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Int J Mol Med. 2017 Jul;40(1):226-234. doi: 10.3892/ijmm.2017.2997. Epub 2017 May 19.

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

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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.


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.

[Indexed for MEDLINE]

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