The National Center for Complementary and Alternative Medicine (NCCAM) of the US National Institutes of Health (NIH) has designated several herbs as funding priorities for a recent $8.1 million grant project.¹ “Mechanistic Research on CAM Natural Products” is sponsored by NCCAM, the National Cancer Institute (NCI), and the Office of Dietary Supplements (ODS).² It funds only research on the action mechanisms of natural products, so studies on products’ clinical efficacy will not be funded by this particular project. Acceptance of applications began November 1, 2010. (More information on the grant and its various due dates is available here.)

While the investigation of herbs’ and other CAM products’ efficacy is essential and ongoing at NCCAM, understanding how the substances work in humans to produce specific outcomes is also important.² And, according to NIH’s grant announcement, “Despite the widespread use of these products, insight into potential biological mechanisms of action frequently is lacking.” Additionally, the composition of many natural products, botanicals especially, is complex and makes understanding their action mechanisms significantly more difficult.

NCCAM has listed the following herbs as areas of priority in regards to the mechanistic research grant project.¹ Below are more details on what types of research NCCAM is focusing on funding with the grant.

• Ashwagandha (Withania somnifera)
• Astragalus (Astragalus membranaceus)
• Devil's claw (Harpagophytum procumbens)
• Echinacea (Echinacea purpurea)
• Ginseng, Asian & American (Panax ginseng, P. quinquefolius)
• Hops (Humulus lupulus)
• Milk thistle (Silybum marianum)
• Thunder god vine (Tripterygium wilfordii)
• Turmeric (Curcuma longa)

More specifically, NCCAM will focus on funding ashwagandha research that investigates whether a more systemic type of activity is responsible for the herb’s diverse effects on the body, which include anti-leishmanial activity, immune modulation, decreased anxiety, and possible prevention of neurodegenerative diseases and cancer. Accepted research might examine such physical responses to the herb as changes in gene, protein, or regulatory RNA expression or localization.

Though recent research has identified several active components of astragalus, NCCAM would like to fund research that aims to “fully characterize the bioactive compounds” of this herb and its activities and mechanisms of action, particularly looking at complex polysaccharides.

Research on devil’s claw funded by this particular NCCAM grant would, in part, aim to identify a biomarker of anti-inflammatory activity (other than the harpagoside compound), as well as study the herb’s documented analgesic properties, analgesic mechanisms of action, and the compounds responsible for these effects.

Because some in vitro activity of echinacea has depended on the plant part and extraction method used, funded studies would seek to identify both optimal species and extraction methods. Also, research would focus on identifying components responsible for immune activities and marker components for standardization and pharmacokinetics, and clarifying the biological signature.

As for ginseng research, NCCAM is encouraging investigations using systems biology approaches to study the potential action mechanisms of specific components, such as individual ginsenosides and ginseng-derived glycans or terpenoids from different ginseng species or preparations.

Prioritized hops research would seek to establish better understanding of its phytoestrogenic principles, including receptor or tissue specificity, and which components are responsible for any sedative activity and their action mechanisms.

Further, NCCAM will focus on funding milk thistle research that investigates the in vitro and in vivo activity of the plant’s individual components and how the components work collectively, as well as studies into mechanisms associated with the hepatoprotective and chemopreventive activities and the herb/drug interactions of silymarin, an extract of milk thistle.

Thunder god vine research that receives NCCAM funding from this particular grant would focus on identifying compounds other than triptolide that might influence the plant’s overall activity. Lastly, turmeric studies would investigate the metabolites responsible for activity and their tissue distribution, pharmacokinetics, and pharmacodynamics, as well as the bioavailability of individual curcuminoids compared with different formulations of mixtures and extracts.

Additional CAM areas of interest for the mechanistic action grant project include beta-glucans, coenzyme Q 10, polyphenols (e.g., flavonoids, catechins, anthocyanins), probiotics, polyunsaturated fatty acids (PUFAs), and vitamin D. According to NCCAM, this listing of research priority areas is not exhaustive and might change over time as new science emerges and brings with it new priorities. More detailed information on these research priorities, as well as examples of responsive projects funded by this grant is available here.

—Lindsay Stafford

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