Skip to main content
Log in

Preventive Effect and Mechanism of Anthocyanins from Aronia Melanocarpa Elliot on Hepatic Fibrosis Through TGF-β/Smad Signaling Pathway

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

In order to explore the effect and mechanism of Aornia mealnocarpa Elliot anthocyanins (AMA) at the cellular level on hepatic fibrosis (HF), molecular docking, RT-PCR and Western Blotting were used to explore the molecular mechanism and the effects of different doses AMA on HSC-T6 cells by TGF-β1 induction. The results showed that the binding energy of anthocyanins on TGF-β1 (PDB ID: 3KFD) was in the range of −9.5 to 8.6 kcal/mol, with good low energy parameters and binding positions. AMA could effectively inhibit the expressions of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin (TSB), and improved the expressions of total protein (TP) and albumin (ALB). RT-PCR and Western bloting results showed that AMA could inhibited the secretion of inflammatory cytokines IL-1, IL-6, TNF-α and COX-2, and inhibit the expression of TGF-β1, P-Smad2, α-SMA and Collagen I in TGF-β /Smad signaling pathway. This study revealed the AMA’s inhibition effects and mechanism of malignant biological behavior of HSC-T6 cells, in order to provide theoretical basis for the prevention and treatment of HF by Aronia melanocarpa Elliot.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

Data availability

The data obtained in this study are included within the article.

References

  1. Mikolašević, I. et al.(2016). NONALCOHOLIC FATTY LIVER DISEASE-A MULTISYSTEM DISEASE?. Lijec Vjesn, 138, 353–358.

    PubMed  Google Scholar 

  2. Shalmani, H. M. et al. (2015). Burden of Hepatitis C in Iran Between 1990 and 2010: findings from the Global Burden of Disease Study 2010. Archives of Iranian Medicine, 18(8), 508–514.

    Google Scholar 

  3. Jung, K. H. et al.(2017). Multifunctional Effects of a Small-Molecule STAT3 Inhibitor on NASH and Hepatocellular Carcinoma in Mice. Clinical Cancer Research, 23(18), 5537–5546.

    Article  CAS  Google Scholar 

  4. Doillon, C. J. et al. (1984). Fibroblast-collagen sponge interactions and the spatial deposition of newly synthesized collagen fibers in vitro and in vivo. Scan Electron Microscopy, (Pt 3), 1313–1320.

  5. Manchiero, C., Nunes, A., Magri, M. C., Dantas, B. P., Mazza, C. C., Barone, A. A., & Tengan, F. M. (2017). The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C. BMC Infectious Diseases, 17(1), 780.

    Article  Google Scholar 

  6. Wei, J. et al. (2018). Analysis of the interaction mechanism of Anthocyanins (Aronia melanocarpa Elliot) with β-casein. Food Hydrocolloids, 84(NOV), 276–281.

    Article  CAS  Google Scholar 

  7. Bermúdez-Soto, M.-J. et al. (2007). Stability of polyphenols in chokeberry (Aronia melanocarpa) subjected to in vitro gastric and pancreatic digestion. Food Chemistry, 102(3), 865–874.

    Article  Google Scholar 

  8. Oszmianski, J. et al. (2005). Aronia melanocarpa phenolics and their antioxidant activity. European Food Research and Technology, 221, 809–813.

    Article  CAS  Google Scholar 

  9. Kay, C. D., Mazza, G., Holub, B. J., & Wang, J. (2004). Anthocyanin metabolites in human urine and serum. The British Journal of Nutrition, 91(6), 933–942.

    Article  CAS  Google Scholar 

  10. ZHANG, S. et al. (2018). Analysis and Development Proposals of Aronia mealnocarpa Planting Industry in Heilongjiang Province. Asian Agricultural Research, 10(08), 28–30.

    Google Scholar 

  11. Bräunlich, M. et al.(2013). Extracts, Anthocyanins and Procyanidins from Aronia melanocarpa as Radical Scavengers and Enzyme Inhibitors. Nutrients, 5(3), 663–678.

    Article  Google Scholar 

  12. Wei, J. et al. (2020). Anthocyanins from Aronia melanocarpa Induce Apoptosis in Caco‐2 Cells through Wnt/β‐Catenin Signaling Pathway. Chemistry and Biodiversity, 17(11), e2000654.

    Article  Google Scholar 

  13. Hoebe, K. H., Witkamp, R. F., Fink-Gremmels, J., Van Miert, A. S., & Monshouwer, M. (2001). Direct cell-to-cell between Kupffer cells and hepatocytes augments endotoxin-induced hepatic injury. American Journal of Physiology. Gastrointestinal and Liver Physiology, 280(4), G720–G728.

    Article  CAS  Google Scholar 

  14. Mirantes, C., Passegué, E., & Pietras, E. M. (2014). Pro-inflammatory cytokines: Emerging players regulating HSC function in normal and diseased hematopoiesis. Experimental Cell Research, 329(2), 248–254.

    Article  CAS  Google Scholar 

  15. Afrin, F. et al. (2018). Downregulation of common cytokine receptor γ chain inhibits inflammatory responses in macrophages stimulated with Riemerella anatipestifer. Developmental and Comparative Immunology, 81, 225–234.

    Article  CAS  Google Scholar 

  16. Tada, H., & Isogai, S. J. N. (1998). The Fibronectin Production Is Increased by Thrombospondin via Activation of TGF-β in Cultured Human Mesangial. Cells, 79(1), 38–43.

    CAS  Google Scholar 

  17. Mclaughlin, P. et al. (2001). Role of PLCgamma and Ca(2+) in VEGF- and FGF-induced choroidal endothelial cell proliferation. American Journal of Cell Physiology, 281(5), 1448–56.

