Phenols and Tannins Pharmacognosy I Mosul University College

Phenols and Tannins Pharmacognosy I Mosul University/ College of Pharmacy L. A. Dilbreen Barzanji

Phenols and phenolic glycosides Phenols probably constitute the largest group of plant secondary metabolites. Widespread in nature, and to be found in most classes of natural compounds having aromatic moieties, they range from simple structures with one aromatic ring to highly complex polymeric substances such as tannins and lignins. Phenols are important constituents of some medicinal plants and in the food industry they are utilized as colouring agents, flavouring, aromatizers and antioxidants.

Phenolic classes of pharmaceutical interest, namely: 1) simple Phenolic compounds 2) Tannins 3) Coumarins and their glycosides 4) Anthraquinones and their glycosides 5) Naphthoquinones 6) Flavones and related flavonoids glycosides 7) Anthocyanidins and anthocyanins 8) Lignans and lignin

Simple phenolic compounds • The biosynthetic origin of some of these compounds involving the shikimic acid pathway. • Catechol (o-dihydroxybenzene) occurs free in kola seeds and in the leaves of Gaultheria spp. • Derivatives of resorcinol (m-dihydroxybenzene) constitute the narcotic principles of cannabis and the glucosides arbutin involves quinol (hydroquinone, p-dihydroxybenzene).

• The Phenolic compounds in this group often also posses alcoholic, aldehydic and carboxylic acid groups; they include eugenol ( a phenolic phenylpropane), vanillin (a phenylic aldehyde) and various phenolic acids, such as salicylic, ferulic and caffeic acids. • Glycosides formation is common, and the widely distributed glycoside coniferin and other derivatives of phenolic cinnamic alcohols are precursors of lignin.

Willow bark • Various species of Salix wich include S. purpurea L. (purple willow) • The commercial drug occurs as thin, channeled pieces of varying length, about 1. 5 cm wide and 1. 5 mm thick. It is easily fractured longitudinally and, transversely, shows an inner inconspicuous fiber fracture. • Willow bark is a source of salicin; a phenolic glycoside now seldom used but generally regarded as the natural forerunner of aspirin.

• The composition of the glycoside mixture is variable in the bark depending on the species, age of bark and time of collection. The latter is usually made in spring when the bark is easily removed from the branches. • Other phenolic glycosides are salicortin (an ester of salicin), acetylated salicin (fragilin). • The BP requires the dried drug to contain a minimum of 1. 5% total salicylic acid derivatives, calculated as salicin. • Willow is employed as an anti-inflammatory in the treatment of rheumatism, arthritis and muscular pains.

Tar (Pix Liquida) • Wood tar is known in commerce as Stockholm tar. It is prepared by destructive distillation of various trees of the family Pinaceae. • Wood tar is a blackish semiliquid with a characteristic odour and taste. • Pine tar is characterized by the large amount of guaiacol and its homologues which are present. • Tar is mainly used externally, in the form of ointment or tar parogen, as a stimulating antiseptic in certain skin diseases.

Coal tar • Coal tar is prepared by destructive distillation of bituminous coal. • It is a nearly black viscous liquid and when shaken with water gives an aqueous alkaline solution. • Both coal tar and wood tar are used in the treatment of psoriasis.

Vanilla and vanillin • Vanilla (Vanilla Pods) consists of the carefully cured fully grown but unripe fruits of Vanilla fragrans (Salis). • The fruits are collected when the upper part of the pod changes in colour from green to yellow. The characteristic colour and odour of the commercial drug are only developed as a result of enzyme action during the curing. • Vanilla pods are 15 -25 cm long, 8 -10 mm diameter and somewhat flattened.

• Green vanilla contains glycosides, namely glucovanillin (vanilloside) and glucovanillic alcohol. • Glucovanillic alcohol yields on hydrolysis glucose and vanillic alcohol; the latter compound is then by oxidation converted into vanillic aldehyde (vanillin). • Glucovanillin, as its name implies, yields on hydrolysis glucose and vanillin.

