Cyclocarya paliurus (Batalin) Iljinsk., a medicinal and edible plant widely utilized in China, is a rich source of triterpenoids and flavonoids, which are recognized for their hypoglycemic, hypolipidemic, antioxidant, and antitumor properties. However, recent comprehensive summaries of its bioactive constituents and associated biosynthetic mechanisms remain limited. In this review, we systematically categorized the principal bioactive compounds isolated from C. paliurus, classifying triterpenoids into seven structural groups and flavonoids into four, based on their core skeletal frameworks. Notably, C-11 glycosylation was identified as a distinctive structural feature specific to C. paliurus triterpenoids. Furthermore, we summarized the key enzymes involved in the biosynthesis of these triterpenoids and flavonoids and, for the first time, proposed putative biosynthetic pathways by integrating current biochemical and genomic evidence. This review provides a comprehensive overview of the bioactive constituents and their associated biosynthetic enzymes in C. paliurus, offering valuable insights into the molecular basis of these natural products and establishing a foundation for future in vitro biosynthesis efforts.
Funding
This work was supported by the National Natural Science Foundation of China (No. 82574280), the Natural Science Foundation of Jiangsu Province of China (No. BK20252070), and the TCM Science and Technology Development Plan of Jiangsu Province (No. ZD202418).
Availability of supporting information
Supporting information for this work can be obtained by contacting the corresponding authors via E-mail.
Declaration of competing interest
These authors have no conflict of interest to declare.
| [1] |
Wu Y, Li YY, Wu X, et al. Chemical constituents from Cyclocarya paliurus (Batal.) Iljinsk. Biochem Syst Ecol. 2014; 57:216-220. https://doi.org/10.1016/j.bse.2014.08.022.
|
| [2] |
Xie JH, Wang ZJ, Shen MY, et al. Sulfated modification, characterization and antioxidant activities of polysaccharide from Cyclocarya paliurus. Food Hydrocoll. 2016; 53:7-15. https://doi.org/10.1016/j.foodhyd.2015.02.018.
|
| [3] |
Zhao JJ, Wang ZT, Xu DP, et al. Advances on Cyclocarya paliurus polyphenols: extraction, structures, bioactivities and future perspectives. Food Chem. 2022; 396:133667. https://doi.org/10.1016/j.foodchem.2022.133667.
|
| [4] |
Shao YM, Li TT, Wu C, et al. A review on extraction and biological activities of triterpenoid from Cyclocarya paliurus. Food Rev Int. 2024; 40(5):1374-1394. https://doi.org/10.1080/87559129.2023.2213307.
|
| [5] |
Wu CQ, Zhang WH, Luo HH, et al. Research progress on chemical constituents, pharmacological effects and application of Cyclocarya Paliurus. Shandong Chem Indust. 2022; 51(11):65-67. https://doi.org/10.19319/j.cnki.issn.1008-021x.2022.11.019.
|
| [6] |
Xie JH, Dong CJ, Nie SP, et al. Extraction, chemical composition and antioxidant activity of flavonoids from Cyclocarya paliurus (Batal.) Iljinskaja leaves. Food Chem. 2015; 186:97-105. https://doi.org/10.1016/j.foodchem.2014.06.106.
|
| [7] |
Liu Y, Cao YN, Fang SZ, et al. Antidiabetic effect of Cyclocarya paliurus leaves depends on the contents of antihyperglycemic flavonoids and antihyperlipidemic triterpenoids. Molecules. 2018; 23(5):1042. https://doi.org/10.3390/molecules23051042.
|
| [8] |
Li SB, Zou J, Zhao TS, et al. Antitumor effects of cypaliuruside F from Cyclocarya paliurus on HepG 2 cells. Nat Prod Res. 2025; 39(17):4984-4990. https://doi.org/10.1080/14786419.2024.2355590.
