Skip to main content
Erschienen in: Inflammation Research 1/2014

01.01.2014 | Original Research Paper

Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells

verfasst von: Su Jung Hwang, Yong-Wan Kim, Yohan Park, Hyo-Jong Lee, Kyu-Won Kim

Erschienen in: Inflammation Research | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Objectives and design

Chlorogenic acid, which belongs to the polyphenols, is an anti-oxidant and anti-obesity agent. In this study, we investigated the role of chlorogenic acid in inflammation.

Materials and methods

Anti-inflammatory effects of chlorogenic acid were examined in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and BV2 microglial cells. We observed the level of various inflammation markers such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 1 (CXCL1) under LPS treatment with or without chlorogenic acid. To clarify the specific effect of chlorogenic acid, we evaluated the adhesion activity of macrophages and ninjurin1 (Ninj1) expression level in macrophages. Finally, we confirmed the activation of the nuclear factor-κB (NF-κB) signaling pathway, which is one of the most important transcription factors in the inflammatory process.

Results

Chlorogenic acid significantly inhibited not only NO production but also the expression of COX-2 and iNOS, without any cytotoxicity. Chlorogenic acid also attenuated pro-inflammatory cytokines (including IL-1β and TNF-α) and other inflammation-related markers such as IL-6 in a dose-dependent manner. Additionally, endotoxin-induced adhesion of macrophages and the expression level of ninjurin1 (Ninj1) were decreased by chlorogenic acid. Finally, chlorogenic acid inhibited the nuclear translocation of NF-κB.

