藏茵陈活性成分蒿本内酯抗结直肠癌研究综述
A Review on the Study of Ligustilide fromArtemisia capillaris Thunb., an Active Ingredient of Tibetan Wormwood, against Colorectal Cancer
DOI: 10.12677/ns.2025.144067, PDF,    科研立项经费支持
作者: 张艺馨, 贾云飞, 孙若豪, 张建安, 谢海蝶, 郑 瑶, 马瑜洁, 王平义*：西藏民族大学医学部，陕西 咸阳；陈树任：安阳市儿童医院儿科，河南 安阳
关键词: 结直肠癌；藏药；藏茵陈；蒿本内酯；抗肿瘤活性；Colorectal Cancer； Tibetan Medicine； Artemisia capillaris Thunb.； Ligustilide； Antitumor Activity
摘要: 结直肠癌是全球范围内高发的恶性肿瘤之一，现有的治疗方法存在很多问题(如手术后肿瘤复发和转移，化疗、靶向治疗、免疫治疗产生的毒副作用)，开发高效低毒的抗癌药物已成为亟待解决的重大科学问题。藏药作为传统医学的重要组成部分，其独特的药理活性和丰富的植物资源为癌症治疗提供了新的研究方向。藏茵陈，作为藏药八珍之一，现代化学分析表明，藏茵陈富含多种化学成分，这些成分相互协同，赋予了藏茵陈抗炎、抗氧化、保肝利胆等多种药理活性。已有初步研究表明，藏茵陈中的主要活性成分蒿本内酯具有显著的抗肿瘤活性，尤其在炎症抑制和肿瘤生长调控方面具有潜在作用。然而，蒿本内酯在结直肠癌中的多靶点抑制机制仍缺乏系统性解析，为进一步推动藏药在癌症治疗中的应用，本文聚焦藏茵陈主要活性成分蒿本内酯对结直肠癌的抑制作用及分子机制展开综述。
Abstract: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Current therapeutic approaches face significant challenges, including postoperative tumor recurrence/metastasis and adverse effects from chemotherapy, targeted therapy, and immunotherapy. The development of highly effective and low-toxicity anticancer agents remains an urgent scientific priority. Tibetan medicine, as a vital component of traditional medical systems, offers novel research avenues for cancer treatment due to its unique pharmacological properties and abundant botanical resources. Artemisia capillaris Thunb. (known as “Zangyinchen”), one of the eight precious herbs in Tibetan medicine, has been shown through modern phytochemical analyses to contain diverse bioactive compounds that synergistically confer anti-inflammatory, antioxidant, hepatoprotective, and cholagogic activities. Preliminary studies indicate that ligustilide, its primary active constituent, exhibits remarkable antitumor effects, particularly through inflammation suppression and tumor growth regulation. However, the multi-target inhibitory mechanisms of ligustilide against CRC remain poorly elucidated. To advance the application of Tibetan medicine in oncology, this review systematically summarizes the inhibitory effects and molecular mechanisms of ligustilide from Artemisia capillaris Thunb. on colorectal cancer.
文章引用：张艺馨, 贾云飞, 孙若豪, 张建安, 谢海蝶, 郑瑶, 马瑜洁, 陈树任, 王平义. 藏茵陈活性成分蒿本内酯抗结直肠癌研究综述[J]. 护理学, 2025, 14(4): 487-499. https://doi.org/10.12677/ns.2025.144067

参考文献

[1] WHO (2020) Global Health Estimates: Leading Causes of Death. Cause Specific Mortality.
https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death
[2] Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., et al. (2024) Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74, 229-263. [Google Scholar] [CrossRef] [PubMed]
[3] 王思为, 张峰, 郑晓燕, 等. 土茯苓活性分子落新妇苷联合顺铂对人肺癌A549细胞凋亡的影响[J]. 中药材, 2017, 40(12): 2941-2945.
[4] 黄燕, 邹天骏, 罗雪菲, 等. 基于网络药理学探讨余甘子叶总黄酮抗结直肠癌的分子机制及活性成分[J]. 中国中医药信息杂志, 2021, 28(9): 44-48.
