Skip to main content
SpringerLink
Log in

Protective effects of hydroxysafflor yellow A (HSYA) on alcohol-induced liver injury in rats

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Hydroxysafflor yellow A (HSYA), the main active natural constituent extracted from Carthamus tinctorius L., has been widely used for the treatment of cerebrovascular and cardiovascular diseases. The aim of this study is to explore the effect of HSYA on alcohol-induced liver injury and the underlying mechanism. Male Sprague-Dawley rats were used to establish the liver injury model induced by alcohol. HSYA treatment ameliorated serum biochemical indicators by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronan (HA), laminin (LN), and type III precollagen (III-C) in rats. HSYA efficiently increased the activity and messenger RNA (mRNA) of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in rat liver tissue compared with those of model group, which was obviously reduced by alcohol. HSYA also apparently decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in rat liver tissue compared with those of model group, which was obviously enhanced by alcohol. Histological studies demonstrated that HSYA substantially reduced the number of macro- and micro-vesicular steatosis, suppressed hepatic fibrogenesis and shrunk ballooning degeneration areas, ameliorated the severity of liver damage induced by long-term drinking, and finally improved the liver architecture. In addition, immunohistochemistry study indicated that the activation of transforming growth factor β1 (TGF-β1) stimulated by alcohol in rat liver tissue was significantly blocked by HSYA. Collectively, these data demonstrated that HSYA can effectively protect the liver of rats from long-term alcohol injury, which relates with the enhanced antioxidant capacity of liver tissues and inhibition of TGF-β1 expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abhilash PA, Harikrishnan R, Indira M (2013) Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs. J Physiol Biochem 69:785–798

    Article  CAS  PubMed  Google Scholar 

  2. Adachi M, Brenner DA (2005) Clinical syndromes of alcoholic liver disease. Dig Dis 23:255–263

    Article  PubMed  Google Scholar 

  3. Arteel G, Marsano L, Mendez C, Bentley F, McClain CJ (2003) Advances in alcoholic liver disease. Best Pract Res Clin Gastroenterol 17:625–647

    Article  CAS  PubMed  Google Scholar 

  4. Basu S (2003) Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189:113–127

    Article  CAS  PubMed  Google Scholar 

  5. Bonner JC (2007) Lung fibrotic responses to particle exposure. Toxicol Pathol 35:148–153

    Article  CAS  PubMed  Google Scholar 

  6. Chang Y, Yang S, Li H (2004) Protective effects of nutmeg ethanol extract on acute liver lesion in rats induced by D-galactosamine. Chin Pharmacol Bulletin 20:118–119

    CAS  Google Scholar 

  7. Cheng D, Kong H (2011) The effect of Lycium barbarum polysaccharide on alcohol-induced oxidative stress in rats. Molecules 16:2542–2550

    Article  CAS  PubMed  Google Scholar 

  8. Comporti M, Signorini C, Arezzini B, Vecchio D, Monaco B, Gardi C (2008) Isoprostanes and hepatic fibrosis. Mol Aspects Med 29:43–49

    Article  CAS  PubMed  Google Scholar 

  9. Friedman SL (1999) Cytokines and fibrogenesis. Semin Liver Dis 19:129–140

    Article  CAS  PubMed  Google Scholar 

  10. Friedman SL (2003) Liver fibrosis—from bench to bedside. J Hepatol 38(Suppl 1):S38–S53

    Article  PubMed  Google Scholar 

  11. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S (2002) Roles of TGF-beta in hepatic fibrosis. Front Biosci 7:d793–d807

    Article  CAS  PubMed  Google Scholar 

  12. Hayasaka A, Saisho H (1998) Serum markers as tools to monitor liver fibrosis. Digestion 59:381–384

    Article  CAS  PubMed  Google Scholar 

  13. Huang Q, Li Y, Zhang S, Huang R, Zheng L, Wei L, He M, Liao M, Li L, Zhuo L, Lin X (2012) Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats. J Ethnopharmacol 143:889–895

    Article  CAS  PubMed  Google Scholar 

  14. Huang QF, Zhang SJ, Zheng L, Liao M, He M, Huang R, Zhuo L, Lin X (2012) Protective effect of isoorientin-2”-O-alpha-L-arabinopyranosyl isolated from Gypsophila elegans on alcohol induced hepatic fibrosis in rats. Food Chem Toxicol 50:1992–2001

