臺灣博碩士論文加值系統

研究背景：
當歸為常用中藥材，於中醫典籍記載具有活血、補血、調經、治便祕等功能，並含有許多不同的成分。在許多藥理學的研究中，發現當歸具有抗氧化、抗發炎及保護肝臟的作用。然而，當歸的水溶性不佳導致無法更有效被吸收及利用，因此我們想要探討是否能有效提高當歸在水溶液中的溶解度進而增加生物吸收性及增加保護肝臟的作用。
環糊精(Cyclodextrin，CD)由6～12個葡萄糖分子，以α-1,4糖苷鍵相連接而成。環糊精屬於奈米包覆材料，其特徵是具有環外親水、環內疏水的立體性空腔結構。透過包覆技術可將藥物包覆於環糊精的空腔內，透過環糊精包覆的包覆物可以顯著地改善被包合藥物的溶解度、穩定性等諸多理化性質並具有降低毒性副作用、提高溶解度和穩定性的功效。
本實驗之主要目的在於利用當歸之醇萃物，透過羥丙基β環糊精(HP-β-CD)進行包覆作用，使其形成當歸羥丙基β環糊精包覆物，並透過不同的化學分析方式確認羥丙基β環糊精能包覆住當歸。此外，並比較當歸與當歸羥丙基β環糊精的包覆物對肝臟受到四氯化碳誘發急性肝損傷的保護作用、抗氧化能力及抑制肝癌細胞生長的影響。
材料方法：
我們使用熱重分析儀(TGA)，熱分析相變化實驗(DSC)及核磁共振方法(NMR)來確認當歸能夠被羥丙基β環糊精包覆，並形成當歸羥丙基β環糊精包覆物。並以液相層析串聯式質譜儀(LC/MS Assay)證實當歸及包覆物是否含有當歸的成分。
接著透過動物實驗，以當歸與當歸羥丙基β環糊精包覆物一天一次方式餵食小鼠，並在第七天腹腔注射四氯化碳以誘發小鼠急性肝損傷，探討當歸與當歸羥丙基β環糊精包覆物對四氯化碳誘發小鼠急性肝損傷的保護情況。
結果：
從熱重分析實驗，熱分析相變化實驗及核磁共振方法確認了當歸能被羥丙基β環糊精包覆形成包覆物，並且在水溶液中可以增加溶解性。而液相層析串聯式質譜儀檢測證實當歸及包覆物都含有當歸的主成分-阿魏酸及藁本內酯。
動物實驗中證實當歸在四氯化碳誘發小鼠急性肝損傷中具有保護肝臟的作用，同樣的，當歸羥丙基β環糊精包覆物，在保護肝臟效果方面也有效用，保護作用比當歸本身更佳。其原因是水溶性增加進而促進細胞更容易吸收藥物。

Angelica sinensis (AS) is a traditional Chinese medicinal herb used extensively in the East for its hepatoprotective effects. The ingredients of AS extract have minimal solubility in water. To overcome this problem, inclusion complexes of hydroxylpropyl-β-cyclodextrin (HP-β-CD) and AS extract, AS-HP-β-CD, will be prepared by freeze-drying and subsequently characterized by thermogravimetric analysis, differential scanning calorimeter, and nuclear magnetic resonance. The major components of ferulic acid and ligustilide were confirmed by HPLC-MS assay in both AS extract and AS-HP-β-CD. Furthermore, the effect of complexing HP-β-CD with AS extract on the extract’s antioxidant activity, human hepatoma cell growth inhibition, and inhibition of carbon tetrachloride (CCl4)-induced hepatotoxicity in mice will be investigated. The results showed that the AS-HP-β-CD complex was more active than the AS extract and showed dose-dependent antioxidant activity and human hepatoma cell growth inhibition. The CCl4-treated mouse model revealed that the AS-HP-β-CD complex more effectively reduced increases in serum aspartate aminotransferase, serum alanine transferase, and hepatic malondialdehyde concentrations than the AS extract. Similarly, positive effects were also observed in histopathological specimens and in liver antioxidant enzyme activities.

