Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
January-2021 Volume 21 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2021 Volume 21 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis

  • Authors:
    • Min Song
    • Heng Zhang
    • Zhitao Chen
    • Jing Yang
    • Jie Li
    • Sue Shao
    • Jing Liu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
  • Article Number: 28
    |
    Published online on: November 10, 2020
       https://doi.org/10.3892/etm.2020.9460
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Liver fibrosis is a tissue repair process that occurs following various types of chronic liver injury and can develop into liver cirrhosis, portal hypertension or liver cancer without effective treatment. Shikonin has anti‑inflammatory, antiviral and antitumor properties. Furthermore, shikonin has an additional effect of antagonizing tissue and organ fibrosis. The aim of the present study was to evaluate the mechanisms of action underlying shikonin against liver fibrosis. Cell viability was assessed using the Cell Counting Kit‑8 and EdU incorporation assays. Protein and mRNA expression levels were measured via western blotting and immunofluorescence assays, respectively. Apoptosis was examined via flow cytometry and autophagy via transmission electron microscopy. Compared with the control group, shikonin did not significantly alter LX‑2 cell viability at 0.2 µmol/ml, which was used as the intervention concentration. However, shikonin significantly inhibited fibrosis, as indicated by a decrease in the expression of α‑smooth muscle actin and collagen‑I in the TGF‑β + shikonin group compared with the TGF‑β group. The results indicated that shikonin potentially inhibited fibrosis via promoting cell apoptosis and inhibiting autophagy. Additionally, the results of the present study indicated that shikonin downregulated the expression levels of platelet‑activating factor (PAF) in TGF‑β‑treated cells, which subsequently activated the MAPK signaling pathway, leading to enhanced cell apoptosis and reduced autophagy. Collectively, the present study indicated that shikonin promoted cell apoptosis and suppressed autophagy via the PAF‑MAPK axis in LX‑2 cells, thus blocking the development of fibrosis. The results of the present study may provide a potential therapeutic strategy for liver fibrosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Friedman SL: Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 7:425–436. 2010.PubMed/NCBI View Article : Google Scholar

2 

Zhang X, Cui JH, Meng QQ, Li SS, Zhou W and Xiao S: Advance in anti-tumor mechanisms of shikonin, alkannin and their derivatives. Mini Rev Med Chem. 18:164–172. 2018.PubMed/NCBI View Article : Google Scholar

3 

Hernandez-Gea V and Friedman SL: Pathogenesis of liver fibrosis. Annu Rev Pathol. 6:425–456. 2011.PubMed/NCBI View Article : Google Scholar

4 

Ma X, Yu M, Hao C and Yang W: Shikonin induces tumor apoptosis in glioma cells via endoplasmic reticulum stress, and Bax/Bak mediated mitochondrial outer membrane permeability. J Ethnopharmacol. 263(113059)2020.PubMed/NCBI View Article : Google Scholar

5 

Guo C, He J, Song X, Tan L, Wang M, Jiang P, Li Y, Cao Z and Peng C: Pharmacological properties and derivatives of shikonin-A review in recent years. Pharmacol Res. 149(104463)2019.PubMed/NCBI View Article : Google Scholar

6 

Nie Y, Yang Y, Zhang J, Cai G, Chang Y, Chai G and Guo C: Shikonin suppresses pulmonary fibroblasts proliferation and activation by regulating Akt and p38 MAPK signaling pathways. Biomed Pharmacother. 95:1119–1128. 2017.PubMed/NCBI View Article : Google Scholar

7 

Ding H, Jiang L, Xu J, Bai F, Zhou Y, Yuan Q, Luo J, Zen K and Yang J: Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis. Am J Physiol Renal Physiol. 313:F561–F575. 2017.PubMed/NCBI View Article : Google Scholar

8 

Fan C, Dong Y, Xie Y, Su Y, Zhang X, Leavesley D and Upton Z: Shikonin reduces TGF-β1-induced collagen production and contraction in hypertrophic scar-derived human skin fibroblasts. Int J Mol Med. 36:985–991. 2015.PubMed/NCBI View Article : Google Scholar

9 

Yang J, Wang Z and Chen DL: Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through suppressing fibrosis, inflammation, apoptosis and ER stress. Biomed Pharmacother. 93:1343–1357. 2017.PubMed/NCBI View Article : Google Scholar

10 

Wang H and Zhang G: Activation of CaMKKβ-AMPK-mTOR pathway is required for autophagy induction by β,β-dimethylacrylshikonin against lung adenocarcinoma cells. Biochem Biophys Res Commun. 517:477–483. 2019.PubMed/NCBI View Article : Google Scholar

11 

Tian R, Li Y and Gao M: Shikonin causes cell cycle arrest and induces apoptosis by regulating the EGFR/NF-κB signaling pathway in human epidermoid carcinoma A431 cells. Biosci Rep. 35(e00189)2015.PubMed/NCBI View Article : Google Scholar

