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肝细胞癌(HCC)是亚洲第五大常见癌症,也是癌症死亡的常见原因,其中中国占亚洲病例的62.4%[1]。HCC晚期治疗方法则有经肝动脉化疗栓塞术(TACE)、广谱络氨酸酶抑制剂(TKI)、免疫疗法和抗血管生成疗法。上述治疗策略延长了患者的生存期,但存在广谱毒副作用,长期应用分子靶向治疗还会出现严重耐药等问题[2]。中药治疗作为HCC的另一种疗法,在HCC中有独特的治疗作用。其能缓解癌症患者的临床症状、改善生活质量、提高免疫功能、预防复发和转移、延缓肿瘤进展和延长生存期[3-5]。因此,探究中药抗肝细胞癌的物质基础和作用机制越来越受到关注。
通关藤又称乌骨藤、通关散、通光藤等,在我国主要分布在云南和贵州两省,其最初记载于明代的《滇南本草》,药用历史悠久。通关藤富含多种生物活性成分,如甾体苷、多糖、有机酸等,其中C21甾体苷被认为是主要的抗肿瘤物质。大量临床研究发现通关藤在肝细胞癌和其它肿瘤中有特异性治疗作用[6]。在Huh7和HepG2细胞系中,通关藤皂苷H(TEH)通过下调PI3K/AKT/mTOR信号通路诱导自噬和凋亡,从而增加肿瘤细胞的敏感性[7]。在肝细胞癌患者来源的肿瘤异种移植物模型中,通关藤提取物通过下调血管生成标志物的表达、阻断血管生成因子的分泌,抑制肿瘤中血管网络的形成,从而延缓HCC的生长[8]。上述研究仅基于单个药物-单个靶点-单个通路的思路进行研究设计,未充分考虑中药成分的复杂性。中药发挥药效是一个多成分-多靶点-多通路的协同作用。因此,本研究拟利用网络药理学,寻找通关藤的多成分-多靶点-多通路的关系,构建药物成分-靶点网络图,从多个角度探讨通关藤治疗肝细胞癌的物质基础和作用机制,结合生物信息学方法,挖掘肝细胞癌基因芯片数据,寻找通关藤治疗HCC的潜在靶点,然后通过分子对接技术验证并展示通关藤活性成分与关键靶点间的相互作用,明确通关藤治疗肝细胞癌的物质基础和作用机制,以期为通关藤在HCC临床应用中提供理论参考。
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通过文献检索[11-18],共收集到50种活性成分(表1)和588个靶基因。其中通关藤苷元甲未查询到靶基因。
表 1 通关藤活性成分信息
编号 化合物名称 Simles结构式 1 2,4-Decadienal(2,4-癸二烯醛) CCCCC/C=C/C=C/C=O 2 2,4-Dihydroxybenzoic Acid(2,4 -二羟基苯甲酸) C1=CC(=C(C=C1O)O)C(=O)O 3 2,6-Dihydroxybenzoic Acid(2,6 -二羟基苯甲酸) C1=CC(=C(C(=C1)O)C(=O)O)O 4 3,4-Dihydroxybenzoic Acid(3,4 -二羟基苯甲酸) C1=CC(=C(C=C1C(=O)O)O)O 5 Betulinic Acid(白桦脂酸) CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)O)C)C(=O)O 6 Caffeic Acid(咖啡酸) C1=CC(=C(C=C1/C=C/C(=O)O)O)O 7 Chlorogenic Acid(绿原酸) C1C(C(C(CC1(C(=O)O)O)OC(=O)C=CC2=CC(=C(C=C2)O)O)O)O 8 Cissogenin(西索苷元) CC(C1CCC2(C1(C(C(C3C2CC=C4C3(CCC(C4)O)C)O)O)C)O)O 9 Conduritol(环己烯四醇) C1=CC(C(C(C1O)O)O)O 10 D(+)-Digitoxose(D (+)-洋地黄毒糖) CC(C(C(CC=O)O)O)O 11 Daucosterol(胡萝卜甾醇) CCC(CCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)OC5C(C(C(C(O5)CO)O)O)O)C)C)C(C)C 12 D-Cymarose(加拿大麻糖) CC(C(C(CC=O)OC)O)O 13 Dihydrosarcostin(二氢肉珊瑚苷元) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)O)C)O)O)O 14 Dresgenin(苦绳甙元) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)OC(=O)C5=CC=CC=C5)C)O)O)O 15 Drevogenin A(南山藤皂苷元A) CC(C)CC(=O)OC1C(C2C(CC=C3C2(CCC(C3)O)C)C4(C1(C(CC4)C(=O)C)C)O)OC(=O)C 16 Drevogenin Q(南山藤皂苷元Q) CC(C)CC(=O)OC1C2C(CC=C3C2(CCC(C3)O)C)C4(CCC(C4(C1OC(=O)C)C)C(=O)C)O 17 D-Thevetose(D-黄花夹竹桃糖) CC(C(C(C(C=O)O)OC)O)O 