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研究生: 陳俐彣
Chen, Li-Wen
論文名稱: 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
Alleviative Effect of Ficus formosana Extract on Peripheral Neuropathy in Ovariectomized Diabetic Mice
指導教授: 沈賜川
Shen, Szu-Chuan
吳瑞碧
Wu, Swi-Bea
丁俞文
Ting, Yu-Wen
口試委員: 沈賜川
Shen, Szu-Chuan
吳瑞碧 丁俞文 吳忠信 黃文忠 趙伯寬
口試日期: 2021/08/16
學位類別: 碩士
Master
系所名稱: 營養科學碩士學位學程
Graduate Program of Nutrition Science
論文出版年: 2021
畢業學年度: 109
語文別: 中文
論文頁數: 82
中文關鍵詞: 神經病變臺灣天仙果去卵巢糖尿病鼠抗發炎
英文關鍵詞: Neuropathy, Ficus formosana Maxim, ovariectomized, diabetic mice, anti-inflammatory
研究方法: 實驗設計法
DOI URL: http://doi.org/10.6345/NTNU202101511
論文種類: 學術論文
相關次數: 點閱:113下載:0
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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 in diabetic 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.

    第一章 前言 1 第二章 文獻回顧 第一節. 糖尿病 一、糖尿病定義、流行病學 2 二、胰島素與胰島素阻抗 3 三、糖尿病病徵、分類 4 四、糖尿病臨床診斷 6 第二節 糖尿病周邊神經病變 一、糖尿病周邊神經病變之診斷、流行病學 7 二、周邊神經結構與功能 9 三、氧化壓力對周邊神經之影響 10 第三節 發炎與疼痛性糖尿病神經病變 一、疼痛傳遞機制 13 二、神經受損與發炎疼痛反應 14 三、電壓門控鈉離子通道 14 四、臨床上疼痛性糖尿病神經病變藥物 16 第四節 糖尿病與更年期婦女神經病變 一、更年期定義、症狀 17 二、更年期婦女賀爾蒙之變化 17 三、更年期婦女與糖尿病神經病變之關聯 19 第五節 臺灣天仙果(Ficus formosana Maxim) 一、臺灣天仙果簡介 20 二、臺灣天仙果成分 20 三、臺灣天仙果之藥理作用 20 四、臺灣天仙果莖部熱水萃取物治療糖尿病周邊神經病變之潛力 22 第三章 研究動機及實驗架構 第一節 研究動機與目的 23 第二節 實驗架構 24 第四章 實驗材料與方法 第一節 實驗藥品與儀器 一、 實驗藥品與試劑 25 二、 儀器設備 25 第二節 樣品來源與成分 一、 實驗樣品來源與製備 26 二、 實驗樣品成分 27 第三節. 動物試驗設計 一、實驗動物 27 二、實驗動物飼料 27 三、實驗動物誘導與分組 28 四、實驗方法 29 五、統計分析 34 第五章 結果 第一節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠血糖之影響 一、臺灣天仙果莖部熱水萃取物介入第零週之血糖值 35 二、臺灣天仙果莖部熱水萃取物介入六週後之血糖值 35 三、臺灣天仙果莖部熱水萃取物介入六週後血糖變化值 35 第二節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠行為之影響 一、腳掌機械刺激測試-Von Frey Filament testing 39 二、溫度感應測試Thermal perception testing 39 第三節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠病理切片之影響 一、足部表皮神經分佈 42 二、坐骨神經病理切片 42 第四節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠胰島素阻抗、髓鞘合成相關蛋白mRNA表現之影響 一、胰島素受體底物-2(IRS-2)mRNA表現量 49 二、生長因子受體蛋白-2(Grb2)mRNA表現量 49 第五節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠發炎相關蛋白mRNA表現之影響 一、腫瘤壞死因子-α(TNF-α)mRNA表現量 52 二、干擾素-γ (IFN-γ) mRNA表現量 52 三、白細胞介素-6(IL-6)mRNA表現量 55 四、白細胞介素-1β(IL-β)mRNA表現量 55 五、環氧合酶-2(Cox-2)mRNA表現量 55 第六節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠發炎疼痛鈉離子通道相關蛋白mRNA表現之影響 一、電壓門控鈉離子通道-Nav1.8 mRNA表現量 59 二、蛋白激酶-ε (PKC- ε) mRNA表現量 59 第六章 討論 第一節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠血糖與血液生化代謝指標之影響 一、胰島素、血糖變化 62 二、血脂變化 62 第二節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠行為試驗及足底末梢神經之影響 一、行為試驗之影響 63 二、足底末梢神經之變化 64 三、保護足底末梢的可能機制 64 第三節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠坐骨神經氧化傷害及髓鞘合成之影響 一、減緩氧化傷害 65 二、髓鞘合成相關蛋白之mRNA表現 65 第四節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠之抗發炎效應 66 第五節 臺灣天仙果莖部熱水萃取物對去卵巢糖尿病雌性小鼠之疼痛通道mRNA表現之影響 67 第七章 結論 69 參考文獻 71 附錄 82

