[논문]헤스페레틴(Hesperetin)과 사이클로덱스트린(Cyclodextrin) 포접 복합체의 항산화, 항염증, 항균 활성

최성숙; 이경애

doi:10.12925/jkocs.2023.40.5.988

헤스페레틴(Hesperetin)과 사이클로덱스트린(Cyclodextrin) 포접 복합체의 항산화, 항염증, 항균 활성
Antioxidant, anti-inflammatory, and antimicrobial activity of hesperetin and its cyclodextrin inclusion complexes 원문보기

Journal of the Korean Applied Science and Technology = 한국응용과학기술학회지, v.40 no.5, 2023년, pp.988 - 1000

최성숙 (영진바이오 연구소) , 이경애 (안양대학교 식품영양학과)

초록
AI-Helper

Hesperetin은 Hesperidin에서 유도되는 강한 항산화 기능의 플라보노이드 비당체이다. 본 연구에서는 Hesperetin과 이의 Cyclodextrin 포접 복합체에 대하여 항산화, 항염증 및 항균 활성을 비교하였다. Hesperetin은 Hesperidin에 효소처리하여 제조되었으며, Hesperetin/Cyclodextrin 포접체는 용매 증류법에 의해 𝛽-Cyclodextrin 및 Hydroxypropyl-𝛽-Cyclodextrin을 사용하여 제조되었다. Hesperetin에 비해 Hesperetin/Hydroxypropyl-𝛽-Cyclodextrin 포접체의 용해도는 93.5배 증가하였고, Hesperetin/𝛽-Cyclodextrin 포접체의 용해도는 22.5배 증가하였다. 항산화 분석에서 Hydroxypropyl-𝛽-Cyclodextrin 포접체는 Hesperetin과 유사한 라디칼 소거 활성능을 보인 반면, 𝛽-Cyclodextrin 포접체는 Hesperetin 보다 약간 낮은 활성을 나타내었다. RAW 264.7 세포에 대한 세포독성은 Hydroxypropyl-𝛽-Cyclodextrin 포접체, 𝛽-Cyclodextrin 포접체, Hesperetin의 순으로 세포독성이 낮았다. Hesperetin과 Cyclodextrin 포접체는 모두 세포내 산화질소(NO), 종양괴사인자-𝛼(TNF-𝛼) 및 인터루킨-6(IL-6)과 같은 염증 매개체를 감소시켰다. Hesperetin 및 Hydroxypropyl-𝛽-Cyclodextrin 포접체는 상대적으로 𝛽-Cyclodextrin 포접체 보다 더 효과적이었다. 피부 유해성 세균인 황색 포도상구균과 녹농균에 대해 억제 효과를 시험한 결과, 황색 포도상구균에 대해서는 Hesperetin = Hydroxypropyl-𝛽-Cyclodextrin 포접체 > 𝛽-Cyclodextrin 포접체의 순서로 항균 효과를 나타내었으나, 녹농균에 대해서는 뚜렷한 억제효과를 나타내지 않았다. 결론적으로, Hesperidin의 비당체 형태인 Hesperetin과 이의 Cyclodextrin 포접체는 다양한 생물학적 활성을 보여주었으며, 용해도가 높은 Hydroxypropyl-𝛽-Cyclodextrin 포접체가 𝛽-Cyclodextrin 포접체에 비해 상대적으로 더 높은 활성을 나타내었다.

Abstract ▼ AI-Helper

Hesperetin(HT) is a potent antioxidant flavonoid aglycone derived from hesperidin(HD). The antioxidant, anti-inflammatory, and antimicrobial activities of HT and its cyclodextrin(CD) inclusion complexes were compared in vitro. HT was prepared by enzymatic hydrolysis of HD, and HT/CD complexes were prepared using 𝛽-cyclodextrin(𝛽-CD) and hydroxypropyl-𝛽-cyclodextrin(HP-𝛽-CD) by solvent co-evaporation method. The solubility of the HT/HP-𝛽-CD inclusion complex increased 93.5-fold compared to HT, and the solubility of HT/𝛽-CD increased 22.5-fold. The HT/HP-𝛽-CD inclusion complex showed a similar effect as HT on radical scavenging activity in antioxidant assays, whereas the HT/𝛽-CD inclusion complex showed slightly lower activity than HT. Cytotoxicity was low in the following order; HT/HP-𝛽-CD, HT/𝛽-CD, and HT in murine macrophage RAW264.7 cells. Treatment with HT and HT/CD inclusion complexes reduced the levels of inflammatory mediators such as nitric oxide(NO), tumor necrosis factor-𝛼(TNF-𝛼) and interleukin-6(IL-6) in the cells. HT and HT/HP-𝛽-CD inclusion complex were more effective than HT/𝛽-CD inclusion complex at relatively low concentrations. Inhibitory effects were tested on skin-pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, and they showed an antimicrobial effect on S. aureus in the order of HT = HT/HP-𝛽-CD > HT/𝛽-CD, but they did not show any significant inhibitory effect on P. aeruginosa. In conclusion, HT, the aglycone form of HD, and its CD inclusion complexes showed various biological activities. HT/HP-𝛽-CD inclusion complex, which is the highly soluble form of HT, showed relatively higher activity compared to HT/𝛽-CD inclusion complex.

