Acetate-mevalonate Pathway (Part 1) - Pharmacognosy & Phytochemistry PDF

Pharmacognosy and Phytochemistry Acetate-mevelonate pathway (part1)/ monoterpenes By Dr. Farah Al-Mamoori  Large structurally diverse family of natural products >35,000  Formed from C5 Isoprene units joined together Head to tail or Tail to tail...

Pharmacognosy and Phytochemistry Acetate-mevelonate pathway (part1)/ monoterpenes By Dr. Farah Al-Mamoori  Large structurally diverse family of natural products >35,000  Formed from C5 Isoprene units joined together Head to tail or Tail to tail  Classification is based on the number of isoprene units forming the carbon skeletons Isoprene (2-methyl-1,3-butadiene)   Based on the number of Isoprene units in the compound.  Carbon skeletons represented by (C5)n (n=number of isoprene units)  Classes of Terpenes: Hemiterpenes C5 Monoterpenes C10 Sesquiterpenes C15 Diterpenes C20 Sesterpenes C25 Triterpenes C30 Teteraterpenes C40 Polyterpenes >C40  The isoprene units of myrcene are joined "head-to-tail."  Representative Monoterpenes Citral -Phellandrene Menthol (peppermint) (lemon grass) (eucalyptus) OH O H  Representative Sesquiterpenes -Selinene (celery)  Representative Diterpenes Vitamin A OH  Representative Triterpenes Squalene (shark liver oil) isoprene units(tail-tail) - The isoprene units in terpenes do not come from isoprene. - They come from isopentenyl pyrophosphate. - Isopentenyl pyrophosphate (5 carbons) comes from acetate (2 carbons) via mevalonate (6 carbons). Isopentenyl pyrophosphate is interconvertible with 2-methylallyl pyrophosphate. OPP OPP Isopentenyl pyrophosphate Dimethylallyl pyrophosphate Dimethylallyl pyrophosphate has a leaving group (pyrophosphate) at an allylic carbon; it is reactive toward nucleophilic substitution at this position.  OPP + OPP The key process involves the double bond of isopentenyl pyrophosphate acting as a nucleophile toward the allylic carbon of dimethylallyl pyrophosphate.  OPP + OPP – OPP + OPP  After C—C Bond Formation... OPP The carbocation can lose a proton to give a double bond. + –H + OPP  After C—C Bond Formation... OPP This compound is called geranyl pyrophosphate. It can undergo hydrolysis of its pyrophosphate to give geraniol (rose oil).  From 10 Carbons to 15 OPP + OPP Geranyl pyrophosphate + OPP  OPP + –H + OPP  OPP This compound is called farnesyl pyrophosphate. Hydrolysis of the pyrophosphate ester gives the alcohol farnesol  OPP OPP Farnesyl pyrophosphate is extended by another isoprene unit by reaction with isopentenyl pyrophosphate.  Rings form by intramolecular carbon-carbon bond formation.  Bicyclic terpenes  Volatile Oils /essential oils Large group of natural products of a complex mixture of aromatic- smelling volatile components containing either phenylpropanes (shikimic acid-derived) or terpenes (Acetate-Mevalonate-derived). *Volatile or essential oils are volatile in steam. *They differ entirely in both chemical and physical properties from fixed oils They are secreted in: Oil cells in Cinnamon  Oil glands e.g. Clove Secretion ducts (vittae) e.g. Anise  How To Test Essential Oil Purity? This simple test will tell you if your essential oils are pure, or have base (e.g., fixed) oils added. Difficulty: Easy Time Required: 10 - 15 min. Here's How: 1. Place 1-2 drops of the essential oil on tissue. 2. Place the tissue in an open air area. 3. Eventually the oil should completely evaporate leaving no oily residue. 12/2/2024 28  Preparation of Volatile Oils Steam Distillation:  Steam distillation is the most common method of extracting essential oils.  Many distillers favor this method for most oils, and considers none of the newer methods to produce better quality oils.  Steam distillation is done in a still. Fresh, or sometimes dried, botanical material is placed in the plant chamber of the still, and pressurized steam is generated in a separate chamber and circulated through the plant material.  The heat of the steam forces the tiny intercellular pockets that hold the essential oils to open and release them.  