    李昆錚。(2009)。臺灣天仙果之抗氧化活性及其對STZ誘導糖尿病大白鼠之影響。中國醫藥大學中國藥學研究所碩士班碩士論文,台中市。https://hdl.handle.net/11296/awr2p2
    田秉玉。(2020)。臺灣天仙果萃取物對人類腸道上皮細胞株Caco-2鈣離子運輸與糖尿病去卵巢雌性小鼠骨質疏鬆之影響。國立臺灣師範大學營養科學碩士學位學程碩士論文,台北市。https://hdl.handle.net/11296/qcu9ub
    楊惠婷。(2012)。臺灣天仙果根部熱水萃取物之抗氧化性質研究。嘉南藥理科技大學保健營養系碩士論文,台南市。https://hdl.handle.net/11296/273yyz
    郭子揚(2012)。台灣天仙果莖部化學成分及生物活性之研究。國立屏東科技大學生物科技研究所碩士論文,屏東縣。https://hdl.handle.net/11296/pz9u29
    王亭今(2016)。台灣天仙果莖部血管收縮素轉化酶抑制活性成分之研究。國立屏東科技大學生物科技系所碩士論文,屏東縣。https://hdl.handle.net/11296/tbrrmk
    陳枻瑋(2011)。台灣天仙果分離出成分繖型花內酯抑制蝕骨細胞生成和小鼠骨再吸收。中國醫藥大學基礎醫學研究所碩士班碩士論文,台中市。https://hdl.handle.net/11296/8rm3j7
    邱年永、張光雄。(1992)。原色臺灣藥用植物圖鑑. 台灣台北:南天書局
    衛生福利部國民健康署。(2018)。三高防治專區(高血壓、高血脂、糖尿病)。https://www.hpa.gov.tw/Pages/List.aspx?nodeid=359
    衛生福利部國民健康署。(2016)。104年健康促進統計年報。https://www.hpa.gov.tw/Pages/List.aspx?nodeid=268
    Abbadie C. (2005). Chemokines, chemokine receptors and pain. Trends in immunology, 26(10), 529–534. https://doi.org/10.1016/j.it.2005.08.001
    Adeshara, K. A., Diwan, A. G., & Tupe, R. S. (2016). Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies. Current drug targets, 17(11), 1309–1328. https://doi.org/10.2174/1389450117666151209124007
    Ahsan H. (2013). 3-Nitrotyrosine: A biomarker of nitrogen free radical species modified proteins in systemic autoimmunogenic conditions. Human immunology, 74(10), 1392–1399. https://doi.org/10.1016/j.humimm.2013.06.009
    Alqahtani, S., Welton, K., Gius, J. P., Elmegerhi, S., & Kato, T. A. (2019). The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition. International journal of molecular sciences, 20(6), 1274. https://doi.org/10.3390/ijms20061274
    American Diabetes Association. (2019). Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care. 42(Supplement 1): S13-S28
    Basu, P., & Basu, A. (2020). In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain. Molecules (Basel, Switzerland), 25(5), 1171. https://doi.org/10.3390/molecules25051171
    Cai, E. P., & Lin, J. K. (2009). Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic beta cells. Journal of agricultural and food chemistry, 57(20), 9817–9827. https://doi.org/10.1021/jf902618v
    Celik, S., & Erdogan, S. (2008). Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats. Molecular and cellular biochemistry, 312(1-2), 39–46. https://doi.org/10.1007/s11010-008-9719-3