    Article  CAS  PubMed  Google Scholar 

  15. Iimuro Y, Brenner DA (2008) Matrix metalloproteinase gene delivery for liver fibrosis. Pharm Res 25:249–258

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Korner T, Kropf J, Gressner AM (1996) Serum laminin and hyaluronan in liver cirrhosis: markers of progression with high prognostic value. J Hepatol 25:684–688

    Article  CAS  PubMed  Google Scholar 

  17. Kuo LM, Kuo CY, Lin CY, Hung MF, Shen JJ, Hwang TL (2014) Intracellular glutathione depletion by oridonin leads to apoptosis in hepatic stellate cells. Molecules 19:3327–3344

    Article  PubMed  Google Scholar 

  18. Lee JS (2004) Supplementation of Pueraria radix water extract on changes of antioxidant enzymes and lipid profile in ethanol-treated rats. Clin Chim Acta 347:121–128

    Article  CAS  PubMed  Google Scholar 

  19. Lewindon PJ, Pereira TN, Hoskins AC, Bridle KR, Williamson RM, Shepherd RW, Ramm GA (2002) The role of hepatic stellate cells and transforming growth factor-beta(1) in cystic fibrosis liver disease. Am J Pathol 160:1705–1715

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Li CC, Yang CZ, Li XM, Zhao XM, Zou Y, Fan L, Zhou L, Liu JC, Niu YC (2012) Hydroxysafflor yellow A induces apoptosis in activated hepatic stellate cells through ERK1/2 pathway in vitro. Eur J Pharm Sci 46:397–404

    Article  CAS  PubMed  Google Scholar 

  21. Li H, Jiang T, Lin Y, Zhao Z, Zhang N (2006) HGF protects rat mesangial cells from high-glucose-mediated oxidative stress. Am J Nephrol 26:519–530

    Article  CAS  PubMed  Google Scholar 

  22. Li HX, Han SY, Wang XW, Ma X, Zhang K, Wang L, Ma ZZ, Tu PF (2009) Effect of the carthamins yellow from Carthamus tinctorius L. on hemorheological disorders of blood stasis in rats. Food Chem Toxicol 47:1797–1802

    Article  CAS  PubMed  Google Scholar 

  23. Limaye PV, Raghuram N, Sivakami S (2003) Oxidative stress and gene expression of antioxidant enzymes in the renal cortex of streptozotocin-induced diabetic rats. Mol Cell Biochem 243:147–152

    Article  CAS  PubMed  Google Scholar 

  24. Lin CF, Wong KL, Wu RS, Huang TC, Liu CF (2003) Protection by hot water extract of Panax notoginseng on chronic ethanol-induced hepatotoxicity. Phytother Res 17:1119–1122

    Article  PubMed  Google Scholar 

  25. Liu H, Qi X, Cao S, Li P (2014) Protective effect of flavonoid extract from Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit on alcoholic liver oxidative injury in mice. J Nat Med 68:521–529

    Article  CAS  PubMed  Google Scholar 

  26. Liu SQ, Yu JP, Chen HL, Luo HS, Chen SM, Yu HG (2006) Therapeutic effects and molecular mechanisms of Ginkgo biloba extract on liver fibrosis in rats. Am J Chin Med 34:99–114

    Article  CAS  PubMed  Google Scholar 

  27. Manke A, Luanpitpong S, Dong C, Wang L, He X, Battelli L, Derk R, Stueckle TA, Porter DW, Sager T, Gou H, Dinu CZ, Wu N, Mercer RR, Rojanasakul Y (2014) Effect of fiber length on carbon nanotube-induced fibrogenesis. Int J Mol Sci 15:7444–7461

    Article  PubMed Central  PubMed  Google Scholar 

  28. Murawaki Y, Ikuta Y, Koda M, Nishimura Y, Kawasaki H (1996) Clinical significance of serum hyaluronan in patients with chronic viral liver disease. J Gastroenterol Hepatol 11:459–465

    Article  CAS  PubMed  Google Scholar 

  29. Patek AJ (1979) Alcohol, malnutrition, and alcoholic cirrhosis. Am J Clin Nutr 32:1304–1312

    CAS  PubMed  Google Scholar 

  30. Peng Y, Yang H, Zhu T, Zhao M, Deng Y, Liu B, Shen H, Hu G, Wang Z, Tao L (2013) The antihepatic fibrotic effects of fluorofenidone via MAPK signalling pathways. Eur J Clin Invest 43:358–368

