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Abstract：
BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of human death worldwide. Herbal prescription SH003 has been developed to treat several cancers including NSCLC. Due to the multi-component nature of SH003 with multiple targets and pathways, a network pharmacology study was conducted to analyze its active compounds, potential targets, and pathways for the treatment of NSCLC.
METHODS: We systematically identified oral active compounds within SH003, employing ADME criteria-based screening from TM-MC, OASIS, and TCMSP databases. Concurrently, SH003-related and NSCLC-associated targets were amalgamated from various databases. Overlapping targets were deemed anti-NSCLC entities of SH003. Protein-protein interaction networks were constructed using the STRING database, allowing the identification of pivotal proteins through node centrality measures. Empirical validation was pursued through LC-MS analysis of active compounds. Additionally, in vitro experiments, such as MTT cell viability assays and western blot analyses, were conducted to corroborate network pharmacology findings.
RESULTS: We discerned 20 oral active compounds within SH003 and identified 239 core targets shared between SH003 and NSCLC-related genes. Network analyses spotlighted 79 hub genes, including TP53, JUN, AKT1, STAT3, and MAPK3, crucial in NSCLC treatment. GO and KEGG analyses underscored SH003\'s multifaceted anti-NSCLC effects from a genetic perspective. Experimental validations verified SH003\'s impact on NSCLC cell viability and the downregulation of hub genes. LC-MS analysis confirmed the presence of four active compounds, namely hispidulin, luteolin, baicalein, and chrysoeriol, among the eight compounds with a median of > 10 degrees in the herb-compounds-targets network in SH003. Previously unidentified targets like CASP9, MAPK9, and MCL1 were unveiled, supported by existing NSCLC literature, enhancing the pivotal role of empirical validation in network pharmacology.
CONCLUSIONS: Our study pioneers the harmonization of theoretical predictions with practical validations. Empirical validation illuminates specific SH003 compounds within NSCLC, simultaneously uncovering novel targets for NSCLC treatment. This integrated strategy, accentuating empirical validation, establishes a paradigm for in-depth herbal medicine exploration. Furthermore, our network pharmacology study unveils fresh insights into SH003\'s multifaceted molecular mechanisms combating NSCLC. Through this approach, we delineate active compounds of SH003 and target pathways, reshaping our understanding of its therapeutic mechanisms in NSCLC treatment.
METHODS: We systematically identified oral active compounds within SH003, employing ADME criteria-based screening from TM-MC, OASIS, and TCMSP databases. Concurrently, SH003-related and NSCLC-associated targets were amalgamated from various databases. Overlapping targets were deemed anti-NSCLC entities of SH003. Protein-protein interaction networks were constructed using the STRING database, allowing the identification of pivotal proteins through node centrality measures. Empirical validation was pursued through LC-MS analysis of active compounds. Additionally, in vitro experiments, such as MTT cell viability assays and western blot analyses, were conducted to corroborate network pharmacology findings.
RESULTS: We discerned 20 oral active compounds within SH003 and identified 239 core targets shared between SH003 and NSCLC-related genes. Network analyses spotlighted 79 hub genes, including TP53, JUN, AKT1, STAT3, and MAPK3, crucial in NSCLC treatment. GO and KEGG analyses underscored SH003\'s multifaceted anti-NSCLC effects from a genetic perspective. Experimental validations verified SH003\'s impact on NSCLC cell viability and the downregulation of hub genes. LC-MS analysis confirmed the presence of four active compounds, namely hispidulin, luteolin, baicalein, and chrysoeriol, among the eight compounds with a median of > 10 degrees in the herb-compounds-targets network in SH003. Previously unidentified targets like CASP9, MAPK9, and MCL1 were unveiled, supported by existing NSCLC literature, enhancing the pivotal role of empirical validation in network pharmacology.
CONCLUSIONS: Our study pioneers the harmonization of theoretical predictions with practical validations. Empirical validation illuminates specific SH003 compounds within NSCLC, simultaneously uncovering novel targets for NSCLC treatment. This integrated strategy, accentuating empirical validation, establishes a paradigm for in-depth herbal medicine exploration. Furthermore, our network pharmacology study unveils fresh insights into SH003\'s multifaceted molecular mechanisms combating NSCLC. Through this approach, we delineate active compounds of SH003 and target pathways, reshaping our understanding of its therapeutic mechanisms in NSCLC treatment.