Conclusions

Chlorogenic acid may be beneficial for the prevention and treatment of anti-inflammatory diseases.
Literatur
1.
Zurück zum Zitat Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol. 2007;147:227–35.PubMedCentralPubMed Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol. 2007;147:227–35.PubMedCentralPubMed
2.
Zurück zum Zitat Boyce JA. Eicosanoids in asthma, allergic inflammation, and host defense. Curr Mol Med. 2008;8:335–49.PubMedCrossRef Boyce JA. Eicosanoids in asthma, allergic inflammation, and host defense. Curr Mol Med. 2008;8:335–49.PubMedCrossRef
4.
Zurück zum Zitat Barin JG, Rose NR, Cihakova D. Macrophage diversity in cardiac inflammation: a review. Immunobiology. 2011;217:468–75.PubMedCrossRef Barin JG, Rose NR, Cihakova D. Macrophage diversity in cardiac inflammation: a review. Immunobiology. 2011;217:468–75.PubMedCrossRef
5.
Zurück zum Zitat Papageorgiou AP, Heymans S. Interactions between the extracellular matrix and inflammation during viral myocarditis. Immunobiology. 2011;217:503–10.PubMedCrossRef Papageorgiou AP, Heymans S. Interactions between the extracellular matrix and inflammation during viral myocarditis. Immunobiology. 2011;217:503–10.PubMedCrossRef
6.
Zurück zum Zitat Chen YW, Pat B, Gladden JD, Zheng J, Powell P, Wei CC, et al. Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol. 2011;300:H2251–60.PubMedCrossRef Chen YW, Pat B, Gladden JD, Zheng J, Powell P, Wei CC, et al. Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol. 2011;300:H2251–60.PubMedCrossRef
7.
Zurück zum Zitat Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:471–9.PubMedCrossRef Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005;4:471–9.PubMedCrossRef
8.
Zurück zum Zitat Montiel-Duarte C, Ansorena E, Lopez-Zabalza MJ, Cenarruzabeitia E, Iraburu MJ. Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine (“Ecstasy”) on hepatic stellate cells. Biochem Pharmacol. 2004;67:1025–33.PubMedCrossRef Montiel-Duarte C, Ansorena E, Lopez-Zabalza MJ, Cenarruzabeitia E, Iraburu MJ. Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine (“Ecstasy”) on hepatic stellate cells. Biochem Pharmacol. 2004;67:1025–33.PubMedCrossRef
9.
Zurück zum Zitat Francisco V, Costa G, Figueirinha A, Marques C, Pereira P, Miguel Neves B, et al. Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappaB pathway inhibition: contribution of chlorogenic acid. J Ethnopharmacol. 2013;148:126–34.PubMedCrossRef Francisco V, Costa G, Figueirinha A, Marques C, Pereira P, Miguel Neves B, et al. Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappaB pathway inhibition: contribution of chlorogenic acid. J Ethnopharmacol. 2013;148:126–34.PubMedCrossRef
10.
Zurück zum Zitat Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-kappa B pathway. Mediators Inflamm. 2013;2013:562154. doi:10.1155/2013/562154.PubMedCentralPubMed Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-kappa B pathway. Mediators Inflamm. 2013;2013:562154. doi:10.​1155/​2013/​562154.PubMedCentralPubMed
11.
12.
Zurück zum Zitat Li X, Li Z, Zheng Z, Liu Y, Ma X. Unfractionated heparin ameliorates lipopolysaccharide-induced lung inflammation by downregulating nuclear factor-kappaB signaling pathway. Inflammation. 2013; doi: 10.1007/s10753-013-9656-5. Li X, Li Z, Zheng Z, Liu Y, Ma X. Unfractionated heparin ameliorates lipopolysaccharide-induced lung inflammation by downregulating nuclear factor-kappaB signaling pathway. Inflammation. 2013; doi: 10.​1007/​s10753-013-9656-5.
13.
Zurück zum Zitat Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr. 2003;133:1853–9.PubMed Gonthier MP, Verny MA, Besson C, Remesy C, Scalbert A. Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr. 2003;133:1853–9.PubMed
14.
Zurück zum Zitat Hulme AC. The isolation of chlorogenic acid from the apple fruit. Biochem J. 1953;53:337–40.PubMed Hulme AC. The isolation of chlorogenic acid from the apple fruit. Biochem J. 1953;53:337–40.PubMed
15.
Zurück zum Zitat Zang LY, Cosma G, Gardner H, Castranova V, Vallyathan V. Effect of chlorogenic acid on hydroxyl radical. Mol Cell Biochem. 2003;247:205–10.PubMedCrossRef Zang LY, Cosma G, Gardner H, Castranova V, Vallyathan V. Effect of chlorogenic acid on hydroxyl radical. Mol Cell Biochem. 2003;247:205–10.PubMedCrossRef
16.
Zurück zum Zitat Ong KW, Hsu A, Tan BK. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol. 2013;85:1341–51.PubMedCrossRef Ong KW, Hsu A, Tan BK. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem Pharmacol. 2013;85:1341–51.PubMedCrossRef
17.
Zurück zum Zitat Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, et al. Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens. 2006;24:1065–73.PubMedCrossRef Suzuki A, Yamamoto N, Jokura H, Yamamoto M, Fujii A, Tokimitsu I, et al. Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats. J Hypertens. 2006;24:1065–73.PubMedCrossRef
18.
Zurück zum Zitat Jung HA, Park JC, Chung HY, Kim J, Choi JS. Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica. Arch Pharm Res. 1999;22:213–8.PubMedCrossRef Jung HA, Park JC, Chung HY, Kim J, Choi JS. Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica. Arch Pharm Res. 1999;22:213–8.PubMedCrossRef
19.
Zurück zum Zitat Han HE, Kim TK, Son HJ, Park W, Han PL. Activation of autophagy pathway suppresses the expression of iNOS, IL6 and cell death of LPS-stimulated microglia cells. Biomol Ther. 2013;21:21–8.CrossRef Han HE, Kim TK, Son HJ, Park W, Han PL. Activation of autophagy pathway suppresses the expression of iNOS, IL6 and cell death of LPS-stimulated microglia cells. Biomol Ther. 2013;21:21–8.CrossRef
20.
Zurück zum Zitat Kang TJ, Moon JS, Lee SY, Yim DS. Polyacetylene compound from Cirsium japonicum var. ussuriense inhibits the LPS-induced inflammatory reaction via suppression of NF-κB activity in Raw 264.7 cells. Biomol Ther 2011; 19:97–101. Kang TJ, Moon JS, Lee SY, Yim DS. Polyacetylene compound from Cirsium japonicum var. ussuriense inhibits the LPS-induced inflammatory reaction via suppression of NF-κB activity in Raw 264.7 cells. Biomol Ther 2011; 19:97–101.
