Presentation on theme: "Glycosides Sugar + non-sugar"— Presentation transcript:
1 Glycosides Sugar + non-sugar In the body they are broken down by enzymes or acids into:sugars= glycone/ water solublenon sugar= aglycone/ active portionAglycone may be an alcohol, sulfur or phenol compound.
2 Classification of glycosides Based on the nature of the aglyconeAglycones can be:phenolsquinonesterpenessteroidsHuge variety of medicinal activity from one glycoside to the next.
3 How are they broken down? Pro-drugs: glycosides remain inactive until they are hydrolized in the large intestines by the help of specialized bacteriaThis leads to the release of the aglycone which is the active constituentThe body can absorb some aglycones better than others depending on the herb
6 Cyanogenic glycosides Colorless plant constituentHydrogen cyanide was first isolated from Prussian blue dyeaglycone contains nitrogenBREAK DOWN:Cyanogenic glycoside hydrocyanic acid (prussic acid) cyanide
7 Cyanogenic Glycosides Cyanogenic glycosides are found in pits and seeds of apples, apricots, peaches, plums and elderberries leaves and stems.Their function in plants is not really known but they are suspected to be anti-feedants.
8 Cyanogenic glycosides Main cyanogenic glycosidesAmygdalin- found in bitter almonds and peach kernels (Chinese herb)- used in to make Marizpan flavoring in cooking.2. Prunusin- found in wild cherry bark3. Sambunigrin- from the leaves of the elder tree, Sambucus nigraOther food plants that contain cyanogenic glycosides include flaxseed and manioc.Manioc root must be boiled and the water discarded in order to remove the toxins.
9 Cyanogenic glycocides-toxicology In large doses hydrogen cyanide (hydrocyanic acid) inactivates respiratory enzymes, shuts down the CNS and leads to death.However large doses of raw plant material are needed for toxicity to occur.Our bodies can nuetralize cyanides and eliminate them through the urine.Cyanogenic glycosides are broken down slowly and are easily detoxified by the body in smaller doses.500mg three times a day to produce a toxic effect, which is A LOT!!-there are 4-9 mg hydrogen cyanide per bitter almondYou would have to eat 150 bitter almonds a day for a toxic effect!!!
10 Cyanogenic Glycosides: Properties Sedative and expectorant to the respiratory tract.Wild Cherry Bark (prunus serotina) is a classic prunasin conataining respiratory herb for dry irritable coughs.Apricot kernels in Chinese medicine are used for coughs and asthma.CoolingHydrocyanic acid cuts down heat at a cellular level.Ex- peach, apple and pear are all cooling fruits that contain Cyanogens.Anti-cancerAmygdalin/Laetrile- has been researched as an anti-tumor remedy.
12 Cardiac GlycosidesCardiac glycosides have a long history of use in herbalismThe famous cardiac glycoside, digitoxin, was isolated in 1785 by William Withering. He found out about the use of foxglove by an elder lady herbalist in his village using it for CHF (dropsy). Of course she gets no credit!Digitoxin and other cardiac glycosides from plants day play a large role in modern medicine.
13 Cardiac GlycosidesFound in many medicinal plants such as Digitalis purpurea and lilly of the valley (Convallaria majalis)Direct action on the heart supporting its strength and rate of contraction when it is failing.
14 Cardiac Glycosides- Plant protection Plants and animals create cardiac glycosides as a strategy for protection against being eaten by other creatures. Some animals, like monarch butterflies, have evolved immunity to the toxins. They consume plants like milkweed (Asclepias syriaca) that are high in cardiac glycosides and store the toxins in their tissues. This makes them poisonous to other predatorsUsed as arrow poisons by hunters
15 Cardiac Glycosides- chemistry Steroidal structure- 3 six carbon rings and one five-carbon ringThe sugar portion of the cardiac glycoside is important in the absorbtion and distribution in the body.The aglycone portion is important in binding to Na/K pumps in the heart cells
16 Cardiac GlycosidesCONDITIONS: Used in arrhythmias and congestive heart failure(dropsy)In the past dropsy was the only sign of heart failure. Dropsy (CHF) fluid accumulation in the lower limbs and abdomen due to the heart not being strong enough to handle venous return.ACTIONS:increase the force and speed of contractionInhibit sodium potassium pump leading to a rise in intracellular calcium which increases contraction of the heart.Decrease heart rateSlows conduction velocity in the pace maker- used for arryhthmias
17 Cardiac glycosidesToxicity- Narrow therapeutic window. The therapeutic dose is not much smaller than the toxic dose.Too high of a dose can make the pace maker more sensitive and lead to atrial fibrillation.Cardiac Glycosides are antagonistic to Potassium. If person is low in K+ they will be more likely to have digitalis intoxication.Taraxicum in combition helps to replenish K+Digitalis Intoxication- nausea, vomiting, diarrhea, vision disturbances, headache, arrhythmias.
