臺灣博碩士論文加值系統

異位性皮膚炎(Atopic dermatitis)是一種反覆發作的皮膚發炎疾病，在嬰幼兒盛行率高，具有複雜的病理生理學，可用療法的反應有限，因此治療異位性皮膚炎的藥物開發仍然具有挑戰性。
檸檬馬鞭草為馬鞭草科(Verbenaceae) Aloysia citrodora，原產於南美洲。主要成分是 verbascoside (VB)和 isoverbascoside(isoVB)等苯乙醇苷類，而苯乙醇苷具有抗氧化、抗發炎、抗焦慮、鎮靜和神經保護等活性，然而檸檬馬鞭草尚未有對皮膚炎相關的研究。 植物藥是許多藥物開發的來源，其中萃取法的不同會影響其組成與功效。因此，本研究以熱迴流與高壓萃取法來萃取檸檬馬鞭草，探討不同萃取法對檸檬馬鞭草的抽出率、主要成分含量以及萃取物的抗氧化和抗皮膚炎活性影響。
以熱迴流法和高壓輔助萃取法(300及600 MPa, 1, 3及5分鐘)利用不同溶劑(水、水:乙醇=1:1及乙醇)進行檸檬馬鞭草葉部萃取，經過過濾及減壓濃縮後分別得到熱萃取物(HRE)和高壓萃取物(HPE)，分析這些萃取物的抽出率、VB及isoVB含量變化探討較佳萃取條件。發現熱迴流萃取法的抽出率為9.8±0.4-25.1±0.5%，高壓萃取法抽出率為2.4±0.1-23.4±0.7%；VB及isoVB含量分析發現HRE中VB及isoVB的含量分別為2.9±0.3-21.1±1.1及7.4±1.1-24.4±4.1% g dw-1，而HPE為1.8±0.2-10.3±0.6及1.2±0.4-5.9±0.3% g dw-1，顯示以水為溶劑的熱迴流萃取法是較佳的檸檬馬鞭草萃取方法。
以DPPH、TEAC、還原力試驗及TNF-α誘導HaCaT細胞的DCFH-DA試驗，結果發現HRE及HPE在DPPH清除試驗的IC50分別為168.8及372.1 μg/ml；在TEAC試驗中的IC50分別為57.2及87.5 μg/ml；在還原力試驗中 EC50 分別為132及338 μg/ml；在DCFH-DA試驗中發現HRE及HPE在1, 10及25 μg/ml均能顯著抑制ROS生成，顯示不同萃取法的檸檬馬鞭草萃取物有抗氧化活性，尤以HRE抗氧化活性較佳。
以TNF-α誘導HaCaT細胞進行皮膚炎細胞模式，發現HRE在10及25 μg/ml時，對TNF-α誘導HaCaT細胞皮膚障壁蛋白重要蛋白filaggrin的表現量，均有顯著增加；HR及HPE在1-25 μg/ml均能顯著抑制核內NF-κB，而在發炎因子IL-6分泌量測定中，發現HRE及HPE可顯著抑制 IL-6 的分泌。
綜合以上結果顯示，以水為溶劑的熱迴流萃取法對檸檬馬鞭草是較佳的萃取方法，所得的萃取物(HRE)在抗氧化、抑制發炎與修復皮膚細胞障壁均有較佳的活性，可以作為開發檸檬馬鞭草抗皮膚炎相關產品之依據。

Atopic dermatitis (AD)is a relapsing inflammatory skin disease with high prevalence in infants and children. AD exhibit complex pathophysiology, and limited response to current therapies. Therefore, drug development for the treatment of AD remains a challenge.
Aloysia citrodora, also named as lemon verbena, is a medicinal herb native to South America. Phytochemical studies showed that the major phenylethanoid of A. citrodora was verbascoside (VB) and isoverbascoside (isoVB). Phenylethanoid exhibited antioxidative, anti-inflammatory, anti-anxiety, sedative, and neuroprotective activities. Therefore, the aims of this study was assessed the effects of high-pressure-assisted extraction (HPE) and heat reflux extraction (HRE) on the extraction yields, phenylethanoid compounds profile, antioxidative and anti-inflammatory activities of lemon verbena.