주제어

표/그림 (7)

그림 Fig. 1. Mass spectrum of prepared HT by LC-MS analysis.
그림 Fig. 2. FT-IR spectra of HT and HT/CD inclusion complexes. (a) HT, (b) HT/β-CD inclusion complex, (c) HT/HP-β-CD inclusion complex.
표 Table 1. Solutility of HT and its CD inclusion complexes in water
그림 Fig. 3. Antioxidant activity of HT and HT/CD inclusion complexes. Results were expressed as a mean ± SD (n=3). (a) DPPH radical scavenging activity, (b) ABTS radical scavenging activity.
그림 Fig. 4. Effect of HT and HT/CD inclusion complexes on RAW 264.7 cell viability. Cells were treated with HT and HT/CD inclusion complexes, respectively, for 1 hr and incubated for 24 hours with LPS(final concentration of 1 μg/mL_. Results were represented as mean ± SD (n=3). Significant differences from the control(*p < 0.05; **p < 0.01). CTR; Control(LPS)
그림 Fig. 5. Effect of HT and HT/CD inclusion complexes on the production of nitric oxide(NO), tumor necrosis factor-α(TNF-α) and interleukin 6(IL-6). RAW 264.7 cells were cultured with different concentrations of HT and HT/CD inclusion complexes for 24 hours with LPS(1 μg/mL). Results were represented as mean ± SD (n=3). (a) Effect on NO levels, (b) Effect on TNF-α levels, (c) Effect on IL-6 levels. Different letters (a, b, c, d) above the bars indicate significant differences(p < 0.05), where ab or bc represents the intermediate significance value between a and b or b and c, respectively. CTR-; Negative control, CTR+; Positive control(LPS).
그림 Fig. 6. Effect of HT and HT/CD inclusion complexes on the growth of S. aureus and P. aeruginosa. Equal amounts of HT equivalents were loaded onto the discs on agar plates. (a) S. aureus, (b) P. aeruginosa. A: HT, B: HT/β-CD, C: HT/HP-β-CD, D: Negative control.

참고문헌 (36)

G. R. Beecher, "Overview of Dietary Flavonoids: Nomenclature, Occurrence and Intake", Journal of Nutrition, Vol.133, No.10, pp. 3248S-3254S, (2003).？
K. Nemeth, G. W. Plumb, J.-G. Berrin, N. Juge, R. Jacob, H. Y. Naim, G. Williamson, D. M. Swallow, P. A. Kroon, "Deglycosylation by Small Intestinal Epithelial Cell Β-Glycosidases Is a Critical Step in the Absorption and Metabolism of Dietary Flavonoid Glycosides in Humans", European Journal of Nutrition, Vol.42, No.1, pp. 29-42, (2003).？
H, Matsumoto, Y. Ikoma, M. Sugiura, M. Yano, Y. Hasegawa, "Identification and Quantification of the Conjugated Metabolites Derived from Orally Administered Hesperidin in Rat Plasma", Journal Of Agriculture and Food Chemistry, Vol.52, No.2, pp. 6653-6659, (2004).？
F. Haidari, S. A. Keshavarz, M. R. Rashidi, M. M. Shahi, "Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoredutase Activity", Journal of Clinical Biochemtry and Nutrition, Vol.45, No.3, pp. 285-291, (2009).？
A. Hirata, Y. Murakami, M. Shoji, Y. Kadoma, S. Fujisawa, "Kinetics of Radical-Scavenging Activity of Hesperetin and Hesperidin and their Inhibitory Activity on Cox-2 Expression", Anticancer Research, Vol.25, No.5, pp. 3367-3374, (2005).？