18 Galactitol(半乳糖醇) C(C(C(C(C(CO)O)O)O)O)O 19 Gallic Acid(没食子酸) C1=C(C=C(C(=C1O)O)O)C(=O)O 20 Kaempferol(山奈酚) C1=CC(=CC=C1C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O)O 21 Kaempferol-4'-Methylether(山柰酚-4-甲醚) COC1=CC=C(C=C1)C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O 22 Lupeol(羽扇豆醇) CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)OC(=O)C6=
CC=CC=C6)C)C23 Marsectobiose(直立牛奶菜双糖) CC1C(C(C(C(O1)OC(C(C)O)C(CC=O)OC)O)OC)O 24 Marstenacigenin A(二氢肉珊瑚苷元的衍生物) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)C(=O)C=CC5=CC=CC=C5)C)O)O)O 25 Methyl Shikimate(莽草酸甲酯) COC(=O)C1=CC(C(C(C1)O)O)O 26 Nerolidol(橙花叔醇) CC(=CCCC(=CCCC(C)(C=C)O)C)C 27 Oleandrose(齐墩果糖) CC(C(C(CC=O)OC)O)O 28 P-Hydroxycinnamic Acid(对羟基肉桂酸) C1=CC(=CC=C1C=CC(=O)O)O 29 Propionic Acid(丙酸) CCC(=O)O 30 Protocatechualdehyde(中原儿茶醛) C1=CC(=C(C=C1C=O)O)O 31 Scopoletin(东莨菪素) COC1=C(C=C2C(=C1)C=CC(=O)O2)O 32 Scutellarein-4-Methylether(灯盏乙素-4-甲醚) COC1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C=C(C(=C3O)O)O 33 Shikimic Acid(莽草酸) C1C(C(C(C=C1C(=O)O)O)O)O 34 Sinapic Acid(芥子酸) COC1=CC(=CC(=C1O)OC)C=CC(=O)O 35 Stigmasterol(豆甾醇) CCC(C=CC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C)C(C)C 36 Succinic Acid(琥珀酸) C(CC(=O)O)C(=O)O 37 Syringic Acid(丁香酸) COC1=CC(=CC(=C1O)OC)C(=O)O 38 Taraxasterol(蒲公英甾醇) CC1C2C3CCC4C5(CCC(C(C5CCC4(C3(CCC2(CCC1=C)C)C)C)(C)C)O)C 39 Tenacigenin B(通光散苷元B) CC(=O)C1CCC23C1(C(C(C4C2(O3)CCC5C4(CCC(C5)O)C)O)O)C 40 Tenacigenin D(通光散苷元D) CCC(C)C(=O)OC1C2C3(CCC(=O)CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)C 41 Tenacissoside A(通关藤皂苷A) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)OC8C(C(C(C(O8)CO)O)O)O)OC)O)OC)C 42 Tenacissoside B(通关藤皂苷B) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C(=CC)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)OC8C(C(C(C(O8)CO)O)O)O)OC)O)OC)C 43 Tenacissoside G(通关藤皂苷G) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)O)OC)O)OC)C 44 Tenacissoside H(通关藤皂苷H) CCC(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)O)OC)O)OC)C 45 Tenacissoside I(通关藤皂苷I) CC1C(C(C(C(O1)OC2C(OC(CC2OC)OC3CCC4(C(C3)CCC56C4C(C(C7(C5(O6)CCC7C(=O)C)C)OC(=O)C)OC(=O)C8=CC=CC=C8)C)C)O)OC)O 46 Tenasogenin(通关苷元) CC(C1CCC2(C1(C(C(C3C2CC=C4C3(CCC(C4)O)C)OC(=O)C=C(C)C)O)C)O)O 