Extraction of lemon verbena leaves with different solvents (water, water:ethanol=1:1 and ethanol) by heat reflux extraction and high-pressure-assisted extraction (300 and 600 MPa, 1, 3 and 5 minutes), filtered and concentrated under reduced pressure, the extracts of HRE and HPE were obtained, respectively, and the extraction yields, VB and isoVB content changes of these extracts were analyzed to explore the best extraction conditions. It was found that the extraction yield of the HRE can reach up to 9.8±0.4-25.1±0.5%, and that of the HPE can reach up to 2.4±0.1-23.4±0.7% using water as extraction solvent. Under the condition of HRE, the content of VB and isoVB is 2.9±0.3-21.1±1.1 and 7.4±1.1-24.4±4.1% g dw-1, and under HPE conditions, they are1.8±0.2-10.3±0.6 and 1.2±0.4-5.9±0.3% g dw-1, showing that the HRE using water as solvent is a better extraction method for lemon verbena.
In DPPH, TEAC, reducing power test and DCFH-DA test of TNF-α-induced HaCaT cells, it was found that the IC50 of HRE and HPE in the DPPH radical scavenging test were 168.8 and 372.1 μg/ml, respectively; the IC50 in the TEAC test were 57.2 and 87.5 μg/ml; in the reducing power test, EC50 were 132 and 338 μg/ml. It was found that HRE and HPE could significantly inhibit ROS at 1, 10 and 25 μg/ml in the DCFH-DA test on TNF-α-induced HaCaT cells. According above results, the lemon verbena extract has antioxidative activity, especially HRE antioxidative activity is better.
HaCaT cells were induced by TNF-α to carry out skin inflammation cell model, and it was found that HRE (10 and 25 μg/ml) significantly increased the expression of filaggrin, an important protein in the skin barrier protein, on TNF-α-induced HaCaT cells. HRE and HPE can significantly decrease the nuclear NF-κB (p65) levels, and inhibit the proinflammatory factor IL-6 secretion on TNF-α-induced HaCaT cells. Therefore, the HRE and HPE could significantly inhibit the inflammation of skin through downregulation of NF-κB signal pathway.
Based on the above results, the HRE using water as the solvent is a better extraction method for lemon verbena, and its extract has better activities in antioxidative, anti-inflammation and repair of skin barriers. It can be used as the basis for developing related products of lemon verbena for anti-inflammatory skin therapy.

摘要..........i
Abstract..........ii
誌謝..........iv
目錄..........v
表目錄..........vii
圖目錄..........viii
縮寫對照表..........iv
第一章 緒論..........1
1.1 前言..........1
1.1.1 皮膚炎介紹..........1
1.1.2 異位性皮膚炎介紹..........2
1.1.3 檸檬馬鞭草介紹及植物型態..........4
1.2 萃取技術..........5
1.3 研究目的..........6
第二章 文獻回顧..........7
2.1 檸檬馬鞭草化學成分回顧..........7
2.2 檸檬馬鞭草生物活性回顧..........13
2.3 檸檬馬鞭草主成分活性回顧..........16
2.4 專利檢索..........20
第三章 實驗材料方法..........23
3.1 實驗材料與儀器..........23
3.2 溶液配製..........26
3.3 實驗方法..........27
3.3.1 檸檬馬鞭草萃取物製備..........27
3.3.2 檸檬馬鞭草萃取物主成分含量分析...........27
3.3.3 DPPH自由基清除率試驗..........27
3.3.4 TEAC活性試驗..........28
3.3.5 還原力試驗..........28
3.3.6 細胞培養..........28
3.3.7 細胞存活率試驗..........29
3.3.8 細胞內ROS含量試驗..........29
3.3.10 細胞核內NF-κB表現量測定..........29
3.3.11 Filaggrin 表現量測定..........30
3.3.12 西方墨點法..........30
3.3.13 數據分析..........30
第四章 實驗結果與討論..........31
4.1 傳統萃取與高壓萃取檸檬馬鞭草的抽出率比較..........31
4.2 傳統萃取與高壓輔助萃取的檸檬馬鞭草萃取物主成分含量分析..........32
4.2.1 VB和isoVB標準品含量分析..........32
4.2.2 檸檬馬鞭草水萃取物的VB和isoVB含量分析結果..........32
4.3 檸檬馬鞭草水萃取物抗氧化試驗結果..........36
4.4 檸檬馬鞭草水萃取物對人類角質形成細胞(HaCaT cells)細胞存活率分析..........38
4.5 檸檬馬鞭草水萃取物抑制細胞內ROS含量分析結果..........39
4.7 檸檬馬鞭草水萃取物抑制NF-κB表現量分析結果..........41
4.8 檸檬馬鞭草水萃取物對於Filaggrin表現量分析結果..........42
4.9 討論..........43
第五章 結論..........45
參考文獻..........46
Extended Abstrac..........60

1.L.S. Chan and V.Y. Shi, Skin Barrier, in Atopic Dermatitis : Inside Out Or Outside in. 2023, Elsevier: New Delhi. p. 34-43.