상세보기
Y. Hao, Z. Wei, Z. Wang, G. Li, Y. Yao, B. Dun, "Biotransformation of Flavonoids Improves Antimicrobial and Anti-Breast Cancer Activities In Vitro", Foods, Vol.10, No.10, 2367, (2021).？

상세보기
B. Olas, "A Review Of In Vitro Studies of the Anti-Platelet Potential of Citrus Fruit Flavonoids", Food Chemistry And Toxicology, Vol.150, 112090, (2021).？
A. Paredes, M. Aluzuru, J. Mendez, M. Rodriguez-Ortega, "Anti-Sindbis Activity of Flavanones Hesperetin and Naringenin", Biological and Pharmaceutical Bulletin, Vol.26, No.1, pp. 108-109, (2003).？

상세보기
K. Pyrzynska, "Hesperidin: A Review on Extraction Methods, Stability and Biological Activities", Nutrients, Vol.14, No.12, 2387, (2022).？

상세보기
F. J. Cheng, T. K. Huynh, C. S. Yang, D. W. Hu, Y. C. Shen, C. Y. Tu, Y. C. Wu, C. H. Tang, W. C. Huang, Y. Chen, "Hesperidin Is a Potential Inhibitor Against Sars-Cov-2 Infection", Nutrients, Vol.13, No.8, 2800, (2021).？

상세보기
H, Zalpoor, M. Bakhtiyari, H. Shapourian, R. Puria, T. Chanour, N. Mohsen, "Hesperetin as An Anti-SARS-CoV-2 agent Can Inhibit COVID-19-Associated Cancer Progression by Suppressing Intracellular Signaling Pathways", Inflammopharmacology, Vol.30, No.5, pp. 1533-1539, (2022).？

상세보기
M. Q. Man, B. Yang, P. M. Elias, "Benefits of Hesperidin for Cutaneous Functions", Evidence-Based Complementary and Alternative Medicine, 266307, (2019).？
R. Cao, Y. Zhao, Z. Zhou, X. Zhao, "Enhancement of the Water Solubility and Antioxidant Activity of Hesperidin by Chitooligosaccharide", Journal of the Science of Food and Agriculture, Vol.98, No.6, pp. 2422-2427, (2018).？

상세보기
K. Slamova, J. Kapesova, K. Valentova, "Sweet flavonoids: Glycosidase-catalyzed Modifications", International Journal of Molecular Sciences, Vol.19, No.7, 2126, (2018).？

상세보기
M. Yamamoto, A. Suzuki, T. Hase, "Short-term Effects of Glucosyl Hesperidin and Hesperetin on Blood Pressure and Vascular Endothelial Function in Spontaneously Hypertensive Rats", Journal of Nutritional Science and Vitaminology, Vol.54, No.1, pp. 95-98, (2008).？

상세보기
G. M. Sulaiman, H. M. Waheeb, M. S. Jabir, S. H. Khazaal, Y. H. Dewir, Y. Naidoo, "Hesperidin Loaded on Gold Nanoparticles as a Drug Delivery System for a Successful Biocompatible, Anti-Cancer, Anti-Inflammatory and Phagocytosis Inducer Model", Scientific Reports, Vol.10, 9362, (2020).？

상세보기
J.-W. Wang, K.-X. Yu, X.-Y. Ji, H. Bai, W.-H. Zhang, X. Hu, G. Tang, "Structural Insights into the Host-Guest Complexation between β-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives:, Molecules, Vol.26, No.9, 2412, (2021).？
S. S. Hur, "Ginsenoside Composition and Change of Taste Quality in Red Ginseng Extract by Acid treatment and Complexation with Cyclodextrin", Journal of the Korean Applied Science and Technology, Vol.33, No.4. pp. 751-761, (2016).？
A, Corciova, C. Ciobanu, A. Poiata, A. Nicolescu, M. Drobota, C. D. Varganici, T. Pinteala, A. Fifere, N. Marangoci, C. Mircea, "Inclusion Complexes of Hesperidin with Hydroxypropyl-β-cyclodextrin. Physicochemical Characterization and Biological Assessment", Digest Journal of Nanomaterials and Biostructures, Vol.9, No.4, pp. 1623-1637, (2014).？
A. Stasilowicz-Krzemien, M. Golebiewski, A. Plazinska, W. Plazinski, A. Miklaszewski, M. Zarowski, Z. Adamska-Jernas, J. Cielecka-Piontek, "The Systems of Naringenin with Solubilizers Expand Its Capability to Prevent Neurodegenerative Diseases", International Journal of Molecular Sciences. Vol.23, No.2, 755. (2022).？

