拟层孔菌属中7种羊毛甾烷型三萜抗肿瘤活性及构效关系研究(1)
[摘要]对拟层孔菌属中红缘拟层孔菌Fomitopsis pinicola和药用拟层孔菌F. officinalis子实体的7种羊毛甾烷型三萜类化合物fomitopsin C(1)、3-酮基-去氢硫色多孔菌酸(2)、去氢齿孔酮酸(3)、3-乙酰氧基-8，24-羊毛甾二烯-21-酸(4)、松苓酸A(5)、栓菌酸(6)和齿孔酸(7)进行了分离纯化；体外抗肿瘤方面，采用MTT法测试7种单体化合物对人乳腺癌MCF-7细胞、人宫颈癌Hela细胞、人肝癌HepG2细胞和人肺癌A549细胞增殖的影响，结果表明7种化合物对MCF-7细胞较为敏感，对MCF-7半数抑制浓度IC50为2<5<4<1<3<6<7；体内抗肿瘤方面，采用H22荷瘤小鼠模型，对比研究体外抗肿瘤活性较好的化合物2～5对小鼠的影响，结果表明化合物2和化合物4抗肿瘤活性好，并呈现一定的剂量依赖关系，化合物2， 4， 5剂量为20 mg·kg-1时的抑瘤率分别为65.31%， 59.75%， 58.72%，接近阳性药组的抑瘤率69.19%；近一步试验表明抗肿瘤作用与抑制VEGF表达和免疫调节相关，对细胞因子IL-4和IFN-γ表达的影响较大，与抗氧化作用关联性较少，根据结果推断出羊毛甾烷型四环三萜结构抗肿瘤构效关系可能为，在3位羟基被酮基或乙酰基取代和C环中15位连有羟基时，此类化合物的抗肿瘤作用增强。
, 百拇医药
[关键词] 红缘拟层孔菌； 药用拟层孔菌； 羊毛甾烷型四环三萜； 抗肿瘤； 构效关系
[Abstract] Seven lanostane-type triterpenes including fomitopsin C(1)，3-keto-dehydrosulfurenic acid(2)，dehydroeburiconic acid(3)，3-acetyloxylanosta-8， 24-dien-21-oic acid(4)，pinicolic acid A(5)，trametenolic acid B(6)，and eburicoic acid(7)，were isolated from the fruitbodies of Fomitopsis pinicola and F. officinalis. In vitro assay， all compounds were evaluated against MCF-7， HeLa， HepG2 and A549 cells lines using the MTT assay and the structure-activity relationship of antitumor activity was discussed. The results showed that the seven compounds were more sensitive to MCF-7 cells.The IC50 value for MCF-7 was 2<5<4<1<3<6<7. H22 tumor mouse model was used to assay compounds 2， 3， 4 and 5 in vivo. Compounds 2 and 4 had obvious effect and the necrosis area and measurement were positively correlated. The results showed that compounds 2， 4 and 5 had significant antitumor activities at a dose of 20 mg·L-1with 65.31%， 56.71%， 58.72% suppression， respectively， approaching to CTX group with 69.19% suppression in subcutaneous H22-implanted mice.The results showed that these compounds had significant against the expression of VEGF，cytokines IL-4 and IFN-γ tumor， additionally， the structure-activity relationship of lanostane-type triterpenes indicated that the acetoxyl or carbonyl at C-3 and hydroxy at C-15 can enhance the antitumor activity.