2.Tricarico, P.M., et al., Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases. Int J Mol Sci, 2022. 23(7), p. 4020.
3.Hay, R.J., et al., The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions. Journal of Investigative Dermatology, 2014. 134(6): p. 1527-1534.
4.Giesey, R.L., et al. Global Burden of Skin and Subcutaneous Disease: A Longitudinal Analysis from the Global Burden of Disease Study From 1990-2017. 2021, 2, p.98-108.
5.Li, Y. and L. Li, Contact Dermatitis: Classifications and Management. Clin Rev Allergy Immunol, 2021. 61(3): p. 245-281.
6.Heller, A.J., Allergic skin disease. Facial Plast Surg Clin North Am, 2012. 20(1): p. 31-42.
7.Dawson, Annelise L et al. Infectious skin diseases: a review and needs assessment. Dermatol Clin, 2012. 30(1): p. 141-51, ix-x.
8.Gordon, R., Skin cancer: an overview of epidemiology and risk factors. Semin Oncol Nurs, 2013. 29(3): p. 160-9.
9.Sternbach, G. and J.P. Callen, Dermatitis. Emerg Med Clin North Am, 1985. 3(4): p. 677-92.
10.Brown, C. and J. Yu, Pediatric Allergic Contact Dermatitis. Immunol Allergy Clin North Am, 2021. 41(3): p. 393-408.
11.Holness, D.L., Occupational Dermatosis. Current Allergy and Asthma Reports, 2019. 19(9): p. 42.
12.Novak-Bilić, G., et al., IRRITANT AND ALLERGIC CONTACT DERMATITIS - SKIN LESION CHARACTERISTICS. Acta Clin Croat, 2018. 57(4): p. 713-720.
13.Usatine, R.P. and M. Riojas, Diagnosis and management of contact dermatitis. Am Fam Physician, 2010. 82(3): p. 249-55.
14.Sundaresan, S., M.R. Migden, and S. Silapunt, Stasis Dermatitis: Pathophysiology, Evaluation, and Management. Am J Clin Dermatol, 2017. 18(3): p. 383-390.
15.Dissemond, J., et al., Successful treatment of stasis dermatitis with topical tacrolimus. Vasa, 2004. 33(4): p. 260-2.
16.Trayes, K.P., et al., Edema: diagnosis and management. Am Fam Physician, 2013. 88(2): p. 102-10.
17.Clark, G.W., S.M. Pope, and K.A. Jaboori, Diagnosis and treatment of seborrheic dermatitis. Am Fam Physician, 2015. 91(3): p. 185-90.
18.Borda, L.J., M. Perper, and J.E. Keri, Treatment of seborrheic dermatitis: a comprehensive review. J Dermatolog Treat, 2019. 30(2): p. 158-169.
19.Lofgren, S.M. and E.M. Warshaw, Dyshidrosis: epidemiology, clinical characteristics, and therapy. Dermatitis, 2006. 17(4): p. 165-81.
20.Lambert, D., [Dyshidrosis]. Rev Prat, 1998. 48(9): p. 968-70.
21.Fortuna, G. and M.T. Brennan, Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent Clin North Am, 2013. 57(4): p. 631-55.
22.Boehncke, W.H. and M.P. Schön, Psoriasis. Lancet, 2015. 386(9997): p. 983-94.
23.Armstrong, A.W. and C. Read, Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. Jama, 2020. 323(19): p. 1945-1960.
24.Kamiya, K., et al., Risk Factors for the Development of Psoriasis. Int J Mol Sci, 2019. 20(18), p. 4347.
25.Das, P., et al., Keratinocytes: An Enigmatic Factor in Atopic Dermatitis. Cells, 2022. 11(10), p. 1683.
26.Pan, C., A. Zhao, and M. Li, Atopic Dermatitis-like Genodermatosis: Disease Diagnosis and Management. Diagnostics (Basel), 2022. 12(9), p. 1683.
27.Alam, M.J., et al., Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies. Pathogens, 2022. 11(6), p. 642.
28.Cork, M.J., S.G. Danby, and G.S. Ogg, Atopic dermatitis epidemiology and unmet need in the United Kingdom. J Dermatolog Treat, 2020. 31(8): p. 801-809.
29.俞佑, 兒童異位性皮膚炎之臨床表現及處置. 2022. 26(5): p. 557-564.
30.T U V, W., Handout on Health: Atopic Dermatitis (A type of eczema). National Institute of Arthritis and Musculoskeletal and Skin Diseases, 2016.
