Anthraquinone Glycosides PDF

Pharmacognosy and Phytochemistry By Dr. Farah Al-Mamoori Primary metabolites are compounds produced by a living organism that are essential for its life and growth. *They are derived from sugars via primary metabolic pathways and include: sugars, lipids, amino acids, pe...

Pharmacognosy and Phytochemistry By Dr. Farah Al-Mamoori Primary metabolites are compounds produced by a living organism that are essential for its life and growth. *They are derived from sugars via primary metabolic pathways and include: sugars, lipids, amino acids, peptides and proteins. Secondary metabolites are low molecular weight compounds that are not required for the growth of an organism, but are produced for adaptation for its specific functions in nature and are considered a phenotype of the organism. They are derived from primary metabolites via secondary metabolic pathways. They are more important than primary metabolites as a therapeutic agents End products Acetate-Malonate Pathway includes synthesis of fatty acids and aromatic compounds with the help of secondary metabolites. Main precursors of Acetate-Malonate Pathway are Acetyl- CoA and Malonyl-CoA. End product of this pathway can be saturated or unsaturated fatty acids or polyketides. *Polyketides are a group of natural products that are synthesized by bacteria, fungi, and plants. Derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups *Most anthraquinone glycosides, aglycones are derived from the acetate pathway, which usually starts from acetic acid units which will form the active form acetyl Co enzyme A, then form the malonyl Co enzyme A by the addition of another acetate unit.Likewise, the octa-β keto methylene chain undergoes simultaneous loss of CO2 and cyclization gives anthraquinones. Anthraquinones (polyketides compounds) are an important chemical group. They are basically an aromatic organic compound with a large structure. Anthraquinones are found in fungi and lichens and plants Anthracene Anthraquinone Anthrone Anthranol O O OH 8 1 8 1 7 9 2 4H 7 9 2 6 10 3 6 10 3 5 4 5 H H 4 O H O 2H 8 1 7 9 2 6 10 3 Anthraquinones sparingly soluble in 5 H 4 cold water, and soluble in organic OH solvents and alcohols Oxanthrone During plant storage (drying), anthranol and antrone(have stronger laxative effect cause “griping” effect are oxidized to the anthraquinones. The anthraquinone and related glycosides are stimulant cathartics and exert their action by increasing the tone of the smooth muscle in the wall of the colon and stimulate the secretion of water and electrolytes into the large intestine. After oral administration, the anthraquinone glycosides are hydrolyzed in the colon by the enzymes of the microflora to the pharmacologically active free aglycones, which usually produce their action in 8 to 12 hours after administration. These agents are indicated for constipation in patients who do not respond to milder drugs and for bowel evacuation before investigational procedures or surgery Anthraquinone laxatives should not be the first choice for treatment of constipation. Bulk laxatives are preferable  Long term use of anthraquinones might have notable side effects some of which are as follows: *Development of Melanesia coli, a condition in which the colon lining takes on a dark brownish black hue increasing the risk for cancer *Unsafe when used for more than one week *Laxative dependence *Hypokalemia * Albuminuria and hematuria. *In rare cases, anthraquinones cause heart arrhythmia, nephropathy, edemas, accelerated bone deterioration  1- O-glycosides where the aglycone moiety is 1,8 dihydroxyanthraquinone derivatives, e.g., Gl O O OH O 1 Gl O OH Gl O O OH 1 1 8 9 2 8 9 2 8 9 2 10 CH2 OH 10 10 5 4 COOH CH3 5 4 5 4 O O O Aloe-emodin-8-glycoside Rhein-8-glycoside Chrysophanol-8-glycoside 2- O-glycoside where the aglycone moiety partially reduced 1,8 dihydroxy anthraquinone, e.g., Oxanthrone- type. Gl OH OH H O 7 8 9 1 2 6 10 3 5 4 O Emodin-oxanthrone-9-glucoside 3- C-glycoside where the aglycone structure (anthrone der.) O OH OH 7 8 9 1 2 6 10 4 3 5 CH2 OH H C6 H11 O5 Aloin  4- C-glycoside and O-glycoside Cascaroside O-glycosides. C-glycosides. 1. Emodin: 1, 3,8-trihydroxy-6-methyl anthraquinone 1. Aloe-emodin:  1,8-dihydroxy-3-(hydroxymethyl)-9,10- anthraquinone  1,8-dihydroxy-3- (hydroxymethyl)anthracene-9,10-dione. 5 1. Rhein: 5 4 Carboxyl group 1 4, 5-dihydroxy -9,10-dioxoanthracene-2-carboxylic acid 1. Chrysophanol: 1 3 1, 8-dihydroxy -3-methyl anthraquinone Senna ‫السنامكي‬: Cassia acutifolia: (Alexandrian senna) Cassia angustifolia: (Indian senna or Tinnevelly senna) Family: Leguminoseae. Leaves Pod(fruits) Chemistry: Dimeric anthracene glycosides derived from two anthrones moieties which may be: O OH OH 1 O OH OH 8 9 1 2 8 9 2 10 CH2 OH 10 5 4 COOH 5 4 Aloe-emodin anthrone Rhein anthrone Sennoside A&B Sennoside A and B, which are the main components, are dianthrones and have their aglycones as Rehein but sterioisomers((i.e. trans and cis at the connection bridge 10-10’). Gl O O OH 7 8 9 1 2 Rehein 6 10 4 3 COOH 5 H H COOH Rehein Gl O OH O Sennoside C&D Sennoside C and D are heterodianthrones, i.e. the aglycones are rhein and aloe-emodin