Vanillin BP • It is the aldehyde corresponding to methylprotocatechuic acid and has been synthesized in a number of ways. 1) Large quantities of it is prepared from eugenol isolated from oil of gloves or from guaiacol (methyl catechol). 2) It can also be produced by microbial oxidation of eugenol. 3) In the plant glucovanillin is biosynthesized via ferulic acid. • Uses: vanilla pods are widely used in confectionary and in perfumery. They have been replaced to some extent by synthetic vanillin.

Bearberry leaves (Uva Ursi) • The dried leaves of Arctostaphylus uva-ursi; a small evergreen shrub found in central and northern Europe and in North America. The leaves are dark green to brownish green. • The drug is odourless but has astringent and somewhat bitter taste. • Bearberry contains the glycosides arbutin and methyl arbutin, about 6 -7% of tannin, catechol, ursone and flavones derivative quercetin. • The pharmacopoeial drug is required to contain at least 7. 0% of hydroquinone derivatives calculated as arbutin. • Uses: Bearberry is diuretic and astringent and during excretion it exerts an antiseptic action on urinary tract.

Capsicum • Consists of the dried ripe fruits of Capsicum annuum, also refered as ‘African chillies’ which are oblong-conical in shape, 12 -25 mm long and up to 7 mm wide. Constituents: • Capsaicin; an intensely pungent compound. • The pungent phenolic fraction of capsicum also contains a proportion of 6, 7 -dihydrocapsaicin. • The capsaicin contents of fruits varies appreciably in a range of up to 1. 5% and is much influenced by environmental conditions and age of the fruit. It occurs principally in the dissepiments of the fruits- for example, entire fruit 0. 49, pericarp 0. 10, dissepiment 1. 79, seed 0. 07.

• The pungency of capsicum is not destroyed by treatment with alkalis (distinction from gingerol, which also contains the vinyllyl group) but is destroyed by oxidation with potassium dichromate or permanganate. • Chillies also contain ascorbic acid (0. 1 -0. 5%), thiamine and red carotenoids. • Uses: the drug is given internally for atonic dyspepsia and flatulence. • It is used externally as counter-irritant, in the form of ointment, plaster, medicated wool, etc. • For the relief of rheumatism, lumbago, etc. • Capsaicin cream are available for the relief of pain in osteoarthritis, post-herpetic neuralgia and painful diabetic neuropathy.

Tannins • The term tannin was first applied by Seguin in 1796 to denote substances present in plant extracts which were able to combine with protein of animal hides, prevent their putrefaction and convert them into a leather. • Tannins comprise a group of compounds with a wide diversity in structure that share their ability to bind and precipitate proteins. Tannins are polyphenols and include oligomerics and polymeric constituents and are widely distributed in plants. • Most true tannins have molecular weight from 1000 -5000. • Many tannins are glycosides. • Two main groups of tannins are usually recognized; these are the hydrolysable tannins and the condensed tannins (proanthocyanidins).

Hydrolysable tannins • These may be hydrolysed by acids or enzymes such as tannase. • They are formed from several molecules of phenolic acids such as gallic and hexa-hydroxydiphenic acids which are united by ester linkages to a central glucose molecule.

• A simple tannin illustrating this point is one derived from a species of sumac (Rhus). • They were formerly known as pyrogallol tannins, because on dry distillation gallic acid and similar components are converted into pyrogallol. • Two principal types of hydrolysable tannins are gallitannins and ellagitannins. • Ellagic acid (the depside of gallic acid) can arise by lactonization of hexa-hydroxy-diphenic acid during chemical hydrolysis of the tannin; thus, the term ellagitannin is a misnomer.

Condensed tannins (proanthocyanidins) • Unlike hydrolysable tannins, these are not readily hydrolysed to simpler molecules and they do not contain a sugar moiety. • They are related to the flavonoid pigments and have polymeric flavan-3 -ol structures. • On treatment with acids or enzyme condensed tannins are converted into red insoluble compounds known as phlobaphenes. • On dry distillation they yield catechol and these tannins are therefore sometimes called catechol tannins.