47 Vanillic Acid(香草酸) COC1=C(C=CC(=C1)C(=O)O)O 48 β-Amyrin(β-香树脂醇) CC1(CCC2(CCC3(C(=CCC4C3(CCC5C4(CCC(C5(C)C)O)C)C)C2C1)C)C)C 49 β-Sitosterol(β-谷甾醇) CCC(CCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C)C(C)C 50 17β-Tenacissoside B(17β-通光藤皂苷B) O[C@H]1CC[C@]2(C(C1)CC[C@@]13C2[C@H](O)[C@@H](O)[C@]2([C@]3(O1)CC[C@@H]2C(=O)C)C)C -
GSE147888包括12个正常人肝组织样本和12个肝细胞癌组织样本,对样本进行差异基因表达分析。结果显示(见图1),共有1251个差异基因,其中上调基因532个,下调基因719个。从Genecards和OMIM数据库中获得靶基因783个。
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将活性成分靶点、GEO数据库筛选的靶基因和疾病数据库筛选的靶点取交集(见图2A),得到共同靶点基因12个,分别是ESR1、CYP1A1、PARP1、PTGS2、AR、JUN、MAP2K1、IL6、MMP1、MMP9、PPARG、PLA2G2A。将共同靶点基因与其对应的活性成分构建“成分-靶点网络图”。如图2B所示,网络图含44个节点、75条边,节点包含12个靶点基因和32个化合物。以度值对化合物进行排序,发现化合物野黄芩素四甲醚、通关苷元、芥子酸、苦绳苷元、山奈酚排名靠前。将交集基因构建PPI网络(见图2C和图2D),发现基因度值排名靠前。提示这些化合物和基因可能是通关藤治疗肝细胞癌的关键成分和关键靶点。
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为了进一步探索通关藤活性成分对肝细胞癌的潜在作用机制和共同靶基因的功能,对共同靶基因进行GO/KEGG分析。GO分析获得条目BP 505个、CC 6个、MF 59个。图3A所示,生物过程主要涉及基因沉默调节、炎症反应调节、平滑肌细胞增殖,细胞组成涉及转录调节复合物、RNA聚合酶II转录调节复合物、转录前起始复合物、蛋白质-DNA复合物、细胞器外膜、外膜;分子功能涉及外膜、R-SMAD结合、RNA聚合酶II特异性DNA结合转录因子结合等。KEGG分析得61条通路(图3B),其中排名前列与肝细胞癌相关通路有IL-17信号通路、脂质和动脉粥样硬化、TNF信号通路等。
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为证明关键基因与HCC之间的关系,通过GEPIA在线数据库中分析了共同靶基因与HCC患者的生存曲线。在12个靶基因中,ESR1、MMP1、MMP9、JUN、PPARG高表达的HCC患者的总生存期较差,与低表达患者相比,生存时间有明显差异(图4A)。ESR1和MMP9在肝细胞癌组织中mRNA水平表达存在显著差异(图4B)。HPA数据库中免疫组织化学结果显示(图4C),ESR1和MMP9在正常肝脏组织不表达,在肝癌组织中分别呈现中度表达和低表达状态。未在数据库中查询到MMP1、JUN、PPARG 在正常肝脏组织和肝癌组织中的表达。
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根据“2.3”项中结果,将度值排名靠前化合物野黄芩素四甲醚(Scutellarein-4-Methylether)、通关苷元(Tenasogenin)、芥子酸(Sinapic Acid)、苦绳苷元(Dresgenin)、山奈酚(Kaempferol)分别与基因IL6、PTGS2、JUN、ESR1、MMP9进行分子对接。对接结果如图5A所示,除PTGS2与野黄芩素四甲醚、芥子酸的结合自由能大于−5 kcal/mol,其余化合物与蛋白质受体结合能均低于−5 kcal/mol,有良好的结合活性。部分分子对接可视化结果如图5B所示。
Exploring the mechanism of Marsdenia tenacissima in the treatment of hepatocellular carcinoma based on network pharmacology
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摘要:
目的 通过生物信息学、网络药理学和分子对接技术研究通关藤治疗肝细胞癌(HCC)的作用机制。 方法 通过文献检索和ADME平台筛选通关藤活性成分并利用Swiss Target Prediction预测化合物的作用靶点;从GEO数据库获得HCC数据芯片GSE147888并筛选表达差异显著基因;通过Genecards和OMIM数据库获得HCC疾病相关靶点;Venny在线对上述靶点取交集。利用Cytoscape软件和String数据库构建药物成分-靶点网络图和PPI网络图;利用R软件进行GO功能富集分析和KEGG通路富集分析;利用GEPIA数据库对靶基因进行生存分析,筛选在HCC生存率中显著差异表达的基因,并用Proteinatlas数据库分析基因在HCC组织中免疫组化表达情况;将排名前5的靶蛋白与对应药物活性成分进行分子对接验证。 结果 共筛选通关藤活性成分50个,药物与疾病交集靶基因12个。通关藤治疗HCC的重要成分有野黄芩素四甲醚、通关苷元、芥子酸、苦绳苷元、山奈酚等,关键基因有JUN、MMP9、PTGS2等。GO、KEGG分析结果显示,关键靶点主要涉及基因沉默调节、炎症反应调节等过程,主要富集在IL-17、TNF等信号通路。生存分析显示ESR1、MMP1、MMP9、JUN、PPARG在高低风险组之间有显著差异。免疫组化结果显示ESR1和MMP9在正常组织和肝癌组织中差异表达。分子对接结果验证了药物活性成分与靶蛋白可稳定结合。 结论 研究体现了中草药通关藤治疗HCC的多成分、多靶点、多通路的特点,为通关藤在HCC的临床应用中提供科学依据。 Abstract:Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC. -
表 1 通关藤活性成分信息
编号 化合物名称 Simles结构式 1 2,4-Decadienal(2,4-癸二烯醛) CCCCC/C=C/C=C/C=O 2 2,4-Dihydroxybenzoic Acid(2,4 -二羟基苯甲酸) C1=CC(=C(C=C1O)O)C(=O)O 3 2,6-Dihydroxybenzoic Acid(2,6 -二羟基苯甲酸) C1=CC(=C(C(=C1)O)C(=O)O)O 4 3,4-Dihydroxybenzoic Acid(3,4 -二羟基苯甲酸) C1=CC(=C(C=C1C(=O)O)O)O 5 Betulinic Acid(白桦脂酸) CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)O)C)C(=O)O 6 Caffeic Acid(咖啡酸) C1=CC(=C(C=C1/C=C/C(=O)O)O)O 7 Chlorogenic Acid(绿原酸) C1C(C(C(CC1(C(=O)O)O)OC(=O)C=CC2=CC(=C(C=C2)O)O)O)O 8 Cissogenin(西索苷元) CC(C1CCC2(C1(C(C(C3C2CC=C4C3(CCC(C4)O)C)O)O)C)O)O 9 Conduritol(环己烯四醇) C1=CC(C(C(C1O)O)O)O 10 D(+)-Digitoxose(D (+)-洋地黄毒糖) CC(C(C(CC=O)O)O)O 11 Daucosterol(胡萝卜甾醇) CCC(CCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)OC5C(C(C(C(O5)CO)O)O)O)C)C)C(C)C 12 D-Cymarose(加拿大麻糖) CC(C(C(CC=O)OC)O)O 13 Dihydrosarcostin(二氢肉珊瑚苷元) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)O)C)O)O)O 14 Dresgenin(苦绳甙元) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)OC(=O)C5=CC=CC=C5)C)O)O)O 15 Drevogenin A(南山藤皂苷元A) CC(C)CC(=O)OC1C(C2C(CC=C3C2(CCC(C3)O)C)C4(C1(C(CC4)C(=O)C)C)O)OC(=O)C 16 Drevogenin Q(南山藤皂苷元Q) CC(C)CC(=O)OC1C2C(CC=C3C2(CCC(C3)O)C)C4(CCC(C4(C1OC(=O)C)C)C(=O)C)O 17 D-Thevetose(D-黄花夹竹桃糖) CC(C(C(C(C=O)O)OC)O)O 18 Galactitol(半乳糖醇) C(C(C(C(C(CO)O)O)O)O)O 19 Gallic Acid(没食子酸) C1=C(C=C(C(=C1O)O)O)C(=O)O 20 Kaempferol(山奈酚) C1=CC(=CC=C1C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O)O 21 Kaempferol-4'-Methylether(山柰酚-4-甲醚) COC1=CC=C(C=C1)C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O 22 Lupeol(羽扇豆醇) CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)OC(=O)C6=