    Chapman, G. A., Moores, K., Harrison, D., Campbell, C. A., Stewart, B. R., & Strijbos, P. J. (2000). Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. The Journal of neuroscience : the official journal of the Society for Neuroscience, 20(15), RC87. https://doi.org/10.1523/JNEUROSCI.20-15-j0004.2000
    Chen, Y., Guo, W., Xu, L., Li, W., Cheng, M., Hu, Y., & Xu, W. (2016). 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model. BioMed research international, 2016, 7891202. https://doi.org/10.1155/2016/7891202
    Chiang, J. L., Kirkman, M. S., Laffel, L. M., Peters, A. L., & Type 1 Diabetes Sourcebook Authors (2014). Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes care, 37(7), 2034–2054. https://doi.org/10.2337/dc14-1140
    Cortelazzi, D., Marconi, A., Guazzi, M., Cristina, M., Zecchini, B., Veronelli, A., Cattalini, C., Innocenti, A., Bosco, G., & Pontiroli, A. E. (2013). Sexual dysfunction in pre-menopausal diabetic women: clinical, metabolic, psychological, cardiovascular, and neurophysiologic correlates. Acta diabetologica, 50(6), 911–917. https://doi.org/10.1007/s00592-013-0482-x
    Davidson, E., Coppey, L., Lu, B., Arballo, V., Calcutt, N. A., Gerard, C., & Yorek, M. (2009). The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine experimental diabetic neuropathy. Experimental diabetes research, 2009, 431980. https://doi.org/10.1155/2009/431980
    Davis, S. R., Lambrinoudaki, I., Lumsden, M., Mishra, G. D., Pal, L., Rees, M., ... & Simoncini, T. (2015). Menopause. Nature reviews Disease primers, 1(1), 1-19.
    Esposito, K., Ciotola, M., Giugliano, F., Carleo, D., Schisano, B., Maglione, E., Di Tommaso, D., De Sio, M., & Giugliano, D. (2007). Quantitative sensory and autonomic testing in nondiabetic women with sexual dysfunction. The journal of sexual medicine, 4(5), 1367–1372. https://doi.org/10.1111/j.1743-6109.2007.00572.x
    Ellis, L. Z., Liu, W., Luo, Y., Okamoto, M., Qu, D., Dunn, J. H., & Fujita, M. (2011). Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion. Biochemical and biophysical research communications, 414(3), 551–556. https://doi.org/10.1016/j.bbrc.2011.09.115
    Feldman, E. L., Nave, K. A., Jensen, T. S., & Bennett, D. (2017). New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain. Neuron, 93(6), 1296–1313. https://doi.org/10.1016/j.neuron.2017.02.005
    Fernández-Mejía, C. (2013). Oxidative stress in diabetes mellitus and the role of vitamins with antioxidant actions. Oxidative stress and chronic degenerative diseases-a role for antioxidants, 209.
