COX-1 enzymatic activity to decrease the formation of pro-inflammatory prostaglandins. Salicylate may competitively inhibit prostaglandin formation. Salicylate's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms. Salicylic acid, when applied to the skin surface, works by causing the cells of the epidermis to slough off more readily, preventing pores from clogging up, and allowing room for new cell growth. Salicylic acid inhibits the oxidation of uridine-5-diphosphoglucose (UDPG) competitively with nicotinamide adenine dinucleotide and noncompetitively with UDPG. It also competitively inhibits the transferring of glucuronyl group of uridine-5-phosphoglucuronic acid to the phenolic acceptor. The wound-healing retardation action of salicylates is probably due mainly to its inhibitory action on mucopolysaccharide synthesis. Safety If high concentrations of salicylic ointment are applied to a large percentage of body surface, high levels of salicylic acid can enter the blood, requiring hemodialysis to avoid further complications. Production and chemical reactions Biosynthesis Salicylic acid is biosynthesized from the amino acid phenylalanine. In Arabidopsis thaliana, it can be synthesized via a phenylalanine-independent pathway. Industrial synthesis Sodium salicylate is commercially prepared by treating sodium phenolate (the sodium salt of phenol) with carbon dioxide at high pressure (100atm) and high temperature (115°C) – a method known as the Kolbe-Schmitt reaction. Acidification of the product with sulfuric acid gives salicylic acid: It can also be prepared by the hydrolysis of aspirin (acetylsalicylic acid) or methyl salicylate (oil of wintergreen) with a strong acid or base. Reactions Upon heating, salicylic acid converts to phenyl salicylate: 2HOC6H4CO2H → C6H5O2C6H4OH + CO2 + H2O Further heating gives xanthone. Salicylic acid as its conjugate base is a chelating agent, with an affinity for iron(III). Salicylic acid slowly degrades to phenol and carbon dioxide at 200–230 °C: C6H4OH(CO2H) → C6H5OH + CO2 History Willow has long been used for medicinal purposes. Dioscorides, whose writings were highly influential for more than 1,500 years, used 'Itea' (which was possibly a species of willow) as a treatment for 'painful intestinal obstructions,' birth control, for 'those who spit blood,' to remove calluses and corns and, externally, as a 'warm pack for gout.' William Turner, in 1597, repeated this, saying that willow bark, 'being burnt to ashes, and steeped in vinegar, takes away corns and other like risings in the feet and toes.' Some of these cures may describe the action of salicylic acid, which can be derived from the salicin present in willow. It is, however,