臺灣天仙果萃取物減緩去卵巢糖尿病小鼠周邊神經病變之研究
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2021
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國人糖尿病盛行率逐年攀升，而更年期婦女因女性賀爾蒙分泌紊亂易造成血糖的波動，為罹患糖尿病重要的高風險族群。神經病變為臨床常見的糖尿病合併症之一，糖尿病患者易因氧化壓力的增加導致末梢周邊神經受損等病變，起初會有蟲爬、疼痛等感覺過敏之情形，當神經完全凋亡時即會失去知覺並造成行動上的障礙。臺灣天仙果 (Ficus formosana Maxim.) 為桑科榕屬植物，生長於臺灣中低海拔山坡地，為坊間常見之食補藥材，具強筋健骨、調整經期等功效。本研究以去卵巢糖尿病雌性小鼠模擬更年期糖尿病婦女，探討臺灣天仙果熱水萃取物減緩其神經病變之效果。透過給予C57BL/6J去卵巢雌性小鼠餵食60%高脂飲食及施打低劑量STZ誘導為糖尿病，並以自由採食或管餵方式(含萃取物200、2000ppm)分別連續處理6週後，觀察小鼠血糖、神經相關行為之變化、足底末梢及坐骨神經病理切片以及發炎疼痛相關mRNA表現。結果顯示，自由採食高劑量(2000ppm)臺灣天仙果萃取物飼料可以顯著改善去卵巢糖尿病小鼠負控制組之血糖(p<0.05)；去卵巢糖尿病小鼠不論是以飼料或是管餵給予臺灣天仙果萃取物處理均能有效改善小鼠腳掌過度敏感、減緩C纖維的異常增生和斷裂、坐骨神經損失、減少氧化損傷之情形發生(p<0.05)，表示臺灣天仙果莖部萃取物可延緩去卵巢糖尿病小鼠腳掌因末梢神經受損所導致之過度敏感反應。文獻指出，坐骨神經中發炎相關激素的大量表達會引發疼痛感覺，本研究發現不論以自由採食飼料或是管餵(200、2000 ppm)天仙果萃取物處理，均能顯著降低去卵巢糖尿病小鼠坐骨神經中IL-1β、IL-6、IFN-γ、COX-2等發炎相關激素mRNA表現量 (p<0.05)。推測這可能是減緩疼痛及敏感的關鍵機制。本研究之結果可作為臺灣天仙果開發糖尿病神經病變藥物時參考，而其主要活性化合物及發炎與疼痛詳細機制有待未來進一步探討。
The prevalence of diabetes is increasing year by year in Taiwan. The menopausal women are prone to have fluctuations in blood sugar due to unstable secretion of female hormones, making them to be one of the high risk groups on suffering diabetes. Neuropathy is a common clinical diabetic complication. The peripheral nerves will be gradually damaged due to the increase of oxidative pressure. Initially, patients will be hyperesthesia, such as insect crawling, pain, etc., and lost feeling and action abilities when the nerves are completely apoptosis. Ficus formosana Maxim is a ficus plant in the moraceae family. It mainly grows on the slopes of low and middle-altitude hills in Taiwan. In this study, ovariectomized mice with type 2 diabetes were used to mimic menopausal diabetic women, and the effect of Ficus formosana Maxim extract (FFE) on reducing neuropathy in ovariectomized diabetic mice was invaluated. C57BL/6J ovariectomized female mice were fed high-fat diet (60% calorie of diet) and injected low-dose STZ (50mg/kg BD) to induce type 2 diabetes, and were given the extract daily by ad libitum and tube feeding FEE at dosages of 200, 2000ppm, respectively, for 6 weeks. At the end of animal trial, the blood chemicals, nerve-related behaviors, pathological sections of the intraepidermal and sciatic nerves, inflammation and pain response-related mRNA expressions in mice were analyzed. The results showed that the blood glucose level of high-dose FFE group significantly decreased compared to the STZ group (p<0.05). Moreover, FFE significantly alleviated the hypersensitivity, abnormal proliferation and rupture of C fiber, loss of sciatic nerve, and reduce oxidative damage in ovariectomized diabetic female mice. The high-dose FFE administered by tube shows the higest benefit (p<0.05) and is better than lipoic acid, which is currently used for diabetic neuropathy in the European Union. In this study, the administration of FFE significantly decreased the mRNA expression of IL-1β, IL-6, IFN-γ, COX-2 indiabetic mice (p<0.05). We speculated it may be associated to the key mechanism on alleviating pain and sensitivity, and the active compound may be associated to the abundant polyphenols of FFE. The further investigation on detail mechanisms of inflammation and pain, as well as the active compounds of FFE are necessary to evaluate the potential of Ficus formosana Maxim as a therapeutic drug of diabetic peripheral neuropathy.
The prevalence of diabetes is increasing year by year in Taiwan. The menopausal women are prone to have fluctuations in blood sugar due to unstable secretion of female hormones, making them to be one of the high risk groups on suffering diabetes. Neuropathy is a common clinical diabetic complication. The peripheral nerves will be gradually damaged due to the increase of oxidative pressure. Initially, patients will be hyperesthesia, such as insect crawling, pain, etc., and lost feeling and action abilities when the nerves are completely apoptosis. Ficus formosana Maxim is a ficus plant in the moraceae family. It mainly grows on the slopes of low and middle-altitude hills in Taiwan. In this study, ovariectomized mice with type 2 diabetes were used to mimic menopausal diabetic women, and the effect of Ficus formosana Maxim extract (FFE) on reducing neuropathy in ovariectomized diabetic mice was invaluated. C57BL/6J ovariectomized female mice were fed high-fat diet (60% calorie of diet) and injected low-dose STZ (50mg/kg BD) to induce type 2 diabetes, and were given the extract daily by ad libitum and tube feeding FEE at dosages of 200, 2000ppm, respectively, for 6 weeks. At the end of animal trial, the blood chemicals, nerve-related behaviors, pathological sections of the intraepidermal and sciatic nerves, inflammation and pain response-related mRNA expressions in mice were analyzed. The results showed that the blood glucose level of high-dose FFE group significantly decreased compared to the STZ group (p<0.05). Moreover, FFE significantly alleviated the hypersensitivity, abnormal proliferation and rupture of C fiber, loss of sciatic nerve, and reduce oxidative damage in ovariectomized diabetic female mice. The high-dose FFE administered by tube shows the higest benefit (p<0.05) and is better than lipoic acid, which is currently used for diabetic neuropathy in the European Union. In this study, the administration of FFE significantly decreased the mRNA expression of IL-1β, IL-6, IFN-γ, COX-2 indiabetic mice (p<0.05). We speculated it may be associated to the key mechanism on alleviating pain and sensitivity, and the active compound may be associated to the abundant polyphenols of FFE. The further investigation on detail mechanisms of inflammation and pain, as well as the active compounds of FFE are necessary to evaluate the potential of Ficus formosana Maxim as a therapeutic drug of diabetic peripheral neuropathy.
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Keywords
神經病變, 臺灣天仙果, 去卵巢, 糖尿病鼠, 抗發炎, Neuropathy, Ficus formosana Maxim, ovariectomized, diabetic mice, anti-inflammatory