{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:36:23Z","timestamp":1790836583451,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Inflamm"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The effects of proanthocyanidins (PACs), isolated from blackcurrant (<jats:italic>Ribes nigrum<\/jats:italic> L.) leaves, on neutrophil accumulation during inflammatory processes were investigated <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>\n              <jats:italic>In vivo<\/jats:italic> studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections.<\/jats:p>\n            <jats:p>\n              <jats:italic>In vitro<\/jats:italic> studies were conducted on endothelial LT2 cells, stimulated with TNF-\u03b1, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment.<\/jats:p>\n            <jats:p>Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Pretreatment of the animals with PACs (10, 30 and 60 mg\/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules.<\/jats:p>\n            <jats:p>\n              <jats:italic>In vitro<\/jats:italic> experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF<jats:sub>165<\/jats:sub> mRNA expression. Moreover, VEGF<jats:sub>121<\/jats:sub> mRNA expression was dose-dependently enhanced.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-\u03b1-induced VEGF transcription.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1476-9255-2-9","type":"journal-article","created":{"date-parts":[[2005,8,10]],"date-time":"2005-08-10T18:13:55Z","timestamp":1123697635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1"],"prefix":"10.1186","volume":"2","author":[{"given":"N","family":"Garbacki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kinet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Nusgens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Desmecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Damas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,8,9]]},"reference":[{"key":"13_CR1","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1182\/blood.V84.7.2068.2068","volume":"84","author":"TM Carlos","year":"1994","unstructured":"Carlos TM, Harlan JM: Leukocyte-endothelial adhesion molecules. Blood. 1994, 84: 2068-2101.","journal-title":"Blood"},{"key":"13_CR2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/sj.bjp.0702328","volume":"126","author":"J Pan\u00e9s","year":"1999","unstructured":"Pan\u00e9s J, Perry M, Granger DN: Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention. Br J Pharmacol. 1999, 126: 537-550. 10.1038\/sj.bjp.0702328.","journal-title":"Br J Pharmacol"},{"key":"13_CR3","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/S0016-5085(98)70328-2","volume":"114","author":"J Pan\u00e9s","year":"1998","unstructured":"Pan\u00e9s J, Granger DN: Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastro-intestinal disease. Gastroenterology. 1998, 114: 1066-1090.","journal-title":"Gastroenterology"},{"key":"13_CR4","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/0092-8674(90)90661-W","volume":"60","author":"MJ Elices","year":"1990","unstructured":"Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler M, Lobb RR: VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4\/fibronectin binding site. Cell. 1990, 60: 577-584. 10.1016\/0092-8674(90)90661-W.","journal-title":"Cell"},{"key":"13_CR5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1096\/fasebj.13.1.9","volume":"13","author":"G Neufeld","year":"1999","unstructured":"Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999, 13: 9-22.","journal-title":"FASEB J"},{"key":"13_CR6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0065-2776(08)60509-X","volume":"55","author":"M Baggiolini","year":"1994","unstructured":"Baggiolini M, Dewald B, Moser B: Interleukin-8 and related chemotactic cytokines-CXC CC chemokines. Adv Immunol. 1994, 55: 97-119.","journal-title":"Adv Immunol"},{"key":"13_CR7","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1152\/physrev.00023.2002","volume":"83","author":"AR Burns","year":"2003","unstructured":"Burns AR, Smith CW, Walker DC: Unique structural features that influence neutrophil emigration into the lung. Physiol Rev. 2003, 83: 309-336.","journal-title":"Physiol Rev"},{"key":"13_CR8","first-page":"H1054","volume":"274","author":"JD Hood","year":"1998","unstructured":"Hood JD, Meininger CJ, Ziche M, Granger HJ: VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol. 1998, 274: H1054-H1058.","journal-title":"Am J Physiol"},{"key":"13_CR9","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1182\/blood.V90.10.4153","volume":"90","author":"M Gaudry","year":"1997","unstructured":"Gaudry M, Bregerie O, Andrieu V, El Benna J, Pocidalo MA, Hakim J: Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood. 1997, 90: 4153-4161.","journal-title":"Blood"},{"key":"13_CR10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jlb.62.3.397","volume":"62","author":"NS Taichman","year":"1997","unstructured":"Taichman NS, Young S, Cruchley AT, Taylor P, Paleolog E: Human neutrophils secrete vascular endothelial growth factor. J Leukoc Biol. 1997, 62: 397-400.","journal-title":"J Leukoc Biol"},{"key":"13_CR11","doi-asserted-by":"crossref","first-page":"C1568","DOI":"10.1152\/ajpcell.2001.281.5.C1568","volume":"281","author":"SM Seo","year":"2001","unstructured":"Seo SM, McIntire LV, Smith CW: Effects of IL-8, Gro-alpha, and LTB4 on the adhesive kinetics of LFA-1 and Mac-1 on human neutrophils. Am J Physiol Cell Physiol. 