新型茶叶/茶枝柑融合纳米囊泡的构建及其抗炎抗肿瘤活性评价

doi:10.13305/j.cnki.jts.2026.02.012

摘要/Abstract

摘要： 植物外泌体样纳米囊泡（Exosome-like nanovesicles,ELNVs）作为植物的组成成分之一,是由植物细胞分泌的小型纳米级囊泡。它富含生物活性物质,其囊泡结构使其成为理想的“绿色”药物递送载体。为规避单一来源植物ELNVs的缺陷,本研究采用膜融合技术,首次将茶叶ELNVs和茶枝柑ELNVs相结合,形成新型融合纳米囊泡,随后表征其物理化学特性,解析其物质基础,分析其在模拟消化液中的稳定性,并在细胞水平探究其抗氧化、抗炎和抗肿瘤活性。结果表明,新型融合纳米囊泡是一种集茶多酚（儿茶素）、橙皮素、橙皮苷、川陈皮素、槲皮素、活性磷脂、蛋白质等多重功效成分于一体的重组脂质体,具有磷脂双分子层结构,外观呈球形,分散性良好,粒径大小均一。另外,在模拟胃液、肠液中,新型融合纳米囊泡均具有良好的稳定性。细胞试验结果表明,新型融合纳米囊泡显著下调了脂多糖（Lipopolysaccharide,LPS）诱导的RAW264.7细胞氧化应激损伤及炎症反应,并具有优越的抗肿瘤作用。本研究结果为天然植物ELNVs的应用拓展了新思路,也为开发新型多功能口服保健品提供了科学依据。

关键词: 植物外泌体样纳米囊泡（植物ELNVs）, 重组脂质体, 抗炎, 抗氧化, 抗肿瘤

Abstract: Plant exosome-like nanovesicles (ELNVs), as inherent components of plants, are nanoscale vesicles secreted by plant cells. They are inherently rich in bioactive compounds, and their vesicular structure makes them ideal “green” drug delivery vehicles. To overcome the limitations of single-source plant ELNVs, this study employed membrane fusion technology to combine tea ELNVs and Citrus reticulata ‘Chachiensis’ ELNVs for the first time, creating novel fusogenic nanovesicles. We subsequently characterized the physicochemical properties of novel fusogenic nanovesicles, elucidated their fundamental composition, assessed their stabilities in simulated digestive fluids, and evaluated their antioxidant, anti-inflammatory and anti-tumor activities through cellular assays. The results indicate that the novel fusogenic nanovesicles are a reconstituted liposome integrating multiple functional components, including tea polyphenols (catechins), hesperetin, hesperidin, nobiletin, quercetin, active phospholipids and proteins. They exhibit a spherical morphology with a phospholipid bilayer structure, demonstrating good dispersibility with uniform particle size. Additionally, the novel fusogenic nanovesicles demonstrate excellent stability in both simulated gastric and intestinal fluids. Cell-based experimental results show that the novel fusogenic nanovesicles significantly alleviated lipopolysaccharide (LPS)-induced oxidative stress damage and inflammatory responses in RAW264.7 cells, while exhibiting superior antitumor efficacy. The findings of this study not only provided novel insights into the application of natural plant ELNVs, but also established a scientific foundation for developing innovative multifunctional oral nutraceuticals.

Key words: plant exosome-like nanovesicles (plant ELNVs), reconstituted liposomes, anti-inflammatory, antioxidant, antitumor

中图分类号:

王颖, 周闯, 高健健, 彭佳堃, 王佳童, 施江, 彭群华, 林智, 戴伟东, 周梦雪. 新型茶叶/茶枝柑融合纳米囊泡的构建及其抗炎抗肿瘤活性评价[J]. 茶叶科学, 2026, 46(2): 343-358. doi: 10.13305/j.cnki.jts.2026.02.012.

WANG Ying, ZHOU Chuang, GAO Jianjian, PENG Jiakun, WANG Jiatong, SHI Jiang, PENG Qunhua, LIN Zhi, DAI Weidong, ZHOU Mengxue. Construction of Novel Tea/Citrus reticulata ‘Chachiensis’ Fusogenic Nanovesicles and Evaluation of Their Anti-inflammatory and Antitumor Activities[J]. Journal of Tea Science, 2026, 46(2): 343-358. doi: 10.13305/j.cnki.jts.2026.02.012.

