Medicinal plants and medical plant materials that contain phenol compounds, simple phenols and their glycosides

Planner 1. Phenolic compounds and their classification. 2 Planner 1. Phenolic compounds and their classification. 2. Biosynthesis of phenolic compounds. 3. MP and MPM containining simple phenols and phenolic glycosides.

Phenolic compounds are the substances containing benzoic nucleus with one or several hydroxylic groups and their derivatives. If the molecule contains two or more hydroxylic groups there is polyphenols.

Phenolic compounds with one benzoic nucleus Basic skeleton Class Examples C6 Simple phenols, Benzoquinones Catechol, Hydroquinone, 2,6-Dimethoxybenzoquinone, phenol, pirocatechol C6-1 Alkilphenol Phenolic alcohol Phenolic aldehydes Phenolic acids p-cresol Saligenin Vanilin, Salicylic Gallic, salicylic C6-C2 Acetophenones, Tyrosine derivatives, Phenylacetic acids 3-Acetyl-6-methoxybenzaldehyde, Tyrosol, p-Hydroxyphenylacetic acid C6-C3 Hydroxycinnamic acids, Phenylpropenes, Coumarins, Isocoumarins, Chromones Caffeic, ferulic acids, Myristicin, Eugenol, Umbelliferone, aesculetin, Bergenon, Eugenin C6-C4 Naphthoquinones Juglone, Plumbagin

Simple phenols Phenolic acid Phenolic alcohol Phenolic aldihyde Acetophenone Phenylacetic acid

Hydroxycinnamic acid Coumarin Isocoumarin Chromone

Phenolic compounds with two benzoic nucleus Basic skeleton Class Examples C6-C1-C6 Xanthonoids Mangiferin C6-C2-C6 Stilbenoids, Anthraquinones Resveratrol, Emodin C6-C3-C6 Chalconoids, Flavonoids, Isoflavonoids, Neoflavonoids Quercetin, cyanidin, Genistein (C6-C3)2 Lignans, Neolignans Pinoresinol, Eusiderin, rosmarinic acid Polymeric compounds (polyphenols) (C6-C3)n, (C6)n, (C6-C3-C6)n Lignins, Catechol melanins, Flavolans (Condensed tannins), Polyphenolic proteins, Polyphenols Raspberry ellagitannin, Tannic acid

C6-C1-C6 Benzophenones Xantones Stilbenes Flavonoids

Biosynthesis some natural compounds p-hydroxycinnamic (p-coumaric) acid Phenolic acid Combined forms of hydroxycinnamic acids reducing, dimerization polymerisation + malonat 3 molecules Acetophenones Phenilacetate acids oxidation Stilbens Lignans Lignins Phlavonoids Coumarins

Phenol Pyrocatechin Pyrogalol Phloroglucinol Hydroquinone Salicylic alcohol Salicylic aldehyde Salicine Salidroside

Physicochemical properties Free phenolics and their glycosides are crystals of white and yellow colour with a fixed melting point, soluble in water, ethanol, methanol, ethyl acetate, water solution of alkali and sodium acetate and insoluble in ether or chlorophorm. All glycosides possess optical rotation. They can hydrolyse while heated with mineral acids.

Extraction. Most phenolic acid derivatives accumulated in the plant matrix are stored in vacuoles and are commonly extracted with alcoholic or organic solvents. The common solvents for extractions are hot water, ethanol, acetone, diethyl ether, chloroform, ethyl acetate, and methanol (or aqueous methanol), the latter being the most common. The following liquid-solid extraction methods may be used: Soxhlet extraction, ultrasonification (USAE), microwave-assisted extraction (MAE), and accelerated solvent extraction (ASE). Hydrolysis of the esters and glycosides to a free phenolic acid has been a strategy employed to simplify the analysis. There are two main procedures to cleave the ester and glycoside bond: acidic hydrolysis (for glycosides), and alkaline hydrolysis (for esters). A third, less prevalent technique is cleavage through the use of enzymes (esterases or glucosidases).

IDENTIFICATION Phenolic compounds react with diazonium salts, iron alum (ferric ammonium sulphate), ferric (III) chloride, lead (II) acetate (sediment). An azo coupling is an organic reaction between a diazonium compound and a phenol or other aromatic compound, which produces an azo compound. The product will absorb longer wavelengths of light than the reactants because of increased conjugation. Aromatic azo compounds tend to be brightly coloured (red, orange) due to the extended conjugated systems; many are used as dyes.

Quantitative analysis Phenolic acids are substances, which absorb in the UV region and their detection on thin layers containing a fluorescent indicator is relatively easy. TLC is widely used for qualitative analysis of phenolics. The advantage of separation on thin layer is possibility of additional detection after treatment by various reagents. The simple way of detection is treatment the plates with ammonia vapour. Phenolic compounds should be observed in the UV light at λ=254 or 366 nm. Quantitative analysis Titration can be used for quantitative analysis of phenolic compounds. The most common types of titrations used are acid-base titration (alkalimetry) and red-ox titrations (iodometry, bromatometry). For example, the State Pharmacopoeia of the USSR of the XI edition suggested using iodometry for qualitative analysis of arbutin in bearberry leaves.