2001, 281: C1568-1578.","journal-title":"Am J Physiol Cell Physiol"},{"key":"13_CR12","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0031-9422(92)80196-L","volume":"31","author":"M Tits","year":"1992","unstructured":"Tits M, Angenot L, Poukens P, Warin R, Dierckxsens Y: Prodelphinidins from Ribes nigrum. Phytochemistry. 1992, 31: 971-973.","journal-title":"Phytochemistry"},{"key":"13_CR13","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/0731-7085(91)80128-V","volume":"10","author":"M Tits","year":"1992","unstructured":"Tits M, Poukens P, Angenot L, Diercksens Y: Thin-layer chromatographic analysis of proanthocyanidins from Ribes nigrum leaves. J Pharm Biomed Anal. 1992, 10: 1097-1100. 10.1016\/0731-7085(91)80128-V.","journal-title":"J Pharm Biomed Anal"},{"issue":"suppl 2","key":"13_CR14","doi-asserted-by":"publisher","first-page":"A134","DOI":"10.1055\/s-2006-960433","volume":"57","author":"M Tits","year":"1991","unstructured":"Tits M, Angenot L, Damas J, Dierckxsens Y, Poukens P: Anti-inflammatory prodelphinidins from black currant (Ribes nigrum) leaves. Planta Med. 1991, 57 (suppl 2): A134-","journal-title":"Planta Med"},{"key":"13_CR15","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s00210-002-0553-y","volume":"365","author":"N Garbacki","year":"2002","unstructured":"Garbacki N, Angenot L, Bassleer C, Damas J, Tits M: Effects of prodelphinidins isolated from Ribes nigrum on chondrocytes metabolism and COX activity. Naunyn-Schmiedeberg's Arch Pharmacol. 2002, 365: 434-441. 10.1007\/s00210-002-0553-y.","journal-title":"Naunyn-Schmiedeberg's Arch Pharmacol"},{"key":"13_CR16","first-page":"R5","volume":"446","author":"N Garbacki","year":"2003","unstructured":"Garbacki N, Tits M, Damas J: Anti-inflammatory effect of natural proanthocyanidins : pharmacological evaluation on in vivo models. Pfl\u00fcgers Archiv Eur J Physiol. 2003, 446: R5-","journal-title":"Pfl\u00fcgers Archiv Eur J Physiol"},{"key":"13_CR17","first-page":"270","volume":"18","author":"N Garbacki","year":"2004","unstructured":"Garbacki N, Damas J: Some effects of proanthocyanidins isolated from Ribes nigrum on the cardiovascular system of the rat. Fund Clin Pharmacol. 2004, 18: 270-","journal-title":"Fund Clin Pharmacol"},{"key":"13_CR18","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1471-2210-4-25","volume":"4","author":"N Garbacki","year":"2004","unstructured":"Garbacki N, Tits M, Angenot L, Damas J: Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats. BMC Pharmacol. 2004, 4: 25-10.1186\/1471-2210-4-25.","journal-title":"BMC Pharmacol"},{"key":"13_CR19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth. 1983, 65: 55-63. 10.1016\/0022-1759(83)90303-4.","journal-title":"J Immunol Meth"},{"key":"13_CR20","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/sj.onc.1205108","volume":"21","author":"CF Deroanne","year":"2002","unstructured":"Deroanne CF, Bonjean K, Servotte S, Devy L, Colige A, Clausse N, Blacher S, Verdin E, Foidart JM, Nusgens BV, Castronovo V: Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene. 2002, 21: 427-436. 10.1038\/sj.onc.1205108.","journal-title":"Oncogene"},{"key":"13_CR21","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1080\/1071576021000005249","volume":"36","author":"R Kalfin","year":"2002","unstructured":"Kalfin R, Righi A, Del Rosso A, Bagchi D, Generini S, Matucci Cerinic M, Das DK: Activin, a grape seed-derived proanthocyanidin extract, reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1, and E-selectin) in systemic sclerosis. Free Rad Res. 2002, 36: 819-825. 10.1080\/1071576021000005249.","journal-title":"Free Rad Res"},{"key":"13_CR22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0891-5849(99)00229-4","volume":"28","author":"T Bito","year":"2000","unstructured":"Bito T, Roy S, Sen CK, Packer L: Pine bark extract pycnogenol downregulates IFN-\u03b3-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Rad Biol Med. 2000, 28: 219-227. 