18 Cardiac GlycosidesCardiac remedies in other than drop doses should be used with discretion.Digitalis lasts a long time in the body and its effects are cumulative. Half life is over 6 days!Convallaria should be considered before digitalis because it has a lower toxicity
19 Cardiac Glycosides Plants containing cardiac glycosides include: Digitalis purpurea- Used for CHF and edemaApocyanum cannabinum (Dogbane)Strophanthus hispidus (Kombe Seed)Adonis vernalis (False Hellibore)Urginea Maritima (Squill)Convallaria margalis (Lily of the Valley)
21 Isothiocyanate glycosides (Glucosinolates) Found in the Brassicaceae (Mustard) Family.Sulpher link between the glycone and the aglycone.Sulpher is what gives the brassicas their pungent quality. ( Horseradish clears the sinuses, mustard oil opens the lungs)In plants they are used as protection against microbes that disrupt their cell walls.
22 Isothiocyanate Glycosides Therapeutic Actions:Culinary- black and brown mustard seeds used in cooking are high in nutrients, stimulate digestion.Rubefacients- mustard seed oils act as irritants when applied topically, causing local vasodilationMustard poultices over the lungs break up congestion.Decongestant for the sinus and bronchial conditions (horseradish, onion and garlic).Large doses may have an emetics effect.
23 Isothiocyanates- goiterogens When consumed in excess they inhibit pumping of iodine into the thyroid follicles. This leads to goiter formation especially in those who are iodine deficient.pertains more to people who are very iodine deficient like in parts of Asia or central Africa.Isothiocyanate botanicals are low enough not to cause a problem.
24 Isothiocyanate glycosides- Antitumor Glucobrassicin is widely distributed amongst the Brassicaceae familyGlucobrassicin produces indoles when broken down.Indole-3-carbinol and diindoylmethane (DIM)Indoles are known for their ability to induce tumor inhibiting enzymes. Thus are protective against cancer.Indoles do not break down under heat.
25 Isothyocyanate Glycosides Toxicology: External use of should not be sustained for longer than two weeks because of irritating effects.mustard seed oils should never be used internally or externally because it toxic to the skin and mucus membranes.
27 Saponins- DefinitionSaponins are glycosides with foaming characteristics.Saponin- comes from “sapo” in Latin which means soap.Historically soap was made from the soapwart plant.In plants they are anti-feedants and protect plants against microbes and fungi
28 Saponins- synthesisSynthesized from acetyl CoA via the mevalonic pathway (similar to cholesterol in animals)Major economic importance: saponins are used to synthesize pharmaceutical steroids (corticosteroids, estrogens, progesterone and progestins)Agave, fenugreek and wild yam root are examples of plants used for their steroidal properties in the laboratory.Human body doesn’t possess the gut flora to interconvert plant steroids to human steroids.Steroidal saponins from agave have antibacterial, cytotoxic and contraceptive effects.Diosgenins in fenugreek inhibit cholesterol absorption and synthesis. Sapogenins found in fenugreek also lower serum triglycerides, total cholesterol (TC), and low-density lipoprotein cholesterol. Diosgenin and trigogenin (saponins) are chemically similar to estrogen.
29 Saponins- classification Consist of polycyclic aglycones attached to one or more sugar side chains.Two subcategories of saponinsTriterpenoid: pentacyclic structureSteroidal saponins (phytosterols): tetracyclic structureLicorice is aPentacyclic triterpenoid
30 Saponins= SudsThe foaming ability of saponins is caused by the combination of a hydrophobic (fat soluble) aglycone along with the the sugar which is hydrophilic (water loving).Allows lipids to dissolve in waterEmulsification in foods that allow water and fat to mix.They have a detergent effect on the skin and the mucus membranes.
