygi H, Mohammadi MT, Sahebkar A. Crocin potentiates antioxidant defense system and improves oxidative damage in liver tissue in diabetic rats. Biomed Pharmacother. 2018;98:333–7.
23. Chhimwal J, Sharma S, Kulurkar P, Patial V. Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats. Hum Exp Toxicol. 2020;39(12):1639–49.
24. Kalantar M, Kalantari H, Goudarzi M, Khorsandi L, Bakhit S, Kalantar H. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacol Reports. 2019;71(4):746–52.
25. Topsakal S, Ozmen O, Cicek E, Comlekci S. The ameliorative effect of gallic acid on pancreas lesions induced by 2.45 GHz electromagnetic radiation (Wi-Fi) in young rats. J Radiat Res Appl Sci. 2017;10(3):233–40.
26. Vakili A, Einali MR, Bandegi AR. Protective effect of crocin against cerebral ischemia in a dose-dependent manner in a rat model of ischemic stroke. J Stroke Cerebrovasc Dis. 2014;23(1):106–13.
27. Qi SS, Zheng HX, Jiang H, Yuan LP, Dong LC. Protective effects of chromium picolinate against diabetic-induced renal dysfunction and renal fibrosis in streptozotocin-induced diabetic rats. Biomolecules. 2020;10(3):398.
28. Sharma R, Tiwari S. Renal gluconeogenesis in insulin resistance: A culprit for hyperglycemia in diabetes. World J Diabetes. 2021;12(5):556.
29. Schalkwijk CG, Stehouwer CDA. Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol Rev. 2020;100(1):407–61.
30. Hanssen NMJ, Stehouwer CDA, Schalkwijk CG. Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease. Curr Opin Nephrol Hypertens. 2019;28(1):26–33.
31. Biddinger SB, Hernandez-Ono A, Rask-Madsen C, Haas JT, Alemán JO, Suzuki R, et al. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab. 2008;7(2):125–34.
32. Shirali S, Zahra Bathaie S, Nakhjavani M. Effect of crocin on the insulin resistance and lipid profile of streptozotocin‐induced diabetic rats. Phyther Res. 2013;27(7):1042–7.
33. Hewedy WA. Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice. Brazilian J Pharm Sci. 2021;56.
34. Sun L, Wen S, Li Q, Lai X, Chen R, Zhang Z, et al. L-theanine relieves acute alcoholic liver injury by regulating the TNF-α/NF-κB signaling pathway in C57BL/6J mice. J Funct Foods. 2021;86:104699.
35. Fouad D, Badr A, Attia HA. Hepatoprotective activity of raspberry ketone is mediated via inhibition of the NF-κB/TNF-α/caspase axis and mitochondrial apoptosis in chemically induced acute liver injury. Toxicol Res (Camb). 2019;8(5):663–76.
36. Ramos V, Kowaltowski A, Kakimoto P. Autophagy in hepatic steatosis: A structured review. Front cell Dev Biol. 2021;9:801.
37. Hosny S, Sahyon H, Youssef M, Negm A. Prunus Armeniaca L. Seed Extract and Its Amygdalin Containing Fraction Induced Mitochondrial-Mediated Apoptosis and Autophagy in Liver Carcinogenesis. Anti-Cancer Agents Med Chem (Formerly Curr Med Chem Agents). 2021;21(5):621–9.
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