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Anti-Inflammatory Agents
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In the 1st century CE, Cornelius Celsus described the signs of acute inflammation as: calor (heat), dolor (pain), rubor (redness) and tumor (swelling).1 This accurate depiction of the sequence of events that occurs in inflammation is characteristic of all types of inflammation regardless of the provocative stimuli, which can include injury, friction, emotion, exposure to irritants or allergens, or infectious agents.2 The initial insult to the skin causes vasodilation that is seen as redness. The endothelial lining of the blood vessels becomes more permeable and leads to extravasation. In other words, substances leak out of the vessel causing increased fluid in the tissues, which results in swelling. Inflammatory mediators such as cytokines and interleukins are released and activate multiple pathways that can lead to pain, redness, and swelling as well as serve to beckon immune cells to the area.
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The process of inflammation is orchestrated by a large array of inflammatory mediators including histamines, cytokines, eicosanoids (e.g., prostaglandins, thromboxanes, and leukotrienes), complement cascade components, kinins, fibrinopeptide enzymes, and free radicals. For a more extensive review, see Cosmetic Dermatology: Principles and Practice, 2nd edition, Chapter 35 (McGraw-Hill, 2009).
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Although the many causes of inflammation are very complicated and beyond the scope of this book, arachidonic acid (AA) and its pathways are important to understand when considering the anti-inflammatory claims of skin care products. AA production is a major cause of inflammation because AA is broken down into inflammation-causing substances such as prostaglandins and leukotrienes. Production of AA is blocked by corticosteroids, which is one of the ways that topical steroids decrease inflammation (they also cause vasoconstriction). Two important pathways involved in the breakdown of AA are worth noting (Figure 64-1).
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Cyclooxygenase pathway: Results in the production of prostaglandins. This is the pathway in which salicylates (aspirin) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen work.
Lipoxygenase pathway: Results in the production of the inflammatory mediator group leukotrienes.
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Several categories of anti-inflammatory ingredients are considered in this section: salicylates, prostaglandin antagonists, leukotriene antagonists, polyphenols, and vasoconstrictors. Examples of salicylates include salicylic acid and Aloe vera.
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Prostaglandin antagonists include feverfew, licorice extract, and oatmeal, while turmeric and chamomile are leukotriene antagonists. Coumarin and its derivatives, found in tamanu oil, for example, suppress prostaglandin biosynthesis through inhibition of the lipoxygenase and cycloxygenase systems.3 Horse chestnut is a vasoconstrictor, as are corticosteroids such as hydrocortisone. Polyphenols are also discussed in the Antioxidants section introduction as well as several chapters in that section. Anti-inflammatory polyphenols considered here include calendula, ...