31.Appiah, M.M., et al., Atopic dermatitisReview of comorbidities and therapeutics. Ann Allergy Asthma Immunol, 2022. 129(2): p. 142-149.
32.Guraya, A., et al., Review of the holistic management of pediatric atopic dermatitis. Eur J Pediatr, 2022. 181(4): p. 1363-1370.
33.Murota, H., et al., Exacerbating factors and disease burden in patients with atopic dermatitis. Allergol Int, 2022. 71(1): p. 25-30.
34.Debinska, A., New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression. J Clin Med, 2021. 10(11), p. 2506.
35.Chan, L.S., Keratinocytes, in Atopic Dermatitis : Inside Out Or Outside in, L.S. Chan and V.Y. Shi, Editors. 2023, Elsevier: New Delhi. p. 90-105.
36.Chong, A.C., et al., Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis. J Asthma Allergy, 2022. 15: p. 1681-1700.
37.Sivaranjani N, Rao SV, Rajeev G., Role of reactive oxygen species and antioxidants in atopic dermatitis. Journal of Clinical and Diagnostic Research, 2013. 7(12): p. 2683 - 2685.
38.Fischer, R. and O. Maier, Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxid Med Cell Longev, 2015. 2015: p. 610813.
39.Hussain, T., et al., Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev, 2016. 2016, p. 7432797.
40.Sul, O.J. and S.W. Ra, Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2/ROS/NF-kB in Lung Epithelial Cells. Molecules, 2021. 26(22), p. 6949.
41.Minatel, I.O., et al., Antioxidant Activity of gamma-Oryzanol: A Complex Network of Interactions. Int J Mol Sci, 2016. 17(8), p.1107.
42.Jang, Y.A. and B.A. Kim, Protective Effect of Spirulina-Derived C-Phycocyanin against Ultraviolet B-Induced Damage in HaCaT Cells. Medicina (Kaunas), 2021. 57(3), p.273.
43.Papaccio, F., et al., Focus on the Contribution of Oxidative Stress in Skin Aging. Antioxidants (Basel), 2022. 11(6), p. 1121.
44.Segaud, J., et al., Context-dependent function of TSLP and IL-1beta in skin allergic sensitization and atopic march. Nat Commun, 2022. 13(1): p. 4703.
45.Wang, S.H. and Y.G. Zuo, Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases. Front Immunol, 2021. 12: p. 698522.
46.Ebina-Shibuya, R. and W.J. Leonard, Role of thymic stromal lymphopoietin in allergy and beyond. Nat Rev Immunol, 2023, 23(1). p. 24-37.
47.Sanjuan, M.A., D. Sagar, and R. Kolbeck, Role of IgE in autoimmunity. J Allergy Clin Immunol, 2016. 137(6): p. 1651-1661.
48.Langan, S.M., A.D. Irvine, and S. Weidinger, Atopic dermatitis. Lancet, 2020. 396(10247): p. 345-360.
49.Sabat, R., et al., T cell pathology in skin inflammation. Semin Immunopathol, 2019. 41(3): p. 359-377.
50.Wilson, S.R., et al., The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell, 2013. 155(2): p. 285-95.
51.He, L., et al., Smooth muscle cell-specific knockout of interferon gamma (IFN-gamma) receptor attenuates intimal hyperplasia via STAT1-KLF4 activation. Life Sci, 2021, p. 119651.
52.Nakajima, S., et al., Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses. Allergol Int, 2020. 69(2): p. 197-203.
53.Maintz, L., et al., From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine. J Pers Med, 2022. 12(6), p. 893.
54.Kleinman, E., et al., What's New in Topicals for Atopic Dermatitis? Am J Clin Dermatol, 2022. 23(5): p. 595-603.
55.Johnson, H. and J. Yu, Current and Emerging Therapies in Pediatric Atopic Dermatitis. Dermatol Ther (Heidelb), 2022. 12(12): p. 2691-2703.
56.Salvati, L., L. Cosmi, and F. Annunziato, From Emollients to Biologicals: Targeting Atopic Dermatitis. Int J Mol Sci, 2021. 22(19), p.10381.
57.Fishbein, A.B., et al., Update on Atopic Dermatitis: Diagnosis, Severity Assessment, and Treatment Selection. J Allergy Clin Immunol Pract, 2020. 8(1): p. 91-101.
58.Mandlik, D.S. and S.K. Mandlik, Atopic dermatitis: new insight into the etiology, pathogenesis, diagnosis and novel treatment strategies. Immunopharmacol Immunotoxicol, 2021. 43(2): p. 105-125.
