臺灣扁柏葉子熱水抽出物之降血糖活性

Antihyperglycemic Activity of Hot Water Extract from Chamaecyparis obtusa var. formosana Leaves

許嘉紜(Chia-Yun Hsu)

指導教授 ： 張上鎮

國立臺灣大學/生物資源暨農學院/森林環境暨資源學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10588

摘要

臺灣扁柏 (Chamaecyparis obtusa var. formosana) 為本地特有樹種，也是臺灣藥用植物之一，本研究探討其葉子熱水抽出物之降血糖活性，首先評估α-葡萄糖苷酶抑制活性試驗、蛋白酪胺酸去磷酸酶1B (Protein tyrosine phosphatase 1B, PTP1B) 抑制活性試驗、3T3-L1前脂肪細胞分化抑制活性試驗和脂質累積抑制活性試驗，試驗結果顯示，葉子熱水抽出物抑制α-葡萄糖苷酶活性和抑制PTP1B活性極佳，並具有抑制3T3-L1前脂肪細胞分化和脂質累積之活性。
進一步以高血糖大鼠模式評估150和30 mg/kg b.w.臺灣扁柏葉子熱水抽出物之降血糖功效，其結果顯示，150 mg/kg b.w.葉子熱水抽出物具有抑制腸道Maltase、Sucrase、Amylase和Lipase之活性，減少養分的吸收進而減緩血糖的上升速率，以及抑制肝、肌肉、副睪脂肪和腎周脂肪的蛋白酪胺酸去磷酸酶 (Protein tyrosine phosphatases, PTPases) 之活性，降低胰島素阻抗和瘦體素阻抗，進而改善高血糖大鼠葡萄糖耐受性不良之現象。此外，改善瘦體素阻抗可減少高血糖大鼠體重和腎周脂肪的增加程度，並有助於降低胰島素阻抗。在相同劑量30 mg/kg b.w.下，與市售藥Pioglitazone相比，葉子熱水抽出物具控制體重、減少腎周脂肪和避免脂質代謝異常之優點。餵食150 mg/kg b.w.臺灣扁柏葉子熱水抽出物也不影響高血糖大鼠肝臟、膽、骨骼、腎臟和胰臟等的功能，肝臟、腎臟和胰臟組織也未因餵食臺灣扁柏葉子熱水抽出物引起任何病理變化。
此外，臺灣扁柏葉子熱水抽出物4個可溶部中，以正丁醇可溶部抑制α-葡萄糖苷酶活性為最佳，其B14次分離部為最強，並含有豐富之縮合單寧，其終端單體以Catechin、epi-Catechin和 (epi)-Gallocatechin的比例較其他次分離部低，而 (epi)-Catechin-A-(epi)-afzelechin的比例較高；延伸單體以Procyanidin A2、Methyl-(epi)-catechin和(epi)-Afzelechin的比例較高，其平均聚合度為14。本研究結果顯示，臺灣扁柏葉子熱水抽出物極具潛力開發為降血糖及控制體重之健康食品或藥物，非常值得後續更深入研究。

關鍵字

降血糖活性 ； 臺灣扁柏 ； 肥胖 ； 胰島素阻抗 ； α-葡萄糖苷酶 ； PTP1B ； 縮合單寧

並列摘要

Chamaecyparis obtusa var. formosana is a species indigenous to Taiwan, and it has been used as a medicinal plant in Taiwan. The aim of this study was to investigate the antihyperglycemic activity of hot water extract (HWE) from C. obtusa var. formosana leaves. Its antihyperglycemic activity was evaluated using α-glucosidase inhibitory assay, Protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, 3T3-L1 preadipocytes differentiation and lipid accumulation inhibitory assay. Results showed that HWE from C. obtusa var. formosana leaves exhibited the best inhibitory activity with α-glucosidase and PTP1B, and had the inhibitory activity on differentiation and lipid accumulation of 3T3-L1 preadipocytes.
In addition, the antihyperglycemic effect of 150 and 30 mg/kg b.w. HWE was further examined using hyperglycemic rats model. Results showed that HWE inhibited intestinal maltase, sucrase, amylase, and lipase, which led to delayed nutrient absorption and stabilized blood sugar levels. HWE also inhibited protein tyrosine phosphatases (PTPases) in liver, muscle, epididymal fat, and perirenal fat that exerted the improvements of insulin resistance, leptin resistance and glucose tolerance in hyperglycemic rats. Besides, an improvement in leptin resistance also resulted in a decrease of insulin resistance in hyperglycemic rats by reducing weight gain and perirenal fat gain. Compared with the same dosage of pioglitazone (30 mg/kg b.w.), a commercially available drug, HWE had beneficial effects on weight control, decreasing perirenal fat, and avoiding abnormal lipid metabolism. Feeding with 150 mg/kg b.w. HWE had no effect on liver, gall, bone, kidney and pancreas functions of hyperglycemic rats. The histopathological changes of liver, kidney and pancreas in hyperglycemic rats were not observed in this study.
Furthermore, n-butanol soluble fraction showed the highest α-glucosidase inhibitory activity among 4 fractions from HWE. Its B14 subfraction had the best α-glucosidase inhibitory activity and consisted of an abundance of condensed tannins. Compared with the other subfractions, B14 subfraction exhibited lower percentage of catechin, epi-catechin and (epi)-gallocatechin, and higher percentage of (epi)-catechin-A-(epi)-afzelechin in the terminal units; whereas it had higher percentage of procyanidin A2, methyl-(epi)-catechin, and (epi)-afzelechin in the extension units. It was noticeable that B14 subfraction had an average degree of polymerization up to 14. Results obtained in this study revealed that the hot water extract from C. obtusa var. formosana leaves has the potential to be used as a source for antihyperglycemic and weight control health food or drugs and warrants further investigations.

並列關鍵字

Antihyperglycemic activity ； Chamaecyparis obtusa var. formosana ； Obesity ； Insulin resistance ； α-Glucosidase ； PTP1B ； Condensed tannins

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