Effect of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin complex on indomethacin-induced small intestinal injury in mice

Ishida, Tatsuro; Miki, Ikuya; Tanahashi, Takao; Yagi, Saori; Kondo, Yasuyuki; Inoue, Jun; Kawauchi, Shoji; Nishiumi, S; Yoshida, Masaru; Maeda, Hideko; Tode, Chisato; Takeuchi, Atsuko; Azuma, Takeshi; Mizuno, Shigeto

doi:10.1016/j.ejphar.2013.06.007

Cited by 40 publications

(37 citation statements)

References 34 publications

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“…Indomethacin is a non-selective inhibitor of COX enzymes that has a high ulcerogenic potential and causes ulcers in drug-treated animals at the doses used in this study (Kato et al 2001; Peskar et al 2001; Tavares 2000), whereas NS-398 is a COX 2-selective inhibitor (coxib) that does not cause ulceration in drug treated animals, but inhibits ulcer healing once they are induced (Brzozowski et al 2001; Kato et al 2001; Peskar et al 2001; Tavares 2000; Tomisato et al 2004). Animals were treated with indomethacin and NS-398 at a dose of 10 mg/kg/day in this study, which is consistent with the experimental model of indomethacin-induced GI damage that is commonly used (Ishida et al 2013; Kato et al 2009; Lim et al 2012; Rohde et al 2015; Satoh and Urushidani 2016) as well as their experimental use by other research groups in studying the anti-nociceptive effects of NSAIDs (Brzozowski et al 2001; Euchenhofer et al 1998; Lichtenberger et al 2015; Peskar et al 2001; Petchi et al 2015; Pozzoli et al 2007). It will be interesting to evaluate the effects of a greater range of NSAIDs for their effects on cell migration in duodenal epithelia and in the more distant epithelia of the jejunum and ileum in future experiments to determine if there is a correlation between inhibition of calpain protease expression and inhibition of migration following NSAID treatment there.…”

Section: Discussionsupporting

confidence: 61%

Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum

et al. 2017

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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity. Previous efforts demonstrated that treatment of cultured intestinal epithelial cells (IEC) with NSAIDs inhibits expression and activity of calpain proteases, but the effects of specific inhibition of calpain expression in vitro or the effects of NSAIDs on intestinal cell migration in vivo remain to be determined. Accordingly, we examined the effect of suppression of calpain protease expression with siRNA on cell migration in cultured IECs and evaluated the effects of NSAID treatment on epithelial cell migration and calpain protease expression in rat duodenum. Our results show that calpain siRNA inhibits protease expression and slows migration in cultured IECs. Additionally, NSAID treatment of rats slowed migration up the villus axis and suppressed calpain expression in duodenal epithelial cells. Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity.

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Section: Discussionsupporting

confidence: 61%

Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum

et al. 2017

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“…The plasma concentration of glycyrrhetic acid showed two peaks including a small peak at 30 min and a large peak at 11.4 hr, suggesting the slow conversion and complication of glycyrrhizin into glycyrrhetic acid in the intestine of rats . Another limitation of this study was due to the poor absorbability of 18β‐GA in the intestinal lumen because of poor water solubility . Our previous results have demonstrated that glycyrrhizic acid (100 mg/kg of BW) or 18beta‐GA (50 mg/kg of BW) significantly inhibits the accumulation of RAGE‐associated ligand high mobility group box 1 (HMGB1) in cisplatin‐induced nephrotoxicity of BALB/c mice, implying that 18beta‐GA plays an important role in RAGE suppression in vivo .…”

Section: Discussionmentioning

confidence: 84%

Novel findings of 18β‐glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high‐glucose environment

Tung

Chen

et al. 2019

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Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18β‐Glycyrrhetinic acid (18β‐GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18β‐GA on sRAGE secretion via TRPC channels in high glucose (HG)‐induced THP‐1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide‐adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18β‐GA showed the dramatic effects similar to Pyr3 or 2‐aminoethyl diphenyl borinate inhibitors and effectively reversed HG‐elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18β‐GA provides a potential implication to diabetes mellitus and its complications.

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“…The degree of mRNA expression of TNFa in the intestinal mucosa was measured as reported in a previous study [14]. The samples were collected from the distal ileum, avoiding the locations of deep ulcers to eliminate bias [12].…”

Section: Quantitative Rt-pcr For Intestinal Mrna Expressionmentioning

confidence: 99%

Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling

et al. 2016

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Effect of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin complex on indomethacin-induced small intestinal injury in mice

Cited by 40 publications

References 34 publications

Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum

Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum

Novel findings of 18β‐glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high‐glucose environment

Psychological stress exacerbates NSAID-induced small bowel injury by inducing changes in intestinal microbiota and permeability via glucocorticoid receptor signaling

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