The temperature of the steam must be high enough to open the pouches, yet not so high that it destroys the plants or fractures or burns the essential oils.  As they are released, the tiny droplets of essential oil evaporate and, together with the steam molecules, travel through a tube into the still's condensation chamber.  As the steam cools, it condenses into water. The essential oil forms a film on the surface of the water. 12/2/2024 2. Cold Pressing  Another method of extracting essential oils is cold pressed expression.  It is used to obtain citrus fruit oils such as bergamot, grapefruit, lemon, lime, mandarin, orange, and tangerine oils.  In this process, fruit rolls over a trough with sharp projections that penetrate the peel. This pierces the tiny pouches containing the essential oil.  Then the whole fruit is pressed to squeeze the juice from the pulp and to release the essential oil from the pouches.  The essential oil rises to the surface of the juice and is separated from the juice by centrifugation. 30 Dr.Farah Al-Mamoori 02/12/2024 3. Enfleurage Some flowers, such as jasmine, have such low contents of essential oil or are so delicate that heating them would destroy the blossoms before releasing the essential oils. In such cases, an expensive and lengthy process called enfleurage is sometimes used to remove the essential oils. Flower petals are placed on trays of odorless vegetable or animal fat, which will absorb the flowers' essential oils. 12/2/2024 32  Every day or every few hours, after the fat (or oil) has absorbed as much of the essential oil as possible, the depleted petals are removed and replaced with fresh ones.  This procedure continues until the fat or oil becomes saturated with the essential oil. 12/2/2024 33 Liquids at room temperature  Colourless or slightly yellowish  Low solubility in H2O  Soluble in organic solvents  Optically active  High refractive index  Mostly lighter than H2O EXCEPT clove, cinnamon & sassafras  oils Oxidized by O2 from air (resinification)  Light exposure oxidation (small, amber glass containers)  Do not stain filter paper (fixed oils do)  Evaporate at room temp.  Obtained by steam distillation (pharmaceutical use), water  distillation, expression (citrus oils), organic solv. extraction 10 Determination of the structure of terpenes : Chemical constituents of volatile oils may be divided into 2 broad classes based on their biosynthetic origin: -Terpene derivatives formed via acetate mevalonic pathway. -Aromatic compounds formed via shikimic acid. These contain C6 phenyl ring with an attached C3 propane side chain. Terpenes Phenylpropane  Terpenoid Components of V.O Monoterpenes & sesquiterpenes Monopterpenes: Most monoterpene-rich v.o are flavouring agents Some as rubefacients, sedatives & bitters, insecticides Monoterpenes classified by degree of oxidation (hydrocarbons, alcohols, aldehydes, ketones, phenols & oxides)  The oils should not be used undiluted, but should be diluted with an odourless carrier oil, such as sweet almond oil. For adults: 2.5 percent dilution: 15 drops essential oil per 6 teaspoons carrier oil 3 percent dilution: 20 drops essential oil per 6 teaspoons carrier oil 5 percent dilution: 30 drops essential oil per 6 teaspoons carrier oil 10 percent dilution: 60 drops essential oil per 6 teaspoons carrier oil For children:.5 to 1 percent dilution: 3 to 6 drops essential oil per 6 teaspoons carrier oil Some examples:  Cinnamon oil  Anise oil  Fennel oil  Clove oil  Nutmeg oil  Origin: the dried bark of the branches of the coppiced trees of Cinnamomum zylanicum F. Lauraceae Active constituents: *0.5-1% volatile oil contains cinnamaldehyde *Mucilage and tannins. Uses: 1- carminative and flavoring agents 2- Antiseptic O H Cinnamaldehyde is an important flavoring in foods (e.g., candy and cookies) and an odorant for perfumes. It has also been used to eradicate mosquito larvae and repel adult mosquitoes. Taking cinnamon oil by mouth is POSSIBLY UNSAFE. The oil can be irritating to the skin and mucous