12 

Wei Y, Li M, Cui S, Wang D, Zhang CY, Zen K and Li L: Shikonin inhibits the proliferation of human breast cancer cells by reducing tumor-derived exosomes. Molecules. 21(777)2016.PubMed/NCBI View Article : Google Scholar

13 

Wang Y, Zhou Y, Jia G, Han B, Liu J, Teng Y, Lv J, Song Z, Li Y, Ji L, et al: Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway. Biochem Pharmacol. 88:322–333. 2014.PubMed/NCBI View Article : Google Scholar

14 

Wang L, Gai P, Xu R, Zheng Y, Lv S, Li Y and Liu S: Shikonin protects chondrocytes from interleukin-1beta-induced apoptosis by regulating PI3K/Akt signaling pathway. Int J Clin Exp Pathol. 8:298–308. 2015.PubMed/NCBI

15 

Wada N, Kawano Y, Fujiwara S, Kikukawa Y, Okuno Y, Tasaki M, Ueda M, Ando Y, Yoshinaga K, Ri M, et al: Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells. Int J Oncol. 46:963–972. 2015.PubMed/NCBI View Article : Google Scholar

16 

Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, Wang F, He L, Zhang Y, Chengfen W, et al: Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy. Mediators Inflamm. 2014(954502)2014.PubMed/NCBI View Article : Google Scholar

17 

Zhu XF, Un XF, Liu GH and Chen FF: Effects of shikonin on the proliferation, migration and differentiation of HaCaT cells mediated by IL-22. J Clin Dermatol. 43:215–218. 2014.

18 

Qisen Li, Zeng J, Su M, He Y and Zhu B: Acetylshikonin from Zicao attenuates cognitive impairment and hippocampus senescence in D-galactose-induced aging mouse model via upregulating the expression of SIRT1. Brain Res Bulletin. 137:311–318. 2018.PubMed/NCBI View Article : Google Scholar

19 

Wang H and Zhang G: Endoplasmic reticulum stress-mediated autophagy protects against β,β-dimethylacrylshikonin-induced apoptosis in lung adenocarcinoma cells. Cancer Sci. 109:1889–1901. 2018.PubMed/NCBI View Article : Google Scholar

20 

Jing H, Sun W, Fan J, Zhang Y, Yang J, Jia J, Li J, Guo J, Luo S and Zheng Y: Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways. Mol Med Rep. 13:3009–3016. 2016.PubMed/NCBI View Article : Google Scholar

21 

He C and Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annual Rev Genet. 43:67–93. 2009.PubMed/NCBI View Article : Google Scholar

22 

Mallat A, Lodder J, Teixeira-Clerc F, Moreau R, Codogno P and Lotersztajn S: Autophagy: A multifaceted partner in liver fibrosis. Biomed Res Int 2014: 869390, 2014. urihttps://doi.org/10.1155/2014/869390simplehttps://doi.org/10.1155/2014/869390.

23 

Zhang XW, Zhou JC, Peng D, Hua F, Li K, Yu JJ, Lv XX, Cui B, Liu SS, Yu JM, et al: Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation. Autophagy. 16:782–796. 2020.PubMed/NCBI View Article : Google Scholar

24 

Liang H, Pan Z, Zhao X, Liu L, Sun J, Su X, Xu C, Zhou Y, Zhao D, Xu B, et al: LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous RNA of let-7d. Theranostics. 8:1180–1194. 2018.PubMed/NCBI View Article : Google Scholar

25 

Lv XX, Wang XX, Li K, Wang ZY, Li Z, Lv Q, Fu XM and Hu ZW: Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents. PLoS One. 8(e68631)2013.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Song M, Zhang H, Chen Z, Yang J, Li J, Shao S and Liu J: Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis. Exp Ther Med 21: 28, 2021.
APA
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., & Liu, J. (2021). Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis. Experimental and Therapeutic Medicine, 21, 28. https://doi.org/10.3892/etm.2020.9460
MLA
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., Liu, J."Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis". Experimental and Therapeutic Medicine 21.1 (2021): 28.
Chicago
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., Liu, J."Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis". Experimental and Therapeutic Medicine 21, no. 1 (2021): 28. https://doi.org/10.3892/etm.2020.9460
Copy and paste a formatted citation
x
Spandidos Publications style
Song M, Zhang H, Chen Z, Yang J, Li J, Shao S and Liu J: Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis. Exp Ther Med 21: 28, 2021.
APA
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., & Liu, J. (2021). Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis. Experimental and Therapeutic Medicine, 21, 28. https://doi.org/10.3892/etm.2020.9460
MLA
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., Liu, J."Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis". Experimental and Therapeutic Medicine 21.1 (2021): 28.
Chicago
Song, M., Zhang, H., Chen, Z., Yang, J., Li, J., Shao, S., Liu, J."Shikonin reduces hepatic fibrosis by inducing apoptosis and inhibiting autophagy via the platelet‑activating factor‑mitogen‑activated protein kinase axis". Experimental and Therapeutic Medicine 21, no. 1 (2021): 28. https://doi.org/10.3892/etm.2020.9460
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team