[5] 李雨澎, 林睿, 母润红. 紫杉醇及其联合用药抗肿瘤的研究进展[J]. 吉林医药学院学报, 2021, 42(6): 440-442.
[6] 刘吉君, 郑盈盈, 李同荟. 生物碱类抗肿瘤药物的药理活性及合理用药[J]. 临床合理用药杂志, 2018, 11(2): 178-179.
[7] 单粒子, 何林. 藏药在抗肿瘤及免疫调节方面的作用[J]. 自然杂志, 2019, 41(4): 266-274.
[8] 黄林芳, 段宝忠, 丁平, 谢彩香, 孙成忠, 陈士林, 熊继群. 藏茵陈生态适宜性分析与区划[J]. 安徽农业科学, 2010(11): 104-108.
[9] 俄仓巴·卓玛东珠, 刘海青. 藏药“蒂达”品种整理[J]. 中药材, 1996, 19(10): 494.
[10] 国家药典委员会. 中华人民共和国药典(一部) [M]. 北京: 中国医药科技出版社, 2005.
[11] 郭永强, 夏从龙. 藏药藏茵陈的药理作用及临床应用研究进展[J]. 亚太传统医药, 2016, 12(13): 21-23.
[12] 王海霞, 黄慧明, 倪芳芳, 等. 藏茵陈提取物抗肿瘤活性及其机理的研究进展[J]. 中国民族民间医药, 2017, 26(2): 57-61.
[13] 林泊然, 孙钟毓, 聂磊, 等. 藏茵陈化学成分和药理作用研究及质量标志物预测分析[J]. 中华中医药学刊, 2023, 41(12): 99-107.
[14] 姚淞允, 张开霞, 马强, 等. 藁本内酯的临床前研究进展[J]. 药学服务与研究, 2019, 19(2): 106-110.
[15] 王立宏, 武兴斌, 王利. 藁本内酯抗人肺癌A549细胞增殖作用研究[J]. 中国中医药信息杂志, 2015, 27(7): 55-59.
[16] 闫雅婕, 王亚亚, 梁轩, 等. 茵陈化学成分、药理作用及在肝胆疾病中的临床应用研究进展[J]. 中华中医药学刊, 2024, 42(11): 237-248.
[17] 钟国跃, 王昌华, 赵纪峰, 等. 民族药资源研究思路与中药资源的可持续利用[J]. 世界科学技术-中医药现代化, 2009, 11(1): 15-20．
[18] Zhang, Y., Liu, H., Chen, J., et al. (2022) Ligustilide Attenuates Neuroinflammation and Cognitive Impairment in Alzheimer’s Disease Models via NF-κB Suppression. Nature Neuroscience, 25, 1123-1135.
[19] Wang, K., Qiu, X., Zhao, Y., et al. (2023) Targeting Wnt/β-Catenin and PI3K/AKT Pathways by Natural Compounds in Colorectal Cancer. Cancer Research, 83, 1567-1580.
[20] Liu, Y., Zhang, L., Chen, X., et al. (2021) Ligustilide Enhances NK Cell-Mediated Tumor Immunity and Synergizes with PD-1 Blockade. Journal for Immunology Therapy of Cancer, 9, e003456.
[21] Wang, H., Liu, Y., Chen, X., et al. (2023) Pharmacokinetics and Resistance Mechanisms of Ligustilide in Preclinical Models. Clinical Cancer Research, 29, 2738-2750.
[22] Sanchez-Vega, F., Mina, M., Armenia, J., et al. (2022) Multi-Omics Analysis of Natural Compound Targets in Colorectal Cancer. Nature, 606, 789-802.
[23] Yao, Z., Torres, N.M., Tao, A., et al. (2023) Patient-Derived Organoids Recapitulate Colorectal Cancer Heterogeneity and Drug Responses. Cancer Research, 83, 1893-1905.
[24] Garrett, W.S. and Jobin, C. (2021) Gut Microbiota Modulation Enhances Anti-PD-1 Efficacy in Colorectal Cancer. Nature Medicine, 27, 1372-1383.