59.Abe, T., et al., Efficacy and Safety of Fig (Ficus carica L.) Leaf Tea in Adults with Mild Atopic Dermatitis: A Double-Blind, Randomized, Placebo-Controlled Preliminary Trial. Nutrients, 2022. 14(21), p.4470.
60.Matejek, N., et al., Topical glucocorticoid application causing iatrogenic Cushing's syndrome followed by secondary adrenal insufficiency in infants: two case reports. J Med Case Rep, 2022. 16(1): p. 455.
61.Lin, P.Y., et al., Trends and prescription patterns of traditional Chinese medicine use among subjects with allergic diseases: A nationwide population-based study. World Allergy Organ J, 2019. 12(2): p. 100001.
62.Che, D.N., et al., Anti-atopic dermatitis effects of hydrolyzed celery extract in mice. J Food Biochem, 2020. 44(6): p. e13198.
63.Fan, P., et al., Anti-atopic effect of Viola yedoensis ethanol extract against 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction. J Ethnopharmacol, 2021. 280: p. 114474.
64.Sung, Y.Y., et al., Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality. Nutrients, 2020. 12(12), p.3638.
65.Fernando, S., et al., Algal polysaccharides: potential bioactive substances for cosmeceutical applications. Critical Reviews in Biotechnology, 2018. 39: p. 1-15.
66.editor, G.J.e.a., PDR for Herbal Medicines". Thompson PDR, 2007, p.463-464
67.Jaradat, N., et al., Spectral characterization, antioxidant, antimicrobial, cytotoxic, and cyclooxygenase inhibitory activities of Aloysia citriodora essential oils collected from two Palestinian regions. BMC Complementary Medicine and Therapies, 2021. 21(1), p. 143.
68.Hoseinifar, S.H., et al., Dietary supplementation of lemon verbena (Aloysia citrodora) improved immunity, immune-related genes expression and antioxidant enzymes in rainbow trout (Oncorrhyncus mykiss). Fish and Shellfish Immunology, 2020. 99: p. 379 - 385.
69.Rashid, H.M., et al., Antioxidant and Antiproliferation Activities of Lemon Verbena (Aloysia citrodora): An In Vitro and In Vivo Study. Plants (Basel), 2022. 11(6), p. 785.
70.Bahramsoltani, R., et al., Aloysia citrodora Palau (Lemon verbena): A review of phytochemistry and pharmacology. J Ethnopharmacol, 2018. 222: p. 34-51.
71.Shiao, Y.J., et al., Acteoside and Isoacteoside Protect Amyloid beta Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo. Int J Mol Sci, 2017. 18(4): p. 895.
72.Jha, A.K. and N. Sit, Extraction of bioactive compounds from plant materials using combination of various novel methods: A review. Trends in Food Science & Technology, 2022. 119: p. 579-591.
73.Zhang, Q.W., L.G. Lin, and W.C. Ye, Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med, 2018. 13(1): p. 20.
74.Huang, H.-W., et al., Advances in the extraction of natural ingredients by high pressure extraction technology. Trends in Food Science & Technology, 2013. 33(1): p. 54-62.
75.Huang, H.W., et al., Effects of high pressure extraction on the extraction yield, phenolic compounds, antioxidant and anti-tyrosinase activity of Djulis hull. J Food Sci Technol, 2019. 56(9): p. 4016-4024.
76.Moreira, S.A., et al., Effect of High Hydrostatic Pressure Extraction on Biological Activities and Phenolics Composition of Winter Savory Leaf Extracts. Antioxidants (Basel), 2020. 9(9), p.841.
77.Park, C.Y., et al., Enzyme and high pressure assisted extraction of tricin from rice hull and biological activities of rice hull extract. Food Sci Biotechnol, 2016. 25(1): p. 159-164.
78.Alexandre, E.M.C., et al., High-pressure assisted extraction of bioactive compounds from industrial fermented fig by-product. J Food Sci Technol, 2017. 54(8): p. 2519-2531.
79.Santos, M.C., et al., Use of high hydrostatic pressure to increase the content of xanthohumol in beer wort. Food and Bioprocess Technology, 2013. 6(9): p. 2478-2485.
80.Moreira, S.A., M. Pintado, and J.A. Saraiva, High hydrostatic pressure-assisted extraction: A review on its effects on bioactive profile and biological activities of extracts. Present and Future of High Pressure Processing, 2020: p. 317-328.
81.Prasad, K.N., et al., Enhanced antioxidant and antityrosinase activities of longan fruit pericarp by ultra-high-pressure-assisted extraction. Journal of Pharmaceutical and Biomedical Analysis, 2010. 51(2): p. 471-477.