|
| [9] |
Li J, Liu X, Gao YR, et al. Identification of a UDP-glucosyltransferase favouring substrate- and regio-specific biosynthesis of flavonoid glucosides in Cyclocarya paliurus. Phytochemistry. 2019; 163:75-88. https://doi.org/10.1016/j.phytochem.2019.04.004.
|
| [10] |
Zhang SY, Peng YQ, Xiang GS, et al. Functional characterization of genes related to triterpene and flavonoid biosynthesis in Cyclocarya paliurus. Planta. 2024; 259(2):50. https://doi.org/10.1007/s00425-023-04282-1.
|
| [11] |
Shen YB, Peng Y, Zhu XC, et al. The phytochemicals and health benefits of Cyclocarya paliurus (Batalin) Iljinskaja. Front Nutr. 2023; 10:1158158. https://doi.org/10.3389/fnut.2023.1158158.
|
| [12] |
Wang XT, Du YM, Tan DP. A review on spectral characteristics of dammarane-type triterpenoid sapogenins from Gynostemma pentaphyllu. J Zunyi Med Univ. 2024; 47(3):299-312. https://doi.org/10.14169/j.cnki.zunyixuebao.2024.0033.
|
| [13] |
Liang Y, Zhao S. Progress in understanding of ginsenoside biosynthesis. Plant Biol. 2008; 10(4):415-421. https://doi.org/10.1111/j.1438-8677.2008.00064.x.
|
| [14] |
Liu Y, Yang Y, Wang H, et al. Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix. Chin J Nat Med. 2023; 21(8):599-609. https://doi.org/10.1016/S1875-5364(23)60395-4.
|
| [15] |
Shu RG, Xu CR, Li LN, et al. Cyclocariosides II and III: two secodammarane triterpenoid saponins from Cyclocarya paliurus. Planta Med. 1995; 61(6):551-553. https://doi.org/10.1055/s-2006-959369.
|
| [16] |
Wang YR, Cui BS, Han SW, et al. New dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus. J Asian Nat Prod Res. 2018; 20(11):1019-1027. https://doi.org/10.1080/10286020.2018.1457653.
|
| [17] |
Liu Y, Zhang XX, Xu SS, et al. New triterpenoids from the Cyclocarya paliurus (Batalin) Iljinskaja and their anti-fibrotic activity. Phytochemistry. 2022; 204:113434. https://doi.org/10.1016/j.phytochem.2022.113434.
|
| [18] |
Zhang XX, Jiang CH, Liu Y, et al. Cyclocarya paliurus triterpenic acids fraction attenuates kidney injury via AMPK-mTOR-regulated autophagy pathway in diabetic rats. Phytomedicine. 2019; 64:153060. https://doi.org/10.1016/j.phymed.2019.153060.
|
| [19] |
Jiang ZY, Zhang XM, Zhou J, et al. Two new triterpenoid glycosides from Cyclocarya paliurus. J Asian Nat Prod Res. 2006; 8(1-2):93-98. https://doi.org/10.1080/10286020500480217.
|
| [20] |
Zheng X, Zhao MG, Jiang CH, et al. Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates insulin resistance and hepatic steatosis via PI3K/Akt/GSK3β pathway. Phytomedicine. 2020; 66:153130. https://doi.org/10.1016/j.phymed.2019.153130.
|
| [21] |
Cheng L, Chen YH, Zhang X, et al. A metagenomic analysis of the modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiome in a high-fat diet-induced obesity mouse model. J Sci Food Agric. 2019; 99(8):3967-3975. https://doi.org/10.1002/jsfa.9622.
|
| [22] |
Song D, Ho CT, Zhang X, et al. Modulatory effect of Cyclocarya paliurus flavonoids on the intestinal microbiota and liver clock genes of circadian rhythm disorder mice model. Food Res Int. 2020; 138:109769. https://doi.org/10.1016/j.foodres.2020.109769.
|
| [23] |
Lei X, Liu WB, Yang ZW, et al. Enzymolysis-ultrasonic assisted extraction of flavanoid from Cyclocarya paliurus (Batal) Iljinskaja: HPLC profile, antimicrobial and antioxidant activity. Ind Crop Prod. 2019; 130:615-626. https://doi.org/10.1016/j.indcrop.2019.01.027.
