Pharmacognosy: Aloes, Sennas, and Saponins

Glycosides - Overview

• Glycosides are compounds that produce one or more sugars upon hydrolysis.
• Chemically, glycosides are mixed acetals where the hydroxyl group on the anomeric carbon atom is replaced by a nucleophilic atom.
• In aqueous solutions, hexoses and pentoses cyclize, forming alpha (α) and beta (β) forms.
• Trivial names of glycosides usually end in "in," indicating the source.
• Examples include digitoxin from Digitalis, salicin from Salix, and prunasin from Prunus.
• The most frequently occurring sugar in glycosides is β-D-glucose, but other sugars like rhamnose, digitoxose, and cymarose can also be components.
• A glucoside is a glycoside where the sugar formed is specifically glucose.
• A glycoside is any glycoside where the sugar formed is one other than glucose.
• Glycoside components include:
  • Aglycone (or genin): The non-sugar component.
  • Glycone: The sugar component.
• Glycosides are important for regulatory, protective, and sanitary functions in plants, and are also therapeutic agents.
• Occurrence is widespread in the plant kingdom, found in fruits, seeds, barks, and leaves, and are relatively rare in animals.

Classes of Glycosides

• Glycosides are classified based on the chemical nature of their aglycone group.
• Specific classes include Cardioactive Steroid, Anthraquinone, Saponin, Cyanophore, Glucosinolate/Isothiocyanate, Flavonol, Alcohol, Aldehyde, and Phenol groups.

Cardioactive Steroid Glycosides

• Related to steroids, possessing a cyclopentanoperhydrophenanthrene (CPPP) nucleus.
• The sugar component is typically attached at the 3-position of the CPPP nucleus.
• There are 2 aglycones:
  • Cardenolides
  • Bufadienolides, discovered from BUFALIN isolated from toad skin.
• Tests for their identification include:
  • Liebermann-Burchard test
  • Kedde reaction
  • Keller-Killiani test
• Actions:
  • Inotropic effect (increasing the force of systolic contraction).
  • Depletion of potassium ions can increase digoxin toxicity.
• Digitalis:
  • Is an Arrythmogenic.
  • Sources include Foxglove (D. Purpurea) and Grecian foxglove (D. lanata).
  • Belongs to the family Scrophulariaceae.
• D. purpurea contains digitoxin, gitaloxin, and gitoxin.
• lanata features digoxin and desacetyl lanatoside (deslanoside).
• Digoxin:
  • Is more commonly used and is polar due to its –OH group, leading to it being easily eliminated and short-acting.
  • Pigeon is used in the digoxin bioassay for potency
  • The antidote to digoxin is Digoxin Immune Fab
  • Functions as an Inotropic agent
• Digitoxin:
  • Lipophilic with a longer half-life.
  • Was previously the drug of choice for CHF but is managing arrhythmia and atrial fibrillations.
• Deslanoside:
  • Used for rapid digitalization
• Convallaria:
  • Is of the Liliaceae family
• From Convallaria majalis
• Contains Liliaceae and Convallotoxin
• Active components are not recommended.
• For age-related cardiac complaints but not FDA approved.
• Apocynum:
  • From Apocynum cannabinum, family Apocynaceae.
  • Contains Cymarin, an active cardiac glycoside.
• Adonis:
  • From Adonis vernalis, family Ranunculaceae.
  • Contains the constituents Adonitoxin, Cymarin and K-Strophanthin.
• Cactus Grandiflorus (Cactaceae family):
  • Causes a positive inotropic effect.
• Black Hellebore (From Helleborous niger):
  • Of the Ranunculaceae family
  • Contains Hellebrin as a constituent
  • Black variety is glycosidal and cardiac stimulant (inotropic).
  • Green and White varieties are alkaloidal, cardiac depressants.
• Strophanthus:
  • From S. kombe and S. hispidus, family Apocynaceae.
  • Contains K. Strophantoside.
  • Contains G. strophantin, which as ouabain, and is the 3rd most important glycoside available on the market
• Squill or Squill Bulb:
  • From Urginea maritima, family Hyacinthaceae.
  • Contains Scillaren-A, to be converted to Scillarenin, then to active scillarenin.
  • Expectorent
• Adelfa:
  • From Nerium oleander family Apocynaceae
  • Observed genocide in Sri Lanka
  • Contains Oleandrin Digitalinum verum components which is poisonous and mimics digoxin

Anthraquinone Glycosides

• Related to anthracene.
• Hydrolysis yields di-, tri-, or tetrahydroxyanthraquinones.
• Frangulin A hydrolyzes to emodin and rhamnose.
• Penicillium islandicum: Species that produce several anthraquinone glycosides.
• Anthranols are oxidized into anthraquinones.
• The Schonteten's test is used to identify anthraquinones.
• Anthranols and anthrones are the main constituents of chrysarobin.
• Used as stimulant cathartics, increasing tone of smooth muscle in the colon to stimulate water and electrolyte secretion into the large intestine.
• Detected by the Borntrager test, which indicates a positive result with a red coloration within the lower ammoniacal region.

