title: Organ- and species-specific biological activity of rosmarinic acid.
abstract: 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-1β, as well as the fibrosis markers: pro-collagen 1a1, heat shock protein 47, α-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.
authors.affiliation: Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands; Faculty of Pharmacy, Universitas Indonesia, Indonesia. Electronic address: raditya.iswandana@rug.nl.
authors.forename: R
authors.initials: R
authors.lastname: Iswandana
authors.affiliation: 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.
authors.forename: B T
authors.initials: BT
authors.lastname: Pham
authors.affiliation: Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: w.t.van.haaften@umcg.nl.
authors.forename: W T
authors.initials: WT
authors.lastname: van Haaften
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Luangmonkong
authors.affiliation: Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: d.oosterhuis@rug.nl.
authors.forename: D
authors.initials: D
authors.lastname: Oosterhuis
authors.affiliation: Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: h.a.m.mutsaers@rug.nl.
authors.forename: H A M
authors.initials: HA
authors.lastname: Mutsaers
authors.affiliation: Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, University of Groningen, The Netherlands. Electronic address: p.olinga@rug.nl.
authors.forename: P
authors.initials: P
authors.lastname: Olinga
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D002934:Cinnamates / Q000494:pharmacology* / Q000633:toxicity; D016207:Cytokines / Q000235:genetics; D053630:Depsides / Q000494:pharmacology* / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D017208:Rats, Wistar; D013045:Species Specificity; D000097123:Rosmarinic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002934:Cinnamates; D016207:Cytokines; D053630:Depsides; D000097123:Rosmarinic Acid
keywords: Anti-inflammatory; Antifibrotic; Precision-cut intestinal slices; Precision-cut liver slices; Rosmarinic acid; Toxicity