中药及其活性成分治疗2型炎症型哮喘实验研究进展
Experimental Research Progress on the Treatment of Type 2 Inflammatory Asthma with Traditional Chinese Medicines and Their Active Ingredients
DOI: 10.12677/acm.2024.14113030, PDF,   
作者: 李嗣伦：成都中医药大学临床医学院，四川 成都；唐小路：四川省第二中医医院老年病科，四川 成都；杜 磊, 陈云凤*：成都市第一人民医院呼吸与危重症医学科，四川 成都
关键词: 2型炎症型哮喘；中药及活性成分；作用机制；研究进展；Type 2 Inflammatory Asthma； Traditional Chinese Medicine and Active Components； Mechanisms of Action； Research Progress
摘要: 2型炎症型哮喘是由Th2细胞、2型先天淋巴样细胞(ILC2s)、嗜酸性粒细胞、肥大细胞等细胞介导的肺异质性疾病。传统治疗手段如糖皮质激素虽有效，但长期使用会产生副作用。随着生物制剂的发展，靶向药物虽然在治疗上取得了进展，但其局限性和高成本依然存在。近年来，研究表明中药及其活性成分对2型炎症型哮喘具有治疗效果。本文详细介绍了黄芪、补骨脂、贝母、钩藤、大黄、半夏等十五种中药及其活性成分在调节Th1/Th2细胞平衡、抑制炎症因子表达、减少IgE水平、改善气道炎症和重塑等方面的机制和疗效，以期为进一步的研究提供基础。
Abstract: Type 2 inflammatory asthma is a heterogeneous pulmonary disease mediated by Th2 cells, type 2 innate lymphoid cells (ILC2s), eosinophils, mast cells, and other cells. Although traditional treatments, such as glucocorticoids, are effective, long-term use can lead to side effects. With the development of biologics, targeted therapies have made progress in treatment, but they still have limitations and are costly. In recent years, studies have shown that traditional Chinese medicine (TCM) and its active components have therapeutic effects on type 2 inflammatory asthma. This article provides a detailed overview of the mechanisms and efficacy of fifteen kinds of TCM, including Astragalus membranaceus, Psoralea corylifolia, Fritillaria, Uncaria rhynchophylla, Rheum officinale, and Pinellia ternata, in regulating the Th1/Th2 cell balance, inhibiting the expression of inflammatory cytokines, reducing IgE levels, and improving airway inflammation and remodeling. The goal is to provide a foundation for further research.
文章引用：李嗣伦, 唐小路, 杜磊, 陈云凤. 中药及其活性成分治疗2型炎症型哮喘实验研究进展[J]. 临床医学进展, 2024, 14(11): 1438-1447. https://doi.org/10.12677/acm.2024.14113030

参考文献

[1] Papi, A., Brightling, C., Pedersen, S.E. and Reddel, H.K. (2018) Asthma. The Lancet, 391, 783-800. [Google Scholar] [CrossRef] [PubMed]
[2] 屈媛媛, 曹淼, 王静, 等. 1990-2019年中国哮喘患病、疾病负担趋势及其危险因素研究[J]. 中国全科医学, 2024, 27(13): 1594-1600.
[3] Stern, J., Pier, J. and Litonjua, A.A. (2020) Asthma Epidemiology and Risk Factors. Seminars in Immunopathology, 42, 5-15. [Google Scholar] [CrossRef] [PubMed]
[4] Busse, W.W., Kraft, M., Rabe, K.F., Deniz, Y., Rowe, P.J., Ruddy, M., et al. (2021) Understanding the Key Issues in the Treatment of Uncontrolled Persistent Asthma with Type 2 Inflammation. European Respiratory Journal, 58, Article ID: 2003393. [Google Scholar] [CrossRef] [PubMed]
[5] Global Strategy for Asthma Management and Prevention (2024).
https://ginasthma.org/wp-content/uploads/2024/05/GINA-2024-Strategy-Report-24_05_22_WMS.pdf
[6] 钱雪娇, 蒋萍. 2型炎症型哮喘发病机制[J]. 中华临床免疫和变态反应杂志, 2022, 16(6): 629-635.
