Synthesis and Regulation Research Progress of Chicoric Acid, the Active Ingredient of Echinacea purpurea
WANG Zi-Hang1, YU Jian-Bin1, BAI Mei1,2, WU Hong1,2, LIANG Xiang-Xiu1,2,*, YANG Qiao1,*
1 College of Life Sciences, South China Agricultural University, Guangzhou 510642, China; 2 Lingnan Modern Agriculture Science and Technology Laboratory, Guangzhou 510642, China
Abstract：Echinacea purpurea is a widely used medicinal plant worldwide with significant economic value,known for its effects in enhancing immunity, antibacterial, and anti-inflammatory properties. The active ingredient chicoric acid is a crucial substance for exerting the medicinal effects of E. purpurea and serves as a key indicator for evaluating the quality of medicinal herbs. The production of active ingredients is not only regulated by its own genetic factors but is also significantly influenced by environmental factors such as light, temperature, and microorganisms in the synthesis and accumulation of active components in E. purpurea. This article mainly elucidated the efficacy of E. purpurea and its active ingredients, further discussed the synthetic pathways of the main active ingredient chicoric acid, summarized the regulatory mechanisms of the genetic characteristics and various environmental factors on the synthesis of chicoric acid, and finally provided an application outlook on the current status of enhance the accumulation of its active ingredients. This review provides new directions for the rational development of E. purpurea resources and is of great importance for improving the quality and clinical efficacy of medicinal plants.
王子航, 羽健宾, 白玫, 吴鸿, 梁祥修, 杨乔. 紫锥菊活性成分菊苣酸的合成及调控研究进展[J]. 农业生物技术学报, 2025, 33(3): 659-669.
WANG Zi-Hang, YU Jian-Bin, BAI Mei, WU Hong, LIANG Xiang-Xiu, YANG Qiao. Synthesis and Regulation Research Progress of Chicoric Acid, the Active Ingredient of Echinacea purpurea. 农业生物技术学报, 2025, 33(3): 659-669.
[1] 阿顺贤, 张元新, 王爱超, 等. 2020. 菊苣酸(CA)对LPS诱导的牦牛PBMC细胞炎性因子分泌及表达的影响[J]. 中国兽医学报, 40(2): 379-383, 385.(A S X, Zhang Y X, Wang A C, et al. 2020. Effects of chicory acid on the secretion and expression of inflammatory factors by LPS-induced PBMC cells in yak[J]. Chinese Journal of Veterinary Science, 40(2): 379-383; 385.) [2] 白莉霞, 刘希望, 杨亚军, 等. 2023. 菊苣酸介导外泌体对巨噬细胞免疫抑制的影响[J]. 中国畜牧兽医, 50(10):4223-4230. (Bai L X, Liu X W, Yang Y J, et al.2023. Effect of cichoric acid mediated exosomes on macrophage immunosuppression[J]. China Animal Husbandry and Veterinary Medicine, 50(10): 4223-4230.) [3] 陈荣, 杨跃生, 吴鸿. 2011. 广州地区紫锥菊引种与露地栽培试验初报[J]. 广东农业科学, 38(10): 20-22. (Chen R, Yang Y S, Wu H.2011. Introduction and outdoor growing techniques of Echinacea purpurea in Guangzhou[J]. Guangdong Agricultural Sciences, 38(10): 20-22.) [4] 陈荣, 杨跃生, 吴鸿. 2012. 不同采收期紫锥菊产量及菊苣酸动态变化研究[J]. 中药, 43(06): 1186-1190. (Chen R, Yang Y S, Wu H.2012. Dynamic changes of yield and cichoric acid content in Echinacea purpurea at different harvest time[J]. Chines Traditional and Herbal Drugs, 43(06): 1186-1190.) [5] 窦德明, 崔树玉, 曹永智, 等. 2001. 引种紫锥菊有效成分菊苣酸含量研究[J]. 