目錄
第一章 緒論...............................................................................1
第二章 文獻回顧……………….………………..……………..……....3
2.1 當歸簡介……………………….……..…………….……………….3
2.1.1 當歸的主要成分…………………...……….……………………..4
2.1.2 當歸及成分的藥理作用…………...………….…………………..5
2.2 環糊精簡介…………………….…...….……………………………8
2.2.1 環糊精特性…………………...………….………………………..8
2.3 活性氧自由基(reactive oxygen species)……….………..……...11
2.3.1 四氯化碳造成氧化傷害…………………..…….………………..12
第三章 研究方法………………………………………….…....…...…15
3.1 當歸酒精萃取製備………………...…………………………….…15
3.2 當歸羥丙基β環糊精包覆物製備……………………..……...……15
3.3 熱重量分析法 (Thermogravimetric Analysis，TGA)….…......….17
3.4 熱分析相變化實驗………………………………...………………18
3.5 一維、二維核磁共振光譜學……………….……………………..20
3.6 液相層析串聯式質譜儀………………………...…………………21
3.7 水溶性測試…………………………….…………………………..22
3.8 DPPH 抗氧化活性分析…………………………..………………..23
3.9 四氯化碳誘發小鼠肝損傷實驗模式…………………...…………24
3.10 血清轉胺酶 (aminotransferase)活性分析…………………….…26
3.11 脂質過氧化-丙二醛分析(Malondialdehyde，MDA Assay)…….27
3.12 超氧化物歧化酶分析(Superoxide dismutase，SOD)....……….28
3.13 蛋白質濃度測定……………………………...………………..…..30
3.14 肝臟組織切片染色檢驗 (Histological examinations)…….....…...31
3.15 肝癌細胞培養及細胞存活實驗……………………...………...31
3.16 細胞吸收藥物實驗……………………………………………….32
3.17 統計分析………………………………...………………………..33
第四章 結果…………….……………………………………..………34
4.1 熱重量分析結果……………………..…………………………….34
4.2 熱分析相變化結果…………………………...……………………35
4.3 一維、二維核磁共振光譜分析結果…………………...…..……..36
4.4 液相層析串聯式質譜儀分析結果…………….…………………..38
4.5 水溶性測試結果……………………………..…………………….46
4.6 DPPH 抗氧化活性分析…………………...……………………….47
4.7 四氯化碳誘發小鼠肝損傷實驗結果………………...……………48
4.7.1 血液生化值之分析……………..………………………………..48
4.7.2 脂質過氧化-丙二醛分析結果 (Malondialdehyde；MDA Assay)...……………………………………………………….......…..50
4.7.3 超氧化物歧化酶分析結果 (Superoxide dismutase，SOD Assay)...………………..………………………………..…..…….....50
4.7.4 肝臟組織切片染色………………………...…………………….50
4.8 當歸醇萃物及當歸羥丙基β環糊精包覆物對肝癌細胞的毒
殺作用……..………………………………………………....………53
4.9 細胞吸收當歸藥物測試………………………...…………………54
第五章 討論……………………………………………….………….56
第六章 結論………………………….……………………..…………63
參考文獻………………………………………………………………64
英文摘要……………………...……………………………………….72

1.Monograph. Angelica sinensis. Altern Med Rev. 2004; 9(4):429-433.
2.Bradley RR, Cunniff PJ, Pereira BJ, Jaber BL. Hematopoietic effect of Radix angelicae sinensis in a hemodialysis patient. Am J Kidney Dis. 1999; 34(2):349-354.
3.Liu C, Li JQ, Meng FY, Liang SX, Deng RX, Li CK, Pong NH, Lau CP, Cheng SW, Ye JY et al. Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway. Bmc Complementary and Alternative Medicine. 2010; 10.
4.Wu YC, Hsieh CL. Pharmacological effects of Radix Angelica Sinensis (Danggui) on cerebral infarction. Chin Med. 2011; 6:32.
5.Yi L, Liang Y, Wu H, Yuan D. The analysis of Radix Angelicae Sinensis (Danggui). J Chromatogr A. 2009; 1216(11):1991-2001.