[7] 张亚, 杨琳, 姜荣燕, 等. 黄芪对哮喘小鼠支气管肺泡灌洗液中IL-2、IL-4及其行为学变化的影响[J]. 泰山医学院学报, 2019, 40(12): 914-916.
[8] Li, L., Hou, X., Xu, R., Liu, C. and Tu, M. (2016) Research Review on the Pharmacological Effects of Astragaloside IV. Fundamental & Clinical Pharmacology, 31, 17-36. [Google Scholar] [CrossRef] [PubMed]
[9] Huang, X., Tang, L., Wang, F. and Song, G. (2014) Astragaloside IV Attenuates Allergic Inflammation by Regulation Th1/Th2 Cytokine and Enhancement Cd4+Cd25+Foxp3 T Cells in Ovalbumin-Induced Asthma. Immunobiology, 219, 565-571. [Google Scholar] [CrossRef] [PubMed]
[10] Yang, X. and Wang, F. (2019) The Effect of Astragaloside IV on JAK2‐STAT6 Signalling Pathway in Mouse Model of Ovalbumin‐Induced Asthma. Journal of Animal Physiology and Animal Nutrition, 103, 1578-1584. [Google Scholar] [CrossRef] [PubMed]
[11] Çalis, I., Gazar, H.A., Piacente, S. and Pizza, C. (2001) Secondary Metabolites from the Roots of Astragalus zahlbruckneri. Journal of Natural Products, 64, 1179-1182.
https://pubs.acs.org/doi/10.1021/np0102051#
[12] Zhu, X., Cao, Y., Su, M., Chen, M., Li, C., Yi, L., et al. (2021) Cycloastragenol Alleviates Airway Inflammation in Asthmatic Mice by Inhibiting Autophagy. Molecular Medicine Reports, 24, 805. [Google Scholar] [CrossRef] [PubMed]
[13] Yu, L., Zhang, Y., Chen, Q., He, Y., Zhou, H., Wan, H., et al. (2022) Formononetin Protects against Inflammation Associated with Cerebral Ischemia-Reperfusion Injury in Rats by Targeting the JAK2/STAT3 Signaling Pathway. Biomedicine & Pharmacotherapy, 149, Article ID: 112836. [Google Scholar] [CrossRef] [PubMed]
[14] Ma, C., Xia, R., Yang, S., Liu, L., Zhang, J., Feng, K., et al. (2020) Formononetin Attenuates Atherosclerosis via Regulating Interaction between KLF4 and SRA in ApoE−/− Mice. Theranostics, 10, 1090-1106. [Google Scholar] [CrossRef] [PubMed]
[15] Zhang, L., Wu, Q., Huang, Y., Zheng, J., Guo, S. and He, L. (2023) Formononetin Ameliorates Airway Inflammation by Suppressing ESR1/NLRP3/Caspase-1 Signaling in Asthma. Biomedicine & Pharmacotherapy, 168, Article ID: 115799. [Google Scholar] [CrossRef] [PubMed]
[16] Yi, L., Cui, J., Wang, W., Tang, W., Teng, F., Zhu, X., et al. (2020) Formononetin Attenuates Airway Inflammation and Oxidative Stress in Murine Allergic Asthma. Frontiers in Pharmacology, 11, Article ID: 533841. [Google Scholar] [CrossRef] [PubMed]
[17] Zheng, Y., Ren, W., Zhang, L., Zhang, Y., Liu, D. and Liu, Y. (2020) A Review of the Pharmacological Action of Astragalus Polysaccharide. Frontiers in Pharmacology, 11, Article No. 349. [Google Scholar] [CrossRef] [PubMed]
[18] 商玉立, 郭彩霞, 石红梅, 等. 黄芪多糖对哮喘小鼠气道炎症启动因子TSLP和DCs表达的影响[J]. 中国抗生素杂志, 2021, 46(7): 711-716.
[19] 张莹, 吕惠子. 补骨脂的化学成分和药理作用研究进展[J]. 临床医药文献电子杂志, 2020, 7(30): 195.
[20] 杨阔, 高茸, 马亚中, 等. 补骨脂素药理作用及肝毒性机制的研究进展[J]. 中草药, 2021, 52(1): 289-298.
