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Issues in phytotherapy
The part of pharmacognosy focusing on use of crude extracts or semi-pure mixtures originating from nature, namely phytotherapy, is probably the best known and also the most debated area in pharmacognosy. Although phytotherapy is sometimes considered as alternative medicine, when critically conducted, it can be considered the scientific study on the effects and clinical use of herbal medicines.
Constituents and drug synergysm
One characteristic of crude drug material is that constituents may have an opposite, moderating or enhancing effect. Hence, the final effect of any crude drug material will be a product of the interactions between the constituents and the effect of each constituent on its own. To effectively study the existence and affect of such interactions, scientific studies must examine the effect that multiple constituents, given concurrently, have on the system. Herbalists assert that as phytopharmaceuticals rely upon synergy for their activities, plants with high levels of active constituents like ginsenosides or hypericin may not correlate with the strength of the herbs. In phytopharmaceutical or herbal medicine, the therapeutic effects of herbs cannot be determined unless its active ingredient or cofactors are identified or the herb is administered as a whole. One way to indicate strength is standardization to one or several marker compound that are believed to be mainly responsible for the biological effects. However many herbalists believe that the active ingredient in a plant is the plant itself.[3]
Herb and drug interactions
A study of herb drug interactions indicated that the vast majority of drug interactions occurred in four classes of drugs, the chief class being blood thinners, but also including protease inhibitors, cardiac glycosides and the immuno-suppressant ciclosporin.[4] [5]
Natural products chemistry
Most bioactive compounds of natural origin are secondary metabolites, i.e., species-specific chemical agents that can be grouped into various categories[citation needed]. A typical protocol to isolate a pure chemical agent from natural origin is bioassay-guided fractionation, meaning step-by-step separation of extracted components based on differences in their physicochemical properties, and assessing the biological activity, followed by next round of separation and assaying. Typically, such work is initiated after a given crude drug formulation (typically prepared by solvent extraction of the natural material) is deemed "active" in a particular in vitro assay. If the end-goal of the work at hand is to identify which one(s) of the scores or hundreds of compounds are responsible for the observed in vitro activity, the path to that end is fairly straightforward: 1. fractionate the crude extract, e.g. by solvent partitioning or chromatography. 2. test the fractions thereby generated with in vitro assay. 3. repeat steps 1) and 2) until pure, active compounds are obtained. 4. determine structure(s) of active compound(s), typically by using spectroscopic methods. In vitro activity does not necessarily translate to activity in humans or other living systems.
The most common means for fractionation are solvent-solvent partitioning and chromatographic techniques such as high-performance liquid chromatography (HPLC), medium-pressure liquid chromatography, "flash" chromatography, open-column chromatography, vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), with each technique being most appropriate for a given amount of starting material. Countercurrent chromatography (CCC) is particularly well-suited for bioassay-guided fractionation because, as an all-liquid separation technique, concern about irreversible loss or denaturation of active sample components is minimized. After isolation of a pure substance, the task of elucidating its chemical structure can be addressed. For this purpose, the most powerful methodologies available are nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS)[citation needed]. In the case of drug discovery efforts, structure elucidation of all components that are active in vitro is typically the end goal. In the case of phytotherapy research, the investigator may use in vitro BAGF as a tool to identify pharmacologically interesting or important components of the crude drug. The work does not stop after structural identification of in vitro actives, however. The task of "dissecting and reassembling" the crude drug one active component at a time, in order to achieve a mechanistic understanding of how it works in phytotherapy, is quite daunting. This is because it is simply too difficult, from cost, time, regulatory, and even scientific perspectives, to study experimental fractions of the crude drug in humans. In vitro assays are therefore used to identify chemical components of the crude drug that may rationally be expected to have a given pharmacological effect in humans, and to provide a rational basis for standardization of a crude drug formulation to be tested in [and sold/marketed to] humans.