Anthraquinone Glycoside Sources

• Cascara Sagrada (Rhamnus purshiana):
  • Also known as sacred bark.
  • Is used for a cathartic effect and to restore muscle tone to the colon.
  • Contains two types of anthracene compounds: normal O-glycosides (10-20%) and aloinlike C-glycosides (80-90%).
  • Main active principals are Cascarosides A, B, C, and D, based on optical isomers of barbaloin and chrysaloin.
• Frangula (Rhamnus frangula):
  • Also know as buckthorn bark.
  • Provides a laxative effect due to the presence of frangulins A and B and related glucofrangulins.
• Aloes (Aloe barbadensis, Aloe vera, Aloe ferox, Aloe africana, Aloe spicata):
  • Are Pharmaceutic aid for Compound Benzoin Tincture
  • Are Cathartic and elicits a drastic cathartic action
  • Used in the treatment of burns, abrasions and other skin irritations due to its moisturizing and emollient properties taken from mucilage of the leaf
  • Yields at least 50% water-soluble extractives.
  • Occurs as opaque masses from reddish black to brownish brown, is nauseating and bitter, with a disagreeable odor.
  • Typical xerophytic plants. -Aloe is from Arabic alloeh or Hebrew halal, meaning a shining, bitter substance. -Vera is from Latin verus, meaning true. -Barbadensis refers to Barbados. -Ferox from Latin meaning wild or ferocious. -Africana refers to the habitat in southern Africa. -Spicata refers to the flowers in spikes
  • Principal anthraquinone glycosides include Aloin A (barbaloin) and Aloin B (isobarbaloin), with inactive ingredients like resinous material and volatile oil.
• Rhubarb (Rheum officinale, Rheum palmatum, Rheum emodi, Rheum webbianum):
  • Functions as a drastic cathartic.
• Senna (Cassia acutifolia and Cassia angustifolia):
  • Composed of Senna leaves, and is a Cathartic whose active compound is dimeric glycosides.
  • Graded by leaf size and leaflet color, with blue-green leaves being best and yellowish leaves being poorest
  • Principal active constituents are dimeric glycosides whose aglycones consist of aloe-emodin and/or rhein.
  • The name is derived from Arabic sena
• Chrysabrobin
  • Is obtained from Goa powder (neutral principles).
  • They are derived from cavities of wood Abdira araroba using hot benzine extracts.
  • A representative sample contains approximately 30-40% Chrysophenolanthrone or chrysophenolanthranol (or 20% emodinanthrone-monomethyl ether, and 30% dehydro-emodinanthrone-monomethyl ether
  • Treats Keratolytic Psoriasis, trichophytosis, and chronic eczema but can irrigate the skin

Anthraquinone Glycoside Subcomponents

• Danthron (Chrysarin):
  • Is 1,8-Dihydroxyanthraquinone that is prepared synthetically from 1,8-Anthraqumone potassium disulfonate but isolated through the fermentation broth of the marine fungus Chromolaenicola sp.
  • It is Cathartic and a intermediate used in the manufacture of anthralin alizarin.

Saponin Glycosides

• Form colloidal solutions in water that foam upon shaking.
• Have a bitter, acrid taste and drugs containing them are sternutatory and irritating to the mucous membrane.
• Destroy red blood cells by hemolysis and to cold-blooded animals and are widely distributed in the plant kingdom.
• Aglycones, usually prepared via acid-catalyzed hydrolysis and are termed as sapogenins.
• Sapotoxins:
• Are toxic to insects and mollusks and used to control schistosomiasis snails
• Used as fish poisons
• They can be Steroidal or Triterpenoidal:
• The aglycones are termed sapogenins or sapotoxins.
• Chemically either Steroidal or Triterpenoidal.
• RECENTLY, saponins have been used experimentally to enhance the absorption of insulin from the application of nasal aerosols.
• They are excellent emulsifying agents and the aqueous solutions of some of them, eg, quillaja bark were used formerly as replacements to replace salts.

Steroids

• Has two chemical classes such as Steroid
  • Diosgenin and botogenin from Dioscorea
  • Hecogenin, manogenin and gitogenin from agave
  • Sitosterol from crude vegetable oils

Saponin Sources

• Glycyrrhiza:

  • Name from Greek origin meaning sweet root
  • Is the dried rhizome and roots of Glycyrrhiza glabra known in commerce of Spanish Licorice as G. glabra Linne. Var. glandulifera known as Russsian Licorice which have other varieties of G. glabra with a sweet yellow wood
  • Has demulcent and expectorant properties and is used as flavoring agent and to mask of bitter drugs as well as a Surfactant
  • Glycyrrhizin (Glycyrrhizic acid):
  • Is saponinlike glycoside that converts glocuronic acid into the aglycone glycyrrhetic acid
  • Use: increases fluid and sodium retention and promotes potassium depletion
  • Glycyrrhetic acid Is is as anti- inflammatory agent as a triterpene derivative of the 3ẞ-hydroxy-11-oxoolean-12-en-29-oic acid
  • Licorice Root:
  • Prepared from glycyrrhiza and is and is added to chewing gums, chocolate candy, cigarettes, Beer, Porter Root Beet to increase flavors.
  • Licorice root extract Is prepared from glycyrrhiza and is a black pillular mass having a characteristic sweet taste used for peptic ulcers and Addison's disease
  • Dioscorea are popular varieties of potatoes using rich cortisone principle resources for Botogenin and Diosgenin

