Fundamentals of Herbal Medicine

Biological screening for pharmacological activity Since the WHO “General guidelines for methodologies on research and evaluation of traditional medicine” was published in 2001, a lot of effort has been made to improve methods for evaluating medicinal plants. The WHO document clearly highlighted an apparent knowledge deficit in this area, stating that “the quantity and quality of the safety and efficacy data on traditional medicine are far from sufficient to meet the criteria needed to support its use worldwide”. For the most part, it appears that plant medicines are poorly understood by the scientific community and the general public, resulting in a number of studies with questionable conclusions and confusing information on the potential dangers or otherwise of isolated plant constituents. This explain the general misconception that since very little scientific data exists on the efficacy and safety of most herbal medicines, it is not really safe to use them. In an interesting paper published in 2001, Gyllenhaal pointed out the disappointingly low standards of clinical trials carried out with Panax ginseng for performance enhancement, diabetes and as an immunostimulant and Zingiber officinale for treating nausea and vomiting, a traditional Chinese herbal mixture for eczema and another Chinese herbal mixture for atopic dermatitis. A systematic review of twenty-six papers on these four Chinese preparations indicated that only the traditional Chinese herbal mixture for atopic dermatitis was effective. The results on all the other three preparations showed that effectiveness had not been conclusively shown. Gyllenhaal (2001) pointed out that the methodology of the clinical trials was flawed as it had been designed to give equivocal evidence regarding efficacy. The results of trials on Indian plants also showed that only about 30% of the trials were carried out with an acceptable design and protocol (Chaudhury, 2005). In addition to these studies, the controversy generated by the reported toxicity of Comfrey (Symphytum officinale), a plant which has been used for centuries for its antihaemorrhagic and wound healing properties with no observable toxicity, resulted in its ban. Fresh roots of comfrey are reported to contain about ten times the quantity of pyrrolizidine alkaloids (PAs) than the fresh young leaves. Injecting newborn rats with excessive doses of pyrrolizidine alkaloids isolated from Comfrey over a protracted period, caused hepatotoxicity (Obomsawin 2008). However, studies have shown that the fully mature and dried leaves of comfrey have significantly reduced levels of PAs (Obomsawin 2008), and that boiling herbs containing PAs in water for about 20 minutes can effectively neutralize the alkaloids (Obomsawin 2008). Several years after these publications, it would have been expected that there would be a significant improvement in the quality of the studies on herbal medicines, but unfortunately, this has not happened (Chaudhury, 2005). These studies have reinforced the widely-held belief among practitioners of herbal medicine and some workers in the field that the current methods of pre-clinical and clinical evaluation are still very weak, and inappropriate for carrying out good and meaningful studies on traditional medicine. Among the reasons cited for this state of affairs are inadequate working knowledge of traditional medicine practices and the nature of current health care policies. Current health policy in many countries requires that before plant medicines can be accepted for use in health care, extensive laboratory and/or clinical investigations must be carried out to ascertain safety and efficacy. The problem though is that due to the multiplicity of active ingredients plants contain, a lot of material and human resources would need to be invested to be able to isolate and test all the active compounds in a selected plant. As a result, such scientific evaluation is usually limited to one or two specific bioactive compounds (biomarkers) to the exclusion of all others, which often leads to oversimplification or a wrong interpretation of the plant's bioactivity. This biomarker when extracted and taken alone, will to a large extent, be more toxic and possibly trigger undesirable effects than when taken as part of a herbal mixture. Many herbalists would argue that besides a relatively small number of plants that are evidently toxic, the synergistic interaction of the complementary and neutralizing ingredients in whole plants will potentially mitigate any toxicological effects of known active ingredients. For this reason, scientific studies with isolated compounds, on non-human or even non mammalian organisms, or in vitro, with doses far in excess of the equivalent medicinal dose, represents a gross misunderstanding of herbal medicines and cannot be extrapolated to the clinical situation. Besides the problem of inappropriate research methodology, there appears to be a paucity of investigators who have the requisite skills and knowledge to carry out clinical trials in traditional medicine. It is also possible that researchers who are suitably qualified to carry out this type of work may not be interested (Chaudhury 2005). Nevertheless, biological screening can be an essential scientific tool for validating the ethnomedical uses of medicinal plants. According to Chaudhury (1992) “the challenge of the twenty first century will be to carry out clinical evaluation of herbal remedies within the framework of rigid clinical pharmacological principles without trampling on the concepts of the traditional systems of medicine”. Biological screening includes preclinical pharmacological studies and randomized clinical trials. Preclinical studies The preclinical evaluation and authentication of medicinal plants involves documentation and testing of their in vitro and in vivo pharmacological efficacy and safety. The process begins with in vitro testing, which may be followed by in vivo studies. Constituents identified to have bioactivity and deemed to be potential candidates for therapeutic application are then subjected to extensive clinical and toxicological screening before they can be accepted as medicines. In addition to providing important data on efficacy and safety of different plants in a cost effective manner, preclinical studies can help to determine the therapeutic effect of the plant being investigated as well as its mechanism of action. Plants with novel and/or multiple mechanism(s) of action can also be identified and proper screening assays designed (Lipsky and Sharp 2001, Bleicher et al. 2003, Dove 2003, Kenakin 2003, Knowles and Gromo 2003, Verkman 2004).