10.1016\/S0891-5849(99)00229-4.","journal-title":"Free Rad Biol Med"},{"key":"13_CR23","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S0027-5107(02)00324-X","volume":"523\u2013524","author":"D Bagchi","year":"2003","unstructured":"Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG, Vinson JA: Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mut Res. 2003, 523\u2013524: 87-97.","journal-title":"Mut Res"},{"key":"13_CR24","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1210\/mend-5-12-1806","volume":"5","author":"KA Houck","year":"1991","unstructured":"Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW: The vascular endothelial growth factor family-identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991, 5: 1806-1814.","journal-title":"Mol Endocrinol"},{"key":"13_CR25","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1074\/jbc.271.2.736","volume":"271","author":"T Cohen","year":"1996","unstructured":"Cohen T, Nahari D, Cerem-Weiss L, Neufeld G, Levi B: Interleukin-6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996, 271: 736-741. 10.1074\/jbc.271.2.736.","journal-title":"J Biol Chem"},{"key":"13_CR26","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1074\/jbc.270.1.308","volume":"270","author":"J Li","year":"1995","unstructured":"Li J, Perrella MA, Tsai JC, Yet SF, Hsieh CM, Yoshizumi M, Patterson C, Endege WO, Zhou F, Lee ME: Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells. J Biol Chem. 1995, 270: 308-312. 10.1074\/jbc.270.1.308.","journal-title":"J Biol Chem"},{"key":"13_CR27","doi-asserted-by":"publisher","first-page":"28220","DOI":"10.1074\/jbc.271.45.28220","volume":"271","author":"M Ryuto","year":"1996","unstructured":"Ryuto M, Ono M, Izumi H, Yoshida S, Weich HA, Kohno K, Kuwano M: Induction of vascular endothelial growth factor by tumor necrosis facto alpha in human glioma cells \u2013 possible role of SP-1. J Biol Chem. 1996, 271: 28220-28228. 10.1074\/jbc.271.45.28220.","journal-title":"J Biol Chem"},{"key":"13_CR28","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/S0891-5849(01)00544-5","volume":"31","author":"S Khanna","year":"2001","unstructured":"Khanna S, Roy S, Bagchi D, Bagchi M, Sen CK: Upregulation of oxidant-induced VEGF expression in cultured keratinocytes by a grape seed proanthocyanidin extract. Free Rad Biol Med. 2001, 31: 38-42. 10.1016\/S0891-5849(01)00544-5.","journal-title":"Free Rad Biol Med"},{"key":"13_CR29","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/S0891-5849(02)00999-1","volume":"33","author":"S Khanna","year":"2002","unstructured":"Khanna S, Venojarvi M, Roy S, Sharma N, Trikha P, Bagchi D, Bagchi M, Sen CK: Dermal wound healing properties of redox-active grape seed proanthocyanidins. Free Rad Biol Med. 2002, 33: 1089-1096. 10.1016\/S0891-5849(02)00999-1.","journal-title":"Free Rad Biol Med"},{"key":"13_CR30","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1055\/s-2006-957956","volume":"62","author":"R Maffei Facino","year":"1996","unstructured":"Maffei Facino R, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E, Morazzoni P: Procyanidins from Vitis vinifera seeds protect rabbit heart from ischemia\/reperfusion injury: antioxidant intervention and\/or iron and copper sequestering ability. Planta Med. 1996, 62: 495-502.","journal-title":"Planta Med"},{"key":"13_CR31","first-page":"4381","volume":"17","author":"J Aucamp","year":"1997","unstructured":"Aucamp J, Gaspar A, Hara Y, Apostolides Z: Inhibition of xanthine oxidase by catechins from tea (Camellia sinensis). Anticancer Res. 1997, 17: 4381-4385.","journal-title":"Anticancer Res"},{"key":"13_CR32","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/S0306-3623(97)00332-7","volume":"30","author":"D Bagchi","year":"1998","unstructured":"Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation and peritoneal macrophage activation in mice. Gen Pharmacol. 1998, 30: 771-776.","journal-title":"Gen Pharmacol"},{"key":"13_CR33","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1093\/carcin\/20.9.1737","volume":"20","author":"J Zhao","year":"1999","unstructured":"Zhao J, Wang J, Chen Y, Agarwal R: Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent. Carcinogenesis. 1999, 20: 1737-1745. 10.1093\/carcin\/20.9.1737.","journal-title":"Carcinogenesis"},{"key":"13_CR34","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/j.1749-6632.2002.tb02922.x","volume":"957","author":"D Bagchi","year":"2002","unstructured":"Bagchi D, Bagchi M, Stohs SD, Ray SD, Sen CK, Preuss HG: Cellular protection with proanthocyanidins derived from grape seeds. Ann NY Acad Sci. 2002, 957: 260-270.","journal-title":"Ann NY Acad Sci"}],"container-title":["Journal of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1476-9255-2-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T23:11:23Z","timestamp":1630451483000},"score":1,"resource":{"primary":{"URL":"https:\/\/journal-inflammation.biomedcentral.com\/articles\/10.1186\/1476-9255-2-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,9]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["13"],"URL":"https:\/\/doi.org\/10.1186\/1476-9255-2-9","relation":{},"ISSN":["1476-9255"],"issn-type":[{"value":"1476-9255","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,9]]},"assertion":[{"value":"25 January 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"9"}}