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More on milk thistle studies TNF alpha inhibition,antiandrogen

Silymarin inhibits TNF-alpha-induced expression of adhesion molecules in human umbilical vein endothelial cells.
FEBS Lett. 2003 Aug 28;550(1-3):89-93.
Silymarin is known to have an anti-atherosclerotic activity, but the mechanism responsible for it remains unclear. Here, we demonstrate a possible mechanism involved in the anti-atherosclerotic activity of silymarin. Silymarin inhibited THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs). Silymarin also suppressed the TNF-alpha-induced protein and mRNA expression of adhesion molecules, such as VCAM-1, ICAM-1 and E-selectin, in HUVECs. Moreover, silymarin suppressed the TNF-alpha-induced DNA binding of NF-kappaB/Rel in HUVECs. Taken together, these results demonstrate that silymarin exerts an anti-atherosclerotic activity, at least in part, by inhibiting the expression of adhesion molecules.

Characterization of Chemical Constituents in Scutellaria baicalensis with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma
Michael Bonham1, Jeff Posakony1, Ilsa Coleman1, Bruce Montgomery3, Julian Simon1 and Peter S. Nelson1,2
Authors’ Affiliations: Divisions of 1 Human Biology and 2 Clinical Research, Fred Hutchinson Cancer Research Center and 3 Department of Medicine and Oncology, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington

Requests for reprints: Peter S. Nelson, Division of Human Biology, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue North, Seattle, WA 98109-1024. Phone: 206-667-3506; Fax: 206-685-7344; E-mail: pnelson@fhcrc.org.


Materials and Methods

Purpose: 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.

Experimental Design and Results: 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 (r2 = 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 1,000 mm3 from 16 to 47 days (P < 0.001).

Conclusions: 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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