6.Wei SY, Xu CJ, Mok DK, Cao H, Lau TY, Chau FT. Analytical comparison of different parts of Radix Angelicae Sinensis by gas chromatography coupled with mass spectrometry. J Chromatogr A. 2008; 1187(1-2):232-238.
7.Chao WW, Lin BF. Bioactivities of major constituents isolated from Angelica sinensis (Danggui). Chin Med. 2011; 6(1):29.
8.Chiang BH, Huang SH, Chen CC, Lin CM. Antioxidant and flavor properties of Angelica sinensis extracts as affected by processing. Journal of Food Composition and Analysis. 2008; 21(5):402-409.
9.Lv J, Zhao Z, Chen Y, Wang Q, Tao Y, Yang L, Fan TP, Liu C. The chinese herbal decoction danggui buxue tang inhibits angiogenesis in a rat model of liver fibrosis. Evid Based Complement Alternat Med. 2012; 2012:284963.
10.Wang P, Liang YZ. Chemical composition and inhibitory effect on hepatic fibrosis of Danggui Buxue Decoction. Fitoterapia. 2010; 81(7):793-798.
11.Wu SJ, Ng LT, Lin CC. Antioxidant activities of some common ingredients of traditional chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos. Phytother Res. 2004; 18(12):1008-1012.
12.Raafat BM, Saleh A, Shafaa MW, Khedr M, Ghafaar AA. Ginkgo biloba and Angelica archangelica bring back an impartial hepatic apoptotic to anti-apoptotic protein ratio after exposure to technetium 99mTc. Toxicol Ind Health. 2013; 29(1):14-22.
13.Hsiao CY, Hung CY, Tsai TH, Chak KF. A Study of the Wound Healing Mechanism of a Traditional Chinese Medicine, Angelica sinensis, Using a Proteomic Approach. Evid Based Complement Alternat Med. 2012; 2012:467531.
14.Huang SH, Lin CM, Chiang BH. Protective effects of Angelica sinensis extract on amyloid beta-peptide-induced neurotoxicity. Phytomedicine. 2008; 15(9):710-721.
15.Su YW, Chiou WF, Chao SH, Lee MH, Chen CC, Tsai YC. Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-kappaB and AP-1 signaling pathways. Int Immunopharmacol. 2011; 11(9):1166-1172.
16.Yang X, Zhao Y, Zhou Y, Lv Y, Mao J, Zhao P. Component and antioxidant properties of polysaccharide fractions isolated from Angelica sinensis (OLIV.) DIELS. Biol Pharm Bull. 2007; 30(10):1884-1890.
17.Yu F, Li H, Meng Y, Yang D. Extraction optimization of Angelica sinensis polysaccharides and its antioxidant activity in vivo. Carbohydrate Polymers. 2013; 94(1):114-119.
18.Srinivasan M, Sudheer AR, Menon VP. Ferulic Acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr. 2007; 40(2):92-100.
19.Mathew S, Abraham TE. Ferulic acid: an antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications. Crit Rev Biotechnol. 2004; 24(2-3):59-83.
20.Ye YN, Liu ES, Li Y, So HL, Cho CC, Sheng HP, Lee SS, Cho CH. Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury. Life Sci. 2001; 69(6):637-646.
21.Cheng YL, Chang WL, Lee SC, Liu YG, Chen CJ, Lin SZ, Tsai NM, Yu DS, Yen CY, Harn HJ. Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Life Sci. 2004; 75(13):1579-1594.
22.Shang P, Qian AR, Yang TH, Jia M, Mei QB, Cho CH, Zhao WM, Chen ZN. Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis. World J Gastroenterol. 2003; 9(9):1963-1967.
23.Cao W, Li XQ, Liu L, Wang M, Fan HT, Li C, Lv Z, Wang X, Mei Q. Structural analysis of water-soluble glucans from the root of Angelica sinensis (Oliv.) Diels. Carbohydr Res. 2006; 341(11):1870-1877.
