探討抹草萃取物應用於胰臟beta細胞再生之體內外研究

糖尿病(diabetes)因胰島beta-細胞(pancreatic beta-cell)分泌胰島素異常或產生胰島素阻抗，使血糖異常升高，故維持胰島細胞正常生長與正常功能將是糖尿病防治的關鍵，尋找可輔助糖尿病治療之天然物是近年研究方向之一。過去研究發現抹草萃取物(Desmodium caudatum extract, DCE)有抗氧化、抗癌的效果，然而尚未有DCE預防或改善糖尿病的相關研究。本研究探討DCE在體內外試驗中，改善糖尿病之效果。體外試驗以過氧化氫(hydrogen peroxide, H2O2)誘導大鼠胰島β細胞RIN-m5F過氧化損傷並以DCE介入治療，發現DCE可降低氧化傷害並調控胰島細胞之細胞週期(cell cycle)。透過抑制p21與p27(kip1)蛋白，促使胰島細胞由G1期進入S期，同時增加細胞增殖和DNA複製及修復相關蛋白PCNA之表現，最終促進胰島細胞再生及改善胰島素分泌功能。體內試驗以高脂飲食(high fat diet, HFD)合併鏈脲佐菌素(streptozotocin, STZ)誘發C57/BL6小鼠之糖尿病模型，實驗組每日管餵100 mg/kg及200 mg/kg DCE持續六週，並以臨床降血糖藥二甲雙胍(metformin)為對照治療組，實驗結果發現DCE有降低血糖、改善胰島素阻抗、減少脂質過氧化傷害以及促進胰島β細胞再生之效果。總結，DCE可透過促進胰島β細胞再生並改善胰島素分泌之功能，達到降血糖之效果，未來有機會用於糖尿病的輔助治療。

Diabetes is caused by abnormal insulin secretion of pancreatic beta cells or occurrence of insulin resistance, resulting in high blood sugar. Therefore, maintaining the normal growth and function of pancreatic beta-cells will be the key to prevention and treatment of diabetes. In recent years, natural plants with antioxidative activity can have the potential therapeutic application to diabetes. Previous studies have found that Desmodium caudatum extracts (DCE) exert antioxidant and anti-cancer effects. However, the effect and mechanism of DCE on pancreatic beta cell dysfunction, a major event in the pathogenesis of diabetes, is still unknown. This study investigates the effect of DCE on improving diabetes in vitro and in vivo. In vitro study, peroxidative damage of rat pancreatic beta-cells RIN-m5F was induced by hydrogen peroxide (H2O2) and intervened in treatment with DCE. We found that DCE can reduce oxidative damage and regulate the cell cycle of beta-cells. Through inhibiting p21 & p27 (kip1) proteins, the cell cycle of beta-cells were promoted from G1 phase to S phase. Moreover, the expression of PCNA, a protein related to cell proliferation and DNA replication & repair, is increased. Ultimately, DCE protects RIN-m5F by promoting regeneration and improving insulin secretion. In vivo study, the diabetes model of C57/BL6 mice w induced by a high-fat diet (HFD) combined with streptozotocin (STZ). The experimental group was fed 100 mg/kg and 200 mg/kg DCE daily by oral gavage for six weeks, and metformin, the clinical hypoglycemic drug, was used as the control treatment group. The results show that DCE can reduce blood sugar and lipid peroxidation damage, improve insulin resistance and promote the regeneration of pancreatic beta-cells. In conclusion, DCE can achieve the effect of lowering blood sugar by promoting the regeneration of pancreatic β-cells and improving the function of insulin secretion. Therefore, DCE will potentially to use as adjuvant therapy for diabetes in the future.