• 综述与专论 • 下一篇
冯丽琼(
), 郭焜, 陈梓倩, 葛晓瑾, 陈沛涵, 李艺晶, 詹若挺, 陈立凯(
)
收稿日期:2025-03-25
出版日期:2026-03-09
通讯作者:
陈立凯,男,教授,博士生导师,研究方向 :南药资源保护、评价与质量遗传调控;E-mail: chenlk@gzucm.edu.cn作者简介:冯丽琼,女,硕士研究生,研究方向 :药用植物胞外囊泡新资源;E-mail: 1253394389@qq.com
基金资助:
FENG Li-qiong(
), GUO Kun, CHEN Zi-qian, GE Xiao-jin, CHEN Pei-han, LI Yi-jing, ZHAN Ruo-ting, CHEN Li-kai(
)
Received:2025-03-25
Published:2026-03-09
摘要:
药用植物胞外囊泡(Chinese herbal medicine derived extracellular vesicles-like particles, CHM-EVLP)是由药用植物各种细胞分泌的纳米级囊泡的统称,其由脂质双层膜构成,内含核酸、蛋白质、脂质及多种活性小分子等生物活性成分。现多项研究已证明CHM-EVLP具有跨界调控功能,兼具生物相容性好、高稳定性、可透皮吸收、靶向性强、安全性高等特点,使其在药物递送系统和疾病治疗中具有广阔应用前景。本文系统综述了CHM-EVLP的多种提取和纯化技术并比较其优缺点,表征与鉴定方法,并详细分析了其内含的核酸(如具有基因调控功能的miRNA)、蛋白质、脂质及小分子活性成分的组成与功能。进一步地,本文总结了CHM-EVLP在植物生长发育和代谢、胁迫响应、物质信息传递及哺乳动物系统中的多种生物活性,包括抗炎、抗肿瘤和癌症、抗氧化、抗骨质疏松等多种作用活性和机制,并探讨了其作为新型治疗剂和纳米药物载体,在抗癌治疗、炎症性疾病、医疗美容及护肤品等领域的应用潜力。尽管CHM-EVLP研究取得显著进展,但仍面临提取效率低、标准化方法和标志物缺失、作用机制不明确、长期保存困难等挑战。未来研究应聚焦于开发高效、可扩展的制备工艺,建立统一的质量评价体系,深入揭示其跨界调控的分子机制,持续探索以推动其在临床治疗与健康产品中的实际应用和产业化发展,进而促进新的药用植物资源的深度开发利用。
冯丽琼, 郭焜, 陈梓倩, 葛晓瑾, 陈沛涵, 李艺晶, 詹若挺, 陈立凯. 药用植物胞外囊泡的功能分析与应用研究进展[J]. 生物技术通报, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0311.
FENG Li-qiong, GUO Kun, CHEN Zi-qian, GE Xiao-jin, CHEN Pei-han, LI Yi-jing, ZHAN Ruo-ting, CHEN Li-kai. Advances in Functional Analysis and Application of Chinese Herbal Medicine Derived Extracellular Vesicles-like Particles[J]. Biotechnology Bulletin, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0311.
分离技术 Separation technique | 原理 Principle | 优点 Advantages | 缺点 Disadvantages | 应用 Applications |
|---|---|---|---|---|
超速离心法 Ultracentrifugation (UC) | 不同物质在离心条件下沉降系数不同 | 具有良好的兼容性,操作较简单 | 设备成本高,时间长,囊泡易聚集,回收率低 | 芦荟[ |
蔗糖密度梯度离心法 Sucrose density gradient centrifugation (DGC) | 基于密度分离 | 纯度较高 | 设备成本高,操作复杂 | 人参[ |
聚乙二醇沉淀法 Polyethylene glycol precipitation (PEG) | 通过PEG改变EVLP溶解度而使其沉淀 | 设备成本低,样品量兼容性强,效率高 | 产物纯度较低,时间长 | 生姜[ |
超滤法 Ultrafiltration (UF) | 溶液通过不同相对分子质量截留值的超细纳米过滤膜而分离 | 缩短时间 | 外压可能导致囊泡破碎,易堵塞 | 积雪草[ |