24.Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T. Ferulic Acid Is a Nutraceutical beta-Secretase Modulator That Improves Behavioral Impairment and Alzheimer-like Pathology in Transgenic Mice. PLoS One. 2013; 8(2):e55774.
25.Feng Z, Lu Y, Wu X, Zhao P, Li J, Peng B, Qian Z, Zhu L. Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion. J Ethnopharmacol. 2012; 144(2):313-321.
26.Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, Chang WL, Lin SZ, Harn HJ. The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. J Neurochem. 2006; 99(4):1251-1262.
27.Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004; 3(12):1023-1035.
28.Brewster ME, Loftsson T. Cyclodextrins as pharmaccutical solubilizers. Advanced Drug Delivery Reviews. 2007; 59(7):645-666.
29.Yallapu MM, Jaggi M, Chauhan SC. beta-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces. 2010; 79(1):113-125.
30.Del Valle EMM. Cyclodextrins and their uses: a review. Process Biochemistry. 2004; 39(9):1033-1046.
31.Horvath G, Premkumar T, Boztas A, Lee E, Jon S, Geckeler KE. Supramolecular nanoencapsulation as a tool: solubilization of the anticancer drug trans-dichloro(dipyridine)platinum(II) by complexation with beta-cyclodextrin. Mol Pharm. 2008; 5(2):358-363.
32.Mura P, Bettinetti GP, Cirri M, Maestrelli F, Sorrenti M, Catenacci L. Solid-state characterization and dissolution properties of naproxen-arginine-hydroxypropyl-beta-cyclodextrin ternary system. Eur J Pharm Biopharm. 2005; 59(1):99-106.
33.Carbonnier B, Janus L, Lekchiri Y, Morcellet M. High-performance liquid chromatographic stationary phases based on silica coated by in situ polymerization of a methacryloyl beta-cyclodextrin monomer: synthesis, characterization, and chromatographic evaluation. J Chromatogr Sci. 2004; 42(1):37-42.
34.Simal-Gandara J, Astray G, Gonzalez-Barreiro C, Mejuto JC, Rial-Otero R. A review on the use of cyclodextrins in foods. Food Hydrocolloids. 2009; 23(7):1631-1640.
35.Li J, Loh XJ. Cyclodextrin-based supramolecular architectures: syntheses, structures, and applications for drug and gene delivery. Adv Drug Deliv Rev. 2008; 60(9):1000-1017.
36.Uyar T, Havelund R, Hacaloglu J, Zhou X, Besenbacher F, Kingshott P. The formation and characterization of cyclodextrin functionalized polystyrene nanofibers produced by electrospinning. Nanotechnology. 2009; 20(12):125605.
37.Tao T, Zhao Y, Wu J, Zhou B. Preparation and evaluation of itraconazole dihydrochloride for the solubility and dissolution rate enhancement. Int J Pharm. 2009; 367(1-2):109-114.
38.Gould S, Scott RC. 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD): A toxicology review. Food and Chemical Toxicology. 2005; 43(10):1451-1459.
39.Baqar M, Agag T, Ishida H, Qutubuddin S. Polymerization behavior of methylol-functional benzoxazine monomer. Reactive & Functional Polymers. 2013; 73(2):360-368.
40.Irie T, Uekama K. Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J Pharm Sci. 1997; 86(2):147-162.
41.Loftsson T, Konradsdottir F, Masson M. Influence of aqueous diffusion layer on passive drug diffusion from aqueous cyclodextrin solutions through biological membranes. Pharmazie. 2006; 61(2):83-89.
42.Lee DJ, Kang SW. Reactive oxygen species and tumor metastasis. Mol Cells. 2013; 35(2):93-98.
43.Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci. 1998; 854:155-170.
44.Del Vesco AP, Gasparino E. Production of reactive oxygen species, gene expression, and enzymatic activity in quail subjected to acute heat stress. J Anim Sci. 2013; 91(2):582-587.
45.Tasaki M, Kuroiwa Y, Inoue T, Hibi D, Matsushita K, Ishii Y, Maruyama S, Nohmi T, Nishikawa A, Umemura T. Oxidative DNA damage and in vivo mutagenicity caused by reactive oxygen species generated in the livers of p53-proficient or -deficient gpt delta mice treated with non-genotoxic hepatocarcinogens. J Appl Toxicol. 2012.
