Mei Xueting, Xu Donghui, Wang Sheng, Xu Shibo
Lab. of Traditional Chinese Medicine and Marine Drugs, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Zhongguo Zhong Yao Za Zhi. 2009 Nov;34(22):2920-3.
To research the pharmacological action of curcumin solid dispersions (SDs, curcumin and polyvinylpyrrolidone (PVP) k30 in the ratio of 1:8) was investigated on experimental gastric ulcer in rats and mice.
Animals were randomly divided into several experimental groups. Each group consisted of 10 animals. The control group received PVP vehicle (720 mg x kg(-1), po) throughout the course of the experiments. The treatment groups received different doses of curcumin SDs (equivalent to curcumin 10, 30 and 90 mg x kg(-1), po), and ranitidine (27 mg x kg(-1), po) was used as the positive control. In acetic acid-induced gastric ulcers model, serum NO, plasma ET and gastric ulcer indexes of rats were measured after oral administration for 14 d. In rat ulcer model induced by pylorus-ligature, gastric volume pepsin and gastric ulcer indexes of rats were measured after oral administration for 3 d and pylorus-ligature inducement for 16 h. Gastric ulcer indexes of mice were measurement after oral administration for 3 d and subcutaneous injection reserpine 10 mg x kg(-1).
The results showed that curcumin SDs (equivalent to curcumin 30, and 90 mg x kg(-1), po) could reduce the ulcer indexes 4.59 +/- 0.96 and 3.33 +/- 0.93 (P < 0.01), and increase serum NO level (29.75 +/- 5.90) mmol x L(-1) (P < 0.05) and (39.63 +/- 12.73) mmol x L(-1) (P < 0.01), compared to gastric index 5.87 +/- 0.48 and NO level (23.63 +/- 5.73) mmol x L(-1) in control group. Compared to plasma ET (163.65 +/- 63.84) ng x L(-1) in control group, curcumin SDs (equivalent to 90 mg x kg(-1), po) could decrease plasma ET level (104.22 +/- 63.84) ng x L(-1) (P < 0.05). Compared to gastric ulcer indexes 4.25 +/- 0.71 of control group in rat pylorus-ligature model, curcumin SDs (equivalent to curcumin 90 mg x kg(-1)) could reduce gastric ulcer to 2.38 +/- 0.74 (P < 0.01). Compared to gastric volume (14.61 +/- 1.80) mL, acidity of gastric juice (87.70 +/- 9.84) mmol x L(-1), and the activity of pepsin (408.63 +/- 41.75) U x mL(-1), curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric volume to (12.68 +/- 1.46) mL (P < 0.05) and (9.99 +/- 0.79) mL (P < 0.01), reduce acidity of gastric juice to (77.62 +/- 8.34) mmol x L(-1) (P < 0.05) and (65.77 +/- 8.19) mmol x L(-1) (P < 0.01), inhibit the activity of pepsin to (358.13 +/- 37.44) U x mL(-1) (P < 0.05) and (292.13 +/- 41.93) U x mL(-1) (P < 0.01). In reserpine-induce gastric ulcer model, curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric ulcer indexes to 3.88 +/- 0.40 and 3.03 +/- 0.64 (P < 0.01), compared to that of control group 5.13 +/- 0.59.
Several animal gastric ulcer models prove that curcumin SDs has anti-gastric ulcer effects by inhibiting gastric acid secretion, reducing gastric juice acidity, inhibiting the activity of pepsin and promoting healing of ulcer. These findings show a potential application of curcumin SDs as an anti-ulcerogenic drug.
研究姜黄素固体分散体（SDs，姜黄素与聚乙烯吡咯烷酮（PVP）k30按1:8比例制成）对大鼠和小鼠实验性胃溃疡的药理作用。
将动物随机分为若干实验组。每组10只动物。对照组在整个实验过程中给予PVP载体（720 mg·kg⁻¹，口服）。治疗组给予不同剂量的姜黄素固体分散体（相当于姜黄素10、30和90 mg·kg⁻¹，口服），并以雷尼替丁（27 mg·kg⁻¹，口服）作为阳性对照。在醋酸诱导的胃溃疡模型中，口服给药14天后测定大鼠血清一氧化氮（NO）、血浆内皮素（ET）和胃溃疡指数。在幽门结扎诱导的大鼠溃疡模型中，口服给药3天并幽门结扎诱导16小时后，测定大鼠胃体积、胃蛋白酶和胃溃疡指数。口服给药3天并皮下注射利血平10 mg·kg⁻¹后，测定小鼠胃溃疡指数。
结果显示，与对照组胃溃疡指数5.87±0.48和NO水平（23.63±5.73）mmol·L⁻¹相比，姜黄素固体分散体（相当于姜黄素30和90 mg·kg⁻¹，口服）可使溃疡指数降低至4.59±0.96和3.33±0.93（P<0.01），并使血清NO水平升高至（29.75±5.90）mmol·L⁻¹（P<0.05）和（39.63±12.73）mmol·L⁻¹（P<0.01）。与对照组血浆ET（163.65±63.84）ng·L⁻¹相比，姜黄素固体分散体（相当于90 mg·kg⁻¹，口服）可使血浆ET水平降低至（104.22±63.84）ng·L⁻¹（P<0.05）。在大鼠幽门结扎模型中，与对照组胃溃疡指数4.25±0.71相比，姜黄素固体分散体（相当于姜黄素90 mg·kg⁻¹）可使胃溃疡指数降低至2.38±0.74（P<0.01）。与胃体积（14.61±1.80）mL、胃液酸度（87.70±9.84）mmol·L⁻¹和胃蛋白酶活性（408.63±41.75）U·mL⁻¹相比，姜黄素固体分散体（相当于姜黄素30、90 mg·kg⁻¹）可使胃体积降低至（12.68±1.46）mL（P<0.05）和（9.99±0.79）mL（P<0.01），使胃液酸度降低至（77.62±8.34）mmol·L⁻¹（P<0.05）和（65.77±8.19）mmol·L⁻¹（P<0.01），抑制胃蛋白酶活性至（358.13±37.44）U·mL⁻¹（P<0.05）和（292.13±41.93）U·mL⁻¹（P<0.01）。在利血平诱导的胃溃疡模型中，与对照组5.13±0.59相比，姜黄素固体分散体（相当于姜黄素30、90 mg·kg⁻¹）可使胃溃疡指数降低至3.88±0.40和3.03±0.64（P<0.01）。
多种动物胃溃疡模型证明，姜黄素固体分散体通过抑制胃酸分泌、降低胃液酸度、抑制胃蛋白酶活性和促进溃疡愈合而具有抗胃溃疡作用。这些发现表明姜黄素固体分散体作为一种抗溃疡药物具有潜在的应用价值。