参考文献

[1] 黄翔翔, 谭婷, 禹利君, 等. 茯砖茶对葡聚糖硫酸钠诱导UC小鼠炎症及肠道微生物的影响[J]. 茶叶科学, 2021, 41(5): 681-694.
Huang X X, Tan T, Yu L J, et al.Effects of Fu brick tea on inflammation and intestinal microflora diversity in mice with DSS-induced ulcerative colitis[J]. Journal of Tea Science, 2021, 41(5): 681-694.
[2] Wang C P J, Byun M J, Kim SN, et al. Biomaterials as therapeutic drug carriers for inflammatory bowel disease treatment[J]. Journal of Controlled Release, 2022, 345: 1-19. doi: 10.1016/j.jconrel.2022.02.028.
[3] Sun W, Li Z B, Zhang X H, et al.Biomaterial-based therapeutic strategies for inflammatory bowel disease[J]. Biomaterials, 2026, 324: 123462. doi: 10.1016/j.biomaterials.2025.123462.
[4] 胡安恺, 姚立筠, 赵悦伶, 等. 茯砖茶提取物对葡聚糖硫酸钠诱导小鼠炎症性肠病的保护作用研究[J]. 茶叶科学, 2019, 39(6): 641-651.
Hu A K, Yao L Y, Zhao Y L, et al.Protective effects of fu brick tea extracts on inflammatory bowel disease induced by dextran sulfate sodium in mice[J]. Journal of Tea Science, 2019, 39(6): 641-651.
[5] Liu D D, Saikam V, Skrada K A, et al.Inflammatory bowel disease biomarkers[J]. Medicinal Research Reviews, 2022, 42(5): 1856-1887.
[6] Singh S.Positioning therapies for the management of inflammatory bowel disease[J]. Nature Reviews Gastroenterology & Hepatology, 2023, 20(7): 411-412.
[7] Luo H, Cao G Q, Luo C, et al.Emerging pharmacotherapy for inflammatory bowel diseases[J]. Pharmacological Research, 2022, 178: 106146. doi: 10.1016/j.phrs.2022.106146.
[8] Takahashi Y, Takakura Y.Extracellular vesicle-based therapeutics: extracellular vesicles as therapeutic targets and agents[J]. Pharmacology & Therapeutics, 2023, 242: 108352. doi: 10.1016/j.pharmthera.2023.108352.
[9] Mondal J, Pillarisetti S, Junnuthula V, et al.Hybrid exosomes, exosome-like nanovesicles and engineered exosomes for therapeutic applications[J]. Journal of Controlled Release, 2023, 353: 1127-1149. doi: 10.1016/j.jconrel.2022.12.027.
[10] Yang L T, Zhang D Z, Lu D L, et al.Plant-Derived Exosome-like nanovesicles-created injectable hydrogel for augmented cancer immunotherapy[J]. Chemical Engineering Journal, 2024, 491: 152032. doi: 10.1016/j.cej.2024.152032.
[11] Li D, Cao G F, Yao X L, et al.Tartary buckwheat-derived exosome-like nanovesicles against starch digestion andtheir interaction mechanism[J]. Food Hydrocolloids, 2023, 141: 108739. doi: 10.1016/j.foodhyd.2023.108739.
[12] 孙若璠, 高健健, 周丹阳, 等. 基于代谢组学的不同贮藏年份紧压寿眉白茶化学成分分析[J]. 食品科学, 2025, 46(7): 217-228.
Sun R P, Gao J J, Zhou D Y, et al.Metabolomics analysis of chemical constituents in compressed shoumei white tea with different storage periods[J]. Food Science, 2025, 46(7): 217-228.
[13] Zu M, Xie D, Canup B S B, et al. ‘Green’ nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases[J]. Biomaterials, 2021, 279: 121178. doi: 10.1016/j.biomaterials.2021.121178.
[14] 肖佳豪, 张群, 潘兆平, 等. 低温超微粉碎对茶枝柑果肉粉理化性质和功能特性的影响[J]. 食品科学, 2024, 45(20): 220-231.
Xiao J H, Zhang Q, Pan Z P, et al.Effect of low-temperature superfine grinding on the physicochemical and functional properties of the pulp powder of citrus reticulata ‘Chachi’[J]. Food Science, 2024, 45(20): 220-231.
[15] 周闯, 赵燕妮, 周梦雪, 等. 基于代谢组学的‘铁观音’和‘水仙’品种茶叶化学成分解析[J]. 食品科学, 2024, 45(4): 171-182.
Zhou C, Zhao Y N, Zhou M X, et al.Metabolomic analysis of the chemical composition of ‘Tieguanyin’ and ‘Shuixian’ tea[J]. Food Science, 2024, 45(4): 171-182.
[16] Zhou M, Wang J, Pan J, et al.Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy[J]. Nature Communications, 2023, 14(1): 3593. doi: 10.1038/s41467-023-39035-x.
[17] Rome S.Biological properties of plant-derived extracellular vesicles[J]. Food Function, 2019, 10(2): 529-538.