    Green, A. Q., Krishnan, S., Finucane, F. M., & Rayman, G. (2010). Altered C-fiber function as an indicator of early peripheral neuropathy in individuals with impaired glucose tolerance. Diabetes care, 33(1), 174–176. https://doi.org/10.2337/dc09-0101
    Guo, H., Xia, M., Zou, T., Ling, W., Zhong, R., & Zhang, W. (2012). Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1. The Journal of nutritional biochemistry, 23(4), 349–360. https://doi.org/10.1016/j.jnutbio.2010.12.013
    Hanhineva, K., Törrönen, R., Bondia-Pons, I., Pekkinen, J., Kolehmainen, M., Mykkänen, H., & Poutanen, K. (2010). Impact of dietary polyphenols on carbohydrate metabolism. International journal of molecular sciences, 11(4), 1365–1402. https://doi.org/10.3390/ijms11041365
    Herder, C., & Roden, M. (2011). Genetics of type 2 diabetes: pathophysiologic and clinical relevance. European journal of clinical investigation, 41(6), 679–692. https://doi.org/10.1111/j.1365-2362.2010.02454.x
    Ilfeld, B. M., Preciado, J., & Trescot, A. M. (2016). Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves. Expert review of medical devices, 13(8), 713–725. https://doi.org/10.1080/17434440.2016.1204229
    Iqbal, Z., Azmi, S., Yadav, R., Ferdousi, M., Kumar, M., Cuthbertson, D. J., Lim, J., Malik, R. A., & Alam, U. (2018). Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy. Clinical therapeutics, 40(6), 828–849. https://doi.org/10.1016/j.clinthera.2018.04.001
    Ji, R. R., & Strichartz, G. (2004). Cell signaling and the genesis of neuropathic pain. Science's STKE : signal transduction knowledge environment, 2004(252), reE14. https://doi.org/10.1126/stke.2522004re14
    Karvonen-Gutierrez, C. A., Park, S. K., & Kim, C. (2016). Diabetes and Menopause. Current diabetes reports, 16(4), 20. https://doi.org/10.1007/s11892-016-0714-x
    Kim, Y., Keogh, J. B., & Clifton, P. M. (2016). Polyphenols and Glycemic Control. Nutrients, 8(1), 17. https://doi.org/10.3390/nu8010017
    Komirishetty, P., Areti, A., Sistla, R., & Kumar, A. (2016). Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation. Neurochemical research, 41(8), 2029–2042. https://doi.org/10.1007/s11064-016-1914-0
    Kumar, A., Kaundal, R. K., Iyer, S., & Sharma, S. S. (2007). Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life sciences, 80(13), 1236–1244. https://doi.org/10.1016/j.lfs.2006.12.036
    Kurimoto, Y., Shibayama, Y., Inoue, S., Soga, M., Takikawa, M., Ito, C., Nanba, F., Yoshida, T., Yamashita, Y., Ashida, H., & Tsuda, T. (2013). Black soybean seed coat extract ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase in diabetic mice. Journal of agricultural and food chemistry, 61(23), 5558–5564. https://doi.org/10.1021/jf401190y
    Lee, C. C., Perkins, B. A., Kayaniyil, S., Harris, S. B., Retnakaran, R., Gerstein, H. C., Zinman, B., & Hanley, A. J. (2015). Peripheral Neuropathy and Nerve Dysfunction in Individuals at High Risk for Type 2 Diabetes: The PROMISE Cohort. Diabetes care, 38(5), 793–800. https://doi.org/10.2337/dc14-2585
    Lee, J. S., Lee, Y. s., Jeon, B., Jeon, Y. j., Yoo, H., & Kim, T. Y. (2012). EC-SOD induces apoptosis through COX-2 and galectin-7 in the epidermis. Journal of dermatological science, 65(2), 126–133. https://doi.org/10.1016/j.jdermsci.2011.12.013
    Lukic, I. K., Humpert, P. M., Nawroth, P. P., & Bierhaus, A. (2008). The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy. Annals of the New York Academy of Sciences, 1126(1), 76-80.
