Vitro Inhibition with Botanical Products

Therapeutic Products Directorate, Health Canada and Centre for Research in Biopharmaceuticals and Biotechnology, University of Ottawa, Ottawa, Ontario, Canada 

Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada 

The nature of plants having secondary metabolites as defensive agents greatly increases the expectation that there will be interactions with other botanical products and drugs. If well-established traditional botanical products are used according to directions, they are likely a low risk. Risk increases when botanical products are combined with conventional drug therapies and lies in the possibility of unknown natural product-drug interactions. Other risks include product deviation due to misidentification of species, the lack of standardization, or adulteration. Most of the interactions have been reported with cytochrome P-450 (CYP) 3A4, but there are interactions with other metabolism enzymes and transport proteins. 

The intent of this review is to provide an understanding of what constitutes a representative product, experimental test conditions, and the presence 

---

Danshen, the dried root and rhizome of S. miltiorrhizae (Fig. 2), is another Chinese botanical product used for its ability to alleviate menstrual irregularities, as well as for its vasodilative and hypotensive functions in a variety of cardiovascular conditions (8). The botanical product had also been shown to inhibit platelet aggregation in vitro (9). Danshen is widely available in different preparations for oral consumption, with usual dose range of 9 to 15 g per decoction. In addition, its increasing popularity is reflected by its availability even in Chinese cigarettes (10). 

Recruit volunteers who met entrance requirements 2. Screen botanical ingredients for inhibition of IL-1 p production 3. Pilot clinical evaluation of IL-1 inhibitory lead candidate botanicals from activity 2 Establishing a clinical genotyped database Human monocyte cell lines stimulated in vitro with LPS Clinical + laboratory assay of peripheral blood mononuclear cells (PBMCs), and plasma Adequate number of healthy subjects with CRP = 2-10 mg/L and stratified by IL1 composite genotype Select lead candidate botanicals based on IL-1 protein inhibitory dose compared to untreated cultures IL1 gene expression in PBMCs and ex vivo IL-1 production in plasma from test subjects after 2-week dosing of candidate botanicals... 

Screening involved evaluation of 220 candidate botanical ingredients in vitro for their ability to inhibit ILlp gene expression in human mononuclear cells (U937 and THP-1) that were stimulated with lipopolysaccharide (LPS) (Table 11.1, activity 2). The ingredient list was narrowed to twenty-six botanicals that had a 50% inhibitory concentration of <10 pg/ml in the in vitro IL-1 production assay. The potential IL-1 inhibitors were further narrowed to four botanicals (artichoke leaf extract, nettle root extract, olive fruit extract, and rose hips extract) based on criteria such as reliability of sourcing, purity, and others that might contribute to commercial potential. 

---