CC=CC=C6)C)C23 Marsectobiose(直立牛奶菜双糖) CC1C(C(C(C(O1)OC(C(C)O)C(CC=O)OC)O)OC)O 24 Marstenacigenin A(二氢肉珊瑚苷元的衍生物) CC(C1(CCC2(C1(C(CC3C2(CCC4C3(CCC(C4)O)C)O)C(=O)C=CC5=CC=CC=C5)C)O)O)O 25 Methyl Shikimate(莽草酸甲酯) COC(=O)C1=CC(C(C(C1)O)O)O 26 Nerolidol(橙花叔醇) CC(=CCCC(=CCCC(C)(C=C)O)C)C 27 Oleandrose(齐墩果糖) CC(C(C(CC=O)OC)O)O 28 P-Hydroxycinnamic Acid(对羟基肉桂酸) C1=CC(=CC=C1C=CC(=O)O)O 29 Propionic Acid(丙酸) CCC(=O)O 30 Protocatechualdehyde(中原儿茶醛) C1=CC(=C(C=C1C=O)O)O 31 Scopoletin(东莨菪素) COC1=C(C=C2C(=C1)C=CC(=O)O2)O 32 Scutellarein-4-Methylether(灯盏乙素-4-甲醚) COC1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C=C(C(=C3O)O)O 33 Shikimic Acid(莽草酸) C1C(C(C(C=C1C(=O)O)O)O)O 34 Sinapic Acid(芥子酸) COC1=CC(=CC(=C1O)OC)C=CC(=O)O 35 Stigmasterol(豆甾醇) CCC(C=CC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C)C(C)C 36 Succinic Acid(琥珀酸) C(CC(=O)O)C(=O)O 37 Syringic Acid(丁香酸) COC1=CC(=CC(=C1O)OC)C(=O)O 38 Taraxasterol(蒲公英甾醇) CC1C2C3CCC4C5(CCC(C(C5CCC4(C3(CCC2(CCC1=C)C)C)C)(C)C)O)C 39 Tenacigenin B(通光散苷元B) CC(=O)C1CCC23C1(C(C(C4C2(O3)CCC5C4(CCC(C5)O)C)O)O)C 40 Tenacigenin D(通光散苷元D) CCC(C)C(=O)OC1C2C3(CCC(=O)CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)C 41 Tenacissoside A(通关藤皂苷A) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)OC8C(C(C(C(O8)CO)O)O)O)OC)O)OC)C 42 Tenacissoside B(通关藤皂苷B) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C(=CC)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)OC8C(C(C(C(O8)CO)O)O)O)OC)O)OC)C 43 Tenacissoside G(通关藤皂苷G) CC=C(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)O)OC)O)OC)C 44 Tenacissoside H(通关藤皂苷H) CCC(C)C(=O)OC1C2C3(CCC(CC3CCC24C5(O4)CCC(C5(C1OC(=O)C)C)C(=O)C)OC6CC(C(C(O6)C)OC7C(C(C(C(O7)C)O)OC)O)OC)C 45 Tenacissoside I(通关藤皂苷I) CC1C(C(C(C(O1)OC2C(OC(CC2OC)OC3CCC4(C(C3)CCC56C4C(C(C7(C5(O6)CCC7C(=O)C)C)OC(=O)C)OC(=O)C8=CC=CC=C8)C)C)O)OC)O 46 Tenasogenin(通关苷元) CC(C1CCC2(C1(C(C(C3C2CC=C4C3(CCC(C4)O)C)OC(=O)C=C(C)C)O)C)O)O 47 Vanillic Acid(香草酸) COC1=C(C=CC(=C1)C(=O)O)O 48 β-Amyrin(β-香树脂醇) CC1(CCC2(CCC3(C(=CCC4C3(CCC5C4(CCC(C5(C)C)O)C)C)C2C1)C)C)C 49 β-Sitosterol(β-谷甾醇) CCC(CCC(C)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C)C(C)C 50 17β-Tenacissoside B(17β-通光藤皂苷B) O[C@H]1CC[C@]2(C(C1)CC[C@@]13C2[C@H](O)[C@@H](O)[C@]2([C@]3(O1)CC[C@@H]2C(=O)C)C)C -
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