目的通过网络药理学方法筛选小半夏汤治疗化疗性呕吐(chemotheraphy-induced nausea and vomiting,CINV)的活性成分,预测作用靶点,探讨其治疗CINV作用机制。方法通过中药系统药理学数据库等平台筛选小半夏汤的生物活性成分,利用CTD和OMI...目的通过网络药理学方法筛选小半夏汤治疗化疗性呕吐(chemotheraphy-induced nausea and vomiting,CINV)的活性成分,预测作用靶点,探讨其治疗CINV作用机制。方法通过中药系统药理学数据库等平台筛选小半夏汤的生物活性成分,利用CTD和OMIM数据库建立与恶心呕吐相关疾病靶点,从而构建小半夏汤有效药物-靶点-疾病网络,并用STRING数据库和DAVID数据库进行生物过程和信号通路分析。结果从数据库筛选出与治疗CINV有关的小半夏汤活性成分6种,作用于19个核心靶点,27条信号通路。显示小半夏汤治疗CINV主要与调控细胞凋亡、调节炎性反应应答及胃肠道黏膜修复、减轻胃肠道平滑肌痉挛等生物过程和信号通路有关。结论小半夏汤对CINV的治疗作用体现了中药多成分-多靶点-多途径的特点,为进一步探究小半夏汤治疗CINV机制提供实验研究依据和思路。展开更多
Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no eff...Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.展开更多
文摘目的通过网络药理学方法筛选小半夏汤治疗化疗性呕吐(chemotheraphy-induced nausea and vomiting,CINV)的活性成分,预测作用靶点,探讨其治疗CINV作用机制。方法通过中药系统药理学数据库等平台筛选小半夏汤的生物活性成分,利用CTD和OMIM数据库建立与恶心呕吐相关疾病靶点,从而构建小半夏汤有效药物-靶点-疾病网络,并用STRING数据库和DAVID数据库进行生物过程和信号通路分析。结果从数据库筛选出与治疗CINV有关的小半夏汤活性成分6种,作用于19个核心靶点,27条信号通路。显示小半夏汤治疗CINV主要与调控细胞凋亡、调节炎性反应应答及胃肠道黏膜修复、减轻胃肠道平滑肌痉挛等生物过程和信号通路有关。结论小半夏汤对CINV的治疗作用体现了中药多成分-多靶点-多途径的特点,为进一步探究小半夏汤治疗CINV机制提供实验研究依据和思路。
文摘Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.
