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七叶一枝花活性成分pennogenin 3-O-β-chacotrioside对伯基特淋巴瘤的抑制作用及机制

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邓玲, 章美娜, 杨晏, 宋念竹, 黄传玉, 涂冬云, 卢恺婧, 徐林艳, 桑威

中草药 | 药理与临床 2026,57(6): 2120-2132

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中草药 |药理与临床 2026 , 57 (6) : 2120 -2132

七叶一枝花活性成分pennogenin 3-O-β-chacotrioside对伯基特淋巴瘤的抑制作用及机制

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邓玲, 章美娜, 杨晏, 宋念竹, 黄传玉, 涂冬云, 卢恺婧, 徐林艳, 桑威

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作者简介:

邓玲: 邓玲,硕士研究生,研究方向为中药治疗血液疾病淋巴瘤研究。E-mail:dengling0222@163.com

Effect and mechanism of pennogenin 3-O-β-chacotrioside (a bioactive compound from Paris polyphylla) in inhibiting Burkitt lymphoma

DENG Ling, ZHANG Meina, YANG Yan, SONG Nianzhu, HUANG Chuanyu, TU Dongyun, LU Kaijing, XU Linyan, SANG Wei

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doi: 10.7501/j.issn.0253-2670.2026.06.011

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目的探讨七叶一枝花Paris polyphylla活性成分pennogenin 3-O-β-chacotrioside（P3C）抑制伯基特淋巴瘤细胞增殖的作用及其作用机制，以及P3C联合化疗药物依托泊苷（VP-16）对伯基特淋巴瘤细胞增殖的影响。方法 CCK-8法检测不同浓度的P3C以及P3C联合VP-16对Raji和CA46细胞增殖的影响；流式细胞术检测其对细胞周期和凋亡的影响；Western blotting检测周期、凋亡和自噬相关蛋白表达；qRT-PCR检测自噬相关基因表达。以免疫缺陷鼠移植瘤模型为研究对象，给予P3C干预后，采用活体成像技术观察P3C对体内肿瘤生长的影响；Western blotting检测肿瘤组织中Ki67及凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3，Caspase-3）、聚腺苷二磷酸核糖聚合酶（poly ADP-ribose polymerase，PARP）的表达。结果 P3C可呈剂量相关性地抑制Raji和CA46细胞活力，半数抑制浓度（half inhibitory concentration，IC₅₀）分别为1.12、0.97μmol/L，并诱导细胞周期G₀/G₁期阻滞；P3C显著增加凋亡细胞的比例，细胞凋亡相关蛋白Caspase-3、Caspase-9、PARP等表达升高，自噬相关基因及蛋白微管相关蛋白轻链3（microtubule-associated protein light chain 3，LC3）、自噬相关基因5（autophagy-related gene 5，ATG5）、ATG7表达升高，p62表达降低，p38的磷酸化水平升高，细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）的磷酸化水平降低，与对照组比较均具有统计学意义（P＜0.05、0.01、0.001）。P3C和依托泊苷具有良好的协同作用，协同指数（collaboration index，CI）＜1；与单药组相比，药物联合组对Raji和CA46细胞杀伤作用更强，且进一步促进p38和降低ERK的磷酸化水平（P＜0.05、0.01、0.001）。体内实验中，与模型组比较，P3C能够明显抑制肿瘤生长（P＜0.05、0.01、0.001），肿瘤组织中Ki67蛋白表达明显降低（P＜0.001），Caspase-3、PARP蛋白表达显著升高（P＜0.05），与细胞实验结果一致。结论 P3C可以有效抑制伯基特淋巴瘤细胞的增殖，诱导其发生凋亡、自噬和细胞周期G₀/G₁期停滞，以及其在体内的生长和增殖。同时能够加强化疗药物依托泊苷对于伯基特淋巴瘤细胞的杀伤作用，并且可能通过调控p38/ERK信号通路实现抗肿瘤作用。