[18] Reker D, Blum S M, Steiger C, et al. “Inactive” ingredients in oral medications [J]. Science Translational Medicine, 2019, 11(483): eaau6753. doi: 10.1126/scitranslmed.aau6753.
[19] Fadok V A, Voelker D R, Campbell P A, et al.Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages[J]. Journal of Immunology, 1992, 148(7): 2207-2216.
[20] Di Gioia S, Hossain M N, Conese M.Biological properties and therapeutic effects of plant-derived nanovesicles[J]. Open Medicine, 2020, 15(1): 1096-1122.
[21] Sung J, Alghoul Z, Long D, et al.Oral delivery of IL-22 mRNA-loaded lipid nanoparticles targeting the injured intestinal mucosa: a novel therapeutic solution to treat ulcerative colitis[J]. Biomaterials, 2022, 288: 121707. doi: 10.1016/j.biomaterials.2022.121707.
[22] Teslaa T, Bartman C R, Jankowski C S R, et al. The source of glycolytic intermediates in mammalian tissues[J]. Cell Metabolism, 2021, 33(2): 367-378.
[23] Anjum J, Mitra S, Das R, et al.A renewed concept on the MAPK signaling pathway in cancers: polyphenols as a choice of therapeutics[J]. Pharmacological Research, 2022, 184: 106398. doi: 10.1016/j.phrs.2022.106398.
[24] Shah K, Al-Haidari A, Sun J, et al.T cell receptor (TCR) signaling in health and disease[J]. Signal Transduction and Targeted Therapy, 2021, 6(1): 412. doi: 10.1038/s41392-021-00823-w.
[25] Wen P, Sun Z, Gou F, et al.Oxidative stress and mitochondrial impairment: key drivers in neurodegenerative disorders[J]. Ageing Research Reviews, 2025, 104: 102667. doi: 10.1016/j.arr.2025.102667.
[26] Min D K, Kim Y E, Kim M K, et al.Orally Administrated inflamed colon-targeted nanotherapeutics for inflammatory bowel disease treatment by oxidative stress level modulation in colitis[J]. ACS Nano, 2023, 17(23): 24404-24416.
[27] Yang H, Zhu C, Yuan W, et al.Mannose-rich oligosaccharides-functionalized selenium nanoparticles mediates Macrophage reprogramming and inflammation resolution in ulcerative colitis[J]. Chemical Engineering Journal, 2022, 435: 131715. doi: 10.1016/j.cej.2021.131715.
[28] Zhang T, Xu R, Zhao N, et al.Rational design of lycopene emulsion-based nanofood for Lactobacillus plantarum to enhance the growth and flavor production[J]. Food Hydrocolloids, 2022, 127: 107518. doi:10.1016/j.foodhyd.2022.107518.
[29] Yan K, Li M J, Huang J P, et al.Development and stability assessment of Arachidonic acid nanoemulsions stabilized by sodium caseinate-gum arabic complexes[J]. LWT, 2025, 229: 118170. doi: 10.1016/j.lwt.2025.118170.
[30] Li M, Dia V P, Wu T.Ice recrystallization inhibition effect of cellulose nanocrystals: influence of sucrose concentration[J]. Food Hydrocolloids, 2021, 121: 107011. doi: 10.1016/j.foodhyd.2021.107011.
[31] Yang M, Liu J B, Liu C M, et al.Programmable food-derived peptide coassembly strategies for boosting targeted colitis therapy by enhancing oral bioavailability and restoring gut microenvironment homeostasis[J]. ACS Nano, 2025, 19(1): 600-620.
[32] Zhang H J, Deng A J, Zhang Z H, et al.The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-κB pathway[J]. Pharmacological Reports, 2016, 68(3): 514-520.
[33] Wu Z H, Huang S M, Li T T, et al.Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis[J]. Microbiome, 2021, 9(1): 1-22
[34] Nishi K, Nakatani Y, Ishida M, et al.Anti-inflammatory activity of the combination of nobiletin and docosahexaenoic acid in lipopolysaccharide-stimulated RAW 264.7 cells: a potential synergistic anti-inflammatory effect[J]. Nutrients, 2024, 16(13): 2080. doi: 10.3390/nu16132080.
[35] Kovács T, Varga G, Érdes D, et al.Dietary phosphatidylcholine supplementation attenuates inflammatory mucosal damage in a rat model of experimental colitis[J]. Shock, 2012, 38(2): 177-185.