, 百拇医药
[Key words] Fomitopsis pinicola； Fomitopsis officinalis； lanostane-type triterpenes； antitumor； structure-activity relationship
癌癥疾病人们谈之色变，它是人类健康的主要威胁之一，其分布广、患者多，目前各国学者对其研究一直火热，本研究以隶属于真菌界Fungi，担子菌门Basidiomycota，担子菌纲Basidiomy cetes，多孔菌目Polyporales，多孔菌科Polyporaceac拟层孔菌属Fomitopsis红缘拟层孔菌F. pinicola和药用拟层孔菌F. officinalis子实体为试验原材料[1]，红缘拟层孔菌其味微苦、性平，具滋补强壮、扶正培本、祛风除湿、安神定志和强心等作用，在东北地区民间当作“桑黄”药用[2]，赵兴华等[3-5]研究表明其子实体和发酵产物氯仿提取物均具有较高的抑瘤率，能够显著地延长小鼠的生存率，并证明了3-乙酰氧基-8，24-羊毛甾二烯-21-酸和松苓酸A为其活性成分。药用拟层孔菌在新疆被称为“阿里红”，是维吾尔医常用的民族药材，用于治疗腹痛、感冒、肺结核患者盗汗和慢性气管炎[6]。研究表明其子实体乙酸乙酯提取层具有非常好的抗肿瘤活性及提高机体免疫力的活性，进一步研究表明3-酮基-去氢硫色多孔菌酸，去氢齿孔酮酸为其活性成分[7-8]。本研究在前人研究的基础上，分离得到的7种羊毛甾烷型三萜类化合物：fomitopsin C(1)、3-酮基-去氢硫色多孔菌酸(2)、去氢齿孔酮酸(3)、3-乙酰氧基-8，24-羊毛甾二烯-21-酸(4)、松苓酸A(5)、栓菌酸(6)和齿孔酸(7)，进行了体内外的抗肿瘤实验，并对其构效关系进行了分析。, 百拇医药(史帧婷 包海鹰 冯爽)
, 百拇医药
[关键词] 红缘拟层孔菌； 药用拟层孔菌； 羊毛甾烷型四环三萜； 抗肿瘤； 构效关系
[Abstract] Seven lanostane-type triterpenes including fomitopsin C(1)，3-keto-dehydrosulfurenic acid(2)，dehydroeburiconic acid(3)，3-acetyloxylanosta-8， 24-dien-21-oic acid(4)，pinicolic acid A(5)，trametenolic acid B(6)，and eburicoic acid(7)，were isolated from the fruitbodies of Fomitopsis pinicola and F. officinalis. In vitro assay， all compounds were evaluated against MCF-7， HeLa， HepG2 and A549 cells lines using the MTT assay and the structure-activity relationship of antitumor activity was discussed. The results showed that the seven compounds were more sensitive to MCF-7 cells.The IC50 value for MCF-7 was 2<5<4<1<3<6<7. H22 tumor mouse model was used to assay compounds 2， 3， 4 and 5 in vivo. Compounds 2 and 4 had obvious effect and the necrosis area and measurement were positively correlated. The results showed that compounds 2， 4 and 5 had significant antitumor activities at a dose of 20 mg·L-1with 65.31%， 56.71%， 58.72% suppression， respectively， approaching to CTX group with 69.19% suppression in subcutaneous H22-implanted mice.The results showed that these compounds had significant against the expression of VEGF，cytokines IL-4 and IFN-γ tumor， additionally， the structure-activity relationship of lanostane-type triterpenes indicated that the acetoxyl or carbonyl at C-3 and hydroxy at C-15 can enhance the antitumor activity.
, 百拇医药
[Key words] Fomitopsis pinicola； Fomitopsis officinalis； lanostane-type triterpenes； antitumor； structure-activity relationship
癌癥疾病人们谈之色变，它是人类健康的主要威胁之一，其分布广、患者多，目前各国学者对其研究一直火热，本研究以隶属于真菌界Fungi，担子菌门Basidiomycota，担子菌纲Basidiomy cetes，多孔菌目Polyporales，多孔菌科Polyporaceac拟层孔菌属Fomitopsis红缘拟层孔菌F. pinicola和药用拟层孔菌F. officinalis子实体为试验原材料[1]，红缘拟层孔菌其味微苦、性平，具滋补强壮、扶正培本、祛风除湿、安神定志和强心等作用，在东北地区民间当作“桑黄”药用[2]，赵兴华等[3-5]研究表明其子实体和发酵产物氯仿提取物均具有较高的抑瘤率，能够显著地延长小鼠的生存率，并证明了3-乙酰氧基-8，24-羊毛甾二烯-21-酸和松苓酸A为其活性成分。药用拟层孔菌在新疆被称为“阿里红”，是维吾尔医常用的民族药材，用于治疗腹痛、感冒、肺结核患者盗汗和慢性气管炎[6]。研究表明其子实体乙酸乙酯提取层具有非常好的抗肿瘤活性及提高机体免疫力的活性，进一步研究表明3-酮基-去氢硫色多孔菌酸，去氢齿孔酮酸为其活性成分[7-8]。本研究在前人研究的基础上，分离得到的7种羊毛甾烷型三萜类化合物：fomitopsin C(1)、3-酮基-去氢硫色多孔菌酸(2)、去氢齿孔酮酸(3)、3-乙酰氧基-8，24-羊毛甾二烯-21-酸(4)、松苓酸A(5)、栓菌酸(6)和齿孔酸(7)，进行了体内外的抗肿瘤实验，并对其构效关系进行了分析。, 百拇医药(史帧婷 包海鹰 冯爽)