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Author

Elliott Middleton

Other affiliations: Upjohn
Bio: Elliott Middleton is an academic researcher from University at Buffalo. The author has contributed to research in topics: Histamine & Quercetin. The author has an hindex of 33, co-authored 82 publications receiving 9008 citations. Previous affiliations of Elliott Middleton include Upjohn.


Papers
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Journal Article
TL;DR: Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional, and suggestions are made where such possibilities may be worth pursuing.
Abstract: 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.

4,663 citations

Book ChapterDOI
TL;DR: A considerable body of evidence suggests that plant flavonoids may be health-promoting, disease-preventing dietary compounds.
Abstract: The flavonoids are a large group of naturally occurring phenylchromones found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine. Up to several hundred milligrams are consumed daily in the average Western diet. Only limited information is available on the absorption, distribution, metabolism, and excretion of these compounds in man. Some compounds are absorbed, however, and measurable plasma concentrations are achieved which could have pharmacological relevance.

701 citations

Journal ArticleDOI
TL;DR: Analysis of structure-activity data revealed a model of the minimal essential features required for PKC inhibition by flavonoids: a coplanar flavone structure with free hydroxyl substituents at the 3', 4' and 7-positions.

460 citations

Book ChapterDOI
TL;DR: Their increased production seems to accompany most forms of tissue injury, and the formation of free radicals has been implicated in a multitude of disease states ranging from inflammatory/immune injury to myocardial infarction and cancer.
Abstract: The occurrence of reactive oxygen species (ROS), termed as prooxidants, is a characteristic of normal aerobic organisms. The term “reactive oxygen species” collectively denotes oxygen-centered radicals such as superoxide (O2·-)and hydroxyl (·OH), as well as nonradical species derived from oxygen, such as hydrogen peroxide (H2O2), singlet oxygen (1ΔgO2) and hypochlorous acid (HOC1). Radical reactions are central to the maintenance of homeostasis in biological systems. Radical species perform a cardinal role in many physiological processes such as cytochrome P450-mediated oxidative transformation reactions, a plethora of enzymic oxidation reactions, oxidative phosphorylation, regulation of the tone of smooth muscle, and killing of microorganisms.1–3 Excessive generation of free radicals can have deleterious biological consequences.4–6 Organisms are equipped with an armamentarium of defense systems, termed antioxidants in order to safeguard them against the onslaught of ROS.1–3,7 When the generation of prooxidants overwhelms the capacity of antioxidant defense systems oxidative stress ensues. This can cause tissue damage leading to pathophysiological events. ROS play a pivotal role in the action of numerous foreign compounds (xenobiotics). Their increased production seems to accompany most forms of tissue injury.4,5 Whether sustained and increased production of ROS is a primary event in human disease progression or a secondary consequence of tissue injury has been discussed.5,6 Whatever may be the case, the formation of free radicals has been implicated in a multitude of disease states ranging from inflammatory/immune injury to myocardial infarction and cancer.

396 citations

Journal ArticleDOI
TL;DR: The polymethoxylated flavonoids, nobiletin and tangeretin, markedly inhibited cell growth at all concentrations tested on days 5 and 7, whereas quercetin and taxifolin exhibited no significant inhibition at any of the concentrations tested.

213 citations


Cited by
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Journal ArticleDOI
TL;DR: The factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.

8,513 citations

Journal ArticleDOI
TL;DR: The current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity, are summarized and the structure and antimicrobial properties of phytochemicals are addressed.
Abstract: 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.

7,486 citations

Journal ArticleDOI
TL;DR: The nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed, and bioavailability appears to differ greatly between the variousPolyphenols, and the most abundantpolyphenols in the authors' diet are not necessarily those that have the best bioavailability profile.

6,842 citations

Journal ArticleDOI
TL;DR: This review considers recent findings regarding GC action and generates criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stress-response or, as an additional category, is preparative for a subsequent stressor.
Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

6,707 citations

Journal Article
TL;DR: Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional, and suggestions are made where such possibilities may be worth pursuing.
Abstract: 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.

4,663 citations