Natural or herbal medicines are the most ancient form of health remedies known to humanity. In spite of the great advances achieved in modern medicine, plants still make an important contribution to healthcare, and several specific herbal extracts have demonstrated to be efficacious for specific conditions.

Given the nature of products of plant origin, which are highly variable and complex with numerous biologically active components, rarely completely identified, therapeutic results and safety issues vary greatly from product to product, even within a single class. Therefore, the evidence of both benefits and risks are specific to the product tested, and cannot necessarily be extrapolated to other products as is the case for synthetically derived compounds.

For these reasons, and due to the inherent variability of the constituents of herbal products, it is difficult to establish quality control parameters; and batch-to-batch variation, in the absence of reference standards for identification, can start from the collection of raw material, and increase during storage and further processing. Therefore, to minimize variation in final botanical products, standardization of procedures should cover the entire field of study from cultivation of the medicinal plant to its clinical application

Herbal Medicinal Products
Herbal medicinal products (HMP) contain as active ingredients herbal drugs (e.g. parts of plants) or herbal drug preparations (like extracts, essential oils, etc.). HMP contain complex mixtures of organic chemicals (the phytocomplex) that work together to produce an effect on the body, and that are rarely completely identified.

The activity of the phytocomplex is usually stronger than the sum of activity of the single active molecules and the presence of substances apparently having no specific activity can have a very important synergistic effect. Because of the complexity and the synergy of the phytocomplex, HMP are frequently used to treat chronic diseases, and normally do not possess an immediate or strong pharmacological action. Herbal medicines are sold in many forms (fresh, dried, liquid/solid extracts, tablets, capsules, powders, tea bags, topical) and may not contain chemically-defined substances such as synthetic compounds or chemicals isolated from herbs.

Although it is generally believed that most herbal preparations are safe for consumption, some herbs like most biologically active substances could be toxic with undesirable side effects, which are mainly due to active ingredients, contaminants and/or interactions with other drugs. Therefore, the use of herbal medicinal products should be carefully monitored to ensure patient safety.

Variability
Plants are highly variable in their content of the numerous biologically active components, and depending on their origin, the growth conditions and the date of harvest, the content of active components in herbal drugs and herbal preparations will be influenced. Cultivated medicinal plants have specific advantages over wild-harvested plants: they show smaller variation in their constituents due to greater genetic uniformity, and the main secondary metabolites can be monitored, allowing for definition of the best period for harvesting and are therefore generally preferred.

The risk of misidentification of plants is also avoided, and unsustainable harvesting limited. Controlled growth systems also allow manipulation of the phenotypic variation in the concentration of medicinally important compounds present at harvest, to increase potency, reduce toxin levels and increase uniformity and predictability of extracts. However, as the majority of medicinal plants are still harvested from the wild, it is important to use standardized extracts, and to ensure that strict guidelines on good agricultural and collection practices are followed, as the ones provided by the WHO and the European Medicines Agency (EMEA), which cover the cultivation of medicinal plants, as well as their harvesting and post-harvesting processes.

Medicinal products are pharmaceutically equivalent (phytoequivalence) if they contain the same amount of the same active substance(s) in the same dosage forms that meet the same or comparable standards. Unfortunately, phytoequivalence is very difficult to be obtained as phytochemical profiles are so complex, and closely linked to the way the ‘seed to patient’ process has been followed. It is a common experience that batches of medicinal plants with similar specifications, as species and part of plant, may have quite different chemical compositions due to a number of factors such as: Inter- or intra-species variation, Environmental factors, Time of harvesting, Part of plant used, post-harvesting factors: Storage conditions and processing treatments can greatly affect the quality of a herbal ingredient.

One example is St. John’s wort (Hypericum perforatum L). Few studies demonstrated St. John’s wort products available in the U.S. and Australian markets have their hyperforin content varied from 0.01% to 1.89%, and only two products contained sufficient hyperforin likely to be required for antidepressant effects. Similarly, the content of the other active component hypericin varied from 0.03% to 0.29% and, for several products, the actual hypericin content did not correlate with that stated on the product label (range 57–130% of label claim)

Way Forward
Variability and consistent product quality can only be achieved through controlling the “seed to patient” model. Different concentrations of the proportion of constituents in herbal medicine may lead to great variations in therapeutic results and safety issues, and consequently, the evidence of both benefits and risks are specific to the product tested, and cannot necessarily be extrapolated to other products as is the case for synthetically derived compounds, or assume that clinical trials with one brand are relevant to any other product. Health practitioners should become more aware of these issues, in order to recommend to their patients only the exact products that have been consistently proven safe and efficacious in clinical trials conducted according to good clinical practice (GCP).

(Adopted and modified from the submitted book chapter by Ghosh & Zangara (2013), “Role of Seed to patient model in clinically proven natural medicines.”)