尺寸排除色谱法 Size exclusion chromatography (SEC) | 不同尺寸的物质通过多孔树脂颗粒而分离 | 纯度高,可保证囊泡的完整度 | 样品处理量小,易堵塞 | 槲寄生[ |
切向流过滤 Tangential flow filtration (TFF) | 错流过滤的原理来浓缩和过滤颗粒 | 适合大体积料液提取,产量和纯度高 | 设备成本较高,操作复杂 | 紫菀[ |
表1 CHM-EVLP分离技术及应用概况
Table 1 CHM-EVLP separation techniques and application overview
分离技术 Separation technique | 原理 Principle | 优点 Advantages | 缺点 Disadvantages | 应用 Applications |
|---|---|---|---|---|
超速离心法 Ultracentrifugation (UC) | 不同物质在离心条件下沉降系数不同 | 具有良好的兼容性,操作较简单 | 设备成本高,时间长,囊泡易聚集,回收率低 | 芦荟[ |
蔗糖密度梯度离心法 Sucrose density gradient centrifugation (DGC) | 基于密度分离 | 纯度较高 | 设备成本高,操作复杂 | 人参[ |
聚乙二醇沉淀法 Polyethylene glycol precipitation (PEG) | 通过PEG改变EVLP溶解度而使其沉淀 | 设备成本低,样品量兼容性强,效率高 | 产物纯度较低,时间长 | 生姜[ |
超滤法 Ultrafiltration (UF) | 溶液通过不同相对分子质量截留值的超细纳米过滤膜而分离 | 缩短时间 | 外压可能导致囊泡破碎,易堵塞 | 积雪草[ |
尺寸排除色谱法 Size exclusion chromatography (SEC) | 不同尺寸的物质通过多孔树脂颗粒而分离 | 纯度高,可保证囊泡的完整度 | 样品处理量小,易堵塞 | 槲寄生[ |
切向流过滤 Tangential flow filtration (TFF) | 错流过滤的原理来浓缩和过滤颗粒 | 适合大体积料液提取,产量和纯度高 | 设备成本较高,操作复杂 | 紫菀[ |
生物活性 Bioactivity | 药用植物 Medicinal plants | 部位 Part used | 生物活性及作用机制 Bioactivity and mechanism of action | 文献 Reference |
|---|---|---|---|---|
| 抗炎 Anti-inflammatory | 生姜 | 根茎 | 通过下调NF-κB、IL-6、IL-8和TNF-α的表达,拮抗LPS诱导的炎症 | [ |
| 马齿苋 | 地上部分 | 有效抑制促炎性细胞因子(TNF-α、IL-6、IL-12和IL-1β)和髓过氧化物酶(MPO)的表达,增加抗炎性细胞因子(IL-10)的水平,并缓解葡聚糖硫酸钠(DSS)诱导的C57小鼠和IL-10-/-小鼠的急性结肠炎 | [ | |
| 葛根 | 根 | 促进M1表型向M2巨噬细胞的转化,从而发挥和增强抗炎作用 | [ | |
| 姜黄 | 根茎 | 促进M1表型向M2巨噬细胞的转化,并恢复受损的肠上皮屏障以发挥抗结肠炎功效 | [ | |
抗肿瘤和癌症 Anti-tumor and anti-cancer | 青蒿 | 地上部分 | 激活哺乳动物免疫细胞内的信号传导途径,从而重新激活抗肿瘤免疫反应而彻底消除肿瘤 | [ |
| 辣木 | 种子 | 可以降低肿瘤细胞的存活率,增加与B细胞淋巴瘤蛋白表达降低相关的凋亡水平,并降低了线粒体膜电位 | [ | |
| 天冬 | 块根 | 通过吞噬作用内化到肿瘤细胞中,显著抑制肿瘤生长且无副作用 | [ | |
| 鸦胆子 | 果实 | 通过EVLP向4T1细胞递送10个功能性miRNA,调节PI3K/Akt/mTOR信号通路和促进ROS/caspase介导的细胞凋亡显著延缓4T1细胞的生长和转移 | [ | |
| 积雪草 | 地上部分 | 通过HepG2细胞对EVLP进行内化,促进活性氧水平增加、线粒体损伤、细胞周期停滞在G1期和细胞凋亡 | [ | |
| 桑叶 | 叶 | 通过半乳糖受体介导的内吞作用被肝脏肿瘤细胞株优先内化,增加细胞内氧化应激,引发线粒体损伤,从而抑制肿瘤细胞的活力、迁移和侵袭 | [ | |