[21] Jin, H., Wang, L., Xu, C., Li, B., Luo, Q., Wu, J., et al. (2014) Effects of Psoraleae fructus and Its Major Component Psoralen on Th2 Response in Allergic Asthma. The American Journal of Chinese Medicine, 42, 665-678. [Google Scholar] [CrossRef] [PubMed]
[22] Bian, T., Yin, K., Jin, S., Zhang, X., Zhou, J., Ma, X., et al. (2006) Treatment of Allergic Airway Inflammation and Hyperresponsiveness by Imiquimod Modulating Transcription Factors T-Bet and GATA-3. Chinese Medical Journal, 119, 640-648. [Google Scholar] [CrossRef] 
[23] 梁正, 杨春, 李峥, 等. 异补骨脂查尔酮抑制IL-4产生及其机制研究[J]. 中草药, 2013, 44(10): 1299-1304.
[24] 梁正, 郝文龙, 孙雪英, 等. 异补骨脂查尔酮抗哮喘作用的实验研究[J]. 湖南中医杂志, 2016, 32(5): 177-179.
[25] Liang, Z., Luo, Z., Chen, J., Li, B., Li, L. and Shen, C. (2022) Bavachin Inhibits IL-4 Expression by Downregulating STAT6 Phosphorylation and GATA-3 Expression and Ameliorates Asthma Inflammation in an Animal Model. Immunobiology, 227, Article ID: 152182. [Google Scholar] [CrossRef] [PubMed]
[26] Liang, R., Yuan, Y., Bai, Y., Liu, X., Chen, J., Jiang, D., et al. (2022) Neobavaisoflavone Inhibits Allergic Inflammatory Responses by Suppressing Mast Cell Activation. International Immunopharmacology, 110, Article ID: 108953. [Google Scholar] [CrossRef] [PubMed]
[27] 侯从岭, 芦晓帆, 雷小婷, 等. 川贝母对卵清蛋白致敏哮喘小鼠的作用及其机制[J]. 解放军医学杂志, 2022, 47(8): 789-794.
[28] 黎萍, 李敏, 蒋静, 等. 瓦布贝母中生物碱的含量测定[J]. 华西药学杂志, 2020, 35(6): 655-659.
[29] 滕俞希, 王晶金, 陈逸菲, 等. 瓦布贝母组织培养及生物碱的测定[J]. 四川大学学报(自然科学版), 2022, 59(1): 181-185.
[30] Peng, M., Li, J., Zhou, J., Zhang, B., Liao, J., Yang, D., et al. (2023) Total Alkaloids of Fritillaria unibracteata var. wabuensis Bulbus Ameliorate Chronic Asthma via the TRPV1/Ca2+/NFAT Pathway. Phytomedicine, 118, Article ID: 154946. [Google Scholar] [CrossRef] [PubMed]
[31] Wang, L., Gu, Z., Li, J., Yang, W., Li, Y., Qi, D., et al. (2023) Isorhynchophylline Inhibits Inflammatory Responses in Endothelial Cells and Macrophages through the NF-κB/NLRP3 Signaling Pathway. BMC Complementary Medicine and Therapies, 23, Article No. 80. [Google Scholar] [CrossRef] [PubMed]
[32] Zhu, J., Wang, W. and Wu, X. (2020) Isorhynchophylline Exerts Anti-Asthma Effects in Mice by Inhibiting the Proliferation of Airway Smooth Muscle Cells: The Involvement of Mir-200a-Mediated Foxc1/NF-κB Pathway. Biochemical and Biophysical Research Communications, 521, 1055-1060. [Google Scholar] [CrossRef] [PubMed]
[33] 蔡金, 华诏召, 张昌容, 等. 异钩藤碱对哮喘小鼠气道炎症的影响[J]. 中国药房, 2023, 34(22): 2740-2744.
