DA-9601 for erosive gastritis: Results of a double-blind placebo-controlled phase III clinical trial

Seol, Sang Yong; Kim, Myung Hwan; Ryu, Jong Sun; Choi, Myung Gyu; Shin, Dong Wook; Ahn, Byoung Ok

doi:10.3748/wjg.v10.i16.2379

Cited by 49 publications

(46 citation statements)

References 19 publications

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“…For example, it has been reported that a pharmaceutical agent containing eupatilin protects against gastric mucosal injury [27] and carrageenan-induced paw edema [24]. Moreover, animal studies have shown that eupatilin ameliorates acetaminophen-and carbon tetrachloride-induced acute liver injury [28] and dimethyl nitrosamine-induced liver fibrosis [29].…”

Section: Introductionmentioning

confidence: 99%

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Jegal

Park

et al. 2016

Apoptosis

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Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reactive oxygen species (ROS) production. In addition, AA + iron increased the levels of pro-apoptotic proteins and these changes were prevented by eupatilin. Eupatilin also induced autophagy, as evidenced by the accumulation of microtubule-associated protein 1 light chain3-II and the detection of autophagic vacuoles. Furthermore, the protective effects of eupatilin on mitochondrial dysfunction and ROS production were significantly abolished by autophagy inhibitors. Eupatilin also increased the mRNA level of sestrin-2 and its promoter-driven reporter gene activity, which resulted in the up-regulation of sestrin-2 protein. Finally, gene silencing using sestrin-2 siRNA and the ectopic expression of recombinant adenoviral sestrin-2 indicated that sestrin-2 induction by eupatilin was required for autophagy-mediated cytoprotection against AA + iron. Our results suggest that eupatilin activates sestrin-2-dependent autophagy, thereby preventing oxidative stress induced by AA + iron.

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Section: Introductionmentioning

confidence: 99%

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Jegal

Park

et al. 2016

Apoptosis

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“…Eupatilin has been used in clinic as a drug for gastritis and peptic ulcer (36). Therefore, we expect that eupatilin could be repositioned for treating ciliopathy patients carrying CEP290 mutations.…”

Section: This Suggests That Although Eupatilin Can Promote Ciliogenesmentioning

confidence: 99%

Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes

Kim¹,

Kim²,

Jung³

et al. 2018

Journal of Clinical Investigation

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“…6 It has been used to treat erosive gastritis and atrophic gastritis, 22 and its efficacy against erosive gastritis was reported to be higher than that of cetrexate. 23 Even the susceptibility of patients using NSAIDs to gastric mucosal damage by alcohol was also shown to be reduced by DA-9601. 22 The present study demonstrated that the production and secretion of ghrelin increased more in DA-9601-pretreated rats subsequently exposed to alcohol or indomethacin than in the placebo-pretreated rats suggesting that increased production of ghrelin may be responsible for the gastro-protective effect of DA-9601.…”

Section: Discussionmentioning

confidence: 99%

Augmenting Effect of DA-9601 on Ghrelin in an Acute Gastric Injury Model

Baek

Lee²,

Jun³

et al. 2011

Gut Liver

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Background/Aims: Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin. Methods: A total of 140 SpragueDawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively. Results: Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase. Conclusions: DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin. (Gut Liver 2011;5:52-56) Key Words: DA-9601; Ghrelin; Acute gastric injury INTRODUCTIONThe gastric mucosa defends its structural integrity against many noxious substances such as alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs) via pre-epithelial, epithelial and sub-epithelial factors that include the mucus barrier, bicarbonate secretion, epithelial tight junctions, prostaglandin (PG) synthesis, cell restitution, and mucosal blood flow.1 Alcohol ingestion may lead to gastric mucosal lesions by penetrating the gastric mucosa and causing mucosal inflammation, erosions and ulcer formation. 2-4 Alcohol-induced gastric injury is mediated by free radicals, which is supported by the fact that ethanol administration depletes cells of major antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase. Gastric injury induced by NSAIDs such as indomethacin is mediated by nonselective inhibition of the cyclooxygenase pathways, which results in decreased PG synthesis. DA-9601, an extract of Artemisia asiatica, has been reported to have anti-inflammatory, antioxidative and cytoprotective effects and therefore to play a protective role in experimentallyinduced gastrointestinal damage and hepatic and pancreatic lesions. [5][6][7][8][9] However, the underlying mechanisms of its gastric mucosal protective effects have not been fully elucidated. Another gastro-protective agent, ghrelin, which is made endogenously, has been recently found as one of the gut hormones. It affects the secretory and motor functions of gut as well as energy homeostasis by controlling appetite...

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DA-9601 for erosive gastritis: Results of a double-blind placebo-controlled phase III clinical trial

Cited by 49 publications

References 19 publications

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress

Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes

Augmenting Effect of DA-9601 on Ghrelin in an Acute Gastric Injury Model

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