‘Complex tannins’ • This term has been applied to a newlydiscovered group of tannins which are biosynthesized from both a condensed tannin and a hydrolysable tannin (mostly a Cglycoside ellagitannin).

Pseudotannins As already mentioned, pseudotannins are compounds of lower molecular weight than true tannins, e. g. : • Gallic acid • Catechins • Chlorogenic acid • Ipecachuanic acid

Occurrence of tannins: • Tannins are of wide occurrence in plants and are usually found in greatest quantity in dead or dying cells. • They exert an inhibitory effect on many enzymes due to protein precipitation and, hence, they may contribute a protective functions in barks and heartwoods. • Commercial tannins are used in the leather industry. • Pharmaceutical tannin is prepared from oak galls and yields glucose and gallic acid on hydrolysis; many commercial samples contain some free gallic acid. • Some plants (clove, cinnamon , etc. ) contain tannin in addition to the principal therapeutic constituents. This may complicate extraction or produce incompatibilities with other drugs (many alkaloids for example, are precipitated by tannins).

Medicinal and biological properties: • Tannin-containing drug will precipitate protein and have been used traditionally as styptics and internally for the protection of inflamed surfaces of mouth and throat. They act as antidiarrhoeals and have been employed as antidotes in poisoning by heavy metals, alkaloids and glycosides.

Oak bark • Oak bark is the cut and dried bark from the fresh young branches of Quercus robur. • Principal constituents are phlobatannins, elligatannins and gallic acid. • A minimum requirement of 3. 0% calculated as pyrogallol being specified by the BP/EP. • Oak bark is used medicinally for its astringent properties.

Galls and tannic acid • Turkish galls are vegetable growth s formed on the young twigs of the dyer’s oak, Quercus infectoria, as a result of deposition of the eggs of gall-wasp. • Abnormal development of vegetable tissue round the larva is due to an enzyme-containing secretion, produced by the young insect after it has emerged from the eggs. • Galls are collected and dried then they are graded according to colour into three grades: blue green and white.

Characters: Aleppo galls are globular in shape and from 10 -25 mm in diameter. They have a short basal stalk and numerous rounded projections on the surface. Galls are hard heavy , usually sinking in water. The so-called ‘blue’ variety are actually of a grey or brownish-grey colour. These, and to a lesser extent the olive-green ‘green’ galls are preferred to the ‘white’ variety, in which the tannin is said to have been partly decomposed. White galls also differ from the other grades in having a circular tunnel through which the insect has emerged. Galls without the opening have insect remains in the central cavity. Galls have a very astringent taste.

Constituents: galls contain 50 -70% of the tannin known as gallatonic acid (Tannic acid); this is a complex mixture of phenolic acid glycosides varying greatly in composition. Galls also contain gallic acid (about 2 -4%), ellagic acid, etc. Tannic acid is hydrolysable tannin yielding gallic acid and glucose. Solutions of tannic acid tend to decompose on keeping with formation of gallic acid, a substance which is also found in many commercial samples of tannic acid. Uses: • Tannic acid is used as an astringent and styptic.

Hamamelis leaf • Hamamelis leaf (Witch Hazel leaves) consists of the dried leaves of Hamamelis virginiana , a shrub or small tree 2 -5 m high, which is widely distributed in Canada and the USA. • Hamamelis contain gallitannins, ellagitannins, free gallic acid, proanthocyanidins, bitter principles and traces of volatile oil. • Uses: hamamelis owes its astringent and hemostatic properties to the tannins. • Hamamelis Water or distilled Witch hazel, is widely used as an application to sprains, bruises and superficial wounds and as an ingredient of eye lotions.

Pomegranate rind • Pomegranate rind consists of the dried pericarp of the fruit of Punica granatum. • It occurs in thin, curved pieces about 1. 5 mm thick, some of which bear the remains of the woody calyx or a scar left by the stalk. • The outer surface is brownish-yellow or reddish. The inner surface bears impression left by the seeds. • Pomegranate rind used in India as a herbal remedy for non-specific diarrhea, it is very astringent and contains about 28% of tannin (ellagitannins) and colouring matters. • It should be distinguished from the root bark , which contains alkaloids.

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