• Mexican Yam (D. floribunda):

  • Derives D. floribunda through dioscin hydrolysis as a precurser for glucocorticodis though microbial transformation

• Ginseng:

• Root of perennial Panax quinquefolius Linne herbs from Araliaceae that contains triterpenoid saponins of steroid triterpenes

• Used In Chinese medicine for therapeutic, stimulant, diuretic, and carminative properties found in common Health food sources as Rg1 glycosides

• Agave/Guava

Cyanogenic Glycosides

• Yield hydrocyanic acid (HCN) as one of the products of hydrolysis.
• Are accompanied in the plant by enzymes (β-glucosidases) that catalyze the hydrolysis.
• Are derivatives of mandelonitrile (benzaldehdye cyanohydrin).
• Amygdalin is a key example, found in large quantities in bitter almonds, apricot kernels, cherries, peaches, and plums as well as in many other seeds of the Rosaceae.
• Prunasin also occurs here in Prunus serotina.
• Both Amygdalin and Prunasin yield ( R ) - mandelonitrile as the aglycone while Sambucus nigra liberates (S)-mandelonitrile as its aglycone.

Hydrolysis of Amygdalin

1. The molecule is hydrolyzed initially to liberate 1 molecule of glucose and 1 molecule of mandelonitrile glucoside.
2. The second molecule of glucose is liberated with the formation of mandelonitrile.
3. The mandelonitrile then breaks down with the formation of benzaldehyde and hydrocyanic acid through emulsin to form enzymes

Cyanogenic Glycoside Sources

• Emulsin: Is obtained from almond kernels to cause a step in hydrolysis and uses B- glucosidase as a emulsion
• Wild Cherry (Prunus serotina): Is the core ingredient in cough medication
• Apricot pits: kernels contain health benefits and are a source of latrine and mandelonilate of glucoronodine

Isothiocyanate Glycosides

• Features garlic as an ORGANOSULFUR antibiotic where allicin is easily decomposed from air, a characteristic with flavors of diolsuldfires

Isothiocyanate Glycoside Uses

• It reduces blood and contains antithrombin, which inhibits platelet for blood clotting. For effective does with range of 4 g of fresh clove
• It is studies show that fibrinogen blood inhibitor and cloves are the best at antibiotic properties at (20 S protoapratil)

Alcohol Glycosides

• Salicin:
  • Is obtained from several willow(Salix) and popular(Populus tree species and is hydrolyzed glucose and saligenin
  • It is an Anti-rheumatic agent that actions closely resembles that of salicylic that oxidizes cells

Aldehyde Glycosides

• Vanilla
  • A drugh with a aldyHide aglocone a used on skin with is used in medical practices and can be used with food or as a agent such a methyprocatechui aldlyhide or cut during short lengths
  • It has glucovanillin glucose in sugar

Aldehyde Glycoside Facts

• Coniferin is found in glycoside at pine trees

• Eungols are found as fenals in clove oil

• Vanillin has hydroxyaldehyde and ethy vaillin which reduces the strength

Phenol Glycosides

• The naturally occurring glycosides are phenolic and include Aebutin a uva ursi

Flavonol Glycosides

• Flavonol’s are divided by what are being used to make them such as Flavonole which is more better known and that used in citrus

Lacton Glycosides

Skimmim, Aesulin, daptin are found as trees and are the use of Lacto e derivatives

Key Applications of Coumarins

• For Tonka beans coumarin has also shown to interact with different drugs , Coumadin was able be obtained from leaves and flowering tops

Applications of Canthridies

• Used for irritable medical conditions and used for tumor treatments that lead lead to kidney failure . They also cause topical application to get rid of warts that can affect skin condition such as vitiligo and TRIOXALEN use to treat it

Lactone Glycosides

The lactone anhydride of cantharidic acid 12% is associated with the soft body tissues of insects. Irritant

• Rubefacient If taken internally, it is removed the by kidney, and is then excretes that it may damage health, also is a drug to the repotational
• Topical applications of solutions can be used to remove warts
• They can also be Psolaner which reduce plants in various environment by inhibiting potototixity

Methoxale is a source through amani' malus that reduces vitiligo and psoriatic in nature and can be applied topically

• • TRIOXALEN is available to treat vitiligo

Explore key characteristics, origins, and differences among aloes, senna and saponin glycosides. Learn extraction methods for chrysarobin and the structural features of sennosides. Understand various pharmacognosy concepts.