|
| [24] |
Sun HH, Lv WY, Tan J, et al. Cytotoxic triterpenoid glycosides from leaves of Cyclocarya paliurus. Nat Prod Res. 2021; 35(21):4018-4024. https://doi.org/10.1080/14786419.2020.1756801.
|
| [25] |
Liu W, Deng SP, Zhou DX, et al. 3,4-seco-Dammarane triterpenoid saponins with anti-inflammatory activity isolated from the leaves of Cyclocarya paliurus. J Agric Food Chem. 2020; 68(7):2041-2053. https://doi.org/10.1021/acs.jafc.9b06898.
|
| [26] |
Duan YS, Hu Y, Yang WX, et al. Study on chemical constituents and α-glucosidase inhibitory activity of Cyclocarya paliurus in Guizhou Province. Nat Prod Res. 2019; 31(6):940-945. https://doi.org/10.16333/j.1001-6880.2019.6.003.
|
| [27] |
Kennelly E, Cai L, Long L, et al. Novel highly sweet seco-dammarane glycosides from Pterocarya paliurus. J Agric Food Chem. 1995; 43(10):2602-2607. https://doi.org/10.1021/jf00058a009.
|
| [28] |
Peng WW, Zhao SM, Ji CJ, et al. Cyclopalitins A and B, nortriterpenoids from aerial parts of Cyclocarya paliurus. Phytochem Lett. 2019; 31:114-117. https://doi.org/10.1016/j.phytol.2019.03.017.
|
| [29] |
Chen YJ, Na L, Fan JL, et al. Seco-dammarane triterpenoids from the leaves of Cyclocarya paliurus. Phytochemistry. 2018; 145:85-92. https://doi.org/10.1016/j.phytochem.2017.10.013.
|
| [30] |
Zhu LP, Yang HM, Zheng X, et al. Four new dammarane triterpenoid glycosides from the leaves of Cyclocarya paliurus and their SIRT 1 activation activities. Fitoterapia. 2021; 154:105003. https://doi.org/10.1016/j.fitote.2021.105003.
|
| [31] |
Li J, Liang XQ, Chang YL, et al. Review on the constituents and pharmacological activities of Cyclocarya paliurus. J Guangxi Norm Univ (Nat Sci). 2022; 40(5):227-252. https://doi.org/10.16088/j.issn.1001-6600.2022030804.
|
| [32] |
Xu RC, Zhang P, Xiang M. Research progress on chemical constituents and anti-metabolic disease pharmacological effects of Cyclocarya paliurus. Chin Tradit Herb Drugs. 2023; 54(9):2962-2977. https://doi.org/10.7501/j.issn.0253-2670.2023.09.029.
|
| [33] |
Chen Z, Jian Y, Wu Q, et al. Cyclocarya paliurus (Batalin) Iljinskaja: botany, ethnopharmacology, phytochemistry and pharmacology. J Ethnopharmacol. 2022; 285:114912. https://doi.org/10.1016/j.jep.2021.114912.
|
| [34] |
Noushahi HA, Khan AH, Noushahi UF, et al. Biosynthetic pathways of triterpenoids and strategies to improve their biosynthetic efficiency. Plant Growth Regul. 2022; 97(3):439-454. https://doi.org/10.1007/s10725-022-00818-9.
|
| [35] |
Tholl D. Biosynthesis and biological functions of terpenoids in plants. Adv Biochem Eng Biotechnol. 2015; 148:63-106. https://doi.org/10.1007/10_2014_295.
|
| [36] |
Dong LM, Pollier J, Bassard JE, et al. Co-expression of squalene epoxidases with triterpene cyclases boosts production of triterpenoids in plants and yeast. Metab Eng. 2018; 49:1-12. https://doi.org/10.1016/j.ymben.2018.07.002.
