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Effect of Volatile Oil from A. Longiligulare T.L. Wu on Experimental Ulcerative Colitis and Its Safety Assessment

Author: ZhaoJin
Tutor: DongZhi；ZhuYi
School: Chongqing Medical University
Course: Pharmacology
Keywords: The Hainan amomum volatile oil Ulcerative Colitis Anti-inflammatory Analgesic Anti-diarrheal Acute Toxicity Long-term toxicity
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 119
Quote: 1
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Abstract


Objective: To investigate the Hainan the Amomum volatile oil (volatile oil from A.longiligulare TLWu, VOA) role and mechanism of action of experimental ulcerative colitis (ulcerative colitis, UC) security evaluation. Method: (1) steam France extracted VOA, using gas chromatographic analysis of its chemical composition, to study its controllability and stability; (2) using the Bliss method in mice, the acute toxicity studies of the VOA, the determination of its LD50; ( 3) the use of drinking water of 4% dextran sulfate sodium (dextran sulfate sodium, DSS) aqueous solution preparation UC mice model, as control Sulfasalazine (sulfasalazine, SSZ) observed VOA clinical symptoms of UC mice and colon mucosal pathological changes; (4) 2,4 - dinitrochlorobenzene (2,4-dinitrobenzene-1-chlorobenzene, DNCB) Preparation of UC rat model of acetic acid compound enema legal system as a control, SSZ, observed VOA UC colon tissue gross morphology and pathological changes; (5) the effect of different doses of VOA xylene induced mouse ear edema and carrageenan-induced rat paw swelling in mice hot plate method of pain threshold and glacial acetic acid induced mouse writhing and mice diarrhea caused by the impact of senna, and castor oil; nitric oxide (6) the biochemical assay DSS induced UC colon tissue of mice ( nitric oxide, NO), malondialdehyde (maleic dialdehyde, MDA) content and superoxide dismutase (superoxide dismutase, SOD) vitality explore VOA treatment of UC mechanism; (7) biochemical assay UC large DNCB induced by acetic acid mouse colon tissue SOD, glutathione peroxidase (glutathione peroxidase, GSH-Px) activity and nitric oxide synthase (nitric oxide synthase, NOS) content explore mechanism VOA treatment of UC; (8) by immunohistochemical UC mice histochemical Examined VOA DSS-induced colon tissue inducible nitric oxide synthase (inducible nitric oxide synthase, iNOS) in and intercellular adhesion molecule -1 (intercellular adhesion molecule 1, ICAM-1) expression ; (9) the immunohistochemical method investigated VOA UC colon tissue DNCB and acetic acid-induced tumor necrosis factor-α (tumor necrosis factor-α, TNF-α) and nuclear factor-κBp65 (nuclear factor-κBp65, NF -κBp65) expression; (10) observed different doses of VOA Sprague-Dawley rats intragastrically 90d, convalescent observation 15d measuring rat body weight, hematology and blood biochemical parameters during the calculation of organ coefficient, and Pathological examination. Results: (1) the VOA ingredient stability, quality controlled; (2) VOA ig The LD50 for 7.3009g/kg.; (3) the VOA administration significantly improved DSS-induced UC clinical symptoms in mice, reducing Results pathological damage of the intestinal mucosa; (4) the VOA administration significantly reduced of DNCB induced by acetic acid UC rat intestine mucosal gross morphology and Pathology damage; (5) VOA xylene-induced mouse ear swelling and carrageenan due rat paw swelling was inhibited, the role of high-dose group of indomethacin. The VOA of heat induced pain in mice to prolong the pain threshold time, the more obvious the high-dose group; pain caused by acetic acid in mice, each dose group to reduce its writhing, but no significant differences. VOA to senna induced diarrhea and castor oil induced diarrhea invalid; (6) VOA significantly reduce NO and MDA in DSS-induced UC colon tissue of mice, significantly increased activity of SOD; (7) VOA can significantly reduced NOS in UC colon tissue DNCB induced by acetic acid content, significantly increased SOD and GSH-Px activity; (8) VOA colon tissue of DSS-induced UC mice significantly inhibited iNOS and ICAM-1 positive cells general; (9) VOA could significantly inhibit DNCB and acetic acid-induced UC colon tissue TNF-α and of NF-κBp65 positive cells express rate; (10) the VOA dose rats, hematology and blood biochemistry indicators showed no significant differences in animal weight for each dose group compared with the control group, significant differences in pathology and organ examination showed the spleen and lung pathological changes. Conclusions: (1) VOA has the better anti-UC and anti-inflammatory analgesic antidiarrheal effect and low toxicity, quality controlled, suggesting that VOA can be used as an effective UC prevention drugs. (2) A preliminary study of the VOA anti-experimental UC mechanism found anti UC mechanism may be related to the following factors: (1) reduce free radical formation, inhibition of lipid peroxidation; ② regulate colon tissue NO synthesis; ③ relief intercellular adhesion of colon tissue damage; (4) inhibition of the inflammatory cascade; ⑤ anti-inflammatory and analgesic and anti-diarrheal. (3) Sprague-Dawley rats were given of Hainan amomum volatile oil continuous 3 months NOAEL of 1900mg/kg, toxic dose of 3800 mg / kg, spleen and lungs visible pathological changes.

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