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Salicylic acid and related compounds are produced by plants as part of their defence systems against pathogen attack and environmental stress. First identified in myrtle and willow, the medical use of salicylate-rich preparations as anti-inflammatory and antipyretic treatments may date back to the third millennium BC. It is now known that salicylates are widely distributed throughout the plant kingdom, and they are therefore present in plant products of dietary relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid demonstrates several bioactivities that are potentially disease-preventative, including the inhibition of production of potentially neoplastic prostaglandins, which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it appears to be readily absorbed from the food matrix. This has led some to suggestions that the recognised effects of consuming fruit and vegetables on lowering the risk of several diseases may be due, in part, to salicylates in plant-based foods. However, published estimates of daily salicylic acid intake vary markedly, ranging from 0.4 to 200 mg day(-1), so it is unclear whether the Western diet can provide sufficient salicylates to exert a disease-preventative activity. Some ethnic cuisines that are associated with lowered disease risk may contain considerably more salicylic acid than is obtainable from a Western diet. However known protective effects of acetylsalicylic acid (Aspirin™) may have lead to an over-emphasis on the importance of dietary salicylates compared with other bioactive plant phenolics in the diet., (This journal is © The Royal Society of Chemistry 2011)

Listerine, a mouthrinse composed of a mixture of essential oils, was created in 1879 and was originally formulated as a surgical antiseptic. In spite of its known antimicrobial properties it was thought of as a product in search of a use and promoted as a deterrent for halitosis and as a floor cleaner. In the last several years Listerine has emerged as a bona fide therapeutic agent for reduction of plaque induced oral diseases. In contrast to the inconsistent history of Listerine, systemic antibiotics discovered in the 1940's were heralded as miracle drugs. However, the value of prophylactic usage of antibiotics has come under scrutiny as a result of increasing resistance and adverse reactions. Moreover, reports by both American and British professional societies have led to a re-evaluation of the relative risks associated with plaque induced bacteremia when twice-yearly visits to dental professionals are compared to daily activities. These new recommendations and revelations open the door for local antimicrobial approaches to reduce the challenge of plaque-induced bacteremias. These issues will be discussed in the context of Listerine, its intricate and complicated past, and its connection to current uses in oral health and beyond., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name "Aspirin". In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

Although the name of the discoverer of salicylate ototoxicity is still debated, most authors have quoted Muller and his 1877 report. To the best of our knowledge, the true discoverer of the transient ototoxicity of salicylate was the Italian chemist Cesare Bertagnini who reported this evidence in 1855 in the journal Il Nuovo Cimento., ((c) 2008 S. Karger AG, Basel.)

The analgesic and antipyretic effect of the bark of willow has been known in Egypt and Greece for canturies. The modem era of salicylates starts with a letter sent 1758 by Reverend Edward Stone to The Royal Society in London. He described "an account of the success of the bark of willow in the cure of agues". His report. erroneously attributed to Edmond Stone. was published five years later. The active ingredient of willow bark. "salicine". was first isolated 1828 by Joseph Buchner, then by Henri Leroux, and also prepared from the oil of wintergreen (Gaultheria) and meadowsweet (Spirea ulmaria) by J. W. Lowig 1833. and called "Spirsäure", which was already pure acetylsalicylic acid. It was also synthetised 1853 by Ch. Gerhardt and finally 1897 in Bayer's laboratoires by Felix Hoffman, who also demonstrated its antiinflammatory efficacy. After two years of clinical trials with low doses, Bayer's management decided to start the productions and launched Aspirin as an analgetic worldwide in summer 1899. The first ASPIRIN ERA bagun. A completely new epoch started when J. N. Vane and Priscilla Piner demonstrated 1971 that the main mechanism of action of aspirin-like drugs is the inhibition of prostaglandin synthesis. In later studies the potency to inhibit platelet aggregation with small doses of aspirin (30-125 mg) was demonstrated. The Physicians'Health Study 1988 confirmed this effect: aspirin significantly reduced the risk of both, fatal and non-fatal myocardial infarction. and is now used in primary and secondary prevention of atherosclerosis. However the idea was not new: The use of salicylates and aspirin was throughly discussed more than 50 years ago: Paul C. Gibson published 1949 a well-documented case report on efficacy of aspirin in patients with angina, and Kl. Weber and P. Klein in Prague used Gibson's mixture successfully for patients with acute myocardial infarction (1951). Recently, the efficacy and security, the interactions and side-effects of low-dose aspirin have been studied and discussed. In chronic treatment, any combination of two specific platelet antiaggregants should be avoided.

It is well-known that the modern history of salicylates began in 1899 when the compound acetylsalicylic acid was registered and introduced commercially as "aspirin" by the Bayer Company of Germany. As a matter of fact, however, remedies made from willow bark had been used to treat fever and rheumatic complaints at least since 1763, when Edward Stone described their efficacy against malarian fever. A number of Italian scientists made significant contributions during the long period of research leading up to the synthesis of acetylsalicylic acid and its widespread use in rheumatic diseases. In this paper we will review the contributions of some of these researchers, beginning with Bartolomeo Rigatelli, who in 1824 used a willow bark extract as a therapeutic agent, denominating it "salino amarissimo antifebbrile" (very bitter antipyretic salt). In the same year, Francesco Fontana described this natural compound, giving it the name "salicina" (salicin). Two other Italian chemists added considerably to current knowledge of the salicylates: Raffaele Piria in 1838, while working as a research fellow in Paris, extracted the chemical compound salicylic acid, and Cesare Bertagnini in 1855 published a detailed description of the classic adverse event associated with salicylate overdoses--tinnitus--which he studied by deliberately ingesting excessive doses himself. Bertagnini and above all Piria also played conspicuous roles in the history of Italy during the period of the Italian Risorgimento, participating as volunteers in the crucial battle of Curtatone and Montanara during the first Italian War of Independence.

The first clinical reports on the treatment of fever and pain with salicylate-containing natural willow bark remedies were made by the English clergyman Edward Stone in 1763. The pharmacologically active principles were isolated from natural sources by Italian, German and French scientists between 1826 and 1829. Salicylic acid was first synthesised by the German Gerland in 1852 and a year later the Frenchman Gerhardt synthesised acetylsalicylic acid. The first reports on the clinical use of salicylic acid in rheumatic disorders were made independently by the two German physicians Stricher and Reiss in 1876. Acetylsalicylic acid was rediscovered by Hoffmann in 1897 and by the turn of the century it had gained worldwide recognition in the treatment of pain and rheumatological disorders. Reports on adverse events relating to gastrointestinal intolerance and bleeding appeared early, but were largely neglected until the 1950s. Today, salicylates are still widely used as analgesic, antipyretic and anti-inflammatory drugs. New indications, such as thrombosis prophylaxis, have emerged during the last decades, and yet others are being explored.

The use of naturally occurring plant materials for the relief of pain dates back to 3,000 B.C., although rapid advances in antipyretic analgesic therapy have been made more recently. Salicylic acid was synthesized in 1860, and the pyrazolone group, first represented by antipyrine, in 1883. Phenacetin was developed in 1886. Acetaminophen has been in use since the 1890s.