membranes, including the stomach, intestine, and urinary tract. It can cause side effects such as diarrhea, vomiting, dizziness, drowsiness, and others. - Anise Fruit (Fructus Anisi, Aniseed) Origin: the dried ripe fruits of Pimpinella anisum F. Umbelliferae Volatile oil containing anethol Uses: Antispasmodic, carminative, parasiticidal carminative and flavoring agent. OCH3 ANETHOLE H3C OCH3 CH C OCH3 H2C CH3 Dianethol Both Japanese and Chinese star anise are identical in appearance but its fruit is smaller and the Japanese variety has a milder fragrance than its Chinese counterpart, and is thought to smell more like cardamom seeds than aniseed 23 Toxic Compounds Japanese anise contains several toxic compounds that are not found in the Chinese star anise. Anisatin Sikimitoxin Shikimin Japanese star anise should never be ingested in any form. Symptoms of toxicity caused by the Japanese star anise are: Seizures  Inflammation of the urinary tract  Inflammation of the digestive tract  Kidney problems  Symptoms generally show themselves within six hours of  ingestion, beginning with diarrhea and vomiting (Foeniculum vulgare), family (Apiaceae) The main components of fennel oil are trans-anethole (53.51%), fenchone (8.32%) Fennel oil is a remedy for digestive complaints such as flatulence, constipation, and colic CH3 CH CH2 O Fenchone OCH3 Anethole Herbal tea should never be given to a baby under 6 months of age because it could contain harmful bacteria or cause an allergic reaction.  Origin: the dried flower buds of Syzygium aromatica , Eugenia aromaticum or Eugenia caryophyllus F. Myrtaceae Active constituents: Volatile oil (15 -20%) contains eugenol (85%) , eugenol acetate and caryophyllen Uses: *Local anesthetic for toothache. *Antispasmodic and carminative. Bicyclic sesquiterpene Eugenol Caryophyllene Case studies have been reported involving the ingestion of toxic amounts of clove oil (10-30 ml, or roughly 2-6 teaspoons). Symptoms include agitation, declining consciousness, and coma. Consuming clove oil can be dangerous for children and may lead to seizures, liver damage, and fluid imbalances. Pregnant women are advised against using this remedy, as it is not known whether clove oil is safe for the growing baby. The oil should never be applied to the gums undiluted. : Add 3 to 5 drops of clove oil to 1 teaspoon of carrier oil like olive oil Dab a cotton ball into the diluted oil and apply it to the affected gums Biological source: It is the volatile oil obtained from steam distillation of dried kernels of the ripe-seed of Myristica fragrans; Family: Myristicaceae Nutmeg contains of 5 to 15% volatile oil, Nutmeg is aromatic, carminative, flavouring agent. It has narcotic action and peripherally it irritates and produces anesthetics action Small amounts of nutmeg can be used safely in cooking. Most recipes only call for roughly 1/4 to 1/2 teaspoon of nutmeg per recipe. These recipes are often split into multiple portions, leaving the actual exposure to nutmeg very insignificant. According to the case studies from the Illinois Poison Center, even 10 grams (approximately 2 teaspoons) of nutmeg is enough to cause symptoms of toxicity. At doses of 50 grams or more, those symptoms become more severe. The most common symptoms in the 10-year review included: hallucinations  drowsiness  dizziness  dry mouth  confusion  seizure (in two cases)  Some of the other notable side effects were  respiratory, cardiovascular, and gastric distress.  