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柴胡皂苷D-大麻二酚自组装纳米粒的制备及细胞药效学评价

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中草药 | 药剂与工艺 2026,57(15): 5848-5858

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中草药 |药剂与工艺 2026 , 57 (15) : 5848 -5858

柴胡皂苷D-大麻二酚自组装纳米粒的制备及细胞药效学评价

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俞泽如¹, 张怡¹, 于忆骅², 孙琦³, 宋国虎¹, 余马¹, 陈华¹, 辛超¹

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辛超

作者简介:

俞泽如: 俞泽如，硕士研究生，研究方向为药用植物资源与分子生物学研究。E-mail:YY2953457139@126.com

Preparation and cytopharmacology evaluation of self-assembled saikosaponin D-cannabidiol nanoparticles

YU Zeru, ZHANG Yi, YU Yihua, SUN Qi, SONG Guohu, YU Ma, CHEN Hua, XIN Chao

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doi: 10.7501/j.issn.0253-2670.2026.15.007

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目的制备柴胡皂苷D（saikosaponins D，SSD）与大麻二酚（cannabidiol，CBD）自组装纳米粒（SSD-CBD），并初步探究其体外抗肝癌机制。方法采用纳米共沉淀法，以3∶1（投料质量比）制备SSD-CBD自组装纳米粒，利用X射线光电子能谱（X-ray photoelectron spectroscopy，XPS）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）及二维核磁共振氢谱（¹H-¹H nuclear overhauser enhancement spectroscopy，¹H-¹H NOESY）等多技术表征其组装机制；通过透射电子显微镜（transmission electron microscope，TEM）、动态光散射（dynamic light scattering，DLS）等技术评价其理化性质；采用MTT法、流式细胞术（Annexin V-FITC/PI染色）、天冬氨酸特异性的半胱氨酸蛋白水解酶（cysteinyl aspartate specific proteinase，Caspase）活性测定等手段系统评价其体外抗肿瘤活性、凋亡诱导效应及初步机制。结果该组装体通过氢键和疏水作用自组装形成，SSD与CBD表现出协同效应（CI＝0.79）；SSD-CBD纳米粒还具有pH值响应释药特性，在肿瘤微环境（pH 6.8）中特异性释药，而在正常生理环境（pH 7.4）保持稳定；机制研究表明，其主要通过激活线粒体凋亡途径诱导HepG2细胞死亡。结论构建的SSD-CBD自组装纳米粒，提供了一种可同步改善CBD递送效率、实现精准协同给药的无载体策略，为基于SSD的智能纳米药物开发提供了实验依据。

关键词

柴胡皂苷D / 大麻二酚 / 细胞凋亡 / 自组装纳米粒 / 细胞药效学

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Objective To prepare a self-assembled nanoparticles of saikosaponin D (SSD) and cannabidiol (CBD) and preliminarily investigate their anti-hepatoma mechanism in vitro. Methods The SSD-CBD self-assembled nanoparticles were constructed using the nano co-precipitation method at a mass ratio of 3∶1, and their assembly mechanisms were characterized by techniques including X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and ¹H-¹H nuclear overhauser enhancement spectroscopy (¹H-¹H NOESY). Its physicochemical properties were evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The antitumor activity, apoptosis induction, and preliminary mechanisms were systematically assessed by MTT assay, flow cytometry (Annexin V-FITC/PI staining), and cysteinyl aspartate specific proteinase (Caspase) activity assays. Results The assembly was self-assembled through hydrogen bonding and hydrophobic interactions, with SSD and CBD showing a synergistic effect against HepG2 cells (CI = 0.79). It exhibited pH-responsive drug release, specifically releasing drugs in the tumor microenvironment (pH 6.8) while remaining stable at normal physiological environment (pH 7.4). Mechanistic studies indicated that it primarily induced HepG2 cell death by activating the mitochondrial apoptotic pathway. Conclusion The constructed SSD-CBD self-assembled nanoparticles offer a carrier-free strategy that can simultaneously improve the delivery efficiency of CBD and achieve precise collaborative drug delivery, providing an experimental basis for the development of intelligent nanomedicine based on SSD.

