The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

Plant Products as Antimicrobial Agents

The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology--to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?

Photodynamic therapy for cancer

In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators.

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Therapeutic potential of resveratrol: the in vivo evidence.

Advances in flavonoid research since 1992.

Analysis of in vitro serotonergic activity of black cohosh (Cimicifuga racemosa) and identification of a potential active constituent, N-methylserotonin

Even though the American public in 1983 spent in excess of $8.0 billion for prescriptions dispensed from community pharmacies—prescriptions that contained active principles still extracted from higher plants, there is no research program in American pharmaceutical firms designed to discover new drugs from higher plants. In spite of this, more than 119 drugs of known structure that are obtained from higher plants are used by physicians as drugs in countries throughout the world. These 119 drugs are obtained from only about 91 species of plants, of more than 250,000 species known to exist on this planet. The World Health Organization estimates that perhaps 80% of the more than 4 billion inhabitants of the world rely chiefly on traditional medicines (primarily plants) for their primary health care needs. In Japan, Kampo medicines (prescriptions containing several plants) are approved for reimbursement in the National Health Scheme. The value of these Kampo medicines in 1976 was about $12.5 million (US) and t...

International Perspectives regarding the Use of Food/Natural Products as Drugs

Preliminary investigation of Ectopopterys soejartoi.

Transport and metabolism of isoflavones in an extract of Trifolium pratense (red clover) by the human intestinal cell line Caco-2

A new sesquiterpene lactone, rufescenolide C (1), the first furanoheliangolide dimer, was isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. Its structure was determined by analysis of its spectroscopic data, with the absolute configuration being established by analysis of the CD spectrum. A plausible biogenesis of this dimer is proposed. This compound showed potent cytotoxicity with an IC50 value of 150 nM, when tested against HT-29 human colon cancer cells.

Norman R. Farnsworth

Papers

Analysis of in vitro serotonergic activity of black cohosh (Cimicifuga racemosa) and identification of a potential active constituent, N-methylserotonin

International Perspectives regarding the Use of Food/Natural Products as Drugs

Preliminary investigation of Ectopopterys soejartoi.

Transport and metabolism of isoflavones in an extract of Trifolium pratense (red clover) by the human intestinal cell line Caco-2

A Cytotoxic Dimeric Furanoheliangolide from Piptocoma rufescens