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

http://www.dietcan.net/docs/Polifenoles%20en%20alimentos%20y%20biodisponibilidad.pdf

Polyphenols: food sources and bioavailability

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

Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

https://science.sciencemag.org/content/sci/275/5297/218.full.pdf

Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

Phytochemicals as Potential Cancer Chemopreventive Agents

Datura innoxia Mill., Solanaceae, an underexplored ethnomedicinal plant, has been empirically evaluated in the current study for the isolation of bioactive agents. A crude extract of D. innoxia leaves was subjected to normal-phase medium pressure and vacuum liquid chromatography which led to the purification of a withanolide, isowithametelin. The chemical structure was established based on single-crystal X-ray diffraction. Isowithametelin exhibited substantial cytotoxicity against tested human cancer cell lines (breast cancer MCF-7 (ATCC® HTB-22), lung carcinoma LU-1 (human lung carcinoma established in the Department of Surgical Oncology, University of Illinois at Chicago), and prostate adenocarcinoma PC-3 (ATCC® CRL-1435)) with IC50 values of 4.3 ± 0.93, 6.9 ± 1.3, and 0.01 ± 0.001 μg/ml, respectively. It also inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells (IC50 value of 18.5 ± 1.8 μg/ml) and demonstrated moderate protein kinase inhibition. This work suggests a possible anticancer role of isowithametelin; in vivo studies remain necessary to corroborate in vitro efficacy.

Cancer Chemopreventive and Cytotoxic Activities of Isowithametelin from Datura innoxia

Resveratrol as an Activator or Inhibitor of Enzymes and Proteins

From the leaves of Isodon megothyrsus, a novel entkaurene diterpene, megathyrin B, was isolated and its structure determined as 1 alpha,7 beta,11 beta,15 beta-tetrahydroxy-ent-7 alpha,20-epoxykaur-16-ene by 1D- and 2D-NMR spectral analysis. Additionally, its stereochemistry was unambiguously assigned by X-ray crystallography. This compound was cytotoxic to the KB and KB-V cell lines.

Megathyrin B: a cytotoxic diterpene from Isodon megathyrsus.

The degradation product and its stability of deguelin, a naturally occurring rotenoid and potential cancer chemopreventive agent, was evaluated in several vehicles using liquid chromatography‐electrospray mass spectrometry Deguelin was prepared as a 2 mg/mL solution in acetonitrile, corn oil, yohimbine oil, Tween‐80, Cremophor‐EL, liposomes, and phospholipid micelles, and chemical stability was monitored for 28 days using HPLC‐UV and HPLC‐MS systems coupled to C18 reverse phase columns Deguelin was stable in acetonitrile, corn oil, and yohimbine oil for 28 days when stored at 4°C However, it rapidly decomposed in liposomes, Cremophor‐EL, Tween 80, and phospholipid micelles, with daily decay rates of 039%, 086%, 193%, and 282%, respectively The degradation product was determined by physical and spectral data to be tephrosin after isolation by semi‐preparative HPLC Tephrosin was produced by deguelin auto‐oxidation, and this was likely accelerated by endogenous peroxides found in Cremophor‐

John M. Pezzuto

Papers

Phytochemicals as Potential Cancer Chemopreventive Agents

Cancer Chemopreventive and Cytotoxic Activities of Isowithametelin from Datura innoxia

Resveratrol as an Activator or Inhibitor of Enzymes and Proteins

Megathyrin B: a cytotoxic diterpene from Isodon megathyrsus.

Identification of Degradation Product of Deguelin and Its Stability Using Liquid Chromatography and Electrospray/Mass Spectrometry