Inhibitory effects of a β-dunnione compound MB12662 on gastric secretion and ulcers

Jo, In-Geun; Park, Dongsun; Kyung, Jangbeen; Kim, Dajeong; Cai, Jingmei; Kim, Jihyun; Kwak, Tae Hwan; Yoo, Seunghwa; Jeong, Heon‐Sang; Kim, Yun-Bae

doi:10.5625/lar.2013.29.3.178

Cited by 8 publications

(8 citation statements)

References 14 publications

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“…Such an efficacy of MB12662 might be due to its intestine-preserving activity which lowers ensuing retching and vomiting, prevents dehydration and inability of food consumption, and recovers animals as demonstrated in mice. The protective effects of MB12662 on gastric ulcers induced by alcohol and stress were also confirmed in rats ( Jo et al ., 2013 ). Since radiotherapy also induces intestinal injury and emesis as in chemotherapy ( Priestman et al ., 1990 ; Farrell et al ., 1998 ; Jo et al ., 2000 ), it is expected that MB12662 would be effective for the relief of radiation-induced gastrointestinal problems.…”

Section: Discussionmentioning

confidence: 67%

“…In general, anti-cancer agents exert their cytotoxicity via DNA alkylation as well as radical reactions ( Husain et al ., 1998 ; De Martinis and Bianchi, 2001 ; Jeong et al ., 2005 ; Lee et al ., 2008 ). Interestingly, MB12662 and its derivative MB12066 (β-lapachone; 3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-β]pyran-5,6-dione) markedly reduced gastric secretion and prevented alcoholic gastric ulcers accompanied by oxidative tissue damage ( Park et al ., 2011 ; Jo et al ., 2013 ). In spite of anti-oxidative, anti-gastrosecretory, and anti-ulcer activities, it is believed that the major action mechanism of MB12662 might be its NAD + -preserving potential ( Hwang et al ., 2009 ), based on the much higher efficacy in alcoholic ulcers than in stress-induced ulcers ( Jo et al ., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have synthesized dunniones and β-lapachones, the anti-fungal orange-red pigments of Streptocarpus dunnii Mast ( Khambay et al ., 2003 ). The synthetic β-lapachone and dunnione greatly increased NAD + via NADH oxidation ( Hwang et al ., 2009 ; Lee et al ., 2012 ), alleviated cyanide cytotoxicity of preoligodendrocytes (unpublished results), and improved alcohol- and stress-induced gastric ulcers ( Park et al ., 2011 ; Jo et al ., 2013 ). Such results led us to investigate the effects of MB12662, a dunnione compound, on damages of target tissues including intestinal, immune, and hematopoietic systems in mice as well as vomiting reflexes in ferrets following cisplatin administration.…”

Section: Introductionmentioning

confidence: 99%

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A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

Park

Jang

et al. 2015

Biomolecules & Therapeutics

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The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

Park

Jang

et al. 2015

Biomolecules & Therapeutics

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“…For this purpose, pyloric ligation was performed to induce damage to the stomach wall through the retention of gastric acids (Jo et al, 2013). This procedure is essential and can reveal possible changes in parameters related to the gastric contents (Barros et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

Antiulcer activities of the hydroethanolic extract of Sedum dendroideum Moc et Sessé ex DC. (balsam)

Carrasco

Pinto

Cordeiro

et al. 2014

Journal of Ethnopharmacology

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“…Interestingly, intracellular NAD + /NADH ratio can be easily controlled by NQO1 that carry out redox reactions by transferring electrons from NADH to its substrates [19,42,43]. Recently, it has been reported that an increase in the NAD + /NADH ratio by dunnione, an analog of β-lapachone (a well-known NQO1 substrate), shows beneficial effects on various metabolic syndromes [44], alcoholic ulcers [45], and acute pancreatitis [28].…”

Section: Discussionmentioning

confidence: 99%

Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice

Khadka¹,

Kim²,

Oh³

et al. 2018

Journal of Molecular and Cellular Cardiology

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Background: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively used to treat various human neoplasms. However, its clinical utility is hampered due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidative stress, DNA damage, and inflammatory responses. Nonetheless, the remedies for AIC are even not established. Therefore, we illustrate the role of NAD + /NADH modulation by NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action on AIC. Methods and results: AIC was established by intraperitoneal injection of ADR in C57BL/6 wild-type (WT) and NQO1 knockout (NQO1 −/−) mice. All Mice were orally administered dunnione (named NQO1 substrate) before and after exposure to ADR. Cardiac biomarker levels in the plasma, cardiac dysfunction, oxidative biomarkers, and mRNA and protein levels of pro-inflammatory mediators were determined compared the cardiac toxicity of each experimental group. All biomarkers of Cardiac damage and oxidative stress, and mRNA levels of proinflammatory cytokines including cardiac dysfunction were increased in ADR-treated both WT and NQO1 −/− mice. However, this increase was significantly reduced by dunnione in WT, but not in NQO1 −/− mice. In addition, a decrease in SIRT1 activity due to a reduction in the NAD + /NADH ratio by PARP-1 hyperactivation was associated with AIC through increased nuclear factor (NF)-κB p65 and p53 acetylation in both WT and NQO1 −/− mice. While an elevation in NAD + /NADH ratio via NQO1 enzymatic action using dunnione recovered SIRT1 activity and subsequently deacetylated NF-κB p65 and p53, however not in NQO1 −/− mice, thereby attenuating AIC. Conclusion: Thus, modulation of NAD + /NADH by NQO1 may be a novel therapeutic approach to prevent chemotherapy-associated heart failure, including AIC.

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Inhibitory effects of a β-dunnione compound MB12662 on gastric secretion and ulcers

Cited by 8 publications

References 14 publications

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

Antiulcer activities of the hydroethanolic extract of Sedum dendroideum Moc et Sessé ex DC. (balsam)

Augmentation of NAD+ levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice

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