臺灣博碩士論文加值系統

黑蒜為大蒜(Allium sativum L)利用高溫高濕自然發酵熟成，具有相對較高之活性成分，然目前對於黑蒜的熟成變化與免疫調節功能仍不甚清楚，因此本研究將生大蒜，透過不同的溫度、濕度與熟成天數等不同的條件控制(熟成條件：70℃, 80%相對溼度、70℃, 70%相對溼度、60℃, 80%相對溼度，並分別熟成0、10及20天)，以製造出不同的黑蒜，探討熟成期間其內部成分變化，從中挑選出最佳熟成條件。結果顯示，綜合外觀觀察、水分含量變化及色澤變化比較，以70℃, 80% RH為最佳；褐變程度、游離還原糖與游離胺基酸結果比較，以70℃, 80%熟成20天變化最明顯；總多酚、類黃酮、皂苷含量變化顯示，70℃, 80%含量最高，綜合本研究結果，建議以70℃, 80%相對溼度熟成20天為黑蒜之最佳熟成條件。
進一步將最佳熟成黑蒜依序以正己烷、95%乙醇、熱水等低、中、高極性溶劑萃取，以生大蒜作為對照組，探討黑蒜不同萃取物對BALB/c小鼠初代脾臟細胞Th1/Th2細胞免疫調節之影響，以及在脂多醣(lipopolysaccharide, LPS)誘導發炎下對初代腹腔巨噬細胞之促/抗發炎細胞激素分泌之影響，並分析不同萃取物中的成分與免疫細胞受調節之細胞激素的相關性，以及對人類乳腺癌細胞生長之影響。結果顯示，黑蒜熱水萃取物(BGHWE)有效減少脾臟細胞IL-4細胞激素之分泌且有劑量反應關係。在LPS誘導巨噬細胞發炎模式下，發現生大蒜與熟成黑蒜乙醇萃取物皆能有效降低發炎程度，然兩者之間無顯著差異；黑蒜熱水萃取物可以顯著抑制IL-1β分泌以及顯著增加IL-10分泌，較生大蒜更具有抗發炎作用，整體評估黑蒜之免疫調節作用，以熱水萃取物效果最好，具有抗過敏與抗發炎的作用。相關性分析結果顯示，黑蒜熱水萃取物中之指標成分，並無何種單獨成分，對於黑蒜之免疫調節效果中具有特別明顯之貢獻，推測萃取物中各種未知成分之間，可能具有相互影響或互相干擾之作用，導致相關性減弱。另外，黑蒜熱水萃取物對MCF-7細胞生長無論直接與經由免疫細胞調節之間接作用皆無抑制MCF-7細胞生長之效果。

Black garlic is prepared from fresh raw garlic (Allium sativum L.) through aging at high temperature and high humidity for a period of time. It is presumed that black garlic has the better physiological function than that of raw garlic. However, changes in aging process and immunomodulatory effects of black garlic still remain unclear. To clarify the puzzle, raw garlic was treated at different controlled temperature and relative humidity (RH) for different incubation time (aging condition: 70℃ and 80% RH, 70℃ and 70% RH, as well as 60℃ and 80% RH for 0, 10 and 20 days, respectively) to produce different kinds of black garlic for investigating their changes in components during aging process. Based on the results, the best aging condition would be recommended. The results showed that 70℃ and 80% RH was the best aging condition according to the appearance, moisture content and color changes of aged black garlic. Aging at 70℃ and 80% RH for 20 days showed prominent changes in browning index, free reducing sugar content and free amino acid content. Aging at 70℃ and 80% RH had the highest content of total polyphenol, flavonoids and saponins in aged black garlic. Therefore, aging at 70℃ and 80% RH for 20 days was suggested to be the best aging condition for black garlic aging.
To evaluate immunomodulatory effects of aged black garlic, the best aged black garlic was sequentially extracted using n-hexane, 95% ethanol and hot water that were corresponding to low, medium and high polar solvents, respectively. Raw garlic was selected as a control in the experiment. Effects of different aged black garlic extracts on Th1/Th2 immune balance of splenocytes and pro-/anti-inflammatory cytokines secretion by lipopolysaccharide (LPS)-induced peritoneal macrophages form female BALB/c mice were investigated. The relationships between cytokines secretion by regulated immune cells and possible bioactive components in different aged black garlic extracts were analyzed. In addition, effects of different aged black garlic extract on human breast cancer MCF-7 cells were studied. The results showed that black garlic hot water extracts (BGHWE) had anti-allergic potential for it significantly reduced IL-4 secretion by splenocytes dose-dependently. Both ethanol extracts of aged black garlic and raw garlic reduced inflammatory responses in LPS-induced peritoneal macrophages, while the impact were similar to each other. BGHWE significantly suppressed IL-1β secretion but significantly enhanced IL-10 secretion, indicating that it had the strongest anti-inflammatory effects among different aged black garlic extracts. BGHWE had the better anti-inflammatory effect than that of raw garlic hot water extracts. BGHWE exhibited the best anti-allergic and anti-inflammatory potential among different extracts. However, there was no significant correlation between individual marker components in different extracts and cytokines secretion by regulated immune cells. It was assumed that unknown components exist in black garlic extracts might influence or interfere each other, resulting in a decrease of correlation. Unfortunately, BGHWE had no obvious effects on the growth of human breast cancer MCF-7 cells regardless of direct or indirect models.

