(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol (Plaunotol) increases cyclooxygenase-2 expression via nuclear factor κB and cyclic AMP response element in rat gastric epithelial cells

Fu, Haiying; Yabe, Yuki; Asahi, Kayoko; Hayashi, Yujiro; Murata, Hiroaki; Eguchi, Hiroshi; Tsujii, Masahiko; Tsuji, S.

doi:10.1016/j.ejphar.2005.09.044

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…Expression of COX-2 in gastrointestinal epithelia has been examined extensively in many laboratories including ours [17,18,22,23,32]. COX-2 is one of the immediate early genes whose transcripts are fairly unstable due to the AU-rich sequences of the 3 untranslated regions.…”

Section: Discussionmentioning

confidence: 99%

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Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

Nishida

Yabe

et al. 2007

Dig Dis Sci

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Geranylgeranylacetone (GGA) effectively protects the gastric mucosa against noxious agents. The precise mechanisms underlying the gastroprotective actions of GGA are not known. To elucidate the precise mechanism of GGA, the effect of GGA treatment on COX-2 expression in rat gastric epithelial (RGM1) cells was investigated. We used a prostaglandin E2 (PGE2) enzyme-linked immunoassay kit and Western blot analysis to measure PGE2 production and COX-2 induction by GGA treatment in serum-starved RGM1 cells. Gel-shift assay, Western blot analysis, and a reporter assay were performed to determine which COX-2 promoter was involved in GGA-induced COX-2 expression. GGA treatment dose dependently increased COX-2 expression and PGE2 production. The nuclear factor (NF)-kappaB sites of the COX-2 gene promoter were critical for GGA-mediated COX-2 expression. GGA induces COX-2 expression and increases PGE2 production in serum-starved RGM1 cells via activation of the NF-kappaB sites of COX-2 gene promoters.

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Section: Discussionmentioning

confidence: 99%

“…Signal was detected using the enhanced chemiluminescence protocol as described by the manufacturer (Pierce, Rockford, IL). Timepoints of the study were determined according to the results of our previous studies [16,17,22,23].…”

Section: Cell Culturementioning

confidence: 99%

Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

Nishida

Yabe

et al. 2007

Dig Dis Sci

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“…Plaunotol is an acyclic diterpene used to treat gastric ulcers in Japan. The gastroprotective mechanisms of action of plaunotol were investigated employing rat gastric epithelial cells (RGM1) [28]. The results showed that plaunotol increased PGE 2 production and COX-2 expression.…”

Section: Resultsmentioning

confidence: 99%

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

2014

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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 E 2 (PGE 2 ) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE 2 content in AGS cells, all derivatives significantly stimulated PGE 2 synthesis, the best effect being found for the 12-Oindolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. 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 PGE 2 synthesis and cell proliferation.

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“…The latter may be due to responses at the subcellular level, such as stimulation of proteins or enzymes production [21]. Plaunotol exposure has been shown to induce COX2 and PGE 2 expression in gastric epithelial cells of rats [6]. Furthermore, the observed congestion of blood in renal venules, as well as the dilated renal tubules, may have affected the relative weight of kidneys in both male and female rats.…”

Section: Discussionmentioning

confidence: 99%

“…A major constituent isolated from leaves of Plau-Noi is plaunotol [2]. This natural acyclic diterpene has been used as an antigastric ulcer medication based on its pharmacotherapeutic effects in inducing prostaglandin E 2 (PGE 2 ) and eradicating Helicobacter pylori bacteria [3–6]. However, in addition to its application as a single compound that requires a complicated process of extraction and purification [7], plaunotol used in form of a partially purified plaunotol extract (PPE) is also of interest.…”

Section: Introductionmentioning

confidence: 99%

Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract fromCroton stellatopilosusOhba

Chaotham

Chivapat

Chaikitwattana³

et al. 2013

BioMed Research International

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Plaunotol, an acyclic diterpenoid with highly effective antigastric ulcer properties, has been commercially isolated from leaves of Croton stellatopilosus Ohba. This Thai medicinal plant was traditionally used in the form of crude extracts, suggesting that it is possible to administer these plaunotol-containing extracts without toxicity. To confirm its safety, the oral toxicity of a partially purified plaunotol extract (PPE) was evaluated in vivo. The PPE was simply prepared by 95% ethanol reflux extraction followed by hexane partition. The obtained extract was analyzed and found to contain 43% w/w of plaunotol and another compound, likely a fatty acid-plaunotol conjugate that is considered a major impurity. Oral administration of PPE to ICR mice and Wistar rats was conducted to evaluate acute and chronic toxicity of the plaunotol extract, respectively. The acute toxicity study demonstrated that PPE was practically nontoxic based on its high median lethal dose value (LD50 = 10.25 g/kg). The chronic toxicity studies also showed the absence of mortality and clinical symptoms in all rats treated with 11–1,100 mg/kg/day of PPE during a 6-month period. Histopathological and hematological analyses revealed that altered liver and kidney function and increased blood platelet number, but only at the high doses (550–1,100 mg/kg/day). These results suggest that PPE is potentially safe for further development as a therapeutic agent in humans.

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(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol (Plaunotol) increases cyclooxygenase-2 expression via nuclear factor κB and cyclic AMP response element in rat gastric epithelial cells

Cited by 7 publications

References 20 publications

Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

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

Acute and Chronic Oral Toxicity of a Partially Purified Plaunotol Extract fromCroton stellatopilosusOhba

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