Monoterpene-rich volatile oils Some examples:  Peppermint oil  Lavender oil  Lemon oil  Camphor  Thyme oil  Turpentine oil  Rosemary oil  Botanical name: peppermint oil is obtained from the dried leaves and flowering tops of the plant Mentha piperita Use: Carminative;Stimulant; Counter irritant;Flavouring agent; in chewing gum, candy toothpaste. Menthol A counterirritant is a substance that creates irritation or mild inflammation in one location with the goal of lessening discomfort and/or inflammation in another location. This strategy falls into the category of counterstimulation. HARRAR® contains natural active ingredients like Thyme, Eucalyptus, Turpentine, and Topical counter-irritants are non-analgesic, non-anesthetic Menthol. substances or treatments used to treat pain. Capsaicin, menthol (mint oil), methyl salicylate, and camphor are examples of counterirritants. Heat and cold therapy and massage relieve pain by counter stimulation The US FDA defines a counterirritant as: "An externally applied substance that causes irritation or mild inflammation of the skin for the purpose of relieving pain in muscles, joints, and viscera distal to the site of application. They differ from the anesthetics, analgesics, and antipruritic agents, however, in that the pain relief they produce results from stimulation—rather than depression—of the cutaneous sensory receptors and occurs in structures of the body other than the skin areas to which they are applied, for example, in joints, muscles, tendons and certain viscera The Difference Between Peppermint & Spearmint is that peppermint contains a high concentration of menthol, giving it a cooling sensation on the skin and a sinus opening effect. Spearmint is warming and soothing due to its high natural carvone concentration and often experienced as calming and relaxing Spearmint has earned the nickname “The Gentler Mint Oil,” as its scent is softer and its effects are milder than those of Peppermint Essential Oil, making it ideal for children, the elderly, and those with sensitive skin  carvone Peppermint oil should be kept away from children and infants as it may trigger breathing issues. The oil, in large doses, may also lead to seizures and harm the digestive system. Peppermint Oil Peppermint oil feels cool and may help with pain. Rubbing it along your hairline may also help relax the muscles in your face and neck. One small study backs that up. The researchers focused on 41 people with tension headaches and found that applying peppermint oil to the forehead and temples was as effective as taking 1,000 milligrams of acetaminophen. More research would be needed to confirm that, though.  Thymus vulgaris (Lamiaceae) Thyme oil is extracted from the fresh or partly dried flowering tops - and leaves of the plant by water or steam distillation and the yield is 0.7-1.0%. Carvacrol is an isomer of thymol, Thyme oil is used as a germ-killer in mouthwashes.  It is also applied to the scalp to treat baldness and to the ears to  fight bacterial and fungal infections. Thymol, one of the chemicals in thyme, is used with another chemical,  chlorhexidine, as a dental varnish to prevent tooth decay. In foods, thyme is used as a flavoring agent.  In manufacturing, red thyme oil is used in perfumes. It is also used in  soaps, cosmetics, and toothpastes. Recognized worldwide for its fresh and heady fragrance,  the lavender plant (Lavandula angustifolia), a flowering evergreen shrub native to the Mediterranean region, also has a long history in herbal healing. Lavender oil is a classic for calming anxieties and fears. It is also known for helping to combat headaches, insomnia, stress and nervous tension. Highly valuable for its healing effects on the skin, it can be used to soothe skin rashes and irritations and to reduce the excess sebum production that occurs in acne. It helps to reduce inflammation that occurs due to insect bites, bee stings and other toxic bites. Is one of the most versatile oils available.  When diffused (sprayed), it has the effect of purifying the  air, removing odors and uplifting the spirits. When applied topically, it is absorbed into the skin and has  a wide range of uses British aromatherapists use it as an antiseptic to purify hospital air. Because of its very high content of vitamin C and flavonoids, it is ideal for those who have poor circulation and who are trying to rebuild the blood vessels. It is also one of the highest sources of limonene - a highly anti-inflammatory substance Isomerism Carbon number four of the cyclohexene ring is chiral. Limonene therefore has two optical isomers. Chiral