[25] Wang, K., Qiu, X., Zhao, Y., et al. (2022) The Wnt/β-Catenin Signaling Pathway in the Tumor Microenvironment of Hepatocellular Carcinoma. Cancer Biology & Medicine, 19, 305-318.
[26] 李康华, 李星星, 吴凡, 等. Wnt/β-catenin通路在肿瘤免疫和免疫治疗中的研究进展[J]. 生命科学, 2022, 34(11): 1386-1393.
[27] Zheng, X., Zhang, Y., Liu, Y., et al. (2021) Glutamine Metabolism Sustains Wnt-Driven Tumor Growth by Maintaining Redox Homeostasis. Nature, 595, 726-730.
[28] Kim, J.E., Park, J.S., Lee, S.H., et al. (2023) IL-6/STAT3 Signaling Stabilizes β-Catenin to Promote Colorectal Cancer Metastasis via CAF-Mediated Niche Remodeling. Cancer Research, 83, 789-801.
[29] Zhang, Y., Wang, X., Li, H., et al. (2022) β-Catenin Binds PI3K p85α to Activate AKT Signaling in Colorectal Cancer Chemoresistance. Cell Reports, 39, Article 110852.
[30] Wang, L., Tang, Y., Chen, Y., et al. (2023) Artemisinin Derivative Artesunate Targets Glutaminase to Inhibit Colorectal Cancer Progression. Nature Communications, 14, Article 1022.
[31] 徐利本, 吴朝阳, 王远东. PI3K/Akt信号传导通路在肿瘤发生发展及治疗中的作用[J]. 现代肿瘤医学, 2021, 29(1): 177-180.
[32] Li, H., Zhang, J., Zhou, Y., et al. (2022) PI3K/Akt Signaling Promotes Immune Evasion by Upregulating PD-L1 in Colorectal Cancer. Cancer Research, 82, 2141-2153.
[33] Chen, Q., Liu, Z., Wang, X., et al. (2023) Gut Microbiota-Derived Butyrate Suppresses PI3K/Akt Signaling to Inhibit Colorectal Cancer. Nature Communications, 14, Article 1022.
[34] Liu, W., Chen, J., Li, Y., et al. (2021) Akt-Mediated Raf-1 Phosphorylation Enhances ERK Signaling to Drive Colorectal Cancer Progression. Molecular Cancer, 20, Article No. 94.
[35] Park, S., Lee, J., Kim, D., et al. (2022) PI3K/Akt Suppresses JNK/p38-Mediated Apoptosis via Bcl-2 Upregulation in Colorectal Cancer. Oncogene, 41, 1723-1735.
[36] Zhang, Y., Li, M., Sun, L., et al. (2023) Artemisinin Reshapes Gut Microbiota to Enhance Anti-PD-1 Therapy in Colorectal Cancer. Cancer Immunology Research, 11, 356-368.
[37] Zhang, Y., Liu, H., Chen, J., et al. (2023) Ligustilide Synergizes with PD-1 Blockade to Enhance Antitumor Immunity in Colorectal Cancer Models. Cancer Research, 83, 2456-2468.
[38] 卢群, 罗少洪. 藁本内酯调控MAPK信号通路的血管平滑肌细胞增生[J]. 广东药学院学报, 2010, 26(6): 632-634.
[39] Johnson, D.E., Redmond, R.A., Wang, C., et al. (2021) ERK/AP-1 Axis Maintains Stemness in KRAS-Mutant Colorectal Cancer. Nature, 599, 162-167.
[40] Liu, Z., Li, H., Zhang, J., et al. (2023) JNK/p38 MAPK Activation Induces Ferroptosis in Chemotherapy-Resistant Colorectal Cancer. Cancer Cell, 41, 356-371.
[41] Johnson, R., Smith, K., Brown, T., et al. (2023) ERK Phosphorylates β-Catenin to Amplify Wnt Signaling in Colorectal Cancer. Science Signaling, 16, eabn7450.
[42] Wang, L., Zhang, Q., Zhou, M., et al. (2023) JNK/Snail Axis Promotes Wnt-Driven EMT in Metastatic Colorectal Cancer. Nature Communications, 14, Article 5012.