中草药, 2001(11): 30-31. (Dou D H, Cui S Y, Cao Y Z, et al.Assaying of cichoric acid in introducing plant of Echinacea purpurea[J]. Chinese Traditional and Herbal Drugs, 2001(11): 30-31.) [6] 韩琳娜, 周凤琴. 2012. 引种紫锥菊的ISSR和SRAP遗传多样性分析[J]. 四川农业大学学报, 30(04): 439-444. (Han L N, Zhou F Q.2012. The analysis of genetic diversity of introduced Echinacea purpurea moench based on ISSR and SRAP[J]. Journal of Sichuan Agricultural University, 30(04): 439-444.) [7] 姜伟珍. 2022. 紫锥菊核型分析和非整倍体栽培评价[D]. 博士学位论文, 华南农业大学, 导师: 杨跃生, pp. 159-162. (Jiang W Z.2022. Karyotype analysis and cultivation evaluation of aneuploid purple coneflower (Echinacea purpurea L.)[D]. Thesis for Ph.D., South China Agricultural University, Supervisor: Yang Y S, pp. 159-162.) [8] 李晶, 聂斌, 武力, 等. 2011. 引种紫锥菊中菊苣酸的定性定量分析[J]. 药物分析杂志, 31(09): 1804-1807. (Li J, Nie B, Wu L, et al.2011. Determination of cichoric acid in introducing plant of Echinacea purpurea[J]. Chinese Journal of Pharmaceutical Analysis, 31(09): 1804-1807.) [9] 李玲兰, 徐玉善, 雷玉洁, 等. 2023. 紫锥菊活性成分及其提取物在抗炎作用中的研究进展[J]. 陕西医学杂志, 52(01): 114-117. (Li L L, Xu Y S, Lei Y J, et al.2023. Research progress on the anti-inflammatory effects of active components and extracts of Echinacea purpurea[J]. Shaanxi Medical Journal, 52(01): 114-117.) [10] 李鹏, 宁熙平, 吴鸿. 2007. 紫锥菊药用部位的结构及其与多酚类化合物积累的关系[J]. 中草药, 2007(04): 606-610. (Li P, Ning X P, Wu H.2007. Relationship between structure of medicinal fractions and accumulation of polyphenol in Echinacea purpurea[J]. Chinese Traditional and Herbal Drugs, 2007(04): 606-610.) [11] 缪志林. 2006. 紫锥菊的栽培技术[J]. 时珍国医国药, 2006(03):482.(Miao Z L. 2006. Cultivation techniques of Echinacea[J]. Lishizhen Medicine and Materia Medica Research, 2006(03): 482.) [12] 孙俊英. 2012. 引种紫锥菊形态学与有效成分动态积累的初步研究[D]. 硕士学位论文, 山东中医药大学, 导师: 郭庆梅, pp. 45-46. (Sun J Y.2012. The preliminary study on morphology and active components dynamical accumulation of Echinacea purpurea (L.) Moench[D]. Thesis for M.S., Shandong University of Traditional Chinese Medicine, Supervisor: Guo Q M, pp. 45-46.) [13] 孙丽平, 齐海艳, 郑洪伟, 等. 2020. 高效液相色谱法测定紫锥菊中7种酚酸含量及其聚类分析[J]. 医药导报, 39(06): 831-835. (Sun L P, Qi H Y, Zheng H W, et al.2020. Determination of seven phenolic acids in Echinacea purpurea by HPLC and the cluster analysis[J]. Herald of Medicine, 39(06): 831-835.) [14] 王弘, 刘文芝, 鲁晓蕾, 等. 2002. 松果菊中有效成分菊苣酸的含量测定[J]. 中国中药杂志,27(6): 418-423. (W H, L W Z, L X L, et al.2002. Determination of the content of chicoric acid in Echinacea[J]. China Journal of Chines Materia Medica, 27(6): 418-423.) [15] 王红, 冯帅, 史磊, 等. 2021. 菊苣酸的研究进展[J]. 药学研究,40(09): 614-619. (Wang H, Feng S, Shi L, et al.2021. Research progress of cichoric acid[J]. Journal of Pharmaceutical Research, 40(09): 614-619.) [16] 魏秀丽, 张志民, 张传津, 等. 2019. 超高效液相色谱法测定紫锥菊根末中单咖啡酰酒石酸和菊苣酸的含量[J]. 中国兽药杂志, 53(12): 31-37. (Wei X L, Zhang Z M, Zhang C J, et al.2019. Determination of caftaric acid and chicoric acid in Echinacea root powder by UPLC[J]. Chinese Journal of Veterinary Drug, 53(12): 31-37.) [17] 肖培根. 1996. 国际流行的免疫调节剂─紫锥菊及其制剂[J]. 中草药, 1996(01): 46-48. (Xiao P G.1996. Echinacea and its preparations are popular immune modulators in the world[J]. Chines Traditional and Herbal Drugs, 1996(01): 46-48.) [18] 肖珊. 2022. 