重楼抗肿瘤活性成分分类及作用机制研究进展

doi:10.19803/j.1672-8629.20230494

摘要/Abstract

摘要： 重楼是清热解毒传统中药。重楼皂苷是重楼最主要的抗肿瘤活性成分,包括50多种化合物,其中具有抗肿瘤作用的成分为重楼皂苷I、II、II、VII等,对于治疗多种癌症效果显著,如肝癌、结肠癌、脑瘤、大肠癌、食管癌、肺癌、鼻咽癌等。这些成分主要是异螺甾烷醇型甾体皂苷类成分,以重楼皂苷I含量最多,其次有重楼皂苷II、薯蓣皂苷、重楼皂苷A 、纤细薯蓣皂苷、重楼皂苷VI、重楼皂苷VII、重楼皂苷H、重楼皂苷E等。近年来,重楼皂苷抗肿瘤作用逐渐被发现并应用到临床中,但重楼皂苷不良反应也有报道,如重楼皂苷I对肝脏的毒性损伤等。本文对重楼中的皂苷类成分进行分类并综述异螺甾烷醇型皂苷抗肿瘤作用机制的最新研究进展,以总结重楼皂苷抗肿瘤作用的活性成分及作用机制,为进一步研究重楼皂苷抗肿瘤作用及安全用药提供参考。

关键词: 重楼, 重楼皂苷, 抗肿瘤, 异螺甾烷醇型, 活性成分, 作用机制

Abstract: Paridis Rhizoma is a traditional Chinese medicine for clearing away heat and toxic materials. Polyphyllin, as the most important anti-tumor active ingredient of Paridis Rhizoma, contains more than 50 types of compounds, among which the ingredients with anti-tumor effects are polyphyllin I, II, VI, VII. It is effective in treating many types of tumor cancers, such as liver cancer, colon cancer, brain tumor, colorectal cancer, esophageal cancer, lung cancer and nasopharyngeal carcinoma. These ingredients are mostly isospirostanol saponins, dominated by polyphyllin I, followed by polyphyllin II, diosgenin, polyphyllin A, gracillin, polyphyllin VI, polyphyllin VII, polyphyllin H and polyphyllin E. In recent years, the anti-tumor effects of polyphyllin have been gradually discovered and applied in clinic, but the adverse effects of Paris saponins have also been reported, such as the toxic damage of polyphyllin I to the liver. In this paper, the saponin components in Paridis Rhizoma are classified while the latest progress in research on the anti-tumor mechanism of isospirostanol saponins is reviewed in order to summarize the active components and mechanism of action of the anti-tumor effect of Paris saponins and to provide reference for studies on anti-tumor effects of polyphyllin and the safety of medication.

Key words: Paridis Rhizoma, polyphyllin, antitumor, isospirostanol, active ingredient, mechanism

中图分类号:

R979.1

辛灵怡, 杨洋, 朱婧, 何娜, 张静媚, 王航天, 陈琴华, 杨光义. 重楼抗肿瘤活性成分分类及作用机制研究进展[J]. 中国药物警戒, 2024, 21(2): 235-240.

XIN Lingyi, YANG Yang, ZHU Jing, HE Na, ZHANG Jingmei, WANG Hangtian, CHEN Qinhua, YANG Guangyi. Classification of anti-tumor active ingredients of Paridis Rhizoma and research progress in mechanisms of action[J]. Chinese Journal of Pharmacovigilance, 2024, 21(2): 235-240.