46.Kang MA, So EY, Simons AL, Spitz DR, Ouchi T. DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway. Cell Death Dis. 2012; 3:e249.
47.Ayed Y, Boussabbeh M, Zakhama W, Bouaziz C, Abid S, Bacha H. Induction of cytotoxicity of Pelagia noctiluca venom causes reactive oxygen species generation, lipid peroxydation induction and DNA damage in human colon cancer cells. Lipids Health Dis. 2011; 10:232.
48.Perry JJ, Fan L, Tainer JA. Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair. Neuroscience. 2007; 145(4):1280-1299.
49.McGregor D, Lang M. Carbon tetrachloride: genetic effects and other modes of action. Mutat Res. 1996; 366(3):181-195.
50.Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993; 57(5 Suppl):715S-724S; discussion 724S-725S.
51.Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003; 33(2):105-136.
52.Luckey SW, Petersen DR. Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol. 2001; 71(3):226-240.
53.Marques TG, Chaib E, da Fonseca JH, Lourenco AC, Silva FD, Ribeiro MA, Jr., Galvao FH, D''Albuquerque LA. Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection. Acta Cir Bras. 2012; 27(8):589-594.
54.Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology. 2003; 189(1-2):113-127.
55.Liu XX, Wang YF, Yu L, Tong Z, Chen L, Liu HS, Li XX. Thermal degradation and stability of starch under different processing conditions. Starch-Starke. 2013; 65(1-2):48-60.
56.Garbett NC, Chaires JB. Thermodynamic studies for drug design and screening. Expert Opinion on Drug Discovery. 2012; 7(4):299-314.
57.Jager C, Hartmann P, Witter R, Braun M. Neu 2D NMR experiments for determining the structure of phosphate glasses: a review. Journal of Non-Crystalline Solids. 2000; 263(1-4):61-72.
58.Marques HMC. A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour and Fragrance Journal. 2010; 25(5):313-326.
59.Lin YJ, Lai CC, Lai CH, Sue SC, Lin CW, Hung CH, Lin TH, Hsu WY, Huang SM, Hung YL et al. Inhibition of enterovirus 71 infections and viral IRES activity by Fructus gardeniae and geniposide. Eur J Med Chem. 2013; 62C:206-213.
60.S. LS. Research on the Developmemt and the Analysis of Ferulic Acid and Ligustilide, the Chinese Herbal Standards (2). Yearbook of Chinese Medicine and Pharmacy. 2008; 26(4):359-426.
61.Lucas-Abellan C, Mercader-Ros MT, Zafrilla MP, Gabaldon JA, Nunez-Delicado E. Comparative study of different methods to measure antioxidant activity of resveratrol in the presence of cyclodextrins. Food Chem Toxicol. 2011; 49(6):1255-1260.
62.Lee KJ, Choi JH, Kim HG, Han EH, Hwang YP, Lee YC, Chung YC, Jeong HG. Protective effect of saponins derived from the roots of Platycodon grandiflorum against carbon tetrachloride induced hepatotoxicity in mice. Food Chem Toxicol. 2008; 46(5):1778-1785.
63.Seki T, Morimura S, Tabata S, Tang Y, Shigematsu T, Kida K. Antioxidant activity of vinegar produced from distilled residues of the Japanese liquor shochu. J Agric Food Chem. 2008; 56(10):3785-3790.
64.Yang WJ, Luo YQ, Aisa HA, Xin XL, Totahon Z, Mao Y, Hu MY, Xu L, Zhang RP. Hepatoprotective activities of a sesquiterpene-rich fraction from the aerial part of Cichorium glandulosum. Chin Med. 2012; 7(1):21.
65.Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med. 2012; 12:221.
66.Yagi K. Lipid peroxides and related radicals in clinical medicine. Adv Exp Med Biol. 1994; 366:1-15.