一种咖啡酸衍生物(ZZJ)的抑菌活性及抑菌机制研究[D]. 硕士学位论文, 华南农业大学, 导师: 吴鸿, pp. 32-35. (Xiao S.2022. Study on antibacterial activity and antibacterial mechanism of a caffeic acid derivative (ZZJ) of Echinacea[D]. Thesis for M.S., South China Agricultural University, Supervisor: Wu H, pp. 32-35.) [19] 谢惠枫. 2022. 不同倍性紫锥菊多酚物质含量及抗氧化活性比较研究[D]. 硕士学位论文, 华南农业大学, 导师: 吴鸿, pp. 34-38. (Xie H F.2022. Comparative study on polyphenol contents and antioxidant activities of different ploidy Echinacea purpurea (L.) moench[D]. Thesis for M.S., South China Agricultural University, Supervisor: Wu H, pp. 34-38.) [20] 谢继国. 2009. 菊苣酸化学稳定性及其异构体的色谱分离分析研究[D]. 硕士学位论文, 湖南师范大学, 导师: 陈波, pp. 18-22. (Xie J G.2009. The chemical stability of cichoric acid and separation and analysis of its epimers by high performance liquid chromatography[D]. Thesis for M.S., Hunan Normal University, Supervisor: Chen B, pp. 34-38.) [21] 徐丽华, 陈燕平, 马天宇, 等. 2020. 紫锥菊化学成分和药理作用研究进展[J]. 食品与药品, 22(03): 233-237. (Xu L H, Chen Y P, Ma T Y, et al.2020. Research progress on chemical constituents and pharmacological effects of Echinacea purpure[J]. Food and Drug, 22(03): 233-237.) [22] 薛亚峰. 2008. 紫锥菊地上部化学成分研究[D]. 博士学位论文, 西北农林科技大学, 导师: 王俊儒, pp. 53-53. (Xue Y F.2008. The effective constituents of the aerial parts in Echinacea purpurea[D]. Thesis for Ph.D., Northwest A&F University, Supervisor: Wang J R, pp. 53-53.) [23] 闫晓慧, 谈锋. 2006. 3种松果菊属植物的鉴别、活性成分及生物技术研究进展[J]. 中草药, 2006(02): 300-303. (Yan X H, Tan F.2006. Progress in identification of three plants of Echinacea moench. and their active constituents and biotechnology[J]. Chines Traditional and Herbal Drugs, 2006(02): 300-303.) [24] 周娟. 2019. 二倍体与其加倍四倍体紫锥菊的性状比较和杂交育种研究[D]. 华南农业大学, 导师: 杨跃生, pp. 2-6. (Zhou J.2019. Comparison of diploids purple coneflower (Echinacea purpurea (L.) Moench) with their induced tetraploids on several traits and the study of cross breeding[D]. Thesis for M.S., South China Agricultural University, Supervisor: Yang Y S, pp. 34-38.) [25] 朱汉斌, 栗弘儒, 方玮. 2015. “洋草药”成功变身“中兽药”[J]. 农业知识,(12): 28. (Zhu H B, Li H R, Fang W. 2015. "Foreign herbal medicines" successfully transformed into "Chinese veterinary medicines"[J]. Agriculture Knowlege, (12): 28. [26] Araim G, Ammar S, Arnason J T, et al.2009. Root colonization by an Arbuscular mycorrhizal (AM) fungus increases growth and secondary metabolism of purple coneflower, Echinacea purpurea (L.) moench[J]. Journal of Agricultural and Food Chemistry, 57(6): 2255-2258. [27] Chen R, Jiang W Z, Li Q L, et al.2016. Comparison of seven colchicine-induced tetraploid clones with their original diploid clones in purple coneflower (Echinacea purpurea L.)[J]. Euphytica, 207(2): 387-399. [28] Carvalho C R, Wedge D E, Cantrell C L, et al.2016. Molecular phylogeny, diversity, and bioprospecting of endophytic fungi associated with wild ethnomedicinal north American plant Echinacea purpurea (Asteraceae)[J]. Chemistry & Biodiversity, 13(7): 918-930. [29] Fu R, Zhang P Y, Jin G, et al.2021.Versatility in acyltransferase activity completes chicoric acid biosynthesis in purple coneflower[J]. Nature Communications, 12(1): 1563. [30] Goel V, Chang