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参考文献

[1] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China,Volume I(中华人民共和国药典一部)[S]. Beijing: China Medical Science Press, 2020: 271.
[2] PENG LF, ZHANG XN, FENG LP, et al.Identification and content determination of fibrillar diosgenin in paris vietnamensis[J].China Pharmacy(中国药房), 2015, 26(3): 384-386.
[3] MIMAKI Y, SASHIDA Y.Steroidal and phenolic constituents of Lilium speciosum[J]. Phytochemistry, 1991, 30(3): 937-940.
[4] WANG Y, FAN Q, XIANG J, et al.Structural characterization and discrimination of Paris polyphylla var. yunnanensis by a molecular networking strategy coupled with ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry[J]. Rapid Commun Mass Spectrom, 2020, 34(11): e8760.
[5] ZHANG X, WU J, QIN L, et al.Separation and purification of two saponins from paris polyphylla var. yunnanensis by a macroporous resin[J]. Molecules, 2022, 27(19): 6626.
[6] HU JM, TANG HF, LU YY, et al.A new cyclic cholestanol-type steroidal saponin from Narrow-leafed Serpentine saponins[J]. Central South Pharmacy(中南药学), 2022, 20(4): 736-743.
[7] CUI Y.Studies on the chemical structure of some active components of the Chinese traditional medicine Hepatitis Verticillata L[D]. Beijing: Beijing University of Chemical Technology, 2006.
[8] GAO X, ZHANG X, CHEN W, et al.Transcriptome analysis of Paris polyphylla var. yunnanensis illuminates the biosynthesis and accumulation of steroidal saponins in rhizomesandleaves[J]. Phytochemistry, 2020, 178: 112460.
[9] LIU W, CHAI Y, HU LB, et al.Polyphyllin VI induces apoptosis and autophagy via reactive oxygen species mediated JNK and P38 activation in glioma[J]. Onco Targets Ther, 2020, 13: 2275-2288.
[10] YANG L, ZHU T, Ye H, et al.Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway[J]. J Cell Mol Med, 2021, 25(2): 801-812.
[11] SHEN ZC, SHEN JH, XIE XX, et al.Effects of polyphylla var. Yunnanensis saponins on cell cycle and apoptosis in prostate cancer cells[J]. Journal of Modern Urology(现代泌尿外科杂志), 2021, 26(10): 867-872.
[12] LAI L, SHEN Q, WANG Y, et al.Polyphyllin I reverses the resistance of osimertinib in non-small cell lung cancer cell through regulation of PI3K/Akt signaling[J]. Toxicology and Applied Pharmacology, 2021, 419: 115518.
[13] ZHU X, NA X, ZENG Y, et al.Polyphyllin I combined with doxorubicin shows chemosensitization effect in vivo and reduces immunotoxicity of doxorubicin[J]. Molecular & Cellular Toxicology, 2022, 18(3): 359-369.
[14] WU Y, SI Y, XIANG Y, et al.Polyphyllin I activates AMPK to suppress the growth of non-small-cell lung cancer via induction of autophagy[J]. Arch Biochem Biophys, 2020, 687: 108285.
[15] HAN J, KAN J, WANG X, et al.Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation[J]. Translational Cancer Research, 2020, 9(8): 4715.
[16] TANG Q, WANG SM, WU WK, et al.Inhibitory effect of Polyphyllin I regulating Sp1/miR-542-3p/ILK signaling pathway on lung cancer cells[J]. China Journal of Traditional Chinese Medicine and Pharmacy(中华中医药杂志), 2022, 37(5): 2805-2812
[17] LUO Q, JIA L, HUANG C, et al.Polyphyllin I Promotes autophagic cell death and apoptosis of colon cancer cells via the ros-inhibited AKT/mTOR pathway[J]. International Journal of Molecular Sciences, 2022, 23(16): 9368.
[18] LIU MM, ZHU ML, DONG RF, et al.Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer[J]. Chinese Journal of Natural Medicines(中国天然药物), 2021, 19(4): 255-266.
[19] JIA P, LONG FR, WANG LF, et al.Exploring the anti-ovarian cancer effects of rehmannia Polyphyllin I based on epigenetic regulation of DLEC1 gene[J]. Chinese Journal of Biologicals(中国生物制品学杂志), 2017, 30(9): 936-942.
[20] NIU W, XU L, LI J, et al.Polyphyllin II inhibits human bladder cancer migration and invasion by regulating EMT-associated factors and MMPs[J]. Oncol Lett, 2020, 20(3): 2928-2936.
[21] GAO J.Regulation of PI3K/Akt signaling pathway by polyphyllin II induces autophagy and anti-tumor angiogenesis in melanoma B16F10 cells[D]. Hefei: Anhui University of Chinese Medicine, 2021.
[22] SHANGGUAN WJ, YU P, QIAN FF, et al.Polyphyllin VII induces apoptosis in lung adenocarcinoma circulating tumor cell clusters through DNA damage-mediated p53 signaling pathway[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2022, 42(7): 849-855.
[23] WANG LW, XU Q, SUN YH.Inhibition of proliferation and induction of apoptosis by polyphyllin VII in human colon cancer cell lines[J]. China Medicine(中国医药), 2020, 15(1): 92-95.
[24] MA P, CAO TT, LIU D, et al.Studies on the in vitro antitumor effects of gracillin compounds[J]. Journal of Binzhou Medical University(滨州医学院学报), 2008, 31(5): 326-328.
[25] ZHAO X, XU L, ZHENG L, et al.Potent effects of dioscin against gastric cancer in vitro and in vivo[J]. Phytomedicine(植物医学), 2016, 23(3): 274-282.
[26] ZHANG W, LIN L, ZHANG Y, et al.Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation[J]. Biomedicine & Pharmacotherapy, 2022, 150: 112973.
[27] WANG X, ZHANG R, WANG S, et al.Development, characterisation, and in vitro anti-tumor effect of self-microemulsifying drug delivery system containing polyphyllin I[J]. Drug Delivery and Translational Research, 2023, 13(1): 356-370.
