CAM Herbal Cocktails for Boosting Antioxident Activity to Treat Liver Disease

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DESCRIPTION (provided by applicant): This application concerns the exploration of a novel strategy to increase the normally low bioavailability of polyphenolic antioxidants contained in botanical products by using knowledge of their metabolism to target specific herbal-herbal interactions. A major limitation of many prior clinical investigations is their use of inadequate oral dose regimens that failed to account for the rapid elimination and low bioavailability of polyphenolic antioxidants that results in low steady-state exposures to these potentially protective compounds and presumably accounts for their lack of efficacy. The rationale design of CAM herbal cocktails should result in dramatic increases in the steady-state concentrations of these potent antioxidants in additive or synergistic pharmacodynamic effects that may be common or unique for each of the botanical products contained in the cocktail. More than 50% of patients with chronic hepatitis C either have contraindications or do not achieve sustained virological response to therapy and would potentially benefit from the availability of alternative medicines. Our hypothesis is that the coadministration of silymarin with a CAM cocktail containing a structurally diverse mixture of polyphenolic natural products will boost silymarin's antioxidant activity either through pharmacokinetic interactions that will slow elimination pathways for silymarin, or through pharmacodynamic interactions that result from the antioxidant or other beneficial properties of the CAM cocktail that are additive or synergistic with silymarin. The goal of the proposed double blind, placebo controlled, randomized clinical trial is to describe the pharmacokinetics, and to demonstrate the safety, tolerability, and antioxidant activity of a CAM herbal cocktail in patients with chronic hepatitis C genotype 1 infection and who have not received prior peginterferon-based therapies. In Specific Aim 1 we will perform a pharmacokinetic study that will determine the effects of a CAM herbal cocktail containing milk thistle and green tea extracts on the exposures of patients to major silymarin flavonolignans. For Specific Aim 2, we will identify and use an optimal procedure for the assay of 8-isoprostane F2, as a measure of oxidative stress, to determine the antioxidant activity of the CAM herbal cocktail in patients with chronic HCV. The goal of this study is to provide an alternative medicine for patients with hepatitis C where treatment options are unavailable. PUBLIC HEALTH RELEVANCE: Regardless of the positive public perceptions regarding the safety and efficacy of botanical products, data on the use of high doses of herbal combinations to optimize health outcomes are lacking and vigilance regarding adverse effects is warranted. The goal of this proposal is to evaluate the safety, tolerability, and effectiveness of potentially beneficial herbal-herbal interactions using high dose herbal cocktails for the treatment of liver diseases where treatment options are not available.