[34] Li, H., Bi, Q., Cui, H., Lv, C. and Wang, M. (2021) Suppression of Autophagy through JAK2/STAT3 Contributes to the Therapeutic Action of Rhynchophylline on Asthma. BMC Complementary Medicine and Therapies, 21, Article No. 21. [Google Scholar] [CrossRef] [PubMed]
[35] 肖先, 李春燕, 薛金涛. 大黄的主要化学成分及药理作用研究进展[J]. 新乡医学院学报, 2024, 41(5): 486-490+496.
[36] Hua, S., Liu, F. and Wang, M. (2019) Emodin Alleviates the Airway Inflammation of Cough Variant Asthma in Mice by Regulating the Notch Pathway. Medical Science Monitor, 25, 5621-5629. [Google Scholar] [CrossRef] [PubMed]
[37] Song, G., Zhang, Y., Yu, S., Lv, W., Guan, Z., Sun, M., et al. (2019) Chrysophanol Attenuates Airway Inflammation and Remodeling through Nuclear Factor‐kappa B Signaling Pathway in Asthma. Phytotherapy Research, 33, 2702-2713. [Google Scholar] [CrossRef] [PubMed]
[38] 王婷, 李海舰, 廖明, 等. 基于TWEAK/Fn14信号通路探讨大黄酚对OVA诱导哮喘小鼠的保护作用[J]. 天津中医药大学学报, 2022, 41(5): 644-648.
[39] Tao, X., Liu, H., Xia, J., Zeng, P., Wang, H., Xie, Y., et al. (2022) Processed Product (Pinelliae Rhizoma Praeparatum) of Pinellia ternata (Thunb.) Breit. Alleviates the Allergic Airway Inflammation of Cold Phlegm via Regulation of PKC/EGFR/MAPK/PI3K-AKT Signaling Pathway. Journal of Ethnopharmacology, 295, Article ID: 115449. [Google Scholar] [CrossRef] [PubMed]
[40] Zhou, W., Zhang, X., Cai, Y., Sun, W. and Li, H. (2018) Osthole Prevents Tamoxifen-Induced Liver Injury in Mice. Acta Pharmacologica Sinica, 40, 608-619. [Google Scholar] [CrossRef] [PubMed]
[41] Yang, Q., Kong, L., Huang, W., Mohammadtursun, N., Li, X., Wang, G., et al. (2020) Osthole Attenuates Ovalbumin-Induced Lung Inflammation via the Inhibition of IL-33/ST2 Signaling in Asthmatic Mice. International Journal of Molecular Medicine, 46, 1389-1398. [Google Scholar] [CrossRef] [PubMed]
[42] Li, R., Song, P., Tang, G., Wei, J., Rao, L., Ma, L., et al. (2021) Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-κB/MIF Signaling Pathway. Frontiers in Pharmacology, 12, Article ID: 572463. [Google Scholar] [CrossRef] [PubMed]
[43] Sowndhararajan, K., Deepa, P., Kim, M., Park, S.J. and Kim, S. (2017) Baicalein as a Potent Neuroprotective Agent: A Review. Biomedicine & Pharmacotherapy, 95, 1021-1032. [Google Scholar] [CrossRef] [PubMed]
[44] Mabalirajan, U., Ahmad, T., Rehman, R., Leishangthem, G.D., Dinda, A.K., Agrawal, A., et al. (2013) Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation. PLOS ONE, 8, e62916. [Google Scholar] [CrossRef] [PubMed]
[45] Park, B.B., Choi, J.W., Park, D., Choi, D., Paek, J., Kim, H.J., et al. (2019) Structure-Activity Relationships of Baicalein and Its Analogs as Novel TSLP Inhibitors. Scientific Reports, 9, Article No. 8762. [Google Scholar] [CrossRef] [PubMed]
[46] 李露, 戴婷, 李小龙, 等. 苦杏仁苷药理作用的研究进展[J]. 吉林医药学院学报, 2016, 37(1): 63-66.