82.Casquete, R., et al., Evaluation of the effect of high pressure on total phenolic content, antioxidant and antimicrobial activity of citrus peels. Innovative Food Science & Emerging Technologies, 2015. 31: p. 37-44.
83.Grunovaite, L., et al., Fractionation of black chokeberry pomace into functional ingredients using high pressure extraction methods and evaluation of their antioxidant capacity and chemical composition. Journal of Functional Foods, 2016. 24: p. 85 - 96.
84.Quirantes, P., et al., High-performance liquid chromatography with diode array detection coupled to electrospray time-of-flight and ion-trap tandem mass spectrometry to identify phenolic compounds from a lemon verbena extract. Journal of Chromatography, 2009. 1216(28): p. 5391 - 5397.
85.Pereira, E., et al., Is Gamma Radiation Suitable to Preserve Phenolic Compounds and to Decontaminate Mycotoxins in Aromatic Plants? A Case-Study with Aloysia citrodora Palau. Molecules, 2017. 22(3).
86.Zhang, Y., et al., Bioactive Constituents from the Aerial Parts of Lippia triphylla. Molecules, 2015. 20(12): p. 21946-59.
87.Tammar, S., et al., Chemometric profiling and bioactivity of verbena (Aloysia citrodora) methanolic extract from four localities in Tunisia. Foods, 2021. 10(12), p. 2912.
88.Ebadi, M.T., et al., Packaging methods and storage duration affect essential oil content and composition of lemon verbena (Lippia citriodora Kunth.). Food Sci Nutr, 2017. 5(3): p. 588-595.
89.Fontana, D.C., et al., Using essential oils to control diseases in strawberries and peaches. International Journal of Food Microbiology, 2021. 338, p. 108980.
90.Meshkatalsadat, M.H., A.H. Papzan, and A. Abdollahi, Determination of bioactive volatile organic components of lippia citriodora using ultrasonic assisted with headspace solid phase microextraction coupled with GC-MS. Digest Journal of Nanomaterials and Biostructures, 2011. 6(1): p. 361 - 365.
91.Argyropoulou, C., et al., Chemical composition of the essential oil from leaves of Lippia citriodora H.B.K. (Verbenaceae) at two developmental stages. Biochemical Systematics and Ecology, 2007. 35(12): p. 831 - 837.
92.Quirantes-Pine, R., et al., Characterization of phenolic and other polar compounds in a lemon verbena extract by capillary electrophoresis-electrospray ionization-mass spectrometry. Journal of Separation Science, 2010. 33(17-18): p. 2818 - 2827.
93.Di Leo Lira, P., et al., Characterization of lemon verbena (Aloysia citriodora palau) from Argentina by the essential oil. Journal of Essential Oil Research, 2008. 20(4): p. 350 - 353.
94.Hudaib, M., K. Tawaha, and Y. Bustanji, Chemical Profile of the Volatile Oil of Lemon verbena (Aloysia citriodora Palau) Growing in Jordan. Journal of Essential Oil-Bearing Plants, 2013. 16(5): p. 568 - 574.
95.Benelli, G., et al., Acute larvicidal toxicity of five essential oils (Pinus nigra, Hyssopus officinalis, Satureja montana, Aloysia citrodora and Pelargonium graveolens) against the filariasis vector Culex quinquefasciatus: Synergistic and antagonistic effects. Parasitology International, 2017. 66(2): p. 166 - 171.
96.Funes, et al., Correlation between plasma antioxidant capacity and verbascoside levels in rats after oral administration of lemon verbena extract. Food Chemistry, 2009. 117(4): p. 589 - 598.
97.Quirantes, P., et al., Phenylpropanoids and their metabolites are the major compounds responsible for blood-cell protection against oxidative stress after administration of Lippia citriodora in rats. Phytomedicine, 2013. 20(12): p. 1112 - 1118.
98.Adel, M., et al., Effect of the extract of lemon verbena (Aloysia citrodora) on the growth performance, digestive enzyme activities, and immune-related genes in Siberian sturgeon (Acipenser baerii). Aquaculture, 2021. 541, p. 736797.
99.Gomes, D.B., et al., Involvement of Anti-Inflammatory and Stress Oxidative Markers in the Antidepressant-like Activity of Aloysia citriodora and Verbascoside on Mice with Bacterial Lipopolysaccharide- (LPS-) Induced Depression. Evid Based Complement Alternat Med, 2022. 2022: p. 1041656.
100.Ponce-Monter, H., et al., Spasmolytic and anti-inflammatory effects of Aloysia triphylla and citral, in vitro and in vivo studies. Journal of Smooth Muscle Research, 2010. 46(6): p. 309 - 319.
