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Gut Liver. 2014;8(1):49-57.

Gastroprotective effect of Cochinchina momordica seed extract in nonsteroidal anti-inflammatory drug-induced acute gastric damage in a rat model.

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제1저자 임지완 · 교신저자 김나영

PMID 24516701 PMC3916687 DOI 10.5009/gnl.2014.8.1.49 IF 4.1 소화기내과
소속 (5)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  2. Life Science R&D Center, SK Chemicals, Suwon, Korea.
  3. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  4. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  5. Kyungpook National University College of Pharmacy, Daegu, Korea.

Abstract

BACKGROUND/AIMS The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model.

METHODS The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX.

RESULTS All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups.

CONCLUSIONS SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.

Keywords

Anti-inflammatory agents, non-steroidalArachidonate 5-lipoxygenaseCochinchina momordicaGastroprotectionPhospholipases A2, cytosolic

Figures

Fig. 1
Fig. 1 Gross findings of the gastric damage caused by aspirin (200 mg/kg), indomethacin (40 mg/kg), and diclofenac (80 mg/kg), and the gastroprotective effect of SK-MS10 pretreatment in rats. (A) Rat stomach after exposure to aspirin. (B) Rat stomach after exposure to indomethacin. (C) Rat stomach after exposure to diclofenac. (D) Rat stomach after exposure to aspirin with SK-MS10 pretreatment. (E) Rat stomach after exposure to indomethacin with SK-MS10 pretreatment. (F) Rat stomach after exposure to diclofenac with SK-MS10 pretreatment. Asp, aspirin; Indo, indomethacin; DF, diclofenac; NSAIDs, nonsteroidal anti-inflammatory drugs.
Fig. 2
Fig. 2 (A) Gross ulcer index and (B) damage area as assessed by the image program in the stomachs of 7-week-old rats. The areas of gross damage (erosion or ulceration) were measured using a computerized video analysis system (MetaMorph 7.0; Molecular Devices). The area of mucosal damage was expressed as a percentage of the total mucosal area. The mean±SE with six rats per group. Asp 200, aspirin 200 mg/kg; Indo 40, indomethacin 40 mg/kg; DF 80, diclofenac 80 mg/kg. *p<0.05 compared with the nonsteroidal anti-inflammatory drug (NSAID) group; †p<0.05 compared with the control group.
Fig. 3
Fig. 3 (A) Mucosal concentrations of myeloperoxidase (MPO) and (B) real-time polymerase chain reaction of calcitonin gene-related peptide (CGRP) in the stomachs of 7-week-old rats. The mean±SE with six rats per group. Asp 200, aspirin 200 mg/kg; Indo 40, indomethacin 40 mg/kg; DF 80, diclofenac 80 mg/kg. *p<0.05 compared with the nonsteroidal anti-inflammatory drug (NSAID) group; †p<0.05 compared with the control group.
Fig. 4
Fig. 4 (A) Western blotting of cytosolic phospholipase A2 (cPLA2) and (B) 5-lipoxygenase (5-LOX) in the stomachs of 7-week-old rats. The mean±SE with six rats per group. Asp 200, aspirin 200 mg/kg; Indo 40, indomethacin 40 mg/kg; DF 80, diclofenac 80 mg/kg. *p<0.05 compared with the control group.
Fig. 5
Fig. 5 (A) Real-time polymerase chain reaction of cyclooxygenase (COX)-1, (B) COX-2, (C) Western blotting of COX-1, and (D) COX-2 in the stomachs of 7-week-old rats. The mean±SE with six rats per group. Asp 200, aspirin 200 mg/kg; Indo 40, indomethacin 40 mg/kg; DF 80, diclofenac 80 mg/kg. *p<0.05 compared with the nonsteroidal anti-inflammatory drug (NSAID) group; †p<0.05 compared with the control group.

그림 출처: PubMed Central 공개 논문 (PMC3916687)

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Gut and liver · eISSN 2005-1212
전자 출판
2013-11-05
MeSH
Animals · Anti-Inflammatory Agents, Non-Steroidal / adverse effects · Arachidonate 5-Lipoxygenase / drug effects · Calcitonin Gene-Related Peptide / drug effects · Cyclooxygenase 1 / drug effects · Cyclooxygenase 2 / drug effects · Disease Models, Animal · Gastric Mucosa / chemistry / drug effects · Group IV Phospholipases A2 / drug effects · Male · Momordica / chemistry · Peroxidase / drug effects · Plant Extracts / pharmacology · Rats · Rats, Sprague-Dawley · Seeds / chemistry · Stomach Ulcer / chemically induced / prevention & control · Treatment Outcome
Substances
Anti-Inflammatory Agents, Non-Steroidal · Plant Extracts · Peroxidase · Arachidonate 5-Lipoxygenase · Cyclooxygenase 1 · Cyclooxygenase 2 · Group IV Phospholipases A2 · Calcitonin Gene-Related Peptide
참고문헌
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