Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma
ABSTRACT Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action.
We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r(2) = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of approximately 1,000 mm(3) from 16 to 47 days (P < 0.001).
Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted.
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ABSTRACT: Wogonin (Wog; 5,7-dihydroxy-8-methoxy flavone) has been shown to effectively inhibit lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) gene expression and nitric oxide production in our previous study. In the present study, we found that Nor-wogonin (N-Wog; 5,7,8-trihydroxyl flavone), a structural analogue of Wog with an OH substitution at C8, performed different effect on LPS- or lipoteichoic acid (LTA)-induced iNOS gene expression and nitric oxide (NO) production in macrophages. Wog, but not N-Wog, significantly inhibits LPS- or LTA-induced NO production through suppressing iNOS gene expression at both protein and mRNA without affecting NO donor sodium nitroprusside-induced NO production, NOS enzyme activity, and cells viability. Activation of JNKs (not ERKs) via phosphorylation induction, and an increase in c-Jun (not c-Fos) protein expression were involved in LPS- and LTA-treated RAW264.7 cells, and those events were blocked by Wog, but not N-Wog, addition. Furthermore, 5,7-diOH flavone, but not 5-OH flavone, 7-OH flavone, 5-OH-7-OCH(3) flavone, significantly inhibits LPS-induced iNOS protein expression and NO production, and 7,8-diOCH(3) flavone performs more effective inhibitory activity on LPS-induced NO production and iNOS protein expression than 7-OCH(3)-8-OH flavone. These data suggest that OHs at both C5 and C7 are essential for NO inhibition of flavonoids, and OCH(3) at C8 may contribute to this activity, and suppression of JNKs-c-Jun activation is involved.International Immunopharmacology 09/2007; 7(8):1054-63. DOI:10.1016/j.intimp.2007.04.001 · 2.71 Impact Factor
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ABSTRACT: Transgenic hairy root lines from Scutellaria baicalensis overexpressing phenylalanine ammonia-lyase (PAL) (SbPAL1, SbPAL2, and SbAPL3) were established using an Agrobacterium rhizogenes-mediated transformation system. Stable genetic transformation with the SbPAL genes was confirmed by real-time PCR. These transgenic hairy root lines produced higher quantities flavones (i.e., baicalin, baicalein, and wogonin) than the control hairy root line. In particular, the wogonin content was increased by 4-11 times in the SbPAL1-, SbPAL2-, and SbPAL3-overexpressing hairy roots than the S. baicalensis wild-type roots. This research showed the importance of PAL in flavone biosynthesis and demonstrated the efficiency of metabolic engineering in S. baicalensis hairy roots.PROCESS BIOCHEMISTRY 12/2012; 47(12):2575–2580. DOI:10.1016/j.procbio.2012.09.026 · 2.52 Impact Factor
- Evidence-based Complementary and Alternative Medicine 03/2013; · 2.18 Impact Factor