蒟蒻補充劑對人體大腸癌發生相關因子之調節作用

Effect of konjac supplement on indices of colon cancer in human

吳文慈(Wen-tze Wu)

指導教授 ： 陳曉鈴

中山醫學大學/健康管理學院/營養學研究所/碩士(2006年)

https://doi.org/10.6834/CSMU.2006.00095

摘要

蒟蒻主要成分是葡甘聚醣(glucomannan)，是一種可溶性纖維；由D-葡萄糖和D-甘露糖以beta-1,4醣苷鍵鍵結合成的水溶性膳食纖維。本研究的目的是探討給予蒟蒻補充劑(4.5 g蒟蒻精粉/d) 4週後對於大腸癌發生之相關指標的調節作用，如糞便短鏈脂肪酸濃度、一級與二級膽酸濃度、大腸癌相關酵素指標等等；並進一步探討在高脂低纖維飲食型態下，蒟蒻補充劑對糞便水液產生對Caco-2細胞毒性及基因毒性之影響。
參試者依排便情形分為兩組(一)健康組：十六位無習慣性便秘及其他腸胃疾病之健康成人；(二)便秘組：十四位有習慣性排便困難或便秘之便秘成人，兩組參試者皆依年齡及體重配對方式分配於蒟蒻組與安慰劑組。參試者攝食7天循環性高脂低纖控制飲食，並補充蒟蒻精粉或玉米澱粉(安慰劑)膠囊28天 (4.5克/天)。參試者於實驗前一週及實驗期最後一週收集所有糞便樣品，以分析糞便中大腸癌相關指標以及糞便水對Caco-2細胞基因毒性之影響。
結果顯示，相較於控制組，在糞便細菌酵素部分，給予蒟蒻補充劑4週後，顯著降低健康參試者糞便中beta-glucuronidase活性，但顯著提高便秘參試者糞便中beta-glucosidase活性。在短鏈脂肪酸濃度方面，蒟蒻補充劑顯著提高健康參試者糞便中乙酸、丙酸、異丁酸、正丁酸及總短鏈脂肪酸的濃度，而僅顯著增加便秘參試者糞便中異丙酸濃度。糞便pH值部分，蒟蒻補充劑皆顯著降低健康與便秘參試者糞便pH值。給予蒟蒻補充劑4週後，雖然沒有顯著改變健康與便秘參試者糞便水中膽酸的濃度，但是健康參試者糞便水中二級膽酸佔總膽酸的比例由71.00 ± 6.22%降低至57.49 ± 6.56% (p＜0.05)。另外，健康與便秘參試者在給予蒟蒻補充劑4週後，都沒有顯著改變其糞便水螯合亞鐵離子的能力。
糞便水之細胞毒性結果顯示，健康與便秘參試者給予蒟蒻補充劑4週後，可顯著提升細胞存活率；以H2O2進ㄧ步誘發氧化傷害後觀察糞便水1小時及3小時細胞存活率發現，蒟蒻補充劑顯著降低健康參試者糞便水於3小時之細胞毒性，與便秘參試者糞便水於1小時及3小時之細胞毒性。糞便水基因毒性方面，蒟蒻補充劑顯著降低健康參試者糞便水對細胞DNA傷害；進一步以H2O2誘發DNA氧化傷害的表現時，蒟蒻補充劑可同時顯著降低健康與便秘參試者糞便水對Caco-2細胞DNA傷害的程度。
綜合以上結果發現，於高脂低纖飲食中補充蒟蒻四週後，可降低健康與便秘成人糞便中與大腸癌發生之相關酵素指標beta-glucuronidase活性及改善大腸環境指標，如糞便pH、短鏈脂肪酸濃度及糞便水中一級與二級膽酸佔總膽酸的比例，並可能藉此降低了糞便水對大腸細胞的細胞與基因毒性。

關鍵字

蒟蒻 ； 葡甘聚醣 ； 糞便酵素 ； 短鏈脂肪酸 ； 膽酸 ； pH ； 彗星影像分析

並列摘要

Konjac, a soluble dietary fiber, is rich in glucomannan polysaccharides which is composed of D-glucose and D-mannose by beta-1,4 glycosidic bond. The study was aimed to investigate effects of 4-wk glucomannan supplement (4.5 g/d) on biomarkers of colon cancer, such as fecal short chain fatty acid concentrations, fecal primary/secondary bile acid concentration and colon cancer-related enzyme activities, in adults who consumed high-fat, low-fiber diet. In addition, effects of konjac glucomannan supplement on fecal water cytotoxicity and genotoxicity on Caco-2 cells were also determined.
This study recruited two populations-healthy (n=16) and constipated (n=14) subjects. Each of them was age- and weight-matched into konjac (4.5 g glucomannan/d) and placebo (4.5 g cornstarch/d) groups and the experiment lasted for 28 days. All subjects were given a high-fat (35% as fat), low-fiber (＜15 g/d) control diet during the experiment. Feces collected during the week before the study and at the end of experimental period were analyzed for biomarkers of colon cancer and fecal water cytotoxicity and genotoxicity on Caco-2 cells.
Compared with placebo, KGM significantly decreased beta-glucuronidase activity (IU/mg protein), fecal pH and significantly increased acetate, propionate, i-butyrate, n-butyrate and total SCFA concentrations in healthy subjects. The KGM significantly increased beta-glucosidase activity (IU/mg protein), i-butyrate acid concentration and decreased fecal pH in constipated subjects as compared with placebo. Bile acid concentrations in the fecal water were not changed with the KGM supplement. However, KGM supplement significantly decreased the ratio of secondary bile acid to total bile acid from 71.00 ± 6.22% to 57.49 ± 6.56% in healthy subjects. In addition, the ability of ferrous ion chelating ability of fecal water was not significantly affected by KGM supplement.
KGM significantly increased cell survival when cells were treated with fecal water alone or fecal water combined with H2O2, respectively, for 3 h in both healthy and constipated subjects. The tail moment, an index of the DNA damage, induced by fecal water alone and combination with H2O2 were significantly lowered by KGM supplement.
These results indicate that KGM supplementation for four weeks with diet high in fat and low in dietary fiber improved the colon cancer-related enzymes, beta-glucuronidase, activities and colon ecology indices such as fecal pH, short chain fatty acid concentrations and the ratio of secondary bile acid to total bile acid in both healthy and constipated adults. The KGM supplement also decreased the cytotoxicity and genotoxicity of fecal water to colonic cells in both healthy and constipated adults. Therefore, KGM supplement for 4 wk may contribute to a lower risk of colorectal cancer.

並列關鍵字

konjac ； glucomannan ； fecal enzymes ； short chain fatty acid ； bile acid ； pH ； comet assay

參考文獻

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