31 SaponinsWound healing herbs contain saponins such as calendula.
32 Saponins- Actions Saponins are bitter or acrid in taste If injected intravenously they cause hemolysis. Use only orally!Destroy the membranes of red blood cells.Lower cholesterol:Because they are structurally similar to cholesterol they interfere with cholesterol absorptionIncrease cholesterol excretion into the bile which then gets excreted through the feces.Ex. Trigonella foenum-graecum (fenugreek)
33 Saponins- Actions Medicinally they have many uses: anti-inflammatory: Licorice, wild yamanti-viral: licorice, ashwagandaDigestive: licorice,Expectorant: lobelia, squillAdaptogenic: licorice, gensing,ashwaganda
34 Saponins- reflex expectorants Acrid and flavor of saponins make them reflex expectorantsReflex expectorants irritate the upper digestive tract causing emesis. This irritation also causes a reflex action via the vagus nerve to promote expectoration.Historically herbalists have used emesis to clear the lungs in chronic bronchitis
36 Steroidal Saponins Dioscorea villosa (Mexican wild yam) root Diosgenin: saponin aglyconeNOT PROGESTROGENIC in the body. Complex chemical reactions in the laboratory make it progestrogenic. Naturally it is antispasmodic and anti-inflammatory.Human body cannot convert diosgenin into hormones.
37 Steroidal SaponinsPanax gensing (Asian) and P.quinquefoium (American gensing):Gensenosides: immunomodulating, anti-stress, anti-dementiaSaponins foam and enhance absorption of other plant constituents.Withania somnifra (Ashwaganda) rootWithanolides: calming and immunomodulatingPanax gensing
38 Triterpenoid Saponins Glycyrrhiza glabra (Licorice)Glycyrrhizin- reduces toxicity of other saponinsanti-inflammatory, antiviral, immunomodulating, hepatoprotective, anti-ulcerUsed as a synergizer in herbal formulas rendering other ingredients more bioavailabeBupleurum falcatumHepatoprotective, antiviral, immunostimulating
39 Saponins in medicine making Saponins are poorly bioavailable in the human body. Other plant constituents present in the plant aid in assimilation of saponins.Saponin rich plants influence absorption of other plant constituents:Help lipophilic constituents of plants be absorbedSaponins in high doses can cause gastric irritation. Better if they are taken with food.Mostly soluble in dilute ethanol (30%), water and lipids
41 Alkaloids Have had a major impact on humanity Examples are caffeine, morphine, ephedrine, atropine, cocaine and many more…Henbane contains hyoscamine which was known as a flying ointment.Natives using peyote, iboga in africa, south americans and ayahuasca, coca, cacao
42 Alkaloids Most potent of all plant constituents alkaloids are seen in pharmaceuticals such as codeine, morphine, atropine, pseudoepinephrine and vincristine.High doses will cause vomiting, diarrhea, immediate central nervous system symptoms and death.Important for the herbalists to be careful with herbs that have a high alkaloid content.Many herbs that contain alkaloids such as berberis and California poppy are low toxicity.
43 Alkaloids in the plants Why do plants have alkaloids? We don’t know, there are just theories…Unclearalkaloids are a way for plants to excrete excess nitrogen, like mammals excrete nitrogen though urea in the urineAlkaloids serve as defenses from predationsAlkaloids are a way for the plant to store nitrogen which is hard element to come by.
44 Alkaloids in plantsAlkaloids are common in plants: 10-15% of all plants have some kind of alkaloidMay be found in roots, leaves, bark, fruit or seeds.Over 40 different alkaloids can be present in one plant, like Vinca major.Vinca Major
45 Alkaloids- chemistryThe word alkaloid is derived from vegetable alkali, which refers to their alkaline nature due to the presence of nitrogenAlkaloids are best classified according to their biosynthetic origen.Most are synthesized by the plant from amino acidsPsuedoalkaloids- derived from terpenesDifficult to classify alkaloids. Some have nitrogen others don’t, some aren’t even alkaline. For example, mescaline, ephedrine and muscarine don’t have nitrogen. Alkaloids colchicine and ricinine aren’t alkaline.
