Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcer<i>via</i>p38 MAPK/NF-κB pathway

Su, Mei Tzu; Li, Cheng-yuan; Zhou, Lin; Yan, Yun-yi; Ao, Luyao; Wang, Guangji; Fang, Weirong; Li, Yunman

doi:10.1039/c7ra08879e

Cited by 15 publications

(15 citation statements)

References 34 publications

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“…There increasing IL-6 and TNF-α levels in gastric tissue can be attributable to the necrotizing effects of ethanol in the model group. These results of our study showed that pretreatment and treatment with NRNC-CDs could remarkably alleviate in ammation symptoms by suppressing the production of TNF-α and IL-6, which was consistent with previous ndings [36,37].…”

Section: Discussionsupporting

confidence: 93%

Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

Luo

Zhang

et al. 2020

Preprint

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BackgroundGastric ulcers is a common gastrointestinal digestive system disease. Considering the frequency of human gastric ulcers, the side effects and cost of some existing synthetic drugs, the use of natural products is an important choice for many people. The aim of present study was to explore gastroprotective effects of nelumbinis rhizomatis nodus carbonisata carbon dots (NRNC-CDs) on ethanol-induced gastric ulcers in rats.MethodsThe NRNC-CDs were synthesized via high temperature calcinations treatment at 350 ℃ for 1 h were characterized by various spectroscopic and electron microscopy techniques for their structural, morphological, and optical properties. In vitro cytotoxicity of CDs for the human gastric epithelial cells line (GES-1 cells) was assessed by the CCK-8 assay. Furthermore, the study evaluated gastroprotective effects of NRNC-CDs on ethanol-induced gastric ulcers in rats, followed by a preliminary study on the possible mechanisms of gastroprotection.ResultesNRNC-CDs with a quantum yield of 1.38% have an average diameter of 2.89±0.82nm and the lattice spacing of 0.29 nm , and exerted low toxicity to GES-1 cells by CCK-8 test. In vivo experiments showed that NRNC-CDs remarkably reduced gastric mucosal damage and significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px). In addition, NRNC-CDs also significantly inhibited tumor necrosis factor-alpha (TNF-a) and pro-inflammatory interleukin-6 (IL-6) level in gastric tissues. Histological findings demonstrated that NRNC-CDs exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer.ConclussionThe potent gastroprotective effect of NRNC-CDs were thus attributed to its anti-inflammatory and antioxidant effects. This discovery provides guidance for further research the effect of CDs in gastrointestinal digestive diseases.

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Section: Discussionsupporting

confidence: 93%

Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

Luo

Zhang

et al. 2020

Preprint

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“…35 The activation of major subgroups in the MAPK family regulates the expression of pro-inflammatory mediators, a phenomenon that has been reported in EtOHinduced gastric ulcer in mice. 6,14,34,36 In this study, we confirmed that the MAPKs were activated in gastric tissues of EtOH-treated mice. However, the pretreatment of EF-2001 dose dependently suppressed the phosphorylation of MAPKs in the gastric tissues.…”

Section: Discussionsupporting

confidence: 77%

“…Excessive NO generated by iNOS deleterious effects on the pathophysiological conditions of gastric ulcer. 3,34 In the present study, the EtOHtreated group showed an increased phosphorylation of p65NF-kB with upregulation of pro-inflammatory mediators, COX-2, TNF-a, and iNOS with increased NO levels in the gastric tissues. However, EF-2001treated mice notably exhibited suppressed phosphorylation of p65NF-kB, with the accompanying downregulated expression of pro-inflammatory mediators and gastric NO levels in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 53%

“…EtOH-induced acute gastric lesions are characterized by linear or fused hemorrhagic and hyperemic lesions on the glandular area of stomach with various pathological alterations including hemorrhage, edema, and loss of epithelial cells. 4,34 In this study, EtOH treatment to mice caused severe hemorrhagic and hyperemic lesions with a marked increase of gastric mucosal ulcer score. However, oral administration of EF-2001 significantly attenuated the gross lesions with decrease in the gastric mucosal ulcer score.…”

Section: Discussionmentioning

confidence: 59%

“…loss of epithelial cells. These findings suggest that EF-2001 might have anti-ulcerogenic activity on EtOHinduced gastric mucosal injury.The MAPK pathways are involved in diverse cellular responses, including inflammation-related pathways by receiving interior or exterior cell signals 34.…”

mentioning

confidence: 99%

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Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer

et al. 2020

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Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

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Fertility and early embryonic development toxicity and toxicokinetic study of KFP‐H008 in Sprague–Dawley rats

Peng

Shao

et al. 2022

Birth Defects Research

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The novel potassium competitive acid blocker, KFP‐H008, developed to overcome the shortcomings of proton pump inhibitors. In this study, KFP‐H008 was administered by oral gavage at doses of 0 (control), 15, 45, and 150 mg/kg to Sprague–Dawley rats (24 animals per sex per group). Body weight, food consumption, mortality, sexual cycle, mating behavior, pregnancy, sperm motility, and relative organ weights were evaluated. In a concomitant toxicokinetic (TK) study (10 animals per sex per group), plasma TK parameters and tissue distribution of KFP‐H008 were tested. There were obvious effects at the dosage of 150 mg/kg to male rats with decreases of prostate weight and lower weight gain; to female rats with lower weight gain, hair off, and lower corpus luteum count. There were no effects on litter parameters. Time to reach maximum plasma concentrations for KFP‐H008 was between 0.5 and 1.0 hr for the 15 and 45 mg/kg groups, while for the 150 mg/kg group it had a delay to 2 hr. Overall, the NOAEL of KFP‐H008 was considered to be 45 mg/kg in both genders and the TK study shows that exposure (area under the curve) of male rats was about 1,091.0 ± 530.8 μg/Lhr and to female rats was 1,030.5 ± 512.5 μg/Lhr. Administration of KFP‐H008although reaches the reproductive organs, it demonstrated no significant effects on reproductive organs, it did not affect mating, fertility, pregnancy, growth, or morphologic development.

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Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcerviap38 MAPK/NF-κB pathway

Abstract: KFP-H008, a novel potassium-competitive acid blocker developed for the treatment of acid-related diseases, has been reported to inhibit gastric acid secretion effectively, while its effects on gastric ulcer have not been previously explored.

Cited by 15 publications

References 34 publications

Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

Gastroprotective effects of Nelumbinis Rhizomatis Nodus carbonisata-derived carbon dots on ethanol-induced gastric ulcers in rats

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer

Fertility and early embryonic development toxicity and toxicokinetic study of KFP‐H008 in Sprague–Dawley rats

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