三株紫苏内生真菌代谢产物抗肿瘤活性的研究  

Study on the antitumor activity of metabolites from three endophytic fungi of Perilla frutescens

作　　者：张琪金 李春艳 姚香草 许重远[2,3] 黄宝康 ZHANG Qi-jin;LI Chun-yan;YAO Xiang-cao;XU Zhong-yuan;HUANG Bao-kang(School of Pharmacy,Naval Medical University,Shanghai 200433,China;Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China;National Medical Products Administration Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]海军军医大学药学院,上海200433 [2]南方医科大学南方医院临床药学中心,广东广州510515 [3]南方医科大学药学院国家药品监督管理局药物代谢研究与评价重点实验室&广东省新药筛选重点实验室,广东广州510515

出　　处：《中国临床药理学杂志》2023年第22期3291-3295,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究3株从紫苏中分离得到的内生真菌次生代谢产物抗肿瘤活性。方法取处于指数生长期的5种人肿瘤细胞(人肝癌细胞株HepG2、人乳腺癌细胞株MCF-7、人肺腺癌细胞株NCI-H1975、人结肠癌细胞株HT-29、人前列腺癌细胞株DU-145),将细胞分为实验组[内生真菌发酵产物乙酸乙酯萃取部分,菌株暹罗刺盘孢菌(ZC-J4)和产黄青霉(BP-Y6)产物给药浓度为25、50、100、300和400μg·mL^(-1),菌株嗜线虫镰刀菌(ZP-G1)产物给药浓度为1.56、3.13、6.25、12.5、25和50μg·mL^(-1))]、阴性对照组、阳性对照组(阳性药物阿霉素,给药浓度为0.06、0.13、0.25、0.50和1.00μg·mL^(-1))。处理48 h后,用噻唑蓝法(MTT)法测定肿瘤细胞的增殖状况,计算内生真菌代谢产物对肿瘤细胞生长的抑制率和半数抑制浓度(IC50);并通过液相色谱-质谱联用技术(LC-MS)分析代谢产物中的主要成分。结果3株紫苏内生真菌发酵产物对肿瘤细胞的增殖有抑制效果,且在一定浓度范围内呈剂量依赖性;不同菌株代谢产物抑制作用差异较大,ZP-G1的次生代谢产物表现出的抑制作用最强,尤其是对HepG2细胞和HT-29细胞,IC50值分别为(6.28±0.09)和(9.03±1.05)μg·mL^(-1);BP-Y6和ZC-J4的次生代谢产物对肿瘤细胞的毒性较弱,对NCI-H1975的IC50值均大于400μg·mL^(-1)。LC-MS结果分析表明,3种内生真菌的代谢产物含有部分相同成分,真菌ZP-G1中含有香紫苏二醇、杨梅素等成分,在其余2株真菌中未发现。结论紫苏内生真菌的部分菌株具有抗肿瘤活性,菌株ZP-G1对肿瘤细胞增殖的抑制效果较好,具有进一步开发抗肿瘤天然活性成分的潜力。Objective To study the anti-tumor activity of secondary metabolites of three endophytic fungi isolated from Perilla frutescens.Methods Five kinds of human tumor cells(HepG2,MCF-7,NCI-H1975,HT-29,DU-145)in exponential growth stage were cultured.The cells were divided into experimental group[ethyl acetate extract of endophytic fungal fermentation product,with drug concentrations of strains Colletotrichum siamense(ZC-J4)and Penicillium chrysogenum(BP-Y6):25,50,100,300,400μg·mL^(-1),product administration concentration of strain Fusarium nematophilus(ZP-G1):1.56,3.13,6.25,12.5,25,50μg·mL^(-1))],negative control group,positive control group(positive drug doxorubicin,administered at concentrations of 0.06,0.13,0.25,0.50,1.00μg·mL^(-1)).And treated for 48 hours,measure the proliferation status of tumor cells using methyl thiazolyl tetrazolium method(MTT),calculate the inhibitory rate and half inhibitory concentration(IC_(50))of endophytic fungal metabolites on tumor cell growth.The main components in the metabolites were analyzed using liquid chromatography-mass spectrometry(LC-MS).Results The results showed that the fermentation products of three endophytic fungi from Perilla frutescens had an inhibitory effect on the proliferation of tumor cells,and showed a dose-dependent effect within a certain concentration range.The inhibitory effects of metabolites from different strains vary greatly.The secondary metabolites of ZP-G1 exhibit the strongest inhibitory effect,especially on Hep G2 cells and HT-29 cells,with IC_(50)values of(6.28±0.09)and(9.03±1.05)μg·mL^(-1),respectively.The secondary metabolites of BP-Y6 and ZC-J4 are less toxic to tumor cells,and their IC_(50)values to NCI-H1975 are greater than400μg·mL^(-1).LC-MS analysis showed that the metabolites of the three endophytic fungi contained partially identical components.Fungus ZP-G1 contained components such as scareol glycol and myricetin,but was not found in the other two fungi.Conclusion Some strains of endophytic fungi from Perilla frutescens have

关 键 词：紫苏 内生真菌 抗肿瘤活性 次生代谢产物 液相色谱-质谱联用 

分 类 号：R28[医药卫生—中药学]