PMID- 26804033 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20231213 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 32 DP - 2016 Apr TI - Organ- and species-specific biological activity of rosmarinic acid. PG - 261-8 LID - S0887-2333(16)30009-1 [pii] LID - 10.1016/j.tiv.2016.01.009 [doi] AB - Rosmarinic acid (RA), a compound found in several plant species, has beneficial properties, including anti-inflammatory and antibacterial effects. We investigated the toxicity, anti-inflammatory, and antifibrotic effects of RA using precision-cut liver slices (PCLS) and precision-cut intestinal slices (PCIS) prepared from human, mouse, and rat tissue. PCLS and PCIS were cultured up to 48 h in the absence or presence of RA. Gene expression of the inflammatory markers: IL-6, IL-8/CXCL1/KC, and IL-1beta, as well as the fibrosis markers: pro-collagen 1a1, heat shock protein 47, alpha-smooth muscle actin, fibronectin (Fn2) and plasminogen activator inhibitor-1 (PAI-1) were evaluated by qPCR. RA was only toxic in murine PCIS. RA failed to mitigate the inflammatory response in most models, while it clearly reduced IL-6 and CXCL1/KC gene expression in murine PCIS at non-toxic concentrations. With regard to fibrosis, RA decreased the gene levels of Fn2 and PAI-1 in murine PCLS, and Fn2 in murine PCIS. Yet, no effect was observed on the gene expression of fibrosis markers in human and rat PCIS. In conclusion, we observed clear organ- and species-specific effects of RA. RA had little influence on inflammation. However, our study further establishes RA as a potential candidate for the treatment of liver fibrosis. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Iswandana, R AU - Iswandana R AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands; Faculty of Pharmacy, Universitas Indonesia, Indonesia. Electronic address: raditya.iswandana@rug.nl. FAU - Pham, B T AU - Pham BT AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands; Department of Pharmaceutics, Hanoi University of Pharmacy, Vietnam. Electronic address: b.t.pham@rug.nl. FAU - van Haaften, W T AU - van Haaften WT AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: w.t.van.haaften@umcg.nl. FAU - Luangmonkong, T AU - Luangmonkong T AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands; Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Thailand. Electronic address: t.luangmonkong@rug.nl. FAU - Oosterhuis, D AU - Oosterhuis D AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: d.oosterhuis@rug.nl. FAU - Mutsaers, H A M AU - Mutsaers HA AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: h.a.m.mutsaers@rug.nl. FAU - Olinga, P AU - Olinga P AD - Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: p.olinga@rug.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160119 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cinnamates) RN - 0 (Cytokines) RN - 0 (Depsides) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology/toxicity MH - Cinnamates/*pharmacology/toxicity MH - Cytokines/genetics MH - Depsides/*pharmacology/toxicity MH - Gene Expression/drug effects MH - Humans MH - In Vitro Techniques MH - Jejunum/*drug effects/metabolism MH - Liver/*drug effects/metabolism/pathology MH - Liver Cirrhosis/genetics MH - Male MH - Mice, Inbred C57BL MH - Rats, Wistar MH - Species Specificity MH - Rosmarinic Acid OTO - NOTNLM OT - Anti-inflammatory OT - Antifibrotic OT - Precision-cut intestinal slices OT - Precision-cut liver slices OT - Rosmarinic acid OT - Toxicity EDAT- 2016/01/26 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/01/26 06:00 PHST- 2015/11/06 00:00 [received] PHST- 2016/01/11 00:00 [revised] PHST- 2016/01/18 00:00 [accepted] PHST- 2016/01/26 06:00 [entrez] PHST- 2016/01/26 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - S0887-2333(16)30009-1 [pii] AID - 10.1016/j.tiv.2016.01.009 [doi] PST - ppublish SO - Toxicol In Vitro. 2016 Apr;32:261-8. doi: 10.1016/j.tiv.2016.01.009. Epub 2016 Jan 19.