Diterpenoids from Scutellaria barbata induce tumour-selective cytotoxicity by taking the brakes off apoptosis

Medicinal plants are an excellent source of structurally diverse,bio-active compounds with potential in the fight against cancer.One of the most promising is Scutellaria barbata,prescribed traditionally for the treatment of cancers.Scutebarbatine A is the major diterpenoid,produced in specialized large,peltate trichomes on leaves of S.barbata.It induces dose-dependent apoptosis,specifically in cancer cells.The major class of proteins down-regulated are pro-survival proteins,the Inhibitors of Apoptosis(IAPs),and IAP regulating proteins.We propose that scutebarbatine A works by releasing the molecular brakes(the IAPs)on apoptosis in cell death-evading cancer cells.Comparison between the cytotoxicity of methanolic extracts of S.barbata leaves and decoctions(Ban Zhi Lian)prepared traditionally,showed substantially different chemical compositions and differential induction of apoptosis.Analyses suggest polyvalency between the constituents in both extracts,and ways to produce enhanced chemopreventive preparations for the treatment of cancer.

Two CYP82D Enzymes Function as Flavone Hydroxylases in the Biosynthesis of Root-Specific 4＇-Deoxyflavones in Scutellaria baicalensis

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.