|
| [37] |
Jarstfer MB, Zhang DL, Poulter CD. Recombinant squalene synthase. Synthesis of non-head-to-tail isoprenoids in the absence of NADPH. J Am Chem Soc. 2002; 124(30):8834-8845. https://doi.org/10.1021/ja020410i.
|
| [38] |
Thimmappa R, Geisler K, Louveau T, et al.Triterpene biosynthesis in plants. Annu Rev Plant Biol. 2014; 65:225-257. https://doi.org/10.1146/annurev-arplant-050312-120229.
|
| [39] |
Pena RDL, Hodgson H, Liu JCT, et al. Complex scaffold remodeling in plant triterpene biosynthesis. Science. 2023; 379(6630):361-368. https://doi.org/10.1126/science.adf1017.
|
| [40] |
Qu YQ, Shang XL, Zeng ZY, et al. Whole-genome duplication reshaped adaptive evolution in a relict plant species Cyclocarya paliurus. Genom Proteom Bioinf. 2023; 21(3):455-469. https://doi.org/10.1016/j.gpb.2023.02.001.
|
| [41] |
Zheng XH, Xiao HB, Chen JN, et al. Metabolome and whole-transcriptome analyses reveal the molecular mechanisms underlying hypoglycemic nutrient metabolites biosynthesis in Cyclocarya paliurus leaves during different harvest stages. Front Nutr. 2022; 9:851569. https://doi.org/10.3389/fnut.2022.851569.
|
| [42] |
Sun CW, Fang SZ, Shang XL. Triterpenoids biosynthesis regulation for leaf coloring of wheel wingnut (Cyclocarya paliurus). Forests. 2021; 12(12):1733. https://doi.org/10.3390/f12121733.
|
| [43] |
Lin ZX. Study on separation of chemical components, network pharmacology and synthetic pathways of triterpenoids from Cyclocarya paliurus. Shanghai Norm Univ. 2021; 7:000761. https://doi.org/10.27312/d.cnki.gshsu.2021.000761.
|
| [44] |
Sheng XL. The study on the effects and mechanisms of water stress on the synthesis of flavonoids, polysaccharides, and terpenoids in Cyclocarya paliurus. Shanghai Norm Univ. 2022; 10:001821. https://doi.org/10.27312/d.cnki.gshsu.2022.001821.
|
| [45] |
Wang Q, Chen BQ, Chen XL, et al.Squalene epoxidase (SE) gene related to triterpenoid biosynthesis assists to select elite genotypes in medicinal plant: Cyclocarya paliurus (Batal.) Iljinskaja. Plant Physiol Biochem. 2023; 199:107726. https://doi.org/10.1016/j.plaphy.2023.107726.
|
| [46] |
Liu ZB, Xu XX, Yin ZP, et al. Incentive mechanism of triterpenoid synthesis by antioxidant response in the cultured Cyclocarya paliurus cells under the elicitation of Aspergillus niger elicitor. Sci Technol Food Ind. 2018; 39(24):114-121. https://doi.org/10.13386/j.issn1002-0306.2018.24.021.
|
| [47] |
Xi HT, Xu WX, He FX, et al. Spatial metabolome of biosynthesis and metabolism in Cyclocarya paliurus leaves. Food Chem. 2024; 443:138519. https://doi.org/10.1016/j.foodchem.2024.138519.
|
| [48] |
Yin J, Sun L, Li Y, et al. Functional identification of BpMYB21 and BpMYB61 transcription factors responding to MeJA and SA in birch triterpenoid synthesis. BMC Plant Biol. 2020; 20(1):374. https://doi.org/10.1186/s12870-020-02521-1.
|
| [49] |
Jang S, Yu YL, Jang L, et al. Effect of transcription factor PnWRKY on the biosynthesis of Panax notoginseng saponins. Acta Bot Boreal Occident Sin. 2019; 39(3):430-438. https://doi.org/10.7606/j.issn.1000-4025.2019.03.0430.