[28] SHEN Z, WANG J, KE K, et al.Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo[J]. Cell Cycle, 2021, 20(23): 2494-2506.
[29] DENG B.Effects of total saponin from Rhizoma Paris on proliferation and radiosensitivity of human hepatocellular carcinoma HepG2 cells[D]. Wuhan: Hubei University of Chinese Medicine, 2018.
[30] ZHANG L, XIONG YL, REN YL, et al.Mechanism of action of polyphyllin A directly targeting ETS-1 to inhibit proliferation and induce apoptosis in gastric cancer cells[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2022, 47(6): 1650-1657.
[31] LI X, SU DH, GAO XM, et al.Rhizoma paris saponin promotes iron death in triple-negative breast cancer cells via the p53/SLC7A11 axis[J]. Med J Chin PLA(解放军医学杂志), 2023, 48(1): 58-63.
[32] SUN GQ, XUE YY, LU YY, et al.Induction of apoptosis and pyroptosis in temozolomide-resistant glioma SHG44R cells by polyphyllin H[J]. Central South Pharmacy(中南药学), 2022, 20(5): 973-978.
[33] LIU Y, CAO Y, KAI H, et al.Polyphyllin E inhibits proliferation, migration and invasion of ovarian cancer cells by down-regulating the AKT/NF-κB pathway[J]. Biol Pharm Bull, 2022, 45(5): 561-568.
[34] WANG H, HAN H, XU Y, et al.A simple and sensitive LC-MS/MS method for the determination of polyphyllin VII in rat plasma and its application to pharmacokinetic study[J]. Biomedical Chromatography, 2023, 37(5): e5597.
[35] LIU ZY, WANG BF, LI D, et al.Extraction of polyphyllin and its pharmacokinetics in rats[J]. Chinese Journal of Laboratory Diagnosis(中国实验诊断学), 2016, 20(10): 1640-1643.
[36] WANG G, HAO R, LUO C, et al.Pharmacokinetics profiles of polyphyllin II and polyphyllin VII in rats by liquid chromatography with tandem mass spectrometry[J]. Biomedical Chromatography, 2021, 35(6): e5083.
[37] Ministry of Health of the People’s Republic of China. Traditional Chinese Medicine Formulations(中药成方制剂)[S]. Beijing: National Health Commission of the People’s Republic of China, 1989.
[38] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China - Clinical Medication Instructions(中华人民共和国药典临床用药须知)[M]. Beijing: China Hospital Science Press, 2015.
[39] ZHANG WJ.A brief experience on the treatment of malignant tumors by beehives with Paridis Rhizoma[J]. Renowned Doctor(名医), 2019(2): 133.
[40] XU SY, YANG XY, JIA ML, et al. Overview of the application of GongXueNingJiaoNang in gynecological diseases in the past 5 years[J]. World Latest Medicine Information(世界最新医学信息文摘), 2017, 17(54): 77, 79.
[41] GUO SY, YIN Y, LEI T, et al.A cycloartenol synthase from the steroidal saponin biosynthesis pathway of Paris polyphylla[J]. Journal of Asian Natural Products Research, 2021, 23(4): 353-362.
[42] XIAO WH, YANG ZW, LI Y.Analysis of the cytotoxicity of polyphyllin I on human erythrocytes in vitro based on three-dimensional morphology of single cell[J]. Chinese Journal of Blood Transfusion(中国输血杂志), 2019, 32(4): 334-338.
[43] WANG WP.Evaluation of the toxicity of Paris Saponin I,Ⅱ and Ⅶ and investigation of the mechanism of hepatotoxicity of Paris Saponin I[D]. Beijing: Beijing University of Chinese Medicine, 2022.
[44] WANG X, CHEN LZ, LIN RC, et al.Developmental toxicity and anti-neovascularization activity of polyphyllin I on zebrafish and its mechanisms[J]. Chinese Traditional and Herbal Drugs(中草药), 2023, 54(14): 4548-4555.
[45] CHEN XM, YANG HZ, SI M, et al.Study on the antitumor activity and acute toxicity of total saponins of Paris forrestii[J]. Drug Evaluation Research(药物评价研究), 2017, 40(7): 904-910.
[46] LIU Y, LIU MY, BI LL, et al.Cytotoxic steroidal glycosides from the rhizomes of Paris polyphylla var. yunnanensis[J]. Phytochemistry, 2023, 207: 113577.
[47] ZHANG T, ZHANG L, LU JF, et al.Mechanism of polyphyllinⅠtargeting EGFR to affect proliferation and apoptosis of human breast cancer cells[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2022, 47: 721-729.
[48] ZHANG L,XIONG YL,REN YL et al. Mechanism of polyphyllin A in inhibition of proliferation and induction of apoptosis of gastric cancer cells by directly targeting ETS-1[J] . China Journal of Chinese Materia Medica(中国中药杂志), 2022, 47: 1650-1657.
[49] NIU WP, X U LL, JING W, et al. Polyphyllin II inhibits human bladder cancer migration and invasion by regulating EMT-associated factors and MMPs[J]. Oncol Lett, 2020, 20: 2928-2936.
[50] WANG Y, HUANG XL, XIAN B, et al.Paris polyphylla Machine learning and bioinformatics-based insights into the potential targets of saponins in smith against non-small cell lung cancer[J]. Front Genet, 2022, 13: 1005896.
[51] ZHANG C, LI QR, QIN GZ, et al.Anti-angiogenesis and anti-metastasis effects of Polyphyllin VII on hepatocellular carcinoma cells in vitro and in vivo[J]. Chin Med(中医), 2021, 16: 41.
[52] CHEN PS, SHIH YW, HUANG HC, et al.Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression[J]. PLos One, 2011, 6(5): e20164.
[53] YEN ML, SU JL, CHIEN CL, et al.Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts[J]. Mol Pharmacol, 2005, 68(4): 1061-1073.