[47] Cui, W., Zhou, H., Liu, Y., Yang, Y., Hu, Y., Han, Z., et al. (2023) Amygdalin Improves Allergic Asthma via the Thymic Stromal Lymphopoietin-Dendritic Cell-OX40 Ligand Axis in a Mouse Model. Iranian Journal of Allergy, Asthma and Immunology, 22, 430-439. [Google Scholar] [CrossRef] [PubMed]
[48] Jiang, J. and Hu, C. (2009) Evodiamine: A Novel Anti-Cancer Alkaloid from Evodia rutaecarpa. Molecules, 14, 1852-1859. [Google Scholar] [CrossRef] [PubMed]
[49] Wang, Q., Cui, Y., Wu, X. and Wang, J. (2021) Evodiamine Protects against Airway Remodelling and Inflammation in Asthmatic Rats by Modulating the HMGB1/NF-κB/TLR-4 Signalling Pathway. Pharmaceutical Biology, 59, 190-197. [Google Scholar] [CrossRef] [PubMed]
[50] 蹇强, 李明月, 安建峰, 等. 吴茱萸碱通过调控Notch通路抑制Skp2的表达对哮喘小鼠气道重塑和炎症反应的影响[J]. 吉林中医药, 2023, 43(4): 445-450.
[51] 雷俊, 卢丽君, 罗玲艳, 等. 吴茱萸碱对哮喘模型大鼠炎症及上皮细胞凋亡的影响及机制[J]. 中国药房, 2024, 35(11): 1351-1356.
[52] Meng, T., Xiao, D., Muhammed, A., Deng, J., Chen, L. and He, J. (2021) Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules, 26, Article No. 229. [Google Scholar] [CrossRef] [PubMed]
[53] He, Q., Liu, W., Chen, Z., Wei, G., Jiang, J., Zhang, L., et al. (2024) Resveratrol Modulates the Nrf2/NF-κB Pathway and Inhibits TSLP-Mediated Atopic March. Allergologia et Immunopathologia, 52, 1-8. [Google Scholar] [CrossRef] [PubMed]
[54] 武莉莉, 张敏, 陈延伟, 等. 白藜芦醇对哮喘模型鼠气道炎症及JAK-STAT6信号通路的影响[J]. 广东医学, 2022, 43(6): 692-696.
[55] Nguyen, V., Taine, E.G., Meng, D., Cui, T. and Tan, W. (2024) Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline. International Journal of Molecular Sciences, 25, Article No. 3385. [Google Scholar] [CrossRef] [PubMed]
[56] Zhang, W., Zhang, Y., Chen, S., Zhang, H., Yuan, M., Xiao, L., et al. (2021) Trigonelline, an Alkaloid from Leonurus japonicus Houtt., Suppresses Mast Cell Activation and OVA-Induced Allergic Asthma. Frontiers in Pharmacology, 12, Article ID: 687970. [Google Scholar] [CrossRef] [PubMed]
[57] Leong, P.K., Chen, N. and Ko, K.M. (2012) Mitochondrial Decay in Ageing: “Qi-Invigorating” Schisandrin B as a Hormetic Agent for Mitigating Age‐Related Diseases. Clinical and Experimental Pharmacology and Physiology, 39, 256-264. [Google Scholar] [CrossRef] [PubMed]
[58] Chen, Y., Kong, Y., Wang, Q., Chen, J., Chen, H., Xie, H., et al. (2021) Schisandrin B Attenuates Airway Inflammation by Regulating the NF-κB/NRF2 Signaling Pathway in Mouse Models of Asthma. Journal of Immunology Research, 2021, Article ID: 8029963. [Google Scholar] [CrossRef] [PubMed]
[59] 白红丽, 赵梁育, 郑速征, 等. 五味子乙素对过敏性哮喘小鼠IL-4/IL-13/STAT6通路及气道杯状细胞凋亡的影响[J]. 中国免疫学杂志, 2022, 38(11): 1333-1337.
[60] Yang, N., Musa, I., Maskey, A.R., Li, K., Wang, Z., Liang, B., et al. (2023) Formononetin Isolated from Sophorae flavescentis Inhibits B Cell-IgE Production by Regulating ER-Stress Transcription Factor XBP-1. Frontiers in Allergy, 3, Article ID: 1056203. [Google Scholar] [CrossRef] [PubMed]
[61] Zhao, P., Zhou, R., Zhu, X., Hao, Y., Li, N., Wang, J., et al. (2015) Matrine Attenuates Focal Cerebral Ischemic Injury by Improving Antioxidant Activity and Inhibiting Apoptosis in Mice. International Journal of Molecular Medicine, 36, 633-644. [Google Scholar] [CrossRef] [PubMed]
[62] 范爱欣, 袁菲, 唐科毅. 苦参碱通过抑制Lyn/Syk信号通路治疗大鼠过敏性哮喘[J]. 免疫学杂志, 2023, 39(10): 872-878.