Biological Action and Application The British Pharmaopoeia 2009 and Europe Ph. suggest using liquid chromatography for quantative analysis of arbutin. TLC combined with densitometry is often used for quantitative analysis of phenolic compounds in different parts of plants and herbs. Biological Action and Application Stress conditions such as excessive UV light, wounding, or infection induce biosynthesis of phenolic compounds. Thus, environmental factors may have a significant contribution to the content of phenolic acids in plants. Most of them have shown an excellent scavenging activity of active oxygens. The antioxidant activity of phenolic acids and their ethers depends on the number of hydroxyl groups. Recent investigations have linked a series of phenolic acids (ferulic, caffeic, ellagic, tannic, protocatechuic, chlorogenic, rosmarinic acids, and curcumin) with the anticancer activity. Some of phenolic acids (caffeic, gentisic, rosmarinic, ferulic, salicylic acids, curcumin) have

anti-inflammatory and antirheumatic properties anti-inflammatory and antirheumatic properties. Caffeic acid is known as a selective blocker of the biosynthesis of leukotrienes, components involved in inflammatory and immunoregulation diseases, asthma, and allergic reactions. In recent years, more and more clinical studies were focused on phenolic acids as a group of potential immunostimulating compounds. Possibly, systemic application of caffeic, gallic, or salicylic acid could result in suppression of leukocytes accumulation in extravascular sites, that may be beneficial in the treatment of chronic inflammatory diseases. Chlorogenic, ellagic, gallic, caffeic, protocatechuic, and salicylic acids have significant stimulatory influence on the production IgG antibodies. Phenolic acids are currently being investigated for their potential antiviral therapy (rosmarinic, caffeic, ferulic acids). There are other biological activities of phenolic acids: astringent (rosmarinic acid), sedative on the central nervous system (rosmarinic acid, chlorogenic acid), choleretic and cholekinetic (most of phenolic acids), hepatoprotective, analgetic, antipyretic, and keratolytic (salicylic acid).

Uvae ursi folia, Eu Ph Arctostaphylos uva-ursi - Bearberry Ericaceae BAS: leaves – arbutin glicosides (8-12 %), methylarbutin, hydroquinone, galic, elagic acids, tannins (7-19 %), (+)-catechol, triterpenoid saponins α-amyrin - ursolic acid and flavonoids (hyperoside, quercetin, kaempferol).

Arbutin Methylarbutin Hydroquinon Arbutin

It can be used to treat arthritis, back pain, bed wetting, bile problems, bladder infections, bloating, cystitis, diabetes (by removing excessive sugar from the blood), diarrhoea, gallstones, gonorrhoea, haemorrhoids, kidney stones and other diseases It has a strong bacteriostatic action against Staphylococci and E. coli It is advised to use bearberry no more than 7-10 days at a time. Decoctum is the component of the diuretic herbal composition

Vitis idaea folia Vaccinium vitis idaea – cowberry, lingonberry,, foxberry, mountain cranberry Ericaceae Constituents. Up to 9 % arbutin, methylarbutin and melampsorine, hedroquinone; up to 10 % tannins, phenolic acids, flavonoids, ursolic, quinic, ellagic and gallic acid.

Medicines have diuretic and antiseptic action and are used in treatment of cystitis, gonorrhea, pyelonephritis , acute and chronic urinary inflamation. “Brusniver”, it’s a diurenic and nephrolitic herbal composition. Leaves of cowberrycontain less tannins than leaves of bearberry and thus can be prescribed for people with kidney disease. Inhalations and sprays from lingonberry extract can be used for complex treatment of pneumonia and bronchitis. For treatment of stomatitis, parodontitis, angina, chronic tonsillitis, gingivitis, mouth ulcers the decoction is prescribed as rinsing agent It is used at light forms of diabetis.

Tyrosol Rosavin Rosyridol Rhodiolae roseae rhizomata et radices Rhodiola rosea- Golden root, roseroot, Aaron’s root Crassulaceae Constituents. Phenolic glycoside salidroside (up to 1 %), rosavin, rosin, hedrolysable tannins (up to 20 %), flavonoids (kaempferol, quercetin, isoquercetin, hyperoside, rodiolin, tricin), organic acids, essential oils (monoterpenes rosiridol, rosaridin), sugars, proteins, waxes, mineral compounds. Tyrosol Rosavin Rosyridol

Liquid extract has tonic and anti-stress action Liquid extract has tonic and anti-stress action. A clinical trial showed significant effect for a golden rose extract in doses 340-680 mg per day in 18-70-year-old male and female patients with mild-to-moderate depression. Rhodiola is used as adaptogen Medical application: Asthenic condition after suffering nerve and systemic diseases, neurasthenia, vegetative-vascular dystonia, fatigue and .