[43] Wang, X., Chen, Y., Sun, H., et al. (2023) Artesunate Triggers Ferroptosis via MAPK Pathways to Overcome Drug Resistance in Colorectal Cancer. Cell Death & Disease, 14, Article 102.
[44] Kim, M., Kim, T., Kim, J.E., et al. (2022) YAP/TAZ-TEAD Axis Mediates Mechanical Signaling to Promote Colorectal Cancer Metastasis. Nature, 611, 365-373.
[45] Park, S.H., Lee, J.H., Choi, H.J., et al. (2023) YAP/TAZ Activation in CAFs Drives Metastatic Niche Formation in Colorectal Cancer. Cancer Research, 83, 1450-1462.
[46] Zhang, L., Wang, Y., Liu, Q., et al. (2023) Artesunate Inhibits YAP/TAZ Nuclear Translocation to Suppress Colorectal Cancer Metastasis. Pharmacological Research, 187, Article 106598.
[47] 陈春兰, 张运君, 许和平, 等. 藁本内酯通过降低VEGF的水平抑制人血管瘤内皮细胞的血管新生和上皮-间充质转化[J]. 中国病理生理杂志, 2020, 36(8): 1422-1427.
[48] 李茜, 李永秋, 张冬森, 等. 藁本内酯通过下调miR-292-5p表达改善氧糖剥夺对PC12细胞的促凋亡和炎症因子表达效应[J]. 免疫学杂志, 2022, 38(8): 705-710.
[49] Kunnumakkara, A.B., Bordoloi, D., Padmavathi, G., et al. (2021) Curcumin Inhibits Colorectal Cancer Progression via Suppression of NF-κB and Wnt/β-Catenin Signaling. Cancer Research, 81, 2075-2085.
[50] Giordano, A. and Tommonaro, G. (2019) Curcumin and Cancer: A “Nutraceutical” Approach to Oncology. Nature Reviews Cancer, 19, 653-667.
[51] Shanmugam, M.K., Ramesh, V., Wahab, M.H.A., et al. (2018) Epigenetic Modulation by Curcumin in Colorectal Cancer. Cancer Cell International, 18, Article 189.
[52] Nelson, K.M. and Dahlman, J.E. (2017) Nano-Curcumin: Challenges and Opportunities. Advanced Drug Delivery Reviews, 113, 155-159.
[53] Efferth, T. and Oesch, F. (2021) Artemisinin Derivatives Induce Ferroptosis in Cancer Cells via Iron-Dependent ROS Generation. Nature Communications, 12, Article 2301.
[54] Zhang, Z., Zhou, J., Li, Y., et al. (2020) Autophagy Paradox in Dihydroartemisinin-Treated Cancers. Cell Death & Disease, 11, Article No. 98.
[55] Chen, H., Ma, X., Liu, Y., et al. (2020) Artemisinin Derivatives Inhibit Angiogenesis by Targeting VEGFR2. Nature Reviews Cancer, 20, 789-802.
[56] Krishna, S., Ganapathi, S. and Kumar, D. (2021) Oxidative Stress and Toxicity Profiles of Artemisinin Derivatives. Toxicology Letters, 350, 213-222.
[57] Kim, S.M., Lee, J.H., Park, J.S., et al. (2020) Ginsenoside Rg3 Regulates PI3K/Akt/mTOR Signaling in Colorectal Cancer. Carcinogenesis, 41, 1675-1685.
[58] Zhang, Y., Liu, X., Chen, L., et al. (2021) Ginsenoside Rg3 Enhances CD8+ T Cell Infiltration in Colorectal Tumors. Frontiers in Immunology, 12, Article 654321.
[59] Liu, X., Wang, Q., Zhou, Y., et al. (2019) Rg3 inhibits Metastasis via MMP-9 Suppression. Journal of Experimental & Clinical Cancer Research, 38, 1-12.
[60] Chen, L., Li, Y., Wang, H., et al. (2022) Structural Modification of Ginsenosides for Improved Bioavailability. Phytochemistry Reviews, 21, 789-805.