摘要：
背景：非小细胞肺癌（NSCLC）是世界范围内人类死亡的主要原因之一。草药处方SH003已被开发用于治疗包括NSCLC在内的几种癌症。由于SH003具有多种靶标和途径的多组分性质，进行了网络药理学研究以分析其活性化合物，潜在目标,和治疗非小细胞肺癌的途径。
方法：我们采用基于ADME标准的TM-MC筛选，系统地鉴定了SH003中的口服活性化合物，绿洲,和TCMSP数据库。同时,SH003相关和NSCLC相关靶标从各种数据库合并。重叠的靶标被认为是SH003的抗NSCLC实体。使用STRING数据库构建蛋白质-蛋白质相互作用网络，允许通过节点中心性措施鉴定关键蛋白质。通过活性化合物的LC-MS分析进行经验验证。此外,体外实验，如MTT细胞活力测定和蛋白质印迹分析，是为了证实网络药理学的发现。
结果：我们发现了SH003中的20种口服活性化合物，并确定了SH003和NSCLC相关基因之间共有的239种核心靶标。网络分析聚焦了79个集线器基因，包括TP53，JUN，AKT1、STAT3和MAPK3在NSCLC治疗中至关重要。GO和KEGG分析从遗传角度强调了SH003的多方面抗NSCLC作用。实验验证验证了SH003对NSCLC细胞活力和hub基因下调的影响。LC-MS分析证实了四种活性化合物的存在，即hispidulin，木犀草素,黄芩素,和chrysoeriol,在SH003的草药-化合物-靶标网络中中位数>10度的八种化合物中。CASP9，MAPK9和MCL1等以前身份不明的目标被公布，现有非小细胞肺癌文献支持，增强经验验证在网络药理学中的关键作用。
结论：我们的研究开创了理论预测与实际验证的协调。经验验证阐明了NSCLC中特定的SH003化合物，同时发现NSCLC治疗的新靶点。这种综合战略，强调经验验证，为深入的草药探索建立了范式。此外，我们的网络药理学研究揭示了SH003对抗NSCLC的多方面分子机制的新见解.通过这种方法，我们描述了SH003的活性化合物和靶途径，重塑我们对其在NSCLC治疗中的治疗机制的理解。
方法：我们采用基于ADME标准的TM-MC筛选，系统地鉴定了SH003中的口服活性化合物，绿洲,和TCMSP数据库。同时,SH003相关和NSCLC相关靶标从各种数据库合并。重叠的靶标被认为是SH003的抗NSCLC实体。使用STRING数据库构建蛋白质-蛋白质相互作用网络，允许通过节点中心性措施鉴定关键蛋白质。通过活性化合物的LC-MS分析进行经验验证。此外,体外实验，如MTT细胞活力测定和蛋白质印迹分析，是为了证实网络药理学的发现。
结果：我们发现了SH003中的20种口服活性化合物，并确定了SH003和NSCLC相关基因之间共有的239种核心靶标。网络分析聚焦了79个集线器基因，包括TP53，JUN，AKT1、STAT3和MAPK3在NSCLC治疗中至关重要。GO和KEGG分析从遗传角度强调了SH003的多方面抗NSCLC作用。实验验证验证了SH003对NSCLC细胞活力和hub基因下调的影响。LC-MS分析证实了四种活性化合物的存在，即hispidulin，木犀草素,黄芩素,和chrysoeriol,在SH003的草药-化合物-靶标网络中中位数>10度的八种化合物中。CASP9，MAPK9和MCL1等以前身份不明的目标被公布，现有非小细胞肺癌文献支持，增强经验验证在网络药理学中的关键作用。
结论：我们的研究开创了理论预测与实际验证的协调。经验验证阐明了NSCLC中特定的SH003化合物，同时发现NSCLC治疗的新靶点。这种综合战略，强调经验验证，为深入的草药探索建立了范式。此外，我们的网络药理学研究揭示了SH003对抗NSCLC的多方面分子机制的新见解.通过这种方法，我们描述了SH003的活性化合物和靶途径，重塑我们对其在NSCLC治疗中的治疗机制的理解。
