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International Journal of Molecular Medicine
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Article

Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways

  • Authors:
    • Jin-Woo Lee
    • Young Il Kim
    • Youngchul Kim
    • Minji Choi
    • Seoyeon Min
    • Yong Hoon Joo
    • Sung-Vin Yim
    • Namhyun Chung
  • View Affiliations / Copyright

    Affiliations: Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea, Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Nephrology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Clinical Pharmacology, College of Medical Science, Kyung Hee University, Seoul 02447, Republic of Korea
  • Pages: 226-234
    |
    Published online on: May 19, 2017
       https://doi.org/10.3892/ijmm.2017.2997
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Abstract

In the present study, we aimed to investigate the molecular mechanisms and prophylactic effects of grape seed proanthocyanidin (GSP) on lipopolysaccharide (LPS)-stimulated human hepatic stellate cells (HSCs). Cell counting and MTT assays were used to assess cell viability in the absence or presence of GSP. Reverse transcription-quantitative PCR (RT-qPCR) was performed for several inflammation-related genes (NOD1, NOD2, TLR2, TLR4, IL-1 β, IL-6, IL-8, iNOS and COX-2). The expression of anti-inflammatory cell signaling molecules, including c-Jun N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), Akt, nuclear factor-κB (NF-κB), inhibitory-κBα (IκBα), iNOS and COX-2, was evaluated by western blot analysis. Finally, IL-8 levels in the culture supernatant of HSCs were measured by ELISA. Pretreatment with GSP before LPS treatment significantly suppressed the mRNA expression of pro-inflammatory cytokines such as IL-1β, IL-6 and IL-8. GSP inhibited mRNA expression of LPS-induced TLR4, NOD2 and COX-2, in addition to inhibiting the expression of iNOS. GSP also inhibited LPS-induced NF-κB activation and IκBα phosphorylation. Concomitantly, GSP dose-dependently suppressed the activation of MAP kinases (JNK, ERK and p38) and Akt in LPS-stimulated HSCs. These data suggest that GSP inhibits inflammatory responses in HSCs by inactivating the NF-κB signaling pathway via MAP kinases. Thus, GSP may be considered as a novel drug for the treatment of hepatic inflammation, infectious diseases and fibrosis.
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1 

Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS and Pruess HG: Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 148:187–197. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Murphy KJ, Chronopoulos AK, Singh I, Francis MA, Moriarty H, Pike MJ, Turner AH, Mann NJ and Sinclair AJ: Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr. 77:1466–1473. 2003.PubMed/NCBI

3 

Steinberg FM, Bearden MM and Keen CL: Cocoa and chocolate flavonoids: Implications for cardiovascular health. J Am Diet Assoc. 103:215–223. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Maffei Facinó R, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E and Morazzoni P: Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: Antioxidant intervention and/or iron and copper sequestering ability. Planta Med. 62:495–502. 1996. View Article : Google Scholar : PubMed/NCBI

5 

De Bruyne T, Pieters L, Witvrouw M, De Clercq E, Vanden Berghe D and Vlietinck AJ: Biological evaluation of proanthocyanidin dimers and related polyphenols. J Nat Prod. 62:954–958. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Ye X, Krohn RL, Liu W, Joshi SS, Kuszynski CA, McGinn TR, Bagchi M, Preuss HG, Stohs SJ and Bagchi D: The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol Cell Biochem. 196:99–108. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Li WG, Zhang XY, Wu YJ and Tian X: Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds. Acta Pharmacol Sin. 22:1117–1120. 2001.PubMed/NCBI

8 

Ray S, Bagchi D, Lim PM, Bagchi M, Gross SM, Kothari SC, Preuss HG and Stohs SJ: Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract. Res Commun Mol Pathol Pharmacol. 109:165–197. 2001.

9 

Seki E and Schwabe RF: Hepatic inflammation and fibrosis: Functional links and key pathways. Hepatology. 61:1066–1079. 2015. View Article : Google Scholar :

10 

Iredale JP: Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis. 21:427–436. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Wang BB, Cheng JY, Gao HH, Zhang Y, Chen ZN and Bian H: Hepatic stellate cells in inflammation-fibrosis-carcinoma axis. Anat Rec (Hoboken). 293:1492–1496. 2010. View Article : Google Scholar

12 

Xu L, Hui AY, Albanis E, Arthur MJ, O'Byrne SM, Blaner WS, Mukherjee P, Friedman SL and Eng FJ: Human hepatic stellate cell lines, LX-1 and LX-2: New tools for analysis of hepatic fibrosis. Gut. 54:142–151. 2005. View Article : Google Scholar

13 

Henderson NC and Iredale JP: Liver fibrosis: Cellular mechanisms of progression and resolution. Clin Sci (Lond). 112:265–280. 2007. View Article : Google Scholar

14 

Yi HS and Jeong WI: Interaction of hepatic stellate cells with diverse types of immune cells: Foe or friend? J Gastroenterol Hepatol. 28(Suppl 1): 99–104. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Fallowfield JA: Therapeutic targets in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 300:G709–G715. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Duval F, Moreno-Cuevas JE, González-Garza MT, Maldonado-Bernal C and Cruz-Vega DE: Liver fibrosis and mechanisms of the protective action of medicinal plants targeting inflammation and the immune response. Int J Inflamm. 2015:9434972015. View Article : Google Scholar

17 

Moon JE, Kim DM and Kim JY: Anti-inflammatory effect of Rhus verniciflua stokes extract in the murine macrophage cell line, Raw264.7. J Korean Soc Appl Biol Chem. 58:481–486. 2015. View Article : Google Scholar

18 

Piccinini AM and Midwood KS: DAMPening inflammation by modulating TLR signaling. Mediators Inflamm. 21:20102010.

