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.

Agrostistachin, a novel cytotoxic macrocyclic diterpene from

Ipomopsin, a New Biscoumarin from Ipomopsis aggregata

Place des plantes médicinales dans la thérapeutique

rom the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplement Research in Women’s Health; Department of Obstetrics and Gynecology, University of Illinois at Chicago; and Department of Obstetrics and Gynecology, Northwestern University. his work was supported by grant P50 AT00155 provided jointly by the National Center for Complementary and Alternative Medicine (NCCAM), the Office of Dietary Supplements (ODS), the Office for Research on Women’s Health (ORWH), and the National Institute of General Medicine (NIGMS) of the National Institutes of Health (NIH). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, National Cancer Institute, ODS, ORWH, NIGMS, or NIH. Nancy L. Booth received a National Research Service Award from NCCAM (F31 AT00804). eceived for publication July 30, 2004; accepted Aug 11, 2004. eprint requests: Richard B. van Breemen, PhD, Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplement Research in Women’s Health, 833 S Wood St, M/C 781, University of Illinois at Chicago, Chicago, IL 60612. -mail: breemen@uic.edu lin Pharmacol Ther 2004;76:511-6. 009-9236/$30.00 opyright © 2004 by the American Society for Clinical Pharmacology and Therapeutics. a oi:10.1016/j.clpt.2004.08.023 oncurrently with prescription drugs by approximately 6% of the population. As a result, herb-drug interacions and herbal toxicities are receiving more attention han ever in the clinical literature. However, some isconceptions exist in this literature concerning the resence of “coumarins” in botanical dietary suppleents and their anticoagulant effects. It is important to rst note that very few naturally occurring coumarins ave been tested for anticoagulant activity; even fewer re found to be active. A search of the NAPRALERT NAtural PRoducts ALERT) database indicates that nly 13 naturally occurring coumarins have been evalated for antithrombotic or anticoagulant activity, only of which were found to be active. This statistic may e an underestimation of the overall number of natral coumarins studied for these effects, but, neverheless, 7 out of the more than 3400 known natural oumarins is a very small number of coumarins hose antithrombotic-anticoagulant activity has een verified. Naturally occurring coumarins as a hole are sometimes confused with the clinical term oumarin, which is often used to refer to warfarin Coumadin; Bristol-Myers Squibb Company, Princeon, NJ) or other specific synthetic anticoagulant drugs, urther perpetuating the idea that all “coumarins” are nticoagulants. The intent of this commentary is (1) to

Norman R. Farnsworth

Papers

Agrostistachin, a novel cytotoxic macrocyclic diterpene from

Ipomopsin, a New Biscoumarin from Ipomopsis aggregata

Place des plantes médicinales dans la thérapeutique

Confusion regarding anticoagulant coumarins in dietary supplements

Cell culture assay system for the evaluation of natural product-mediated anti-Hepatitis B virus activity