[63] Zhang, Y., Qu, L., Sun, Y., Lin, Y., Zeng, J., He, L., et al. (2022) Daphnetin Contributes to Allergen-Induced Th2 Cytokine Expression and Type 2-Immune Responses in Atopic Dermatitis and Asthma. Food & Function, 13, 12383-12399. [Google Scholar] [CrossRef] [PubMed]
[64] 崔冰冰, 尹榕, 刘天珍, 等. 丁苯酞的药理作用及临床疗效研究进展[J]. 解放军医药杂志, 2019, 31(6): 11-14.
[65] Wang, Z., Yao, N., Fu, X., Wei, L., Ding, M., Pang, Y., et al. (2019) Butylphthalide Ameliorates Airway Inflammation and Mucus Hypersecretion via NF-κB in a Murine Asthma Model. International Immunopharmacology, 76, Article ID: 105873. [Google Scholar] [CrossRef] [PubMed]
[66] 王凯平, 张玉, 戴立泉. 当归多糖的研究进展概况[J]. 中国药师, 2002(5): 292-293.
[67] 王莹巍, 王颖, 张晗. 当归多糖对哮喘小鼠模型氧化应激与炎症反应的影响[J]. 解剖科学进展, 2023, 29(1): 96-98+102.
[68] Chao, C., Wang, C., Huang, H., Kuo, H., Su, M., Lin, H., et al. (2021) Poria Cocos Modulates Th1/Th2 Response and Attenuates Airway Inflammation in an Ovalbumin-Sensitized Mouse Allergic Asthma Model. Life, 11, Article No. 372. [Google Scholar] [CrossRef] [PubMed]
[69] 王艳梅, 甘德堃, 赵润杨, 等. 茯苓酸调节Lyn/Syk信号通路对哮喘大鼠气道炎症的影响[J]. 免疫学杂志, 2023, 39(9): 790-796.
[70] Wu, X., Wang, J., Zou, T., He, S., Zhong, L., Zhang, Q., et al. (2023) Revealing the Mechanisms of Arisaema Cum Bile on Allergic Asthma with Systematic Pharmacology Approach-Experimental Validation. Fitoterapia, 168, Article ID: 105518. [Google Scholar] [CrossRef] [PubMed]
[71] Guo, J., Shi, Y., Wang, Y., Athari, S.S. and Chen, T. (2024) Studying of Anti‐inflammatory and Antioxidant Effects of Tectorigenin in Ovalbumin‐Induced Asthma Mice Models. The Clinical Respiratory Journal, 18, e13742. [Google Scholar] [CrossRef] [PubMed]
[72] Sulaiman, I., Okwuofu, E.O., Mohtarrudin, N., Lim, J.C.W. and Stanslas, J. (2024) An Andrographis paniculata Burm. Nees Extract Standardized for Three Main Andrographolides Prevents House Dust Mite-Induced Airway Inflammation, Remodeling, and Hyperreactivity by Regulating Th1/Th2 Gene Expression in Mice. Journal of Ethnopharmacology, 319, Article ID: 117082. [Google Scholar] [CrossRef] [PubMed]
[73] 杨勇, 刘雅娟, 程立. 穿心莲内酯干预对哮喘大鼠气道IL-33表达的影响[J]. 浙江临床医学, 2015, 17(8): 1274-1276.
[74] Li, Q., Zhai, C., Wang, G., Zhou, J., Li, W., Xie, L., et al. (2021) Ginsenoside Rh1 Attenuates Ovalbumin-Induced Asthma by Regulating Th1/Th2 Cytokines Balance. Bioscience, Biotechnology, and Biochemistry, 85, 1809-1817. [Google Scholar] [CrossRef] [PubMed]

为你推荐