    Article  CAS  PubMed  Google Scholar 

  31. Petrie DJ, Doran CM, Shakeshaft AP, Sanson-Fisher R (2010) The relationship between risky alcohol consumption, crime and traffic accidents in Australian rural communities. Addict Behav 35:359–362

    Article  PubMed  Google Scholar 

  32. Schuckit MA (2009) Alcohol-use disorders. Lancet 373:492–501

    Article  PubMed  Google Scholar 

  33. Szuster-Ciesielska A, Plewka K, Daniluk J, Kandefer-Szerszen M (2011) Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-alpha, TGF-beta) production and by influencing intracellular signaling. Toxicology 280:152–163

    Article  CAS  PubMed  Google Scholar 

  34. Tian JW, Fu FH, Jiang WL, Wang CY, Sun F, Zhang TP (2004) Protective effect of hydroxysafflor yellow A against rat cortex mitochondrial injuries induced by cerebral ischemia. Yao Xue Xue Bao 39:774–777

    CAS  PubMed  Google Scholar 

  35. Tien YC, Lin JY, Lai CH, Kuo CH, Lin WY, Tsai CH, Tsai FJ, Cheng YC, Peng WH, Huang CY (2010) Carthamus tinctorius L. prevents LPS-induced TNFalpha signaling activation and cell apoptosis through JNK1/2-NFkappaB pathway inhibition in H9c2 cardiomyoblast cells. J Ethnopharmacol 130:505–513

    Article  PubMed  Google Scholar 

  36. Tilg H, Day CP (2007) Management strategies in alcoholic liver disease. Nat Clin Pract Gastroenterol Hepatol 4:24–34

    Article  CAS  PubMed  Google Scholar 

  37. Wang CY, Liu Q, Huang QX, Liu JT, He YH, Lu JJ, Bai XY (2013) Activation of PPARgamma is required for hydroxysafflor yellow A of Carthamus tinctorius to attenuate hepatic fibrosis induced by oxidative stress. Phytomedicine 20:592–599

    Article  CAS  PubMed  Google Scholar 

  38. Wang L, Jin M, Zang BX, Wu Y (2011) Inhibitory effect of safflor yellow on pulmonary fibrosis. Biol Pharm Bull 34:511–516

    Article  CAS  PubMed  Google Scholar 

  39. Weng H, Mertens PR, Gressner AM, Dooley S (2007) IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads. J Hepatol 46:295–303

    Article  CAS  PubMed  Google Scholar 

  40. Yamamoto T, Noble NA, Miller DE, Border WA (1994) Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int 45:916–927

    Article  CAS  PubMed  Google Scholar 

  41. Zeng XX, Bian ZX, Wu TX, Fu SF, Ziea E, Woon WT (2011) Traditional Chinese medicine syndrome distribution in chronic hepatitis B populations: a systematic review. Am J Chin Med 39:1061–1074

    Article  PubMed  Google Scholar 

  42. Zhang Y, Guo J, Dong H, Zhao X, Zhou L, Li X, Liu J, Niu Y (2011) Hydroxysafflor yellow A protects against chronic carbon tetrachloride-induced liver fibrosis. Eur J Pharmacol 660:438–444

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The present study was supported by the National Natural Science Foundation of China (No. 81270347), Shaanxi Science and Technology Innovation Project (No. 2013KTCL03-02).

Conflict of interest

The authors state no conflict of interests.

Author information

Author notes

    Authors and Affiliations

    1. Department of Pharmacology, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China

      Yanhao He, Yanxiang Li, Xiaofeng Yang, Weirong Wang, Tingting Li, Wei Zhang & Rong Lin

    2. Department of Medical Oncology, Dongying People’s Hospital, Dongying, 257000, Shandong, People’s Republic of China

      Qiang Liu

    3. School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, Shandong, People’s Republic of China

      Yuexin Cui & Chaoyun Wang

    Authors
    1. Yanhao He
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Qiang Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yanxiang Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Xiaofeng Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Weirong Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Tingting Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Wei Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Yuexin Cui
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Chaoyun Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Rong Lin
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Rong Lin.

    Additional information

    Chaoyun Wang and Rong Lin contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    He, Y., Liu, Q., Li, Y. et al. Protective effects of hydroxysafflor yellow A (HSYA) on alcohol-induced liver injury in rats. J Physiol Biochem 71, 69–78 (2015). https://doi.org/10.1007/s13105-015-0382-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13105-015-0382-3

    Keywords

    Search

    Navigation