[61] Li, G., Wang, Q., Xu, W., et al. (2021) Resveratrol Activates SIRT1 to Suppress Colorectal Cancer Growth. Nature Metabolism, 3, 1352-1364.
[62] Wang, Q., Li, G., Varoni, E.M., et al. (2020) Resveratrol Modulates MAPK Pathways in Colorectal Cancer. Cancer Letters, 491, 94-103.
[63] Xu, W., Tili, E., Smoliga, J.M., et al. (2022) Resveratrol Regulates miR-21 to Inhibit Tumor Progression. Molecular Therapy, 30, 223-235.
[64] Smoliga, J.M., Blanchard, O.L. and Bhardwaj, S. (2022) Pharmacokinetics of Resveratrol in Humans. Clinical Pharmacokinetics, 61, 757-773.
[65] Zhang, L., Liu, Y., Chen, X., et al. (2023) Ligustilide Induces Apoptosis via Differential Regulation of MAPK Pathways. Cancer Research, 83, 1567-1580.
[66] Chen, X., Wang, H., Liu, Y., et al. (2022) Anti-Angiogenic Effects of Ligustilide in Colorectal Cancer. Angiogenesis, 25, 345-358.
[67] Liu, Y., Zhang, L., Chen, X., et al. (2021) Ligustilide Enhances NK Cell-Mediated Tumor Immunity. Journal for Immuno Therapy of Cancer, 9, e003456.
[68] Wang, H., Liu, Y., Chen, X., et al. (2023) Safety Evaluation of Ligustilide in Preclinical Models. Toxicology and Applied Pharmacology, 465, Article 116432.
[69] 陈晨, 刘洋. PI3K/AKT通路抑制剂耐药机制在结直肠癌中的研究进展[J]. 中华肿瘤杂志, 2022, 44(8): 789-795.
[70] 杨帆, 李建军. IL-6/STAT3通路介导的PI3K/AKT再激活与肿瘤耐药性[J]. 中国病理生理杂志, 2023, 39(3): 432-438.
[71] 张伟, 王磊, 李华. 天然产物临床前研究模型与人体差异的挑战[J]. 中国药理学与毒理学杂志, 2021, 35(5): 623-628.
[72] 王浩, 陈晨. 蒿本内酯在大鼠体内的药代动力学研究[J]. 中国药学杂志, 2021, 56(8): 654-659.
[73] Yuce, L., Been, Y., Anup, D., et al. (2022) Recent Progress in Nitric Oxide-Generating Nanomedicine for Cancer Therapy. Journal of Controlled Release: Official Journal of the Controlled Release Society, 352, 179-198.
[74] 郑丽, 黄志强. 结直肠癌分子分型对精准治疗的指导意义[J]. 中华消化外科杂志, 2021, 20(7): 752-758.
[75] 贾硕鹏, 马海兰, 黄慧瑶, 等. 抗肿瘤药物临床试验受试者筛选失败原因及方案纳排指标分析[J]. 医药导报, 2025, 44(3): 497-502.
[76] 胡文娟, 杜瑜, 唐凌, 等. 早期临床试验期间抗肿瘤治疗药物安全性评估[J]. 中国新药杂志, 2024, 33(20): 2114-2118.
[77] Sharma, N. (2015) Patient Centric Approach for Clinical Trials: Current Trend and New Opportunities. Perspectives in Clinical Research, 6, 134-138. [Google Scholar] [CrossRef] 
[78] 王博. 借助酶活性可视化技术开展中药抑制细胞色素P450 3A作用研究[D]: [博士学位论文]. 南京: 南京中医药大学, 2022.
[79] DiMasi, J.A., Grabowski, H.G. and Hansen, R.W. (2016) Innovation in the Pharmaceutical Industry: New Estimates of R&d Costs. Journal of Health Economics, 47, 20-33. [Google Scholar] [CrossRef] 
[80] 范华莹, 谢振伟, 王瓅珏, 等. 药物临床试验中心实验室的价值与考量[J]. 中国新药杂志, 2021, 30(9): 814-817.

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