TY - JOUR
T1 - Organ- and species-specific biological activity of rosmarinic acid
AU - Iswandana, R.
AU - Pham, B. T.
AU - van Haaften, W. T.
AU - Luangmonkong, T.
AU - Oosterhuis, D.
AU - Mutsaers, H. A.M.
AU - Olinga, P.
N1 - Funding Information:
We gratefully acknowledge the funding from De Nederlandse organisatie voor gezondheidsonderzoek en zorginnovatie (ZonMW) -The Netherlands number: 114021010 supporting this work. The authors thank Dr. Koert P. de Jong (Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen) for the arrangements for obtaining human intestinal tissue.
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
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-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.
KW - Anti-inflammatory
KW - Antifibrotic
KW - Precision-cut intestinal slices
KW - Precision-cut liver slices
KW - Rosmarinic acid
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=84958238555&partnerID=8YFLogxK
U2 - 10.1016/j.tiv.2016.01.009
DO - 10.1016/j.tiv.2016.01.009
M3 - Article
C2 - 26804033
AN - SCOPUS:84958238555
SN - 0887-2333
VL - 32
SP - 261
EP - 268
JO - Toxicology in Vitro
JF - Toxicology in Vitro
ER -