Key words

saikosaponin D / cannabidiol / apoptosis / self-assembled nanoparticles / cytopharmacology

引用本文

俞泽如, 张怡, 于忆骅, 孙琦, 宋国虎, 余马, 陈华, 辛超. 柴胡皂苷D-大麻二酚自组装纳米粒的制备及细胞药效学评价. 中草药, 2026 , 57 (15) : 5848 -5858 . DOI: 10.7501/j.issn.0253-2670.2026.15.007

YU Zeru, ZHANG Yi, YU Yihua, SUN Qi, SONG Guohu, YU Ma, CHEN Hua, XIN Chao. Preparation and cytopharmacology evaluation of self-assembled saikosaponin D-cannabidiol nanoparticles[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (15) : 5848 -5858 . DOI: 10.7501/j.issn.0253-2670.2026.15.007

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西藏自治区重点研发计划 (XZ202401ZY0020); 药用植物种质资源库建设 (2021-I2M-1-032); 国家岗位产业体系专家项目 (CARS-21); 四川省区域创新合作项目 (2026YFHZ0163)

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文献

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参考文献引证文献

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胡振宇, 陈春羽, 施林峰, 等. 柴胡化学成分、药理、炮制研究进展[J]. 中华中医药学刊, 2026, 44(1): 187-194.
Teng L L, Guo X W, Ma Y Z, et al. A comprehensive review on traditional and modern research of the genus Bupleurum (Bupleurum L., Apiaceae) in recent 10 years [J]. J Ethnopharmacol, 2023, 306: 116129.
Ovando-Medina V M, García-Martínez C A, Farias-Cepeda L, et al. Cannabidiol encapsulation in polymeric hydrogels and its controlled release: A review [J]. Gels, 2025, 11(10): 815.
Xin C, Zhang Y D, Bao M L, et al. Novel carrier-free, charge-reversal and DNA-affinity nanodrugs for synergistic cascade cancer chemo-chemodynamic therapy [J]. J Colloid Interface Sci, 2022, 606: 1488-1508.
韩悦, 于丽媛, 卢桂兰, 等. 柴胡疏肝散对围绝经期抑郁模型大鼠焦虑抑郁的改善作用及机制研究[J]. 时珍国医国药, 2024, 35(6): 1316-1319.
刘晟文, 刘建英. 槲皮素药理学作用的研究进展[J]. 中华肺部疾病杂志: 电子版, 2020, 13(1): 104-106.
谢冉. 负载大麻二酚纳米胶束的制备及抗乳腺癌作用研究[D]. 北京: 中国中医科学院, 2021.
刘静怡, 周瑜, 彭家昱, 等. 酸响应两亲性聚合物药物载体的研究进展[J]. 高分子通报, 2021, 34(12): 22-30.
Zhang X Y, Hu S Y, Huang L F, et al. Advance progress in assembly mechanisms of carrier-free nanodrugs for cancer treatment [J]. Molecules, 2023, 28(20): 7065.
Chi F Y, Wang W S, Zhai S S, et al. Self-assembled baicalein-2,4-decadienal nanomedicine synergistically inhibits PGE₂ expression and elicits anti-inflammatory responses [J/OL]. Chin Herb Med, (2025-10-25) [2026-05-05]. https://doi.org/10.1016/j.chmed.2025.10.001.
Xin C, Liu S, Qu H, et al. The novel nanocomplexes containing deoxycholic acid-grafted chitosan and oleanolic acid displays the hepatoprotective effect against CCl₄-induced liver injury in vivo [J]. Int J Biol Macromol, 2021, 185: 338-349.
卢照, 魏慧欣, 陈霞, 等. 透射电子显微镜样品的制备方法及技术综述[J]. 科学技术与工程, 2023, 23(19): 8039-8049.
Chung J E, Tan S S, Gao S J, et al. Self-assembled micellar nano complexes comprising green tea catechin derivatives and protein drugs for cancer therapy [J]. Nat Nanotechnol, 2014, 9(11): 907-912.
Cheng T. Drug combination studies and their synergy quantification using the Chou-Talalay method [J]. Cancer Res, 2010, 70(2): 440-446.
Sánchez-Díez M, Romero-Jiménez P, Alegría-Aravena N, et al. Assessment of cell viability in drug therapy: IC₅₀ and other new time-independent indices for evaluating chemotherapy efficacy [J]. Pharmaceutics, 2025, 17(2): 247.
Emadi R, Amiri Z, Mortazavi Moghadam F, et al. Self-assembling nanocomposites for smart drug delivery: Towards personalized and stimuli-responsive therapeutics [J]. RSC Adv, 2026, 16(6): 5088-5127.
Chen Y M, Xu W, Liu Y, et al. Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer [J]. Int J Biol Sci, 2023, 19(8): 2531-2550.
朱卫丰, 邓双雁, 欧阳辉, 等. 中药多糖口服吸收及其标记技术研究进展[J]. 中国实验方剂学杂志, 2024, 30(12): 261-269.
Sun S J, Deng P, Peng C E, et al. Selenium-modified chitosan induces HepG2 cell apoptosis and differential protein analysis [J]. Cancer Manag Res, 2022, 14: 3335-3345.