centres are labelled as R or S The two enantiomers have identical chemical properties but different odours. R-Limonene smells like orange and S-Limonene smells like lemon. Rosemary oil has anti-inflammatory and pain-relieving properties you can benefit from by massaging the oil on 1,8-cineole the affected area Chemical components of rosemary oil are 1,8-cineole *Rosemary oil may help with this type of hair loss. A study of mice with testosterone-related hair loss found that rosemary oil could regrow their hair. Although the study is not conclusive, its authors theorize that rosemary oil might prevent DHT from binding to hormone receptors that enable it to attack the hair follicles. Sage Oil is steam distilled from the leaves of the Salvia officinalis herb Commercial sage oil is generally characterized by thujones, with α-thujone usually predominating (18– 43%) over thujone (3–8.5%), Sage Essential Oil is reputed to ease the muscular and joint pain, address bacterial infections and spasms, promote relief for digestive complaints, and calm skin conditions such as dermatitis and Athlete’s Foot. Sage Oil is also known to regulate and stabilize menstrual cycles and related symptoms. Sage is possibly unsafe when taken in high doses or for a long time. Some species of sage, including common sage (Salvia officinalis), contain a chemical called thujone. Too much thujone can cause seizures and damage the liver and nervous system.  Turpentine is a fluid obtained by the - complex distillation from resin obtained by trees, mainly the various species of pine (Pinus). It is composed of terpenes, mainly the - monoterpenes α-pinene and β-pinene. Turpentine oil is applied to the skin for joint pain, muscle pain, nerve pain, and toothaches. People sometimes breathe in (inhale) the vapors of turpentine oil to reduce the chest congestion that goes along with some lung diseases. In foods and beverages, distilled turpentine oil is used as a flavoring is the oil extracted from the wood of camphor trees and processed by steam distillation. The main components of the essential oil were identified to be D-camphor (40.54%), Camphor is used to relieve chest congestion and inflammatory conditions. It has a strong odor and taste and is easily absorbed through the skin camphor This groups of monoterpenes is produced from folding of the geraniol structure to produce an iridoid moiety. The most notable example is valerian: valerian root is the dried underground portions of Valeriana officinalis L. (Valerianaceae) The plant smells like cat urine. Valeriana officinalis‫الناردين‬ The active constituents are a range of compounds the most important being the epoxy-iridoid-esters called the valepotriates, the most important of which is valtrate (up to 2%) There is also a volatile oil content (up to 1%) and two sesquiterpenes: valerenic acid and valeranone  This herbal is best known for its ability to help with sleeping difficulties.  It is thought that valerian (Valeriana officinalis) promotes sleep and relaxation via increased GABA secretion and inhibition of its reuptake.  Sesquiterpenoids are defined as the group of 15 carbon compounds derived by the assembly of 3 isoprenoid units.  Sesquiterpene structures present several acyclic, mono-, bi-, tri-, and tetracyclic systems.  The addition of another IPP unit to geranyl diphosphate (GPP) gives rise to farnesyl diphosphate (FPP) (C15).  FPP gives rise to the linear and cyclic sesquiterpenes.  Some interesting sesquiterpenes are found in Feverfew, Cotton seeds and Chamomile. Feverfew (Family: Asteraceae) Tanacetum parthenium Chrysanthemum parthenium,(‫)االقحوان الذهبي‬  Various forms of feverfew grow to heights of between 9 inches and 2 feet. The deeply cut leaves are brightly colored and have a sharp, unpleasantly bitter taste. The flowers, which are produced from summer until mid-fall, are thick and daisy like with yellow centers.  Feverfew was mentioned in Greek medical literature as a remedy for inflammation and for menstrual discomforts.  