Gl O O OH 7 8 9 1 2 Aloe-emodin 6 10 4 3 CH2 OH 5 H H Rhein COOH Gl O OH O Warnings: *Senna is POSSIBLY SAFE during pregnancy and breast-feeding when  taken by mouth, short-term. It is POSSIBLY UNSAFE when taken by mouth long-term or in high doses. *Long-term, frequent use, or use of high doses has been linked to serious  side effects including laxative dependence and liver damage. *Electrolyte disturbances, potassium deficiency: Overuse of senna can make these conditions worse. *Dehydration, diarrhea or loose stools: Senna should not be used in people with dehydration, diarrhea, or loose stools. It can make these conditions worse. Senna is frequently marketed as a weight loss tool, but there's no evidence to support this effect. Due to its long-term health risks, you should not use senna to lose weight. Aloe ‫الصبار‬ Dried juice obtained cut leaves of various species of aloe (outer skin). Aloe barbadensis (vera): (Family: Liliaceae):  Aloin is a hydroxyanthracene derivative found in the yellow sap of aloe leaf, aloin is used as a stimulant-laxative, treating constipation by inducing bowel movements  Aloe vera is a medicinal plant, traditionally used to improve skin integrity.  Aloe vera is known for its anti-inflammatory, skin protection, anti-bacterial, anti- viral, antiseptic, and wound healing properties Chemistry: The main constituent is barbaloin (aloin) which is a C-glycoside It is a mixture of aloin A (10-R-isomer) and aloin B (10-S- isomer). Aloin A Aloin A differs from aloin B just by the orientation of the substiteunts on C-10 Warnings: Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Topical application by pregnant women is unlikely to be harmful. However, it should not be taken orally during pregnancy as the aloe latex contains anthraquinones that may stimulate uterus and initiate premature labor or possibly cause abortion. Cascara ‫القشرة المقدست‬ Frangula The dried bark of Cascara sagrada (Frangula purshiana) Family Rhamnaceae. B. Cascara is used as a laxative for constipation Example from pharmaceutical market: Warnings: Cascara is possibly safe when used for less than one week. Side effects include stomach discomfort and cramps. But cascara is possibly unsafe when used for more than one week. There isn't enough reliable information to know if cascara sagrada is safe to use when pregnant.  Chemistry 1- Cascarosides A&B (glycosides of barbaloin/aloin) 2- Cascarosides C&D (glycosides of chrysaloin) Cascaroside O-glycosides. C-glycosides. Glycosides of barbaloin Glycosides of chrysaloin Rhubarb ‫الراوند‬ Is the rhizome of Rheum palmatum L family Polygonaceae. It is used mainly in the form of an  ointment in the treatment and cure of chronic eczema, psoriasis It is also used as a purgative.  :Chemistry Consist of glycoside of rhein The presence of tannins in rhubarb makes the drug * constipating. So in small doses, rhubarb exerts no purgative action but acts only as intestinal astringent, but large doses cause purgation.  Rhubarb is a good source of fiber and antioxidants Rhubarb is probably the most sour-tasting vegetable you can find. Its acidity is mainly due to its high levels of malic and oxalic acid. Malic acid is one of the most abundant acids in plants and contributes to the sour taste of many fruits and vegetable  Carmine A red pigment obtained from the cochineal louse The dried female insect – the crude drug cochineal – contains about 10 % of the intensely, red water-soluble colouring matter, carminic acid, a C- glycoside of an anthraquinone derivative Carminic acid, a C- glycoside of an anthraquinone derivative Specific code names for the pigment include natural red 4, C.I. 75470, or E120.  Hypericin: Is a red-coloured, dimeric anthraqiunone derivative which is present in leaves and flowers of Hypericum perforatum (St. John wort)‫عشبة القديس‬the Example from pharmaceutical market:  Used for the treatment of mild to moderate depression. Mechanism of action :- Reuptake inhibition of monoamines (specifically, serotonin, norepinephrine, and dopamine). Monoamine oxidase inhibitors (MAOIs): There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine. Causes up-regulation of 5-HT2 receptors.  Warnings: Sun-exposure: Photosensitivity Insomnia, , headache, dizziness, nervousness, sexual dysfunction, GI upset and fatigue. Herb-drug interactions of Hypericin with the following medications: HIV Medications  Warfarin  Cyclosporin  Oral Contraceptives  Anticonvulsants  Digoxin  Theophylline  SSRIs   Chrysarobin Chrysarobin, comes from the South American araroba tree. It is used in the treatment of psoriasis, especiaislly on relatively localized plaques resistant to other therapies It inhibits the proliferation of keratinocytes (epidermal skin cells), prevents the action of T-cells, and promotes cell differentiation, likely through mitochondrial dysfunction. In addition, the production of free radicals may contribute to its anti- psoriatic effect Chrysarobin is contraindicated in individuals with known hypersensitivity or allergy to the compound. It should not be used on open wounds or areas with severe inflammation. Additionally, it is not recommended for use in pregnant or breastfeeding women.