Dendrocnide meyeniana（Dm），Urtica thunbergiana Sieb。 ＆Zucc（Ut）和Alocasia odora（Lodd。）Sp​​ach（Ao）含有蕁麻刺或汁液引起接觸性皮炎。然而，這些刺痛植物提取物作為透皮藥物遞送（TDD）滲透促進劑的潛力仍不清楚。該研究試圖研究將應用的易致敏物質與降血糖試劑結合用於高油高糖飲食誘導的糖尿病小鼠皮膚降低血糖之功效。首先，Dm，Ut和Ao輕度誘導小鼠疼痛和發紅，塗抹在皮膚上後沒有任何強烈刺激。接下來，與H＆E染色中的非處理和護手霜組相比，Dm，Ut和Ao處理對小鼠皮膚的角質層（SC）造成輕度損傷。此外，通過使用台盼藍，PI和MTT測定，分別在0.1mg / mL Dm，Ut和Ao處理120分鐘後，進一步證實人皮膚角質形成細胞（HaCaT）輕微損傷（小於5％細胞死亡）。此外，與胰島素或胰島素增敏劑（薑黃素和蘆丁）的敏感物質相結合，分別塗抹在飲食誘導的糖尿病小鼠皮膚上測試120分鐘口服葡萄糖耐量試驗，結合組結果顯示有降低血糖並與注射胰島素和胰島素增敏劑組相比。這意味著易致敏物質導致皮膚和血管擴張，隨後降糖化合物可能滲透到真皮中。最後，Dm，Ut和Ao具有輕度損傷SC的透皮潛力，並進一步發展為用於藥物遞送的皮膚滲透增強劑。

Accordingly Dendrocnide meyeniana (Dm), Urtica thunbergiana Sieb. & Zucc (Ut), and Alocasia odora (Lodd.) Spach (Ao) contain nettle stings or juice to cause mild contact dermatitis. However, the potential of these sting plants extracts as the penetration enhancers of transdermal drug delivery (TDD) remains unclear. This study attempted to investigate the application irritable substances combined with hypoglycemic reagents to mouse skin for measuring the efficacy of reduce blood sugar in diet-induced diabetic mice. Firstly, Dm, Ut, and Ao mildly induced pain and redness in mice without any strong irritating after smear on skin. Next, Dm, Ut, and Ao treatments caused mild damage on the stratum corneum (SC) of mouse skin when compared with non-treatment and hand cream groups in H&E staining. Additionally, human skin keratinocyte (HaCaT) was further confirmed slight damage (less 5% cell death) after 0.1 mg/mL Dm, Ut, and Ao treatment for 120 min, respectively by using trypan blue, PI, and MTT assay. Furthermore, combined with those irritable substances with insulin or insulin sensitizer (curcumin and rutin), respectively were smeared on the skin of diet-induced diabetic mice for 120 min oral glucose tolerance test, the results of combination groups showed in reduce of blood sugar when compared to the insulin and insulin sensitizer alone groups. This implies that irritable substances caused the skin and blood vessels dilated and subsequently hypoglycemic compounds could penetrate into dermis. Conclusively, Dm, Ut, and Ao possess the transdermal potential with mild damage SC and further develop as a skin permeation enhancer for drug delivery.

Abstract 5
Introduction 7
I. Skin model 7
II. Transdermal drug delivery system 8
III. Transdermal drug delivery of penetration enhancer 9
IV. Transdermal drug delivery system pathways 10
V. Diabetes mellitus 11
VI. Diagnosis of diabetes mellitus 11
VII. Type of diabetes mellitus 12
VIII. Diabetes mellitus treatment 12
X. Arbor and flowering plan 13
A. Dendrocnide meyeniana (Walp.) Chew 14
B. Urtica thunbergiana Sieb. & Zucc 15
C. Alocasia odora (Lodd.) Spach 15
Aim 17
Materials and methods 18
I. The experimental flow chart of in vitro cell test 18
II. The experimental flow chart of in vivo animal test 19
III. Chemicals and reagents 20
IV. Extraction of arbor and flowering plant 20
V. In vitro cell test 21
A. Cell culture 21
B. Cell viability test 22
VI. In vivo animal test 23
A. Animal source and care 23
B. Diet-induced obese induction and glucose intolerance test 23
C. Insulin-glucose tolerance test 24
D. Oral glucose tolerance test 24
E. Irritable test 25
F. Evans blue penetration test 25
G. Paraffin Tissue and sectioning 25
VII. Statistical analysis 26
Results 27
I. Human Skin Keratinocyte mild damage after Dm, Ut, and Ao treatment 27
II. Cell viability by MTT test 27
III. The mouse skin expand by Dm, Ut, or Ao in irritable test 27
IV. ICR male mouse skin damage after Dm, Ut, and Ao treatment in the biopsy specimen 28
V. Using transdermal drug delivery with insulin and insulin sensitizer (curcumin and rutin) to reduce blood sugar in OGTT 28
Discussion 30
References 35
Figure 44
Figure 3. The cell viability of Dm, Ut, and Ao (0.02 mg/mL) treatment. 45
Figure 4. The cell viability of Dm, Ut, and Ao (0.05 mg/mL) treatment 47
Figure 5. The cell viability of Dm, Ut, and Ao (0.1 mg/mL) treatment 49
Figure 6. The cell viability of three sting extract against keratinocytes. 50
Figure 7. MTT assays of Dm, Ut, and Ao treatment 51
Figure 8. The observations of mouse skin color after smear Dm, Ut, and Ao 52
Figure 9. The biopsy specimen of mouse skin after treated with various reagents 53
Figure 10. Normal and diabetic mouse of hypoglycemic efficacy of insulin 54
Figure 11. Normal mouse of hypoglycemic efficacy of irritable substance and plus insulin 55
Figure 12. Diabetic mouse of hypoglycemic efficacy of irritable substance and plus insulin 56
Figure 13. Diabetic mouse of hypoglycemic efficacy of irritable substance plus insulin sensitizer curcumin and rutin 57

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