    Manu, M. S., Rachana, K. S., & Advirao, G. M. (2017). Altered expression of IRS2 and GRB2 in demyelination of peripheral neurons: Implications in diabetic neuropathy. Neuropeptides, 62, 71–79. https://doi.org/10.1016/j.npep.2016.12.004
    Nilsen, J., & Brinton, R. D. (2004). Mitochondria as therapeutic targets of estrogen action in the central nervous system. Current drug targets. CNS and neurological disorders, 3(4), 297–313. https://doi.org/10.2174/1568007043337193
    Oates P. J. (2008). Aldose reductase, still a compelling target for diabetic neuropathy. Current drug targets, 9(1), 14–36. https://doi.org/10.2174/138945008783431781
    O'Banion M. K. (1999). Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Critical reviews in neurobiology, 13(1), 45–82. https://doi.org/10.1615/critrevneurobiol.v13.i1.30
    Obrosova, I. G., Drel, V. R., Pacher, P., Ilnytska, O., Wang, Z. Q., Stevens, M. J., & Yorek, M. A. (2005). Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. Diabetes, 54(12), 3435–3441. https://doi.org/10.2337/diabetes.54.12.3435
    Older Adults: Standards of Medical Care in Diabetes—2020American Diabetes Association .Diabetes Care Jan 2020, 43 (Supplement 1) S152-S162; DOI: 10.2337/dc20-S012
    Persson, A. K., Black, J. A., Gasser, A., Cheng, X., Fischer, T. Z., & Waxman, S. G. (2010). Sodium-calcium exchanger and multiple sodium channel isoforms in intra-epidermal nerve terminals. Molecular pain, 6, 1744-8069.
    Pfeilschifter, J., Köditz, R., Pfohl, M., & Schatz, H. (2002). Changes in proinflammatory cytokine activity after menopause. Endocrine reviews, 23(1), 90–119. https://doi.org/10.1210/edrv.23.1.0456
    Phielix, E., & Roden, M. (2013). Assessing multiple features of mitochondrial function. Diabetes, 62(6), 1826–1828. https://doi.org/10.2337/db13-0303
    Plows, J. F., Stanley, J. L., Baker, P. N., Reynolds, C. M., & Vickers, M. H. (2018). The Pathophysiology of Gestational Diabetes Mellitus. International journal of molecular sciences, 19(11), 3342. https://doi.org/10.3390/ijms19113342
    Pop-Busui, R., Boulton, A. J., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., ... & Ziegler, D. (2017). Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes care, 40(1), 136-154.
    Pulivendala, G., Bale, S., & Godugu, C. (2020). Honokiol: A polyphenol neolignan ameliorates pulmonary fibrosis by inhibiting TGF-β/Smad signaling, matrix proteins and IL-6/CD44/STAT3 axis both in vitro and in vivo. Toxicology and applied pharmacology, 391, 114913. https://doi.org/10.1016/j.taap.2020.114913
    Roberts, A. C., & Porter, K. E. (2013). Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diabetes & vascular disease research, 10(6), 472–482. https://doi.org/10.1177/1479164113500680
    Salthouse T. N. (1964). Luxol fast blue G as myelin stain. Stain technology, 39, 123.
    Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S., Allchorne, A., Poole, S., Bonventre, J. V., & Woolf, C. J. (2001). Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature, 410(6827), 471–475. https://doi.org/10.1038/35068566
    Sandireddy, R., Yerra, V. G., Areti, A., Komirishetty, P., & Kumar, A. (2014). Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. International journal of endocrinology, 2014, 674987. https://doi.org/10.1155/2014/674987
    Schweizer, A., Feige, U., Fontana, A., Müller, K., & Dinarello, C. A. (1988). Interleukin-1 enhances pain reflexes. Mediation through increased prostaglandin E2 levels. Agents and actions, 25(3-4), 246–251. https://doi.org/10.1007/BF01965025
    Schweizerhof, M., Stösser, S., Kurejova, M., Njoo, C., Gangadharan, V., Agarwal, N., Schmelz, M., Bali, K. K., Michalski, C. W., Brugger, S., Dickenson, A., Simone, D. A., & Kuner, R. (2009). Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nature medicine, 15(7), 802–807. https://doi.org/10.1038/nm.1976
    Sites, C. K., Calles-Escandón, J., Brochu, M., Butterfield, M., Ashikaga, T., & Poehlman, E. T. (2000). Relation of regional fat distribution to insulin sensitivity in postmenopausal women. Fertility and sterility, 73(1), 61–65. https://doi.org/10.1016/s0015-0282(99)00453-7
    Sowers, M. F., Zheng, H., McConnell, D., Nan, B., Karvonen-Gutierrez, C. A., & Randolph, J. F., Jr (2009). Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging. Human reproduction (Oxford, England), 24(9), 2276–2285. https://doi.org/10.1093/humrep/dep209
    Stavniichuk, R., Shevalye, H., Lupachyk, S., Obrosov, A., Groves, J. T., Obrosova, I. G., & Yorek, M. A. (2014). Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy. Diabetes/metabolism research and reviews, 30(8), 669–678. https://doi.org/10.1002/dmrr.2549
    Sturdee, D. W., Hunter, M. S., Maki, P. M., Gupta, P., Sassarini, J., Stevenson, J. C., & Lumsden, M. A. (2017). The menopausal hot flush: a review. Climacteric : the journal of the International Menopause Society, 20(4), 296–305. https://doi.org/10.1080/13697137.2017.1306507
    Su, C., & Schwarz, T. L. (2017). O-GlcNAc Transferase Is Essential for Sensory Neuron Survival and Maintenance. The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(8), 2125–2136. https://doi.org/10.1523/JNEUROSCI.3384-16.2017
    Terra, X., Pallarés, V., Ardèvol, A., Bladé, C., Fernández-Larrea, J., Pujadas, G., Salvadó, J., Arola, L., & Blay, M. (2011). Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. The Journal of nutritional biochemistry, 22(4), 380–387. https://doi.org/10.1016/j.jnutbio.2010.03.006
    Thorens B. (2015). GLUT2, glucose sensing and glucose homeostasis. Diabetologia, 58(2), 221–232. https://doi.org/10.1007/s00125-014-3451-1
    Turner, B., Williams, S., Taichman, D., & Vijan, S. (2010). Type 2 Diabetes. Annals of Internal Medicine, 152(5), ITC3-1. doi:10.7326/0003-4819-152-5-201003020-01003
    Vincent, A., Bien, C. G., Irani, S. R., & Waters, P. (2011). Autoantibodies associated with diseases of the CNS: new developments and future challenges. The Lancet. Neurology, 10(8), 759–772. https://doi.org/10.1016/S1474-4422(11)70096-5
    Watkins, P. J., & Thomas, P. K. (1998). Diabetes mellitus and the nervous system. Journal of Neurology, Neurosurgery & Psychiatry, 65(5), 620-632.
    Wu, D. F., Chandra, D., McMahon, T., Wang, D., Dadgar, J., Kharazia, V. N., Liang, Y. J., Waxman, S. G., Dib-Hajj, S. D., & Messing, R. O. (2012). PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice. The Journal of clinical investigation, 122(4), 1306–1315. https://doi.org/10.1172/JCI61934
    Yi, X., & Maeda, N. (2006). alpha-Lipoic acid prevents the increase in atherosclerosis induced by diabetes in apolipoprotein E-deficient mice fed high-fat/low-cholesterol diet. Diabetes, 55(8), 2238–2244. https://doi.org/10.2337/db06-0251
    Yorek, M. S., Obrosov, A., Shevalye, H., Coppey, L. J., Kardon, R. H., & Yorek, M. A. (2017). Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: effect on diabetic neuropathy related endpoints. Neuropharmacology, 116, 122-131.
    Zhang, H., & Tsao, R. (2016). Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Current Opinion in Food Science, 8, 33-42.

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