C, Slama J V, et al.2002. Alkylamides of Echinacea purpurea stimulate alveolar macrophage function in normal rats[J]. International Immunopharmacology, 2(2-3): 381-387. [31] Haron M H, Tyler H L, Pugh N D, et al.2014. In vitro macrophage activation by edible mushroom extracts varies considerably and is highly correlated to bacterial LPS content[J]. Planta Medica, 80(10): 839-839. [32] Herms D A, Mattson W J.1994. Plant growth and defense[J]. Trends in Ecology & Evolution, 9(12): 488. [33] Hudec J, Burdová M, Kobida L, et al.2007. Antioxidant capacity changes and phenolic profile of Echinacea purpurea, nettle (Urtica dioica L.), and dandelion (Taraxacum officinale) after application of polyamine and phenolic biosynthesis regulators[J]. Journal of Agricultural and Food Chemistry, 55(14): 5689-5696. [34] Jin G, Deng Z, Wang H, Zhang Y, et al.2024. EpMYB2 positively regulates chicoric acid biosynthesis by activating both primary and specialized metabolic genes in purple coneflower[J]. The Plant Journal, 119(1): 252-265. [35] Karsch-Vlk M, Barrett B, Kiefer D, et al.2015. Echinacea for preventing and treating the common cold[J]. JAMA Clinical Evidence Synopsis, 313(6): 618-619. [36] Kindscher K.1989. La etnobotánica de la Echinacea angustifolia (Asteraceae) y los otros Echinacea especies[J]. Economic Botany, 43(4): 498-507. [37] Lerdau M, Litvak M, Monson R.1994. Plant chemical defense: Monoterpenes and the growth-differentiation balance hypothesis[J]. Trends in Ecology & Evolution, 9(2): 58-61. [38] Li Q L, Yang Y S, Wu H.2016. In vitro segregation of tetraploid and octoploid plantlets from colchicine-induced ploidy chimeras in Echinacea purpurea L[J]. HortScience, 51(5): 549-557. [39] Ma J, Li M R, Kalavagunta P K, et al.2018. Protective effects of cichoric acid on H2O2-induced oxidative injury in hepatocytes and larval zebrafish models[J]. Biomedicine & Pharmacotherapy, 104: 679-685. [40] Maggini V, De Leo M, Granchi C, et al.2019. The influence of Echinacea purpurea leaf microbiota on chicoric acid level[J]. Scientific Reports, 9(1): 1-11. [41] Maggini V, Leo M D, Mengoni A, et al.2017. Plant-endophytes interaction influences the secondary metabolism in Echinacea purpurea (L.) Moench: An in vitro model[J]. Scientific Reports, 7(1): 16924. [42] Maida I, Chiellini C, Mengoni A, et al.2016. Antagonistic interactions between endophytic cultivable bacterial communities isolated from the medicinal plant Echinacea purpurea[J]. Environmental Microbiology, 18(8): 2357-2365. [43] Mengoni A, Maida I, Chiellini C, et al.2014. Antibiotic resistance differentiates Echinacea purpurea endophytic bacterial communities with respect to plant organs[J]. Research in Microbiology, 165(8): 686-694. [44] Nilanthi D, Zhao F C, Chen X L, et al.2010. An efficient in vitro propagation culture protocol for purple coneflower (Echinacea purpurea L.)[J]. IEEE, 94(3): 1-4. [45] Nüsslein B, Kurzmann M, Bauer R, et al.2000. Enzymatic degradation of cichoric acid in Echinacea purpurea preparations[J]. Journal of Natural Products, 63(12): 1615-1618. [46] Pellati F, Benvenuti S, Magro L, et al.2004. Analysis of phenolic compounds and radical scavenging activity of Echinacea spp.