19 

Gabetta B, Fuzzati N, Griffini A, Lolla E, Pace R, Ruffilli T and Peterlongo F: Characterization of proanthocyanidins from grape seeds. Fitoterapia. 71:162–175. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Mosmann T: Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI

21 

Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA and Schwabe RF: TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 13:1324–1332. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Hambleton J, Weinstein SL, Lem L and DeFranco AL: Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. Proc Natl Acad Sci USA. 93:2774–2778. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Hellerbrand C, Wang SC, Tsukamoto H, Brenner DA and Rippe RA: Expression of intracellular adhesion molecule 1 by activated hepatic stellate cells. Hepatology. 24:670–676. 1996. View Article : Google Scholar : PubMed/NCBI

24 

Kayano K and Okita K: Does IL-6 regulate liver fibrosis/cirrhosis directly and indirectly? J Gastroenterol. 35:250–251. 2000. View Article : Google Scholar

25 

Czaja MJ, Geerts A, Xu J, Schmiedeberg P and Ju Y: Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease. J Leukoc Biol. 55:120–126. 1994.PubMed/NCBI

26 

Maher JJ, Lozier JS and Scott MK: Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo. Am J Physiol. 275:G847–G853. 1998.PubMed/NCBI

27 

Reitamo S, Remitz A, Tamai K and Uitto J: Interleukin-10 modulates type I collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts. J Clin Invest. 94:2489–2492. 1994. View Article : Google Scholar : PubMed/NCBI

28 

Underhill DM and Ozinsky A: Toll-like receptors: Key mediators of microbe detection. Curr Opin Immunol. 14:103–110. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Inohara N and Nuñez G: NODs: Intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol. 3:371–382. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Lee MS and Kim YJ: Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem. 76:447–480. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK and Lee SS: Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: Down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res. 480–481:243–268. 2001. View Article : Google Scholar

32 

Uto T, Suangkaew N, Morinaga O, Kariyazono H, Oiso S and Shoyama Y: Eriobotryae folium extract suppresses LPS-induced iNOS and COX-2 expression by inhibition of NF-kappaB and MAPK activation in murine macrophages. Am J Chin Med. 38:985–994. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Schabbauer G, Tencati M, Pedersen B, Pawlinski R and Mackman N: PI3K-Akt pathway suppresses coagulation and inflammation in endotoxemic mice. Arterioscler Thromb Vasc Biol. 24:1963–1969. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lee J, Kim YI, Kim Y, Choi M, Min S, Joo YH, Yim S and Chung N: Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways. Int J Mol Med 40: 226-234, 2017.
APA
Lee, J., Kim, Y.I., Kim, Y., Choi, M., Min, S., Joo, Y.H. ... Chung, N. (2017). Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways. International Journal of Molecular Medicine, 40, 226-234. https://doi.org/10.3892/ijmm.2017.2997
MLA
Lee, J., Kim, Y. I., Kim, Y., Choi, M., Min, S., Joo, Y. H., Yim, S., Chung, N."Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways". International Journal of Molecular Medicine 40.1 (2017): 226-234.
Chicago
Lee, J., Kim, Y. I., Kim, Y., Choi, M., Min, S., Joo, Y. H., Yim, S., Chung, N."Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways". International Journal of Molecular Medicine 40, no. 1 (2017): 226-234. https://doi.org/10.3892/ijmm.2017.2997
Copy and paste a formatted citation
x
Spandidos Publications style
Lee J, Kim YI, Kim Y, Choi M, Min S, Joo YH, Yim S and Chung N: Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways. Int J Mol Med 40: 226-234, 2017.
APA
Lee, J., Kim, Y.I., Kim, Y., Choi, M., Min, S., Joo, Y.H. ... Chung, N. (2017). Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways. International Journal of Molecular Medicine, 40, 226-234. https://doi.org/10.3892/ijmm.2017.2997
MLA
Lee, J., Kim, Y. I., Kim, Y., Choi, M., Min, S., Joo, Y. H., Yim, S., Chung, N."Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways". International Journal of Molecular Medicine 40.1 (2017): 226-234.
Chicago
Lee, J., Kim, Y. I., Kim, Y., Choi, M., Min, S., Joo, Y. H., Yim, S., Chung, N."Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways". International Journal of Molecular Medicine 40, no. 1 (2017): 226-234. https://doi.org/10.3892/ijmm.2017.2997
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