46 Alkaloids-chemistry General characteristics alkaline Contain a nitrogenPart of a heterocyclic ring systemBerberine
47 Alkaloids- Properties Most are white in color when extracted, except berberine alkaloids which are yellowBitter in tasteSoluble in alcoholTinctures (45% ethanol) are very effective at extracting alkaloidsAcetracts extract alkaloids well, such as apple cider vinegar.Less soluble in waterThis may be a good way to deliver medicine if there is a potential for giving too high of a dose of alkaloids.
48 Alkaloids- Properties Irreversibly precipitated by tannins.Alkaloid containing medicines should not be tinctured with tannins, unless you wish to counteract the alkaloid.If you want to mix a tincture that has both alkaloids and tannins use 10% glycerine to the tincture.Black tea (Camelia sinensis), cranesbill (Geranium maculatum) or witch hazel (Hamamelis virginiana) are the three remedies for alkaloid poisoning
50 Alkaloids Many different groups of alkaloids exist The most common groups that we will be covering in this class are:Tropane Alkaloids- Belladonna, Henbane ectIsoquinoline- California poppy, berberisPyridine- Tobacco, LobeliaPyrrolizidine- Comfrey, Western ColtsfootIndole- Peyote, IbogaPurine- Cacoa, Caffeine
57 Pyridine alkaloids Derived from the B vitamin nicotinin acid Nitrogen atoms in six-membered benzene rings
58 Pyridine Alkaloids- Actions Lobeline (lobelia inflata leaf):expectorant, smasmolytic, nicotic agonistNicotine (Nicotiniana tabacum leaf):Nicotinic agonist, addictiveTrigonelline (fenugreek seed):hypolipidemic (lowers blood cholestrol)Piperine (Piper longum fruit):Increases gut permeability, hepatoprotective, used in combination with other herbs to increase efficacy
59 Pyrrolizidine alkaloids Synthesized from ornithine in plantsIngested by butterflies to protect them from invadorsAsteraceae and Boranginaceae families contain PA- ex) comfrey, echinacea and arnicaHerbal medicine containing PA are contraversial and have been banned from use in Australia.Only PA with unsaturated bases are hepatotoxic. Asteraceae herbs including echinacea and arnica have saturated PA which are non-toxic.
60 Pyrrolizidine Alkaloids Hepatotoxic in large dosesPA can cause hepatic venous occlusive disease if large doses are ingestedWhen metabolized in liver they cause DNA damage to liver cells which then fibrose around the venules of the liver. Jaundice and liver failure ensue.PA don’t affect everyone equally. Some people may not have sufficient levels of liver enzymes to metabolize PA.Intake of over 3 gm/day of PA can cause liver damage within three months.PA become dangerous after undergoing metabolism by P450 enzymes in the liver. The toxic byproduct (alkylating pyrrole ester) attack DNA, damaging hepatocytes.Hepatocytes are destroyed and fibrosis occurs.
61 Pyrrolizidine Alkaloids Symphytum off. (Comfrey) has PAMucilagenous, anti-inflammatory, heals ulcers internally and externally.Has been condemned as toxic by many.Few cases of injury have been reported and of those cases people who were poisoned ate the root which is much higher in PA than the leaves.Glycyrrhizin (saponin from licorice) has been found to protect the liver from PA
62 Pyrrolizidine Alkaloids Other plants that contain PA:Tussilago farfara (Eastern coltsfoot)Sencio spp (Life root)Borago officianlis ( Borage)Tussilago farfara
63 Pyrrolizidine Alkaloids Senecio spp. (Liferoot or Ragweed)
64 Indole AlkaloidsLarge number of medicinal alkaloids are found in this groupDerived from tryptophan or tryptamine in plants.Contain 2 nitrogens and often involve multiple rings.Form the basis of several hallucinogenic and pharmaceutical drugs.
66 Indole Alkaloids- Reserpine Reserpine found in Rauwolfia serpentina has been used in Aryuvedic medicine as a hyptotensive, seditave and tranquilizer.Reserpine temporarily inhibits noradreniline and depletes the amino acids in the central nervous system.Hypotensive effects have a slow onset and their duration is long.Use cautiously depression and severe hypotension are indications of overdose.Reserpine blocks the transport of catecholemines (seratonin, NE and dopamine) from their receptors on the nerve endings. Catecholemines are the nuerotransmitters responsible for increasing heart rate, force of contraction of the heart and peripheral resistance.
