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

Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

doi:10.3390/molecules19010581

Cited by 6 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the potential gastroprotective effect of GE in in vitro studies especially on the gastric human cell line has not yet been fully elucidated. Previous studies have shown that a model of gastric cells impaired by NaT was used to explore the gastroprotective effect of different ingredients against bile-induced injury on the gastric mucosa [10,23]. Hence, in our study the model of AGS damaged by NaT was used to determine the gastroprotective effect of GE in culture model of PUD.…”

Section: Discussionmentioning

confidence: 98%

“…Previous research done by De Olinda et al reported that Magonia glabrata was demonstrated to protect against gastric lesions caused by indomethacin and ethanol by increasing production of PG [31]. Likewise, results of our study are in agreement with the study of Theoduloz at al., which showed how derivates of the medicinal plant Jatropha isabelii affect increases of PGE2 synthesis after damage with bile salt [10]. It is known that garlic contains fatty acids responsible for increasing level of PG which modulates inflammation.…”

Section: Discussionmentioning

confidence: 98%

“…Because bile reflux can lead to gastric lesions [10] we propose to generate a model of PUD by treating human adenocarcinoma gastric cell line (AGS) with sodium taurocholate (NaT), a bile salt.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease

et al. 2022

View full text Add to dashboard Cite

Background and Objectives: Peptic ulcer disease is a chronic disease affecting up to 10% of the world’s population. Proton pump inhibitors, such as lansoprazole are the gold standard in the treatment of ulcer disease. However, various studies have shown the effectiveness of garlic oil extracts in the treatment of ulcer disease. A cellular model can be established in the human gastric cell line by sodium taurocholate. The aim of this study was to explore the effects of garlic oil extracts pretreatment and LPZ addition in the cell culture model of peptic ulcer disease by examining oxidative stress and F-actin distribution. Materials and Methods: Evaluation was performed by determination of glutathione and prostaglandin E2 concentrations by ELISA; human gastric cell line proliferation by cell counting; expression of ATP-binding cassette, sub-family G, member 2; nuclear factor kappa B subunit 2 by RT PCR; and F-actin cytoskeleton visualization by semi-quantification of Rhodamine Phalloidin stain. Results: Our results showed significant reduction of cell damage after sodium taurocholate incubation when the gastric cells were pretreated with lansoprazole (p < 0.001) and increasing concentrations of garlic oil extracts (p < 0.001). Pretreatment with lansoprazole and different concentrations of garlic oil extracts increased prostaglandin E2 and glutathione concentrations in the cell culture model of peptic ulcer disease (p < 0.001). Positive correlation of nuclear factor kappa B subunit 2 (p < 0.01) with lansoprazole and garlic oil extracts pretreatment was seen, while ATP-binding cassette, sub-family G, member 2 expression was not changed. Treatment with sodium taurocholate as oxidative stress on F actin structure was less pronounced, although the highest concentration of garlic oil extracts led to a statistically significant increase of total amount of F-actin (p < 0.001). Conclusions: Hence, pretreatment with garlic oil extracts had gastroprotective effect in the cell model of peptic ulcer disease. However, further experiments are needed to fully elucidate the mechanism of this protective role.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In previous work, we investigated the gastroprotective activity and cytotoxicity of carnosic acid γ-lactone derivatives [12] as well as carnosic acid derivatives [13] and their gastroprotective mechanisms of action in human cells [14]. In the present report we used click chemistry reactions to prepare new carnosic acid and carnosol derivatives.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

et al. 2015

Self Cite

View full text Add to dashboard Cite

Abstract:Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1-3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4-46.9 μM and 39.2-48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg·mL In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg·mL −1 .

show abstract

“…Cellular mechanisms involved in the effects of carnosic acid include up-regulation of Nuclear factor (erythroid-derived 2)-like 2 (Nfr2) activity [8, 13,55,56], preservation of mitochondrial respiratory function [11,56], mitochondrial depolarization [47], cytochrome-c release [36], increase in Bax:Bcl-2 ratio [36], caspase activation [36,37], up-regulation of NAD + -dependent deacetylase SIRT1 [2], glutathione S-transferase [8,57], death receptor (DR)5 [19], Bcl-2 interacting mediator of cell death (Bim) [19] and p53 up-regulated modulator of apoptosis (PUMA) [19] expression, down-regulation of c-FLIP and Bcl-2 expression [19] as well as stimulation of PGE 2 synthesis [15]. Signaling involved in the effect of carnosic acid further includes phosphatidylinositol 3-kinase (PI3K)/Akt [26,[46][47][48][49], nuclear factor-kappa B (NF-κB) [21,49], and p38 kinase [8, 16,45,57].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Eryptosis Following Exposure to Carnosic Acid

Stockinger¹,

Bissinger²,

Bouguerra³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The phenolic abietane diterpene component of rosemary and sage, carnosic acid, may either induce or inhibit apoptosis of nucleated cells. The mechanisms involved in the effects of carnosic acid include altered mitochondrial function and gene expression. Human erythrocytes lack mitochondria and nuclei but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include oxidative stress, increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), and ceramide formation. The present study explored, whether and how carnosic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to carnosic acid significantly increased the percentage of annexin-V-binding cells (2.5 µg/ml), significantly decreased forward scatter (10 µg/ml), significantly increased Fluo3 fluorescence (10 µg/ml), significantly increased ceramide abundance (10 µg/ml), significantly increased hemolysis (10 µg/ml), but significantly decreased DCFDA fluorescence (10 µg/ml). The effect of carnosic acid on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca²⁺. Conclusion: Carnosic acid triggers cell shrinkage and phospholipid scrambling of the human erythrocyte cell membrane, an effect paralleled by and/or in part due to Ca²⁺ entry and increased ceramide abundance.

show abstract

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

Cited by 6 publications

References 34 publications

Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease

Pretreatment of Garlic Oil Extracts Hampers Epithelial Damage in Cell Culture Model of Peptic Ulcer Disease

Synthesis, Antiproliferative and Antifungal Activities of 1,2,3-Triazole-Substituted Carnosic Acid and Carnosol Derivatives

Enhanced Eryptosis Following Exposure to Carnosic Acid

Contact Info

Product

Resources

About