Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway.
Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels.N(G)-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, downregulating cPLA(2), 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10.
Kang
Jung Mook
JM
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea.
Kim
Nayoung
N
Kim
Bongcheol
B
Kim
Joo-Hyon
JH
Lee
Bong-Yong
BY
Park
Ji Hyun
JH
Lee
Mi Kyoung
MK
Lee
Hye Seung
HS
Jang
In-Jin
IJ
Kim
Joo Sung
JS
Jung
Hyun Chae
HC
Song
In Sung
IS
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D006595:Hexosamines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D029775:Momordica; D055271:Mucin 5AC / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012639:Seeds; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013276:Stomach Ulcer / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005765:Gastrointestinal Agents; D006595:Hexosamines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C524680:Muc5ac protein, rat; C524736:Muc6 protein, rat; D055271:Mucin 5AC; D055272:Mucin-6; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D009569:Nitric Oxide; D000431:Ethanol; D009195:Peroxidase; D001094:Arachidonate 5-Lipoxygenase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D054513:Group IV Phospholipases A2; C516391:Pla2g4a protein, rat; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone