Molecules 2014, 19(1), 581-594; doi:10.3390/molecules19010581
Article

Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells

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Received: 2 December 2013; in revised form: 30 December 2013 / Accepted: 30 December 2013 / Published: 6 January 2014
(This article belongs to the Section Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 1018 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 1618. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.
Keywords: action mechanisms; gastroprotective; carnosic acid; diterpenes
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MDPI and ACS Style

Theoduloz, C.; Pertino, M.W.; Schmeda-Hirschmann, G. Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells. Molecules 2014, 19, 581-594.

AMA Style

Theoduloz C, Pertino MW, Schmeda-Hirschmann G. Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells. Molecules. 2014; 19(1):581-594.

Chicago/Turabian Style

Theoduloz, Cristina; Pertino, Mariano W.; Schmeda-Hirschmann, Guillermo. 2014. "Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells." Molecules 19, no. 1: 581-594.

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