    Article  Google Scholar 

  18. Wei, H. S. et al. (2000). The regulatory role of AT 1 receptor on activated HSCs in hepatic fibrogenesis: effects of RAS inhibitors on hepatic fibrosis induced by CCl (4). World Journal of Gastroenterology, 6(6), 824–828.

    Article  CAS  Google Scholar 

  19. Farghali, H. et al. (2016). In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs. Physiological Research, 65(4), S417–S425.

    Article  CAS  Google Scholar 

  20. Olas, B., Wachowicz, B., Nowak, P., Kedzierska, M., Tomczak, A., Stochmal, A., Oleszek, W., Jeziorski, A., & Piekarski, J. (2008). Studies on antioxidant properties of polyphenol-rich extract from berries of Aronia melanocarpa in blood platelets. Journal of Physiology and Pharmacology : An Official Journal of the Polish Physiological Society, 59(4), 823–835.

    CAS  Google Scholar 

  21. Li, Y., Luo, Y., Zhang, X., Lin, X., He, M., & Liao, M. (2013). Combined taurine, epigallocatechin gallate and genistein therapy reduces HSC-T6 cell proliferation and modulates the expression of fibrogenic factors. International Journal of Molecular Sciences, 14(10), 20543–20554.

    Article  Google Scholar 

  22. Rangboo, R. et al. (2016). The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis. International Journal of Hepatology, 2016, 1–6.

    Article  Google Scholar 

  23. Hao, L. S., Zhang, J. Q., Liu, B., Zhang, G. L., Chen, J., Wang, Y. L., Zhang, M. T., & Zhang, P. L. (2017). [Influence of PTEN down-regulation by in vitro RNA interference on the migration of HSC-T6 cell line]. Zhonghua gan zang bing za zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 25(3), 223–225.

    CAS  PubMed  Google Scholar 

  24. Cong, M., Wang, P., Liu, T. H., Xu, Y., Lu, Y., Tang, S. Z., Liu, X. M., Wang, B. E., Jia, J. D. & You, H. (2006). [Comparisonbetween the suppression of tissue inhibitor of metalloproteinase-1 geneexpression by recombinant adeno-associated virus carrying antisense RNA andsmall interfering RNA (siRNA) of TIMP-1 in rat hepatic stellate cells]. Zhonghuagan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 14(10), 742–747.

    CAS  Google Scholar 

  25. Chen, X. X. et al. (2015). EZH2 plays a role in HSC-T6 cell proliferation and activation affecting MAPK/ERK and PI3K/AKT pathway. Chinese Pharmacological Bulletin, 31(8), 1061–1065.

    CAS  Google Scholar 

  26. Vogel, S., Piantedosi, R., Frank, J., Lalazar, A., Rockey, D. C., Friedman, S. L., & Blaner, W. S. (2000). An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro. Journal of Lipid Research, 41(6), 882–893.

    Article  CAS  Google Scholar 

  27. Kao, Y. H. (2017). Lipopolysaccharides induce Smad2 phosphorylation through PI3K/Akt and MAPK cascades in HSC T6 hepatic stellate cells. Life Sciences, 184, 37–46.

    Article  CAS  Google Scholar 

  28. Cheng, J., Wang, M., Ma, H., Li, H., Ren, J. & Wang, R. (2015). [Adiponectininhibits oxidative stress and modulates TGFb1 and COL-1 expression via theAMPK pathway in HSC-T6 cells]. ZhonghuaGan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology, 23(1), 69–72.

    CAS  Google Scholar 

  29. Martin-Sanz, P., Casado, M., & Bosca, L. (2017). Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives. World Journal of Gastroenterology, 23(20), 3572–3580.

    Article  CAS  Google Scholar 

  30. Kim, S. M. et al. (2008). Effect of selective cyclooxygenase-2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts. Hepatology Research, 38(8), 800–809.

    Article  CAS  Google Scholar 

  31. Paik, Y. H., Kim, J. K., Lee, J. I., Kang, S. H., Kim, D. Y., An, S. H., Lee, S. J., Lee, D. K., Han, K. H., Chon, C. Y., Lee, S. I., Lee, K. S., & Brenner, D. A. (2009). Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats. Gut, 58(11), 1517–1527.

    Article  CAS  Google Scholar 

  32. Tipoe, G. L., Leung, T. M., Liong, E. C., Lau, T. Y., Fung, M. L., & Nanji, A. A. (2010). Epigallocatechin 3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced liver injury in mice. Toxicology, 273(1–3), 45–52.

    Article  CAS  Google Scholar 

  33. Sun, W. Y., Gu, Y. J., Li, X. R., Sun, J. C., Du, J. J., Chen, J. Y., Ma, Y., Wang, Q. T., & Wei, W. (2020). β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix. Cell Death & Disease, 11(5), 389.

    Article  Google Scholar 

Download references

Funding

This research was supported by Scientific Research Project of the Education Department of Liaoning Province (No. LJC202011), Liaoning provincial key R & D project (No. 2020JH2/10300114) and “Liaoning Talent Program” Project in Liaoning Province (No. XLYC1902081).

Author information

Authors and Affiliations

Authors

Contributions

R.H. wrote the paper, J.G., H.L., C.Z., and J.F. performed the research; J.W. analyzed the data and designed the research study.

Corresponding author

Correspondence to Jie Wei.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, R., Gao, J., Liu, H. et al. Preventive Effect and Mechanism of Anthocyanins from Aronia Melanocarpa Elliot on Hepatic Fibrosis Through TGF-β/Smad Signaling Pathway. Cell Biochem Biophys 80, 737–745 (2022). https://doi.org/10.1007/s12013-022-01079-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-022-01079-z

Keywords

Navigation