A brief discussion of the history of the use of herbal medicines from prehistoric times to the mid-twentieth century precedes an explanation of why usage of such remedies in the United States declined in the 1940s but returned to popularity in the 1980s. The provisions of the Dietary Supplement Health and Education Act of 1994 are presented together with its perceived influence, both positive and negative, on the health of the American people. Possible futures of herbal medicines are considered. The negative viewpoint that they will ultimately be rejected is refuted, and the more optimistic prediction that herbs are ultimately destined to become a part of mainstream medicine is defended. Stumbling blocks to such acceptance are evaluated and methods of overcoming them suggested. The urgent need for the development of a sensible regulatory environment encouraging the approval of botanicals as drugs is emphasized. After predicting a bright future for rational phytomedicines, the author opines that many of them will eventually play significant roles in medicinal practice.

Although clinical trials are needed to prove the efficacy of medicinal herbs and pharmacological studies are essential to the long-term goal of identifying the active ingredients in plants, these will not be forthcoming rapidly enough to meet the acute public health needs for knowledge on efficacy and safety since these substances are currently being widely consumed at various dosages. Resulting from the ongoing ‘natural experiment’ well-conducted observational epidemiology can bridge the gap and determine whether, as consumed its use is of benefit or detrimental, for whom and when in the course of disease prevention or minimization of disease severity. The classic study designs (cohort and case-control) and the more recent development of case-only studies can be put to service for these purposes. The challenges are in dose assessment, understanding mechanisms of effect, determining the relevant time period of exposure for a given disease or symptom, controlling for confounding factors such as disease status, and the special challenges presented by irregular use of medicinal herbs and concurrent use of multiple products and multiple sources.

Ginseng (Panax ginseng, C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years. In North America, the ginseng species indigenous to both Canada and the United States (Panax quinquefolium) represents an important industry for both domestic and export markets. There are numerous theories and claims describing the efficacy of ginseng, which can combat stress, enhance both the central and immune systems and contribute towards maintaining optimal oxidative status against certain chronic disease states and aging. Risk issues concerning the safety of ginseng at recommended dosages are less prominent and scientifically based. While some epidemiological or clinical studies have reported indications of efficacy for specific health benefits or potential toxicity, there are an equal number of studies that provide contradictory evidence. This situation has led to questionable conclusions concerning specific health benefits or risks associated with ginseng. Recent advances in the development of standardized extracts for both Panax ginseng (G-115) and Panax quinquefolius (CNT-2000) have and will continue to assist in the assessment of efficacy and safety standards for ginseng products. This paper reviews the scientific literature and evidence for ginseng efficacy and safety derived mostly from in vitro and animal studies and places emphasis on the need for more randomized, double-blinded, placebo clinical studies that can provide unequivocal conclusions. An example of the efficacy and safety of ginseng is provided with the description of biological activity of a North American ginseng extract (NAGE), which includes illustrating mechanisms for antioxidant activity without prooxidant properties.

This review of the literature documents the efficacy of a standard extract of Ginkgo biloba (EGb) in managing signs and symptoms associated with memory disorders and dementia. Analysis of the discrepant findings reveals that study outcomes may vary with the type of population studied, the outcome measurements selected, and the dosing tested. Overall, the efficacy of EGb was more frequently reported in trials enrolling dementia patients than healthy volunteers. In contrast to narrow memory tests, broad cognitive assessments were more likely to detect the treatment effect. Although a dose–response relationship is not yet established, 240 mg day−1 EGb seems to show a higher rate of treatment response than does 120 mg day−1. Regarding safety, in all trials reviewed the adverse event profile of EGb was not different from that of the placebo.

Herbal medication has gathered increasing recognition in recent years with regard to both treatment options and health hazards. Pyrrolizidine alkaloids have been associated with substantial toxicity after their ingestion as tea and in the setting of contaminated cereals have led to endemic outbreaks in Jamaica, India and Afghanistan. In Western Europe, comfrey has been applied for inflammatory disorders such as arthritis, thrombophlebitis and gout and as a treatment for diarrhoea. Only recently was the use of comfrey leaves recognized as a substantial health hazard with hepatic toxicity in humans and carcinogenic potential in rodents. These effects are most likely due to various hepatotoxic pyrrolizidine alkaloids such as lasiocarpine and symphytine, and their related N-oxides. The mechanisms by which toxicity and mutagenicity are conveyed are still not fully understood, but seem to be mediated through a toxic mechanism related to the biotransformation of alkaloids by hepatic microsomal enzymes. This produces highly reactive pyrroles which act as powerful alkylating agents. The main liver injury caused by comfrey (Symphytum officinale) is veno-occlusive disease, a non-thrombotic obliteration of small hepatic veins leading to cirrhosis and eventually liver failure. Patients may present with either acute or chronic clinical signs with portal hypertension, hepatomegaly and abdominal pain as the main features.

Therapeutic approaches include avoiding intake and, if hepatic failure is imminent, liver transplantation. In view of the known serious hazards and the ban on distributing comfrey in Germany and Canada, it is difficult to understand why comfrey is still freely available in the United States.

Issues concerning the past and future development of medicinal herbs from Chinese medicine (CM) are addressed in this paper. In the Western world, medicinal herbs are becoming increasingly popular and important in the public and scientific communities. In contrast to their regulated status in China and other countries, herbal medicines are regarded as dietary supplements in the US. Accordingly, research must continue worldwide to identify and improve the efficacy of the active principals of herbs both singly and in combination – from active ingredients, active fractions, and active herbal formulations. While Western medicine currently employs pure, single compounds, either natural or synthetic, CM has long used multiple combinations of compounds in the form of processed natural products, primarily medicinal herbs, to treat and relieve the symptoms of many different human diseases. CM may have fewer and less severe side effects than single pure drugs, making CM especially attractive to the consumer. In effect, CM's focus on combination therapy does serve both ancient and modern theories. However, research using modern analytical and chemical techniques is needed to ensure efficacy and safety, to provide qualitative and quantitative analyses for dietary supplements, and to develop new, effective and safe world-class drugs. Drug design is an iterative process. Bioactivity-directed fractionation and isolation identify active natural compounds from single herbs or formulations. These lead structures can be chemically modified and improved through knowledge of structure–activity relationship, mechanism of action, drug metabolism, molecular modelling and combinatorial chemistry studies. Finally, efficacy and toxicity determination as well as clinical trials can contribute to the generation of new drugs from CM. To continue the legacy of CM, as well as the worldwide uses of other medicinal herbs, continued investigation of active formulations, bioactive fractions, and isolated compounds is critical to drug development in the 21st century.