关键词

七叶一枝花 / pennogenin 3-O-β-chacotrioside / 伯基特淋巴瘤 / 凋亡 / 自噬 / MAPK信号通路

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Objective To investigate the inhibitory effect and mechanism of pennogenin 3-O-β-chacotrioside (P3C), an active ingredient from Paris polyphylla, on the proliferation of Burkitt’s lymphoma (BL) cells, as well as the combined effect of P3C and the chemotherapeutic drug etoposide (VP-16) on BL cell proliferation. Methods The inhibitory effects of different concentrations of P3C alone or in combination with VP-16 on Raji and CA46 cells proliferation were assessed using CCK-8 assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. Western blotting was used to detect the expressions of proteins related to cell cycle, apoptosis and autophagy. qRT-PCR was used to detect the expressions of autophagy-related genes. Using an immunodeficient mouse xenograft model, after P3C intervention, the effect of P3C on tumor growth in vivo was monitored via live imaging. Western blotting was performed to detect the expressions of Ki67 and apoptosis-related proteins cystein-asparate protease-3 (Caspase-3) and poly ADP-ribose polymerase (PARP) in tumor tissues. Results P3C inhibited the viability of Raji and CA46 cells in a dose-dependent manner, with half inhibitory concentration (IC₅₀) values of 1.12, 0.97 μmol/L, respectively, and induced G₀/G₁ phase cell cycle arrest. P3C significantly increased the proportion of apoptotic cells and elevated the expressions of apoptosis-related proteins such as Caspase-3, Caspase-9 and PARP, increased the expressions of autophagy-related genes and proteins such as microtubule-associated protein light chain 3 (LC3), autophagy-related gene 5 (ATG5) and ATG7, decreased the expression of p62, increased the phosphorylation level of p38, while decreased the phosphorylation level of extracellular regulated protein kinases (ERK), all of which were statistically significant compared with control group (P < 0.05, 0.01, 0.001). P3C and etoposide had a good synergistic effect, with a collaboration index (CI) < 1. Compared with the monotherapy group, the drug combination group had a stronger killing effect on Raji and CA46 cells, and further promoted p38 and reduced ERK phosphorylation levels (P < 0.05, 0.01, 0.001). In the in vivo experiments, compared with model group, P3C significantly inhibited tumor growth (P < 0.05, 0.01, 0.001), significantly reduced Ki67 protein expression in tumor tissue (P < 0.001), and significantly increases Caspase-3 and PARP protein expressions (P < 0.05), which was consistent with the results of cell experiments. Conclusion P3C could effectively inhibit the proliferation of Burkitt’s lymphoma cells, induce apoptosis, autophagy, and cell cycle G₀/G₁ arrest, as well as their growth and proliferation in vivo. At the same time, it could enhance the killing effect of chemotherapy drug etoposide on Burkitt’s lymphoma cells, and may achieve anti-tumor effects by regulating p38/ERK signaling pathway.

Key words

Paris polyphylla Sm. / pennogenin 3-O-β-chacotrioside / Burkitt lymphoma / apoptosis / autophagy / MAPK signaling pathway

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邓玲, 章美娜, 杨晏, 宋念竹, 黄传玉, 涂冬云, 卢恺婧, 徐林艳, 桑威. 七叶一枝花活性成分pennogenin 3-O-β-chacotrioside对伯基特淋巴瘤的抑制作用及机制. 中草药, 2026 , 57 (6) : 2120 -2132 . DOI: 10.7501/j.issn.0253-2670.2026.06.011

DENG Ling, ZHANG Meina, YANG Yan, SONG Nianzhu, HUANG Chuanyu, TU Dongyun, LU Kaijing, XU Linyan, SANG Wei. Effect and mechanism of pennogenin 3-O-β-chacotrioside (a bioactive compound from Paris polyphylla) in inhibiting Burkitt lymphoma[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (6) : 2120 -2132 . DOI: 10.7501/j.issn.0253-2670.2026.06.011

基金

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国家自然科学基金面上项目 (82470192); 江苏省自然科学基金面上项目 (BK20241768); 江苏省卫生健康委医学科研项目 (Z2024062); 徐州市卫生健康委医学科技创新项目 (XWKYHT20240109); 徐州医科大学附属医院发展基金项目 (XYFY202314); 徐州医科大学-齐鲁制药联合基金资助 (QL-YB014); 江苏省高水平医院建设项目 (GSPJS202501)

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2026年第57卷第6期

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doi: 10.7501/j.issn.0253-2670.2026.06.011

接收时间：2025-11-05
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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