상세보기
P. Ratha, D. Y. Jhon, "Increase of Rutin, Quercetin, and Antioxidant Activity during Germinated Buckwheat (Fagopyrum esculentum Moench) Fermentation", Fermentation Technology, Vol.6, 147, (2017).？

상세보기
R. Re, N. Pellegrini, A. Proteggente, A. Pannala, M. Yang, C. Rice-Evans, "Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay", Free Radical Biology and Medicine, Vol.26, No.9-10, pp. 1231-1237, (1999).？

상세보기
T. Mosmann, "Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays", Journal of Immunological Methods, Vol.65, No.1-2, pp. 55-63, (1983).？

상세보기
I. Wiegand, K. Hilpert, R. Hancock, "Agar and Broth Dilution Methods to Determine the Minimal Inhibitory Concentration (MIC) of Antimicrobial Substance", Nature Protocols, Vol.3, No.2, pp. 163-175, (2008).？
M. Elshikh, S. Ahmed, S. Funston, P. Dunlop, M. McGaw, R. Marchant, I. M. Banat, "Resazurin-based 96-well Plate Microdilution Method for the Determination of Minimum Inhibitory Concentration of Biosurfactants", Biotechnology Letters, Vol.38, No.6, pp. 1015-1019, (2016).？

상세보기
P. K. Sudheeran, R. Ovadia, O. Galsarker, I. Maoz, N. Sela, D. Maurer, O. Feygenberg, M. Oren Shamir, N. Alkan. "Glycosylated Flavonoids: Fruit's Concealed Antifungal Arsenal', New Phytologist, Vol.225, No.4, pp. 1788-1798, (2020).？

상세보기
S. Kobayashi, S. Tanabe, M. Sugiyama, Y. Konishi, "Transepithelial Transport of Hesperetin and Hesperidin in Intestinal Caco-2 cell Monolayers", Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1778, No.1, pp. 33-41, (2008).？

상세보기
J. C. de Miranda, T. E. A. Martins, F. Veiga, H. G. Ferraz, "Cyclodextrins and Ternary Complexes: Technology to Improve Solubility of Poorly Soluble Drugs", Brazilian Journal of Pharmaceutical Sciences, Vol.47, No.4, pp. 665-681, (2011).？
T. J. Guzik, R. Korbut, T. Adamek-Guzik, "Nitric Oxide and Superoxide in Inflammation and Immune Regulation", Journal of Physiology and Pharmacology, Vol.54, No.4, pp. 469-487, (2003).？

상세보기
M. Matsumoto, N. Matsukawa, H. Mineo, H. Chiji, H. Hara, "A Soluble Flavonoid-glycoside, AlphaG-rutin, Is Absorbed as Glycosides in the Isolated Gastric and Intestinal Mucosa", Bioscience, Biotechnology, and Biochemistry, Vol.68, No.9, pp. 1929-1934, (2004)？
D. Prochazkova, I. Bousova, N. Wilhelmova, "Antioxidant and Prooxidant Properties of Flavonoids", Fitoterapia, Vol.82, No.4, pp. 513-523, (2011).？

상세보기
J. H. Kim, S. H. Park, E. J. Baek, C. H. Han, N. J. Kang, "Anti-oxidant and Anti-inflammatory Effects of Rutin and its Metabolites", Current Research in Agriculture and Life Sciences, Vol.31, No.3, pp. 165-169, (2013).？
A. Duda-Chodak, "The Inhibitory Effect of Polyphenols on Human Gut Microbiota", Journal of Physiology and Pharmacology, Vol.63, No.5, pp. 497-503, (2012).？

상세보기
M. Iranshahi, R. Rezaee, H. Parhiz, A. Roohbakhsh, F. Soltani, "Protective Effects of Flavonoids against Microbes and Toxins: The Cases of Hesperidin and Hesperetin", Life Sciences, Vol.137, pp. 125-132, (2015).？

상세보기
G. Yuan, Y. Guan, H. Yi, S. Lai, Y. Sun, S. Cao, "Antibacterial Activity and Mechanism of Plant Flavonoids to Gram-Positive Bacteria Predicted from Their Lipophilicities", Scientific Reports. Vol.18, No.11, 10471, (2021).？
J. Echeverria, J. Opazo, L. Mendoza, A. Urzua, M. Wilkens, "Structure-Activity and Lipophilicity Relationships of Selected Antibacterial Natural Flavones and Flavanones of Chilean Flora", Molecules, Vol.22, No.4, 608, (2017).

상세보기

표제어: PCR

동의어: Packet Collision Rate

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