67 Indole Alkaloids Cantharanthus roseus (Madigascar Periwinkle) Contain vinblastine and vincristine- antineoplastic used in chemotherapy for childhood luekemia and non-Hodgkin’s lymphomaVinca minor, major (Common Periwinkle)Vincamine- anti-hemorrhagic and astringent. Does not contain the anti-cancer alkaloids that cantharanus has.Claviceps purpurea (Ergot)Ergotamine- fungus grows on rye.Migraine reliefSt.Anthony’s Fire- epileptic convulsions and spasms.LSD is derived from ergot. Similar compounds found in Ipomoea spp. (Morning Glory)
70 Purine AlkaloidsCaffeine, theobromine (chocolate), theophylline (from cacao and tea)Methyl xanthines- Derived from the purine nucleotides adenine and guanine with attached methyl groups.Mild stimulants and bronchodilatorsTheophylline is a drug used for respiratory distress and asthma.
72 Purine Alkaloids Increase the rate of cardiac contraction Increase alertness and induce digestive enzyme activity in the GIThey act by stimulating the Central nervous system and prolonging the life of hormones, such as adrenaline.
74 Why are bitters important? Increase the appetite:Have been used in aperitifs or to induce appetite in convalescenceIncrease digestive secretionsLow enzymes or stomach acid aid in depressed digestive ability and leads to proteins from food penetrating into the wall of the gut.Increases stomach and pancreatic enzyme secretions and aid the body in breaking down food.
75 BittersProtect gut tissue: Increase the tone of the lower esophageal sphincterPrevent reflux or heart burn, hiatal hernia or esophageal irritation.Promote bile flow: reduces toxic load on liver by flushing out toxic accumililations by increasing bile.Increases bicarbonate from gallbladder and thins bileGallstone and gallbladder disease
76 Bitters Indicated for symptoms of poor digestions Belching, loss of appetite, constipation, bloating and nausea after eating.Controversy weather bitters are safe to use with people who have ulcers because too much acid could aggravate the ulcerBitters increase secretions of bicarbonate from the pancreas which protect the stomach from acid.
78 Acids Weak acids constitute a main part of all plant material Acids we will coverUnsaturated fatty acidsFormic AcidOxalic AcidCitric AcidOther acids that occur in plants areAcetic, succinic, benzoic and tartaric
79 Unsaturated Fatty Acids Found universally in plants and less so in animals.Linolenic and arachadonic acids- found in seeds and reproductive tissues of the plantsLinolenic acids- found in the green tissues of plantsPUFAs (Polyunsaturated fatty acids) are vitally necessary in the diet = ESSENTIAL FATTY ACIDS
80 Essential Fatty Acids Why are they so important? Build and repair cell membranesForm raw material for prostaglandin production in the bodyProstaglandins are important in smooth muscle contractions, inflammatory mediators, and raise blood pressureExample of PUFA- Evening Primrose (Oenothera biennis) has gamma linolenic acid
81 Evening PrimroseUsed as an anti-inflammatory conditions like rhuematoid arthritis, PMS and eczema
82 Formic AcidThe smallest organic acid and the most corrosive to the skin….just like fire ants!Used in counterirritants and vesicantsFound in red antsFormic Acid is the sting in stinging nettlesOxidizes and is inactive after being exposed to heat.Cook your nettles to eat them!!
83 Oxalic Acid Forms insoluble salts with minerals such as calcium. Found in foods such as spinach, beets and parsleyFound in the dock and rhubarb families.Oxalic acid bound to iron and calcium is what makes Yellow Dock so highly nutritious.Care needs to be taken to not consume too many oxalate rich foods if there is a history of oxalate kidney stones.
84 Citric AcidFound widely in fruits and berries, especially citrus fruitsCleansing in the bodyAlkalinizing effect:citrus breaks down into bicarbonate once in the stomachAlkalinizing effect in mouth provides the environment inhospitable to bacteriaIncreases bile flow from the liverExplains use of lemon for gallbladder cleanses