摘要 i
Abstract iii
目次 v
圖目次 viii
表目次 x
縮寫對照表 xi
緒言 1
第一章 文獻回顧 2
第一節 、免疫系統的組成及反應 2
一、先天性免疫系統 (innate immune system) 2
二、適應性免疫系統(adaptive immune system) 2
第二節 、體內Th1/Th2免疫平衡與健康的關係 5
第三節 、發炎免疫反應與癌症 7
第四節 、黑蒜(black garlic)背景介紹 9
第五節 、黑蒜在免疫調節與癌症的相關研究 11
第六節 、研究動機與目的 12
第七節 、論文架構與實驗大綱 13
第二章 黑蒜之最適發酵熟成條件探討 14
第一節 前言 14
第二節 實驗架構 14
第三節 材料方法 15
一、不同熟成條件之樣品製備 15
二、黑蒜熟成期間色澤變化測定 17
三、黑蒜熟成期間褐變反應程度的變化 18
四、黑蒜熟成期間總多酚、類黃酮與皂苷含量變化 20
五、統計分析 23
第四節 結果與討論 24
一、不同熟成條件之樣品製備 24
二、黑蒜熟成期間色澤變化 28
三、黑蒜熟成期間褐變反應程度的變化 31
四、黑蒜熟成期間總多酚、類黃酮與皂苷含量變化 34
第五節 結論 37
第三章 黑蒜對小鼠初代免疫細胞免疫調節之影響 38
第一節 前言 38
第二節 實驗架構 38
第三節 材料方法 39
一、樣品連續萃取與萃取物之製備 39
二、成分分析 41
三、熟成黑蒜不同萃取物對BALB/c雌鼠初代脾臟免疫細胞生長之影響 42
四、熟成黑蒜不同萃取物對BALB/c雌鼠初代脾臟免疫細胞分泌細胞激素之影響 47
五、熟成黑蒜不同萃取物對BALB/c雌鼠初代巨噬細胞促發炎與抗發炎細胞激素分泌之影響 51
六、黑蒜不同萃取物中之活性成分與小鼠免疫細胞細胞激素分泌之相關性 55
七、黑蒜熱水萃取物對人類乳腺癌MCF-7細胞生長之影響 56
八、 統計分析 62
第四節 結果與討論 63
一、生大蒜與熟成黑蒜不同萃取物之萃取產率 63
二、成分分析 64
三、生大蒜與熟成黑蒜不同萃取物對BALB/c雌鼠初代脾臟細胞生長之影響 66
四、生大蒜與熟成黑蒜不同萃取物對BALB/c雌鼠初代脾臟細胞分泌細胞激素之影響 70
五、熟成黑蒜不同萃取物對初代巨噬細胞發炎反應之影響 75
六、黑蒜不同萃取物與小鼠免疫細胞細胞激素分泌之相關性 80
七、黑蒜熱水萃取物對人類乳腺癌MCF-7細胞生長之影響 86
第五節 結論 90
第四章 總討論與總結 91
第五章 參考文獻 92

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