101.Spyridopoulou, K., et al., Antitumor potential of lippia citriodora essential oil in breast tumor-bearing mice. Antioxidants, 2021. 10(6), p.875.
102.Najar, B., et al., Chemical Composition and in Vitro Cytotoxic Screening of Sixteen Commercial Essential Oils on Five Cancer Cell Lines. Chemistry and biodiversity, 2020. 17(1), p. e1900478.
103.Sabti, M., et al., Elucidation of the molecular mechanism underlying lippia citriodora(Lim.)-Induced relaxation and Anti-Depression. International Journal of Molecular Sciences, 2019. 20(14), p. 3556.
104.Abuhamdah, S., et al., Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora Palau. Journal of Pharmacy and Pharmacology, 2015. 67(9): p. 1306 - 1315.
105.Dos Santos, A.C., et al., Essential oil of Aloysia citriodora Palau and citral: sedative and anesthetic efficacy and safety in Rhamdia quelen and Ctenopharyngodon idella. Vet Anaesth Analg, 2022. 49(1): p. 104-112.
106.Parodi, T.V., et al., The anesthetic efficacy of eugenol and the essential oils of Lippia alba and Aloysia triphylla in post-larvae and sub-adults of Litopenaeus vannamei (Crustacea, Penaeidae). Comparative Biochemistry and Physiology, Toxicology and pharmacology, 2012. 155(3): p. 462 - 468.
107.Lenoir, L., et al., Lemon verbena infusion consumption attenuates oxidative stress in dextran sulfate sodium-induced colitis in the rat. Digestive Diseases and Sciences, 2011. 56(12): p. 3534 - 3545.
108.Funes, L., et al., Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise. European Journal of Applied Physiology, 2011. 111(4): p. 695 - 705.
109.Elgueta, E., J. Mena, and P.A. Orihuela, Hydroethanolic Extracts of Haplopappus baylahuen Remy and Aloysia citriodora Palau Have Bactericide Activity and Inhibit the Ability of Salmonella Enteritidis to Form Biofilm and Adhere to Human Intestinal Cells. BioMed Research International, 2021. 2021.
110.Bataineh, S.M.B., Y.H. Tarazi, and W.A. Ahmad, Antibacterial efficacy of some medicinal plants on multidrug resistance bacteria and their toxicity on eukaryotic cells. Applied sciences (Basel), 2021. 11(18), p. 3491831.
111.Lee, Y.S., et al., Metabolaid((R)) Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation. Nutrients, 2018. 10(9), p. 1204.
112.Lee, M.-C., et al., Evaluation of the efficacy of supplementation with planox lemon verbena extract in improving oxidative stress and muscle damage: A double-blind controlled trial. International Journal of Medical Sciences, 2021. 18(12): p. 2641 - 2652.
113.Cheimonidi, C., et al., Selective cytotoxicity of the herbal substance acteoside against tumor cells and its mechanistic insights. Redox Biol, 2018. 16: p. 169-178.
114.Daneshforouz, A., et al., The cytotoxicity and apoptotic effects of verbascoside on breast cancer 4T1 cell line. BMC Pharmacol Toxicol, 2021. 22(1): p. 72.
115.Zhang, Y., et al., Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma. Int J Cancer, 2018. 143(4): p. 980-991.
116.Ren, Y., et al., The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-kappaB Pathway-Mediated M1 Macrophage Polarization. Front Oncol, 2022. 12: p. 901922.
117.Xiao, Y., Q. Ren, and L. Wu, The pharmacokinetic property and pharmacological activity of acteoside: A review. Biomed Pharmacother, 2022. 153: p. 113296.
118.Deger, A.N., et al., Corrective Effect of Verbascoside on Histomorphological Differences and Oxidative Stress in Colon Mucosa of Rats in Which Colon Ischemia-Reperfusion Injury was Induced. Turk J Gastroenterol, 2021. 32(7): p. 548-549.
119.Zheng, J.N., et al., Phenylethanoid Glycosides From Callicarpa kwangtungensis Chun Attenuate TNF-alpha-Induced Cell Damage by Inhibiting NF-kappaB Pathway and Enhancing Nrf2 Pathway in A549 Cells. Front Pharmacol, 2021. 12: p. 693983.
120.Yoou, M.S., H.M. Kim, and H.J. Jeong, Acteoside attenuates TSLP-induced mast cell proliferation via down-regulating MDM2. Int Immunopharmacol, 2015. 26(1): p. 23-9.