Constituents. Up to 0,3 % salicylic acid and its Violae herba, EuPh Viola tricolor- Heartsease, wild pansy Viola arvensis- Field pansy Violaceae Constituents. Up to 0,3 % salicylic acid and its derivatives as the methyl ester of violutoside, further phenolic carboxylic acids such as caffeic, p-coumaric, gentisic, etc.; 10 % micilage, made up of Glc, Gal, Ara, Rham; up to 5 % tannins; flavonoids ( rutin, violanthin, vitexin…); carotenoids, violaxanthin, coumarins (umbelliferone); small amounts of saponins ascorbic acid. violaxanthin

Medical application: Herbs have expectorant, diuretic, diaphoretic and anti-inflammation action. Viola is the part of diuretic and chest (pectoral) mixes. In homeopathy fresh flowering plant is used for treatment of diathesis in babies, skin problems and night bed wetting

Peoniae anomale herba Peoniae anomale rhizomata et radices Paeonia anomala- Peony Paeoniaceae Tincture of peony has sedative effect on the central nervous system and used for treatment of neurasthenia, insomnia and neuroses. In folk medicine- treatment of gastrointestinal system diseases and epilepsy

Willow bark - Salicis cortex, EuPh Salix acutifolia- Willow, Sallow, Osier Salicaceae Constituents. 0.5 to more than 11% phenolic glycosides, the salicylates salicin, salicorin, tremulacin, populin, fragilin, saliperoside, triandrin, vimalin, picein, grandidentatin, and 3'- and 4'-acetylsalicortin. Aromatic compounds: salidroside, vanillin, syringa-aldehyde, syringin; salicylic, p-coumaric, vanillic, syringic, p-hydroxybenzoic, caffeic and ferulic acids; salicyl alcohol (saligenin). Flavonoids (isoquercitrin, naringenin, chalcone isosalipurposide, catechol), up to 20% tannin.

Medical application. For mild feverish colds and infections, acute and chronic rheumatic disorders, mild headaches, and pain caused by inflammation. It is mainly salicin and the salicyl glycosides, which form salicin after hydrolysis of the acyl group that represent a salicyil acid pro-drug and that like it have antipyretic, analgesic/antirheumatic, and antiseptic actions. Salicin is split by the intestinal flora into saligenin and glucose. Saligenin is absorbed and oxidised in the blood and the liver to salicylic acid. salicin saligenin Assalix® powers of the willow bark. In gut and liver, its main active ingredient salicin is converted to the actual active ingredient salicylic acid. Salicylic acid has an analgesic, antipyretic and anti-inflammatory effect.

Rubi idaei fructus Rubus idaeus- raspberry Rosaceae From fruits we can do a tincture with diaphoretic and diuretic action which can be used to treat infection diseases and high temperature. Syrup is very tasty and used to correct the taste of medicines

Cynarae folia , EuPh Cynara scolymus- Artichoke Asteraceae Constituents. Leaves contain phenolic acids: coffeic, chlorogenic, neochlorogenic, 4-0-caffeoyl-quinic and l-O-cofliyl-D-quinic acids, and also cynarin (l,5-di-O-caffeoyl-D-quinic acid); tannins, flavonoids (luteolin derivatives). Cynarin

Medical application: Leaves stems are used to increase bile production, have cholegogic, diuretic, hepatoprotective action. Induce the metabolism of cholesterol and lipids in blood. The presence of cynarin provides antisclerotic, cholagogue, diuretic activity of artichoke extracts. Similar properties have the phenolic acids of artichoke. They activate the bile synthesis, increase diuresis, increase the volume of excreted urine, regulate the functions of thyroid gland. Artichoke buds are often used in cookery.

Filicis maris rhizomata Dryopteris filix-mas- Male fern Dryopteridaceae Constituents. The major active substances are phloroglucinol derivatives: aspidinol, albaspidin, filixic acid, flavaspidic acid, filmaron, tannins, resins, bitter, flavonoids, starch and essential oil. The plant is poisonous!

Other types of fern can be collected by mistake-lady fern and ostrich fern 8-10 vascular bundle (Dryopteris felix-mas); 2 flatten vascular bundle (Athyrium filix-femina); 2 (Matteuccia struthiopteris). Uses. The rhizome is sometimes used for the treatment of a variety of worm infestations. As the plant is poisonous, the treatment should be conducted under doctor s supervision and the patient should be prepared in a specific way (diet before administration, osmotic laxative in 30 min after administration).

CANNABIS HERB - CANNABIS HERBA Cannabis — Cannabis sativa L., Fam. Cannabaceae. Synonym(s): Bhang, Dagga, Ganja, Hashish, Indian hemp, Marihuana, Marijuana. Constituents. Cannabis is the source of phytocannabinoids — oxygen-containing C21 aromatic hydrocarbon compounds. At least 85 cannabinoids have been isolated from the cannabis plant.

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