[J]. Journal of Pharmaceutical & Biomedical Analysis, 35(2): 289-301. [47] Pomponio R, Gotti R, Hudaib M, et al.2002. Analysis of phenolic acids by micellar electrokinetic chromatography: Application to Echinacea purpurea plant extracts[J]. Journal of Chromatography A, 945(1-2): 239-247. [48] Ravazzolo L, Ruperti B, Frigo M, et al.2022. C3H expression is crucial for methyl jasmonate induction of chicoric acid production by Echinacea purpurea (L.) moench cell suspension cultures[J]. International Journal of Molecular Sciences, 23(19): 11179. [49] Ren W, Ban J, Xia Y, et al.2023. Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization[J]. The Innovation, 4(2): 100391. [50] Richard J, Gualandi R M, Auge Dean A, et al.2014. Fungal mutualists enhance growth and phytochemical content in Echinacea purpurea[J]. Symbiosis, 63: 111-121. [51] Scarpati M L, Oriente G.1958. Chicoric acid (dicaffeyltartic acid): Its isolation from chicory (Chicorium intybus) and synthesis[J]. Tetrahedron, 4(1-2): 43-48. [52] Sharma S M, Anderson M, Schoop S R, et al.2010. Bactericidal and anti-inflammatory properties of a standardized Echinacea extract (Echinaforce): Dual actions against respiratory bacteria[J]. Phytomedicine International Journal of Phytotherapy & Phytopharmacology, 17(8-9): 563-568. [53] Signer J, Jonsdottir H R, Albrich W C, et al.2020. In vitro virucidal activity of Echinaforce, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARSCoV-2[J]. Virology Journal, 17(1): 1-11. [54] Stephens L C.2008. Self-incompatibility in Echinacea purpurea[J]. Hortscience, 43(5): 1350-1354. [55] Tsai Y L, Chiu C C, Chen J Y F, et al.2012. Cytotoxic effects of Echinacea purpurea flower extracts and cichoric acid on human colon cancer cells through induction of apoptosis[J]. Journal of Ethnopharmacology, 143(3): 914-919. [56] Verma N, Shukla S.2015. Impact of various factors responsible for fluctuation in plant secondary metabolites[J]. Journal of Applied Research on Medicinal & Aromatic Plants, 2(4): 105-113. [57] Wagenius S, Lyon S P.2010. Reproduction of Echinacea angustjfolia in fragmented prairie is pollen-limited but not pollinator-limited[J]. Ecology, 91(3): 733-742. [58] Wills R B H, Stuart D L.1999. Alkylamide and cichoric acid levels in Echinacea purpurea grown in Australia[J]. Food Chemistry, 67(4): 385-388. [59] Wu C H, Hahn E J, Murthy H N.2017. Enhanced production of caftaric acid, chlorogenic acid and cichoric acid in suspension cultures of Echinacea purpurea by the manipulation of incubation temperature and photoperiod[J]. Biochemical Engineering Journal, 36(3): 301-303. [60] Xu W, Cheng Y, Guo Y, et al.2022. Effects of geographical location and environmental factors on metabolite content and immune activity of Echinacea purpurea in China based on metabolomics analysis[J]. Industrial Crops and Products, 189: 115782. [61] Yang M, Wu C, Zhang T X, et al.2022. Chicoric acid: Natural occurrence, chemical synthesis, biosynthesis, and their bioactive effects[J]. Frontiers in Chemistry, 10: 888673.
