Mosul University/ College of Pharmacy Flavone and related flavonoid glycosides Anthocyanidins and glycosides Naphthoquinones and glycosides Lignans and lignin Pharmacognosy I Mosul University/ College of Pharmacy L.A. Dilbreen Barzanji

Flavone and related flavonoid glycosides The flavonoids occur both in the free state and as glycosides are the largest groups of naturally occurring phenols. More than 2000 of these compounds are now known, with nearly 500 occurring in the free state. Most are O-glycosides but a considerable number of C-glycosides are known. Dimeric compounds also known as (Biflavonoids). The glycosides are generally soluble in water and alcohol, but insoluble in organic solvents. The genins are only sparingly soluble in water but are soluble in ether. Flavonoids dissolves in alkalis, giving yellow solutions which on the addition of acid become colourless.

The flavones and their close relations are often yellow (Latin flavus, yellow), they are widely distributed in nature but are more common in higher plants and in young tissues, where they occur in the cell sap. The intensity of their yellow colour increases with the number of hydroxyl groups and with increases of pH. The group is known for its anti-inflammatory and anti-allergic effects, for antithrombotic and vasoprotective properties, for inhibition of tumour promotion and as protective for the gastric mucosa. Some of these pharmacological properties can be explained on the basis of antioxidant activity .

Many flavonoids-containing plants are diuretic (e. g Many flavonoids-containing plants are diuretic (e.g. buchu and broom) or antispasmodic (e.g. liquorice and parsley). Some flavonoids have antitumour, antibacterial or antifungal properties. Flavonoids are polyphenolic compounds based on a C15 (C6C3C6) framework. They contain chroman ring (C-ring) with a second aromatic ring (B-ring) at the c-2,c-3 or C-4 position.

Flavonoids types Six major subgroups of flavonoids: Chalcones Flavone Flavonol Flavonone Anthocyanins Isoflavonoids

Phyto-oestrogens isoflavones , along with coumestans (also flavonoids) and lignans , belong to a class of substances known as non-steroidal phyto-oestrogens. Both structurally and functionally they are similar to oestradiol and related sex hormones and exert weak oestrogenic effects. They are present in certain foods and herbal remedies and are well-documented as producing infertility in animals as, for example, clover disease in sheep grazing on clovers containing a high phyto-oestrogen content.

Studies provoking much medical and general press attention have centered on the role of phyto-oestrogens as dietary constituents have positives effects in the prevention of cancers, heart disease and post-menopausal symptoms. Foods containing appreciable quantities of isoflavones are soya beans, soy products and other legumes crops; they are also present in the herbs Red Clover Flower and broomtops.

Agnus castus fruit The drug consist of the whole, ripe, dried fruit of Vitex agnus castus. Synonyms include : chaste tree, chaste berry and monk’s pepper, alluding to its association with chastity. The plant is a shrub or small tree found in the medeterian regions. The small dark berries are collected from the wild in autumn and dried.

The main flavonoids are casticin (should not be less than 0 The main flavonoids are casticin (should not be less than 0.08%) also vitexin, penduletin and kaempferol. Diterpenes including rotundifuran and vitexilactone Various iridoids including aucubin. The drug has a long history in various menstrual problems and in deficient lactation. In 2001 it was recommended as a therapeutic option for premenstrual syndrome where no cause could be identified.

Calendula flower Calendula flower derives from the marigold Calendula officinalis. The EP/BP specify the whole or cut , dried, and fully opened flowers detached from the receptacle and obtained from cultivated varieties. Constituents : flavonoids, triterpenoids, essential oil and polysaccharides are the principal constituents of calendula flower. All groups have been shown to exhibit pharmacological activity and serve to illustrate the difficulty of devising an assay which represents the true therapeutic activity of the drug. The BP/EP determine the flavonoids content, expressed as hyperoside (not less than 0.4%).

The flavonoids mixture involves quercetin and isorahmnetin derivatives. Triterpenoid saponins (calendulosides A-F); the saponins have hemolytic and anti-inflammatory activity. Antitumour and phagocytosis stimulation properties have been reported for the polysaccharide fraction. Calendula is used internally for the alleviation of gastrointestinal disorders and externally, as an ointment or lotion, for the treatment of minor wounds and rashes.

Olive leaves The olive (Olea europea) best known medicinally for its expressed oil, is also used in continental Europe for the antiseptic, astringent and sedative properties of the leaves. It can be employed both internally and externally. Flavonols, including rutin and oleuropein are the principal components. The pentacyclic triterpenoid (maslinic acid) occurs in the petioles and has various biological activities; it may offer advantages in the resistance to oxidative stress in animals. Olive leaves are used as an infusion for their tranquilizing effect in nervous tension and for their antiseptic, astringent and febrifuge properties.

Passiflora Passiflora (Passion Flower) consists of the dried aerial parts of Passiflora incarnata collected during the flowering and fruiting period. Constituents include: flavonoids; mainly C-glycosides of apigenin and luteolin such as vitexin, isovitexin, orientin, iso-orientin and their glycosides. The BP drug is required to contain not less than 1.5% total flavonoids calculated as vitexin . Passiflora has sedative actions; it is popular ingredient of herbal preparations designed to counteract sleeplessness, restlessness and irritability.

Buckwheat herb The drug consist of the dried aerial parts of Fagopyrum esculentum , collected when the plant is flowering and prior to fruiting. Rutin is the most important therapeutic constituent of the herb and the BP/EP requires a minimum content of 4.0% . Buckwheat is used in the treatment of various circulatory disorders, including varicose veins, chilblains and retinal bleeding.