抗骨质疏松 Anti-osteoporosis | 骨碎补 | 根 | 通过人骨髓间充质干细胞内化EVLP,以促进这些细胞的增殖和雌激素受体-α表达水平,成骨分化和骨形成 | [ |
| 巴戟天 | 根 | 通过MAPK通路促进成骨细胞增殖以缓解绝经后骨质疏松症 | [ | |
| 续断 | 根 | 通过激活BMP2/Smads信号通路以促进骨髓间充质干细胞的成骨分化和钙结节的形成,促进成骨分化相关基因(ALP、OCN、RUNX2以及COL1)的表达 | [ | |
| 淫羊藿 | 叶 | 提高血管内皮生长因子VEGF的表达水平,加强血管内皮细胞生成能力以缓解骨质疏松,并且具有体内骨靶向性 | [ | |
| 抗氧化 Antioxidant | 芦荟 | 皮 | 通过Nrf2激活抗氧化防御机制和促进伤口愈合过程 | [ |
| 生姜 | 根茎 | 诱导Nrf2活化,上调肝脏解毒和抗氧化基因的表达,并抑制活性氧的产生 | [ |
表2 CHM-EVLP的生物活性及作用机制
Table 2 Biological activity and mechanism of CHM-EVLP
生物活性 Bioactivity | 药用植物 Medicinal plants | 部位 Part used | 生物活性及作用机制 Bioactivity and mechanism of action | 文献 Reference |
|---|---|---|---|---|
| 抗炎 Anti-inflammatory | 生姜 | 根茎 | 通过下调NF-κB、IL-6、IL-8和TNF-α的表达,拮抗LPS诱导的炎症 | [ |
| 马齿苋 | 地上部分 | 有效抑制促炎性细胞因子(TNF-α、IL-6、IL-12和IL-1β)和髓过氧化物酶(MPO)的表达,增加抗炎性细胞因子(IL-10)的水平,并缓解葡聚糖硫酸钠(DSS)诱导的C57小鼠和IL-10-/-小鼠的急性结肠炎 | [ | |
| 葛根 | 根 | 促进M1表型向M2巨噬细胞的转化,从而发挥和增强抗炎作用 | [ | |
| 姜黄 | 根茎 | 促进M1表型向M2巨噬细胞的转化,并恢复受损的肠上皮屏障以发挥抗结肠炎功效 | [ | |
抗肿瘤和癌症 Anti-tumor and anti-cancer | 青蒿 | 地上部分 | 激活哺乳动物免疫细胞内的信号传导途径,从而重新激活抗肿瘤免疫反应而彻底消除肿瘤 | [ |
| 辣木 | 种子 | 可以降低肿瘤细胞的存活率,增加与B细胞淋巴瘤蛋白表达降低相关的凋亡水平,并降低了线粒体膜电位 | [ | |
| 天冬 | 块根 | 通过吞噬作用内化到肿瘤细胞中,显著抑制肿瘤生长且无副作用 | [ | |
| 鸦胆子 | 果实 | 通过EVLP向4T1细胞递送10个功能性miRNA,调节PI3K/Akt/mTOR信号通路和促进ROS/caspase介导的细胞凋亡显著延缓4T1细胞的生长和转移 | [ | |
| 积雪草 | 地上部分 | 通过HepG2细胞对EVLP进行内化,促进活性氧水平增加、线粒体损伤、细胞周期停滞在G1期和细胞凋亡 | [ | |
| 桑叶 | 叶 | 通过半乳糖受体介导的内吞作用被肝脏肿瘤细胞株优先内化,增加细胞内氧化应激,引发线粒体损伤,从而抑制肿瘤细胞的活力、迁移和侵袭 | [ | |
抗骨质疏松 Anti-osteoporosis | 骨碎补 | 根 | 通过人骨髓间充质干细胞内化EVLP,以促进这些细胞的增殖和雌激素受体-α表达水平,成骨分化和骨形成 | [ |
| 巴戟天 | 根 | 通过MAPK通路促进成骨细胞增殖以缓解绝经后骨质疏松症 | [ | |
| 续断 | 根 | 通过激活BMP2/Smads信号通路以促进骨髓间充质干细胞的成骨分化和钙结节的形成,促进成骨分化相关基因(ALP、OCN、RUNX2以及COL1)的表达 | [ | |
| 淫羊藿 | 叶 | 提高血管内皮生长因子VEGF的表达水平,加强血管内皮细胞生成能力以缓解骨质疏松,并且具有体内骨靶向性 | [ | |
| 抗氧化 Antioxidant | 芦荟 | 皮 | 通过Nrf2激活抗氧化防御机制和促进伤口愈合过程 | [ |
| 生姜 | 根茎 | 诱导Nrf2活化,上调肝脏解毒和抗氧化基因的表达,并抑制活性氧的产生 | [ |
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