121.Wang, Y., et al., Salsolinol Induces Parkinson's Disease Through Activating NLRP3-Dependent Pyroptosis and the Neuroprotective Effect of Acteoside. Neurotox Res, 2022. 40(6): p. 1948-1962.
122.Wang, C., et al., Neuroprotective effects of verbascoside against Alzheimer's disease via the relief of endoplasmic reticulum stress in Abeta-exposed U251 cells and APP/PS1 mice. J Neuroinflammation, 2020. 17(1): p. 309.
123.Chen, S., et al., The Neuroprotection of Verbascoside in Alzheimer's Disease Mediated through Mitigation of Neuroinflammation via Blocking NF-kappaB-p65 Signaling. Nutrients, 2022. 14(7).
124.Gao, W., et al., Effects of phenylethanol glycosides from Orobanche cernua Loefling on UVB-Induced skin photodamage: a comparative study. Photochemical and Photobiological Sciences, 2021. 20(5): p. 599 - 614.
125.Koycheva, I.K., et al., Leucosceptoside A from Devil's Claw Modulates Psoriasis-like Inflammation via Suppression of the PI3K/AKT Signaling Pathway in Keratinocytes. Molecules, 2021. 26(22), p. 7014.
126.Li, M., et al., Neuroprotective Effects of Four Phenylethanoid Glycosides on H(2)O(2)-Induced Apoptosis on PC12 Cells via the Nrf2/ARE Pathway. Int J Mol Sci, 2018. 19(4), p.1135.
127.Al-Massarani, S.M., et al., Insecticidal Activity and Free Radical Scavenging Properties of Isolated Phytoconstituents from the Saudi Plant Nuxia oppositifolia (Hochst.). Molecules, 2021. 26(4), p.914.
128.Pierre Luhata, L. and T. Usuki, Free radical scavenging activities of verbascoside and isoverbascoside from the leaves of Odontonema strictum (Acanthaceae). Bioorg Med Chem Lett, 2022. 59: p. 128528.
129.Gao, H., et al., Isoacteoside, a dihydroxyphenylethyl glycoside, exhibits anti-inflammatory effects through blocking toll-like receptor 4 dimerization. Br J Pharmacol, 2017. 174(17): p. 2880-2896.
130.Shiao, Y.J., et al., Acteoside and Isoacteoside Protect Amyloid beta Peptide Induced Cytotoxicity, Cognitive Deficit and Neurochemical Disturbances In Vitro and In Vivo. Int J Mol Sci, 2017. 18(4), p. 895.
131.Wan, M. and X. Meng, Anthocyanin Composition and Antioxidant Activity of Cranberry. Shipin Kexue/Food Science, 2018. 39(22): p. 45 - 50.
132.Re, R., et al., Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med, 1999. 26(9-10): p. 1231-7.
133.小柳津, 周., 褐変物質に関する研究グルコサミン褐変物質の抗酸化性について. 栄養学雑誌, 1986. 44(6): p. 307-315.
134.LeBel, C.P., H. Ischiropoulos, and S.C. Bondy, Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol, 1992. 5(2): p. 227-31.
135.Rita, I., et al., Exploring reserve lots of Cymbopogon citratus, Aloysia citrodora and Thymus x citriodorus as improved sources of phenolic compounds. Food Chem, 2018. 257: p. 83-89.
136.Polumackanycz, M., et al., Chemical Composition and Antioxidant Properties of Common and Lemon Verbena. Antioxidants (Basel), 2022. 11(11), p. 2247.
137.Ji, S.L., et al., Antioxidant activity of phenylethanoid glycosides on glutamate-induced neurotoxicity. Biosci Biotechnol Biochem, 2019. 83(11): p. 2016-2026.
138.Tandisehpanah, Z., et al., Protective effect of aqueous and ethanolic extracts of Lippia citriodora Kunth. on acrylamide-induced neurotoxicity. Avicenna J Phytomed, 2022. 12(3): p. 281-294.
139.Lee, J.W., et al., Anti-inflammatory effect of stem bark of Paulownia tomentosa Steud. in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and LPS-induced murine model of acute lung injury. J Ethnopharmacol, 2018. 210: p. 23-30.
140.Lee, M.C., et al., Evaluation of the Efficacy of Supplementation with Planox(R) Lemon Verbena Extract in Improving Oxidative Stress and Muscle Damage: A Randomized Double-Blind Controlled Trial. Int J Med Sci, 2021. 18(12): p. 2641-2652.
141.Gao, W., et al., Orobanche cernua Loefling Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts. Photochemistry and Photobiology, 2018. 94(4): p. 733 - 743.