Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9.
Gastric ulcers form as a result of a multifaceted process which includes acid secretion, reactive oxygen species generation and extracellular matrix (ECM) degradation. The aim of this study was to investigate the possible mechanisms underlying the anti-ulcerogenic effects of the Zn(II)-curcumin complex, a curcumin derivative, on the healing of acetic acid-induced gastric ulcers in rats. The severely ulcerated gastric mucosa of control animals had a lower glutathione level (GSH) and superoxide dismutase activity (SOD), and increased malondialdehyde (MDA) content compared to sham operated rats (P<0.001). Zn(II)-curcumin solid dispersions (equivalent to 12, 24 and 48 mg/kg) dose-dependently reduced the gastric ulcer index, significantly increased SOD activity and GSH levels, and reduced the MDA content and matrix metalloproteinase-9 (MMP-9) mRNA expression in the gastric mucosa (P<0.05, compared to control animals). Zn(II)-curcumin exerted a greater anti-ulcerogenic effect than curcumin at the same dose (24 mg/kg), leading to a reduced severity of gastric ulcers, lower MDA content, and increased SOD activity and GSH levels (P<0.05). In conclusion, these results confirm that the Zn(II)-curcumin complex possesses an enhanced mucosal barrier defense activity compared to curcumin alone, due to its synergistic ability to decrease oxidative stress and attenuate MMP-9-mediated inflammation.
Laboratory of Traditional Chinese Medicine and Marine Drugs, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Xue-Ting
XT
Mei
Dong-Hui
DH
Xu
Si-Ka
SK
Xu
Yan-Ping
YP
Zheng
Shi-Bo
SB
Xu
D019342:Acetic Acid / Q000009:adverse effects*; D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D005978:Glutathione; D003474:Curcumin; D015032:Zinc; D019342:Acetic Acid
Antiulcer; Decreasing oxidative stress; Enhancing mucosal barrier defense; Matrix metalloproteinase-9; Zn(II)–curcumin complex