Traditional herbalists in Great Britain used it to treat fevers, rheumatism, and other aches and pains.  It is used for the relief of migraine, to help prevent blood clots, as an anti- inflammatory for relief of arthritis, to relieve some types of menstrual problems, and as a digestive aid.  Feverfew contains a range of compounds known as sesquiterpene lactones. Over 85% of these is a compound called parthenolide.  Parthenolide is the active constituent of feverfew leaves (up to 1%), a natural remedy used in the treatment of acute migraine attacks. parthenolide Tanacetum parthenium  Wormwood (Artemisia annua ‫الشيح‬  Family: Asteraceae.  The constituents of wormwood include absinthin, anabsinthin (both bitter compounds), and a volatile oil that is 70% thujone. Artemisinin present in leaves and flower of the plant in 0.01-0.08% dry weight Artemisia annua Artemisia absinthium Artemisia herba-alba Artemisinin  Artemisinin, is a component of the Chinese traditional antimalarial drug. Used for centuries for the treatment of fever and malaria  Artemisinin shows antimalarial properties against the chloroquine resistant strain of Plasmodium falciparum  The structure is that of a sesquiterpene lactone with a peroxide link that is important for activity  The major metabolite of these molecules is dihydroartemisinin, which is a more active antimalarial than artemisinin, rapidly clearing the blood of the malaria parasite. Peroxide link ‫كان نبات الشيح معروفا لدى الصينيين القدامى‪ ،‬حيث ذكرت بعض النصوص التي تعود لعام ‪ 168‬قبل الميالد تسمية تشينغهاو‬ ‫(‪ )qinghao‬هو االسم الصيني لما يعرف بالغرب بالشيح الحولي )‪)Artemisia annua‬‬ ‫حرب فيتنام شهدت حينها انتشار أنواع أخرى من مرض المالريا فتكت بكثيرين من كال األطراف المتحاربة وقاومت العالج‬ ‫التقليدي باستخدام الكلوروكين‪.‬بالتزامن مع ذلك‪ ،‬خلّفت المالريا أعدادا كبيرة من القتلى بجمهورية الصين الشعبية‪.‬‬ ‫عقد ماو تسي تونغ اجتماعا بالعاصمة الصينية بكين وأمر بإطالق مشروع سري لقّب بالبرنامج ‪ ،523‬نسبة لليوم والشهر‬ ‫الذي عقد خالله االجتماع‪ ،‬اتجه من خالله للبحث عن دواء فعّال ضد المالريا فجنّد لهذا األمر ‪ 500‬عالم وخصص ‪ 60‬معهدا‬ ‫ومختبرا مدنيا وعسكريا إلنجاح هذا المشروع‪.‬‬ ‫سمت طريقة العمل لمجموعتين فتكفلت األولى بالبحث عن دواء كيميائي بينما أوكلت للمجموعة الثانية مهمة إيجاد‬ ‫إلى ذلك‪ ،‬ق ّ‬ ‫عالج للمالريا اعتمادا على الطب التقليدي واألعشاب‪.‬‬ ‫ضمن فريق العلماء تواجدت الصينية تو يويو)‪ )Tu Youyou‬البالغة من العمر ‪ 36‬سنة والحاصلة على شهادة في‬ ‫مجال الصيدلة والمعجبة بمجال األعشاب والعالج الطبيعي والطب الصيني‪.‬وفي خضم البرنامج ‪ ،523‬أجرى‬ ‫فريق تو يويو اختبارات على أكثر من ألفي دواء تم استخالصهم من النباتات والحيوانات والمعادن واألمالح‬ ‫المعدنية‪.‬وقد اتجهت تو يويو الحقا إلجراء اختبارات اعتمادا على نبات الشيح الحولي‪.‬‬ ‫عام ‪ ،1971‬أجريت تجربة ناجحة على عدد من القردة المصابين بالمالريا اعتمادا على مركب وجد بنبات الشيح‬ ‫الحولي وأطلق عليه الصينيون اسم تشينغهاو سو ولقبه الغرب بأرتيميسينين )‪)Artemisinin‬‬ ‫وقد استغرق العمل الحقا سنوات أخرى للحصول على دواء ضد المالريا حيث تم دمج هذا المركب مع مركبات‬ ‫أخرى للوصول لنتيجة إيجابية‪.‬وكتكريم لها على أعمالها في مواجهة المالريا‪ ،‬تقاسمت العالمة الصينية تو يويو‬ ‫عام ‪ 2015‬جائزة نوبل للطب‬  Artemisinin is believed to act via a two-step mechanism. Artemisinin is first activated by intraparasitic heme-iron which catalyzes the cleavage of this endoperoxide.  A resulting free radical intermediate may then kill the parasite by alkylating and poisoning one or more essential malarial protein(s).  Gossypol, a dimeric sesquiterpene, is found in cotton seeds (Gossypium species) in amounts up to 0.6%.  It acts as a male contraceptive, effective multiple aspects of sperm quality and function (sperm maturation, motility, and inactivate sperm enzymes necessary for fertilization).  Clinical trials in China have shown that this infertility can be reversible.  Gossypol is a chiral molecule. Only the (-) isomer is active. Most of the toxic effects are caused by the (+) isomer. 2. Sesquiterpenes Gossypium hirsutum L. ‫القطن‬ Chamomile ‫البابونج‬  Two types of chamomile (Family: Asteraceae) are used in herbal medicine: 1. Roman chamomile or Chamaemelum nobile (Perennial) and 2. German chamomile or Matricaria chamomilla (annual).  