67.Oyanagui Y, Sato S. Superoxide dismutases and anti-oxidants protected mice from no-reflow and necrotic damage induced by ischemia. Free Radic Res Commun. 1993; 18(3):147-157.
68.Lillie RD, Pizzolato P, Donaldson PT. Hematoxylin substitutes: a survey of mordant dyes tested and consideration of the relation of their structure to performance as nuclear stains. Stain Technol. 1976; 51(1):25-41.
69.Hsu CM, Hsu YA, Tsai Y, Shieh FK, Huang SH, Wan L, Tsai FJ. Emodin inhibits the growth of hepatoma cells: finding the common anti-cancer pathway using Huh7, Hep3B, and HepG2 cells. Biochem Biophys Res Commun. 2010; 392(4):473-478.
70.Yadav VR, Prasad S, Kannappan R, Ravindran J, Chaturvedi MM, Vaahtera L, Parkkinen J, Aggarwal BB. Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake. Biochem Pharmacol. 2010; 80(7):1021-1032.
71.Lu GH, Chan K, Liang YZ, Leung K, Chan CL, Jiang ZH, Zhao ZZ. Development of high-performance liquid chromatographic fingerprints for distinguishing Chinese Angelica from related umbelliferae herbs. Journal of Chromatography A. 2005; 1073(1-2):383-392.
72.Lin LZ, He XG, Lian LZ, King W, Elliot J. Liquid chromatographic electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide. Journal of Chromatography A. 1998; 810(1-2):71-79.
73.Tsao JY, Wu CP, Tsai HH, Peng KC, Lin PY, Su SY, Chen LD, Tsai FJ, Tsai YH. Effect of hydroxypropyl-beta-cyclodextrin complexation on the aqueous solubility, structure, thermal stability, antioxidant activity, and tyrosinase inhibition of paeonol. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2012; 72(3-4):405-411.
74.Kalogeropoulos N, Yannakopoulou K, Gioxari A, Chiou A, Makris DP. Polyphenol characterization and encapsulation in beta-cyclodextrin of a flavonoid-rich Hypericum perforatum (St John''s wort) extract. Lwt-Food Science and Technology. 2010; 43(6):882-889.
75.Mourtzinos I, Salta F, Yannakopoulou K, Chiou A, Karathanos VT. Encapsulation of olive leaf extract in beta-cyclodextrin. Journal of Agricultural and Food Chemistry. 2007; 55(20):8088-8094.
76.Li X, Wu X, Huang L. Correlation between antioxidant activities and phenolic contents of radix Angelicae sinensis (Danggui). Molecules. 2009; 14(12):5349-5361.
77.Yang J, Li Y, Wang F, Wu C. Hepatoprotective effects of apple polyphenols on CCl4-induced acute liver damage in mice. J Agric Food Chem. 2010; 58(10):6525-6531.
78.Rezende KR, Soares LA, Leal AFVB, Fraceto LF, Maia ER, Resck IS, Kato MJ, Gil ED, de Sousa AR, da Cunha LC. Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2009; 64(1-2):23-35.
79.Khan S, Fatma K, Ali SM. A comparative study of complexation of enalapril with alpha-, beta- and gamma-cyclodextrins in aqueous medium: structure elucidation of inclusion complexes using NMR spectroscopic and molecular mechanics methods. Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2012; 72(3-4):413-421.
80.Onnainty R, Longhi MR, Granero GE. Complex formation of chlorhexidine gluconate with hydroxypropyl-beta-cyclodextrin (HP beta CD) by proton nuclear magnetic resonance spectroscopy (H-1 NMR). Carbohydrate Research. 2011; 346(8):1037-1046.
81.Jullian C, Orosteguis T, Perez-Cruz F, Sanchez P, Mendizabal F, Olea-Azar C. Complexation of morin with three kinds of cyclodextrin. A thermodynamic and reactivity study. Spectrochim Acta A Mol Biomol Spectrosc. 2008; 71(1):269-275.
82.Smidovnik A, Strazisar M, Andrensek S. Effect of beta-cyclodextrin on antioxidant activity of coumaric acids. Food Chemistry. 2008; 110(3):636-642.