Herbal remedies have become popular over the past decade and they are widely used for the treatment and prevention of various diseases. Many people mistakenly think that all medicinal herbs, being natural, are generally safe and free from undesirable side effects while acting as an effective agent. However, very often, herbs may interact with medications that result in adverse effects. The use of herbal medicine is still poorly understood by the public. Nowadays, toxicity and safety of medicinal herbs is one of the most discussed topics as herbal products have become popular in the Pearl Delta Region as well as worldwide.

Traditional Concepts on Toxicity

The fact that something is natural does not necessarily make it safe. Anyone who uses herbal medicine should understand a few basic safety rules. Traditionally, Chinese medicines are divided into three categories: those with heavy toxicity, minor toxicity and no toxicity. According to Chinese medicinal pharmacology, serious toxic effects are coma, nausea, numbness in the mouth and in the limbs, which can be easily induced by drugs such as unprocessed croton fruits and monkshood. Medicines with minor toxicity like apricot seeds and ginkgo nuts, if used in high dosages, can cause mild breathing difficulties, abnormal heartbeat and dizziness. Drugs without toxicity, i.e., commonly used ingredients, are mild in nature and are less likely to have side effects. In order to reduce the toxicity effects and enhance drug efficacies, TCM has a unique set of pharmaceutical theories that include special processing, combining and decocting methods for herbal application. Most TCMs are safe if applied according to syndrome differentiation and with the correct dosage for the appropriate length of time. See "Questions about Taking Chinese Herbs."

Differences between Conventional Drugs and Medicinal Herbs

Conventional drugs are single target-based which elicit specific metabolic reactions in the body. Their associated side effects are usually traded as a risk against the benefit of the primary effect. Conversely, herbal medicines act multi-systemically, meaning they tend to have broad and non-specific actions on a number of physiological systems simultaneously. These reactions are usually in the same therapeutic action, and are complementary or synergistic with mild adverse effects. Pharmaceutical drug discovery begins with the understanding of the disease mechanism, followed by compound and target identification, validation and optimization. Scientists develop new drugs based on their research and understanding of the human body and disease mechanisms, and a large collection of molecules are screened to select for compounds that may show potential efficacy with low toxicity. Herbal medicine is a holistic therapy which integrates plant remedies with the mental, emotional and spiritual aspects of health into the understanding of the body's functions. It acts gently by supporting systems and processes that have become deficient and helps to remove excesses in the body. The vast majority of herbal medicines contain a complex mixture of compounds such as terpenes, alkaloids, polysaccharides or other chemicals that buffer, modulate and modify the effects of any active ingredient in the herb. Therefore, administration of isolated compounds of a plant cannot easily mimic the effects of extracts from the whole plant. Scientific studies on an isolated component may be easily confused with studies on the plant as a whole. This misinterpretation always leads incorrect data being gathered, till disproved by reviewing the original research study. For example:

• Ma huang (ephedra) is a traditional Chinese medicinal herb that has been used for the treatment of asthma, cough, edema, cold and flu for centuries. It has been sold worldwide as a dietary supplement for weight reduction based on clinical studies that have shown that long-term administration of the herb induces weight loss in diet-restricted obese patients.1,2
• Ephedine-type alkaloids (ETA) are some of the active ingredients, in the herb. Its quality is determined by the amount of ETA contained in it. However, the contents and the profiles of ETA vary with the plant species, parts of the plant, geographic origin, and time of harvest.3 Apart from ETA, it also contains other chemicals which may buffer or modulate its pharmacological and toxicological effects. Therefore, the toxicity of ephedine should not be only accounted for its ETA contents alone.4

Safety Evaluation of Medicinal Herbs

Most of the toxicological studies report that toxic effects due to the use of herbal medicine are associated with hepatotoxicity. Other toxic effects on the kidneys, nervous system, blood, and cardiovascular system, as well as medicinal herbs’ mutagenicity and carcinogenicity have also been published in medical journals. Therefore, numerous advance biological experimental techniques have been used as standard safety tests prior to the efficacy study.

• In-Vitro Toxicity Evaluation Some common standardized experimental techniques are applied in cell culture models to determine the effects of herbal extracts. These methods are based on the extraction of active compounds from herbs which are incubated in different cell lines in various dilations. After exposition of the cells to the herbal extracts, cytotoxicity is assessed by different methods such as microscopic cell morphology evaluation, MTT (methyltetrazolium) assay and lactate dehydrogenase activity (LDH).5Such in-vitro toxicological studies have the advantage of having relatively well-controlled variables and they are widely accepted as the most effective safety and toxicity tests in pharmaceutical development. However, these studies are limited to a single active compound extracted from the whole plant and it is often difficult to determine its mechanism of action in a particular cell line model.
• In-vivo Toxicity Evaluation Cells and tissues do not exist independently in vivo but communicate with and are interdependent on neighboring tissues. It is essential to test both the whole medicinal herb and its active ingredient in vivo in order to get a whole picture of the physiological microenvironment. The complexity of syndrome differentiation system in traditional Chinese medicine further complicates the safety evaluation of herbal medicine; therefore, different animal models based on the theory of syndrome differentiation are crucial to long-term toxicity evaluation.

Challenges of Medicinal Herb Safety Evaluation

Systematic nomenclature, good quality control and accurate identification of herbs are important concerns for scientific research. It is true that the quality of experimental studies and clinical trials on herbs cannot be compared to the studies required by the FDA for a new drug approval, however, experience, education and good information about herbs as well as satisfactory quality control make consumers, physicians and researchers more acceptable and confident of the herbs. The use of the western research approach and existing animal models on herbal medicine toxicological study is controversial. Researchers extract only one or a few active ingredients from a herb in the pre-clinical toxicological study. This cannot represent the whole plant because toxicity of medicinal herbs is related to the complex mixture of active compounds that they contain. These may either interact with other chemicals such as drug-herb interactions or have inherent toxicity. In addition, batch-to-batch variation due to weather conditions, maturity of the plant and soil composition significantly affect the pharmaceutical properties of a herb and therefore the actual dose of active ingredients in the herb is variable, unpredictable or even unknown.

References

1. Astrup, A., Toubro, S., et al. Pharmacology of thermogenic drugs. Am. J. Clin. Nutr. 55, 246S-248S (1992). Abstract
2. Dulloo, A.G., Stock, M.J. Ephedrine as a thermogenic drug. Int. J. Obes. 17 (Suppl. 1), S1-S2 (1993).
3. Lee, M.K., Hsieh, D.P.H., et al. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Toxicological Sci. 56, 424-430 (2000). Abstract
4. FDA (Food and Drug Administration). Dietary supplements containing ephedrine alkaloids; proposed rule. Federal Register 62, 30678-30724. (1997)
5. Saad, B., Said O., et al. Safety of traditional Arab herbal medicine. eCAM 3, 433-439 (2006). Abstract

led and edited by:

Jennifer Eagleton, BA, MA (Asian Studies), Integrated Chinese Medicine Holdings Ltd. Stan Man, Integrated Chinese Medicine Holdings Ltd.