|
| [50] |
Wen WW, Alseekh S, Fernie AR. Conservation and diversification of flavonoid metabolism in the plant kingdom. Curr Opin Plant Biol. 2020; 55:100-108. https://doi.org/10.1016/j.pbi.2020.04.004.
|
| [51] |
Liu WX, Feng Y, Yu SH, et al. The flavonoid biosynthesis network in plants. Int J Mol Sci. 2021; 22(23):12824. https://doi.org/10.3390/ijms222312824.
|
| [52] |
Zhao CY, Wang F, Lian YH, et al. Biosynthesis of citrus flavonoids and their health effects. Crit Rev Food Sci Nutr. 2020; 60(4):566-583. https://doi.org/10.1080/10408398.2018.1544885.
|
| [53] |
Shen N, Wang TF, Gan Q, et al. Plant flavonoids: classification, distribution, biosynthesis, and antioxidant activity. Food Chem. 2022; 383:132531. https://doi.org/10.1016/j.foodchem.2022.132531.
|
| [54] |
Zhang L, Liu Y, Zhang ZJ, et al. Physiological response and molecular regulatory mechanism reveal a positive role of nitric oxide and hydrogen sulfide applications in salt tolerance of Cyclocarya paliurus. Front Plant Sci. 2023; 14:1211162. https://doi.org/10.3389/fpls.2023.1211162.
|
| [55] |
Zhang L, Zhang ZJ, Fang SZ, et al. Integrative analysis of metabolome and transcriptome reveals molecular regulatory mechanism of flavonoid biosynthesis in Cyclocarya paliurus under salt stress. Ind Crop Prod. 2021; 170:113823. https://doi.org/10.1016/j.indcrop.2021.113823.
|
| [56] |
Sun CW, Fang SZ, Shang XL. Flavonoid biosynthesis regulation for leaf coloring of Cyclocarya paliurus. Acta Physiol Plant. 2023; 45(7):91. https://doi.org/10.1007/s11738-023-03571-2.
|
| [57] |
Deng B, Li YY, Xu DD, et al. Nitrogen availability alters flavonoid accumulation in Cyclocarya paliurus via the effects on the internal carbon/nitrogen balance. Sci Rep. 2019; 9:2370. https://doi.org/10.1038/s41598-019-38837-8.
|
| [58] |
Sheng XL, Chen HW, Wang JM, et al. Joint transcriptomic and metabolic analysis of flavonoids in Cyclocarya paliurus leaves. ACS Omega. 2021; 6(13):9028-9038. https://doi.org/10.1021/acsomega.1c00059.
|
| [59] |
Liu Y, Liang Q, Tang DB, et al. Development of suspension culture technology and hormone effects on anthocyanin biosynthesis for red Cyclocarya paliurus cells. Plant Cell Tissue Organ Cult. 2022; 149(1-2):175-195. https://doi.org/10.1007/s11240-021-02215-y.
|
| [60] |
Yu YH, Qu YQ, Wang SY, et al. An integrative analysis of metabolome and transcriptome reveals the molecular regulatory mechanism of the accumulation of flavonoid glycosides in different Cyclocarya paliurus ploidies. Forests. 2023; 14(4):770. https://doi.org/10.3390/f14040770.
|
| [61] |
Zhang H, Tang X. Combining microbial and chemical syntheses for the production of complex natural products. Chin J Nat Med. 2022; 20(10):729-736. https://doi.org/10.1016/S1875-5364(22)60191-2.
|
| [62] |
Depuydt T, De Rybel B, Vandepoele K. Charting plant gene functions in the multi-omics and single-cell era. Trends Plant Sci. 2023; 28(3):283-296. https://doi.org/10.1016/j.tplants.2022.09.008.
|
| [63] |
Zhan CS, Shen SQ, Yang CK, et al. Plant metabolic gene clusters in the multi-omics era. Trends Plant Sci. 2022; 27(10):981-1001. https://doi.org/10.1016/j.tplants.2022.03.002.
|
PDF
(4178KB)