21.
Zurück zum Zitat Lee HJ, Ahn BJ, Shin MW, Choi JH, Kim KW. Ninjurin1: a potential adhesion molecule and its role in inflammation and tissue remodeling. Mol Cells. 2010;29:223–7.PubMedCrossRef Lee HJ, Ahn BJ, Shin MW, Choi JH, Kim KW. Ninjurin1: a potential adhesion molecule and its role in inflammation and tissue remodeling. Mol Cells. 2010;29:223–7.PubMedCrossRef
22.
Zurück zum Zitat Shi H, Dong L, Jiang J, Zhao J, Zhao G, Dang X, et al. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology. 2013;303:107–14.PubMedCrossRef Shi H, Dong L, Jiang J, Zhao J, Zhao G, Dang X, et al. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology. 2013;303:107–14.PubMedCrossRef
23.
Zurück zum Zitat Lee SA, Jung EB, Lee SH, Kim YJ, Bang H, Seo SJ, et al. 3,4,5-Tricaffeoylquinic acid inhibits the lipopolysaccharide-stimulated production of inflammatory mediators in keratinocytes. Pharmacology. 2012;90:183–92.PubMedCrossRef Lee SA, Jung EB, Lee SH, Kim YJ, Bang H, Seo SJ, et al. 3,4,5-Tricaffeoylquinic acid inhibits the lipopolysaccharide-stimulated production of inflammatory mediators in keratinocytes. Pharmacology. 2012;90:183–92.PubMedCrossRef
24.
Zurück zum Zitat Sachithanandan N, Graham KL, Galic S, Honeyman JE, Fynch SL, Hewitt KA, et al. Macrophage deletion of SOCS1 increases sensitivity to LPS and palmitic acid and results in systemic inflammation and hepatic insulin resistance. Diabetes. 2011;60:2023–31.PubMedCrossRef Sachithanandan N, Graham KL, Galic S, Honeyman JE, Fynch SL, Hewitt KA, et al. Macrophage deletion of SOCS1 increases sensitivity to LPS and palmitic acid and results in systemic inflammation and hepatic insulin resistance. Diabetes. 2011;60:2023–31.PubMedCrossRef
25.
Zurück zum Zitat Lee H, Bae S, Choi BW, Yoon Y. WNT/beta-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line. Immunopharmacol Immunotoxicol. 2011;34:56–65.PubMedCrossRef Lee H, Bae S, Choi BW, Yoon Y. WNT/beta-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line. Immunopharmacol Immunotoxicol. 2011;34:56–65.PubMedCrossRef
26.
Zurück zum Zitat Karpurapu M, Wang X, Deng J, Park H, Xiao L, Sadikot RT, et al. Functional PU.1 in macrophages has a pivotal role in NF-{kappa}B activation and neutrophilic lung inflammation during endotoxemia. Blood. 2011;118:5255–66.PubMedCrossRef Karpurapu M, Wang X, Deng J, Park H, Xiao L, Sadikot RT, et al. Functional PU.1 in macrophages has a pivotal role in NF-{kappa}B activation and neutrophilic lung inflammation during endotoxemia. Blood. 2011;118:5255–66.PubMedCrossRef
27.
Zurück zum Zitat Lee HJ, Kim KW. Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells. Inflamm Res. 2012;61:817–25.PubMedCrossRef Lee HJ, Kim KW. Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells. Inflamm Res. 2012;61:817–25.PubMedCrossRef
28.
Zurück zum Zitat Ahn BJ, Lee HJ, Shin MW, Choi JH, Jeong JW, Kim KW. Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the brains of EAE rats. Biochem Biophys Res Commun. 2009;387:321–5.PubMedCrossRef Ahn BJ, Lee HJ, Shin MW, Choi JH, Jeong JW, Kim KW. Ninjurin1 is expressed in myeloid cells and mediates endothelium adhesion in the brains of EAE rats. Biochem Biophys Res Commun. 2009;387:321–5.PubMedCrossRef
29.
Zurück zum Zitat Lee HJ, Ahn BJ, Shin MW, Jeong JW, Kim JH, Kim KW. Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development. Cell Death Differ. 2009;16:1395–407.PubMedCrossRef Lee HJ, Ahn BJ, Shin MW, Jeong JW, Kim JH, Kim KW. Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development. Cell Death Differ. 2009;16:1395–407.PubMedCrossRef
30.
Zurück zum Zitat Tucsek Z, Radnai B, Racz B, Debreceni B, Priber JK, Dolowschiak T, et al. Suppressing LPS-induced early signal transduction in macrophages by a polyphenol degradation product: a critical role of MKP-1. J Leukoc Biol. 2011;89:105–11.PubMedCrossRef Tucsek Z, Radnai B, Racz B, Debreceni B, Priber JK, Dolowschiak T, et al. Suppressing LPS-induced early signal transduction in macrophages by a polyphenol degradation product: a critical role of MKP-1. J Leukoc Biol. 2011;89:105–11.PubMedCrossRef
31.
Zurück zum Zitat Baowen Q, Yulin Z, Xin W, Wenjing X, Hao Z, Zhizhi C, et al. A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis. Eur J Pharmacol. 2010;642:134–9.PubMedCrossRef Baowen Q, Yulin Z, Xin W, Wenjing X, Hao Z, Zhizhi C, et al. A further investigation concerning correlation between anti-fibrotic effect of liposomal quercetin and inflammatory cytokines in pulmonary fibrosis. Eur J Pharmacol. 2010;642:134–9.PubMedCrossRef
32.
Zurück zum Zitat van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care. 2009;32:1023–5.PubMedCrossRef van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care. 2009;32:1023–5.PubMedCrossRef
33.
Zurück zum Zitat Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine. 2009;16:1119–26.PubMedCrossRef Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine. 2009;16:1119–26.PubMedCrossRef
34.
Zurück zum Zitat Ong KW, Hsu A, Tan BK. Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS One. 2012;7:e32718.PubMedCentralPubMedCrossRef Ong KW, Hsu A, Tan BK. Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes. PLoS One. 2012;7:e32718.PubMedCentralPubMedCrossRef
Metadaten
Titel
Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells
verfasst von
Su Jung Hwang
Yong-Wan Kim
Yohan Park
Hyo-Jong Lee
Kyu-Won Kim
Publikationsdatum
01.01.2014
Verlag
Springer Basel
Erschienen in
Inflammation Research / Ausgabe 1/2014
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-013-0674-4

Weitere Artikel der Ausgabe 1/2014

Inflammation Research 1/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.