Unnisa A, Greig N H, Kamal M A. Inhibition of Caspase 3 and Caspase 9 mediated apoptosis: A multimodal therapeutic target in traumatic brain injury [J]. Curr Neuropharmacol, 2023, 21(4): 1001-1012.
Zaib S, Khan I, Hayyat A, et al. Role of mitochondrial membrane potential and lactate dehydrogenase a in apoptosis [J]. Anti Cancer Agents Med Chem, 2022, 22(11): 2048-2062.
Chen W K, Ge P X, Deng M J, et al. Toxicological responses of A549 and HCE-T cells exposed to fine particulate matter at the air-liquid interface [J]. Environ Sci Pollut Res, 2024, 31(18): 27375-27387.
Jiang L, Chen H Y, He C H, et al. Dual-modal apoptosis assay enabling dynamic visualization of ATP and reactive oxygen species in living cells [J]. Anal Chem, 2023, 95(6): 3507-3515.
Wang M M, Zheng D D, Zhang Y L, et al. Carrier-free self-assembled nanomedicines of active ingredients from pomegranate peel: An overview [J]. Discov Nano, 2025, 20(1): 170.
Kumar R, Dhar A, Banerjee A, et al. Sustainable Practices and Technologies [M]. Lausanne: Scientific Frontiers, 2024: 1-297.
Demİrbolat G M, Erdoğan Ö, Coşkun G P, et al. PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: In vitro characterization and the cellular efficacy [J]. Turk J Chem, 2022, 46(4): 1011-1023.
Gao Q, Feng J, Liu W C, et al. Opportunities and challenges for co-delivery nanomedicines based on combination of phytochemicals with chemotherapeutic drugs in cancer treatment [J]. Adv Drug Deliv Rev, 2022, 188: 114445.
Chou T C, Talalay P. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors [J]. Adv Enzyme Regul, 1984, 22: 27-55.
Lan J S, Qin Y H, Liu L, et al. A carrier-free folate receptor-targeted ursolic acid/methotrexate nanodelivery system for synergetic anticancer therapy [J]. Int J Nanomed, 2021, 16: 1775-1787.
Zhu Y, Deng X, Wu Y, et al. Formation mechanism of herpetrione self-assembled nanoparticles based on pH-driven method [J]. Chin Chem Lett, 2025, 36(1): 109733.
Yu S H, Webber M J. Engineering disease analyte response in peptide self-assembly [J]. J Mater Chem B, 2024, 12(42): 10757-10769.
Seltzer E S, Watters A K, MacKenzie D, et al. Cannabidiol (CBD) as a promising anti-cancer drug [J]. Cancers, 2020, 12(11): 3203.
Yavuz B R, Jang H, Nussinov R. Discovering anticancer drug target combinations via network-informed signaling-based approach [J]. Commun Med, 2025, 5(1): 428.
关月宏, 刘桂梅, 刘雨思, 等. 柴胡皂苷D通过Akt/ mTOR通路调控胰腺癌Panc-1细胞凋亡及自噬[J]. 中国中药杂志, 2023, 48(19): 5278-5284.
Ding J R, Sun A P, Hu H, et al. Potential targets and mechanisms of saikosaponin D in psoriasis: A bioinformatic and experimental study on oxidative stress [J]. J Inflamm Res, 2025, 18: 16487-16507.
Mall J, Naseem N, Haider M F, et al. Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications [J]. Intell Pharm, 2025, 3(4): 243-255.
张永苗, 王爱潮, 杜晓英, 等. 智能给药系统的响应机制和递送载体的临床应用进展[J]. 现代药物与临床, 2025, 40(4): 1065-1073.
Sun X F, Zhang Y Z, Lu X, et al. Research progress of enzyme-free DNA self-assembly technology in rapid detection of food safety [J]. J Food Compos Anal, 2025, 148: 108556.
Xu X Q, Xu X, Wang Y, et al. Self-assembled natural product-based carrier-free nanoplatforms for efficient bioactivity [J]. J Exp Res Pharm, 2022, 7(4): 223-233.
Rao C N R, Thomas P J, Kulkarni G U. Nanocrystals: Synthesis, Properties and Applications [M]. Berlin, Heidelberg: Springer Berlin Heidelberg, 2007: 1-182.
Fu Y C, Liang S B, Luo M, et al. Intratumoral heterogeneity and drug resistance in cancer [J]. Cancer Cell Int, 2025, 25(1): 103.
Zhou P, Shi W, He X Y, et al. Saikosaponin D: Review on the antitumour effects, toxicity and pharmacokinetics [J]. Pharm Biol, 2021, 59(1): 1478-1487.

2026年第57卷第15期

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doi: 10.7501/j.issn.0253-2670.2026.15.007

接收时间：2026-01-23
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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