Visnaga The drug consists of the dried ripe fruits of Ammi visnaga, an annual plant about 1-1.5 m high, it grows in the Middle East and is collected particularly in Egypt. Khellin, the most important active constituents, is crystalline and has been synthesized. It occurs to the extent about 1%, the highest concentration being reported in the immature fruits, and is accompanied by two other crystalline compounds, visnagin (about 0.1%) and khellol glucoside (less than 0.03%) The drug has long been used in Egypt. Khellin, which is now commercially available in tablets and injection, is a potent coronary vasodilator. It has been employed in the treatment of angina pectoris and bronchial asthma, but its use appears to be limited by undesirable side reactions. Khellin has smooth muscle relaxant properties and used as adjuvant in treatment of urinary tract diseases.

Silybin and Silymarin A number of flavonolignans for example, silybin and silymarin, have antihepatotoxic properties, and extracts of plants containing them for example Silybum marianum are widely used in germany for the treatment of liver ailments. The fruits of S. marianum contain silybin, silydianin and silychristin.

Hesperidin and Rutin Although flavonoids preparations such as hesperidin and rutin are used in medicine, they do not appear to justified the high hopes which followed the work of scientists in 1935 on the ‘citrin’ (sometimes known as vitamin P) of paprika and lemon peel. Citrus and other fruits have been included in the human diet and, in addition to ascorbic acid and other compounds, provide flavonoids which decrease capillary fragility and are therefore employed in cases of hypertension and radiation energy. The substance formerly known as ‘citrin’ is now known to be a mixture of the rahmnoglucosides of eriodictyol (a tetrahydroxyflavone) and methyl eriodictyl (hesperetin). A similar glycoside, rutin, the rahmnoglucoside of quercetin, is found in many plants, and commercial supplies are made from tobacco residues, Sophora and Eucalyptus spp. or buckwheat which yields about 3-4%.

Anthocyanidins and glycosides Anthocyanidins are flavonoids structurally related to the flavones. Their glycosides are known as anthocyanins. These names are derived from the Greek antho-, flower, and kyanos, blue . They are sap pigments and the actual colour of the plant organ is determined by the pH of the sap. For example, the blue colour of the cornflower and the red of roses is due to the same glycosides and both of these plants on hydrolysis with hydrochloric acid yield cyanidin hydrochloride. The most common anthocyanidin, cyanidin, occurs in about 80% of permanently pigmented leaves, 69% of fruits and 50% of flowers. Cyanidin is followed in order of frequency by delphinidin and pelargonidin.

The sugar components are usually attached in the 3- or (more rarely) 5- position. It may be noted that in flavone glycosides the attachment is usually in the 7-position. They may be monosaccharides (glucose, galactose, rhamnose or arabinose) Disaccharides (e.g. the rhamnoglucoside of Antirrhinum spp.) Trisaccharides (e.g. the 5-glucoside-3-rutinoside of certain Solanaceae) Despite their biological importance the anthocyanidins are of little pharmaceutical significance as such, but as previously considered they constitute the monomers of the polymeric condensed tannins.

Bilberry fruit Bilberry (Vaccinium myrtillus) is distributed throughout Europe, N. Asia and N. America including Canada. The edible sweet-tasting berries are collected from July to Septmeber. Constituents: Anthocyanins, particularly glucosides and galactosides of cyanidin, peonidin, delphinidin, petunidin and malvidin. Anthocyanins are responsible for the final colour of the berries. These pigments increase in quantity during ripening whereas that of the polyphenols (-)-epicatechin, (+)-catechin and dimeric proanthocyanidins decrease.

For the dried fruits, the BP/EP specifies a minimum tannin content of 1.0% expressed as pyrogallol and for the fresh fruits a minimum of 0.30% anthocyanins expressed as cyanidin-3-glucoside chloride. Uses: traditionally used to treat diarrhea, menstrual cramps, eye problems, varicose veins and circulatory problems.

Naphthoquinones and glycosides The nature of these compounds was indicated earlier; they are produced by higher plants, fungi and actinomycetes and exhibit a broad range of biological actions including fungicidal, antibacterial, insecticidal, phytotoxic, cytostatic and anticarcinogenic. In plants they commonly occur in the reduced and glycosidic forms as illustrated by the 4-D-gluside of α-hydrojuglone, a constituent of walnut tree leaves.

Henna Henna consists of the dried leaves of Lawsonia inermis, a shrub cultivated in north Africa, India and Ceylon. Henna contains a colouring matter, lawsone (a hydroxynaphoquinone), various phenolic glycosides, coumarins, xanthones, quinoids, β-sitosterol glucoside, flavonoids including luteolin and its 7-O-glucoside, fats, resin and henna-tannin. Henna is commonly used as a dye for hair. The astringent stem-bark of L. inermis is traditionally used in India for the treatment of jaundice, enlargement of the liver and spleen, and for various skin diseases.

Lignans and lignin Lignans are dimeric compounds formed essentially by the union of two molecules of a phenylpropene derivative. Some 300 lignans have been isolated and categorized into a number of groups according to structural features. Important pharmaceutical examples are the lignans of Podophyllum spp. The aryltetralin-type lignan and other related compounds are the principal active constituents of Podophyllum root and rhizome. Lignin is an important polymeric substance,(C6-C3)n laid down in a matrix of cellulose microfibrils to strengthen certain cell walls. It is an essential component of most woody tissues and involves vessels, tracheids, fibres and sclereids.