The oil contains α-bisabolol which is responsible for antibacterial properties and chamazulene which is anti-inflammatory (inhibits cyclooxygenase enzyme).  German chamomile is mainly employed for its anti-inflammatory and antibacterial properties. Used in creams and ointments.  The primary constituents of chamomile are a volatile oil, flavonoids, and mucilage.  Volatile oil: Contain the terpenoids chamazulene, α-bisabolol  Flavonoids: Apigenin, luteolin and quercetin.  Actions and uses: German chamomile can mainly be classified as a natural remedy for all conditions affecting the mucosa. Hence, the indications for chamomile range from diseases of the skin, mouth, and throat to those of the gastrointestinal tract and bronchial system.  It can be used from childhood to old age. Mechanism of action  The inhibition of prostaglandin synthase and lipoxygenase is responsible for the antiphlogistic action of chamomile.  The principles in the volatile oil have mainly an antiphlogistic action.  Chamomile has also been found to encourage the healing of wounds. This effect is again closely linked with its anti-inflammatory action.  Bisabolol definitely has peptic ulceroprotective, and ulcerocurative effects.  The mucilaginous agents in chamomile may also be responsible for the antiulcerogenic effect of the herb.  The flavonoids also have a powerful spasmolytic activity, three times greater than that of papaverine  Chamomile is able to inactivate toxins produced by bacteria  The spasmolytic and anti-inflammatory action can be effectively used to treat a wide range of intestinal conditions, particularly colitis, irritable colon and also promotes the healing of ulcerative lesions  Chamazulene: This constituent is a derivative of plants such as Chamomile.  It is an aromatic compound that has a deep blue color. The “-azulene” part of its name was given to it based on its blue color and the “Cha” was given to it due to it being first discovered in Chamomile 3 Diterpenes C20 compounds derived from geranylgeranyl diphosphate (GGPP) which is formed by addition of IPP unit to FPP  Phytol, the Taxanes, and the Ginkolides are examples of diterpenes derived from GGPP  Phytol is important due its presence in Chlorophyll, Vitamin E, and Vitamin K  The naturally occurring dipterpene molecule Phytol is an alcohol that can be extracted from the chlorophyll of green plants  Phylloquinone (Vitamin K1) Taxanes and Taxol  Taxanes are of the more pharmaceutically significant diterpenes.  Over 100 taxanes have been identified being obtained from the Taxus species.  The anticancer taxane drug paclitaxel is extracted from the bark (0.02%) of the Pacific yew (Taxus brevifolia).  Taxol (paclitaxel) is a complex fuctionalized diterpene.  Taxol was first isolated from Yew bark in 1962 as part of the National Cancer Institute (NCI) program in search of natural products exhibiting anticancer activity.  Contains a 4-membered oxetane ring and complex ester side chain, both of which are required for activity Taxol (Paclitaxel) Taxane diterpene nucleus  Ginkolides Ginkgo biloba (Ginkgo, ‫)الجنكة‬  It is the only representative species of its family Ginkgoaceae.  Ginkgo tree was discovered in China in 1690 by Kaempfer who wrote the first scientific description of this tree.  In Chinese pharmacopoeia, Ginkgo seed and leaves are reported as “good for heart and lungs”. The main uses are anti-asthma, anti-tussive, expectorant, analgesic, anthelmintic, etc., and most of these actions can be described with modem pharmacology and clinical studies. Ginkolides  The ginkolides are produced from extensive modification of the diterpene structure. They are the active constituents of Ginkgo biloba (Ginkoacea).  Standardised exracts of the leaves found in Europe and USA have been shown to improve peripheral and cerebral circulation.  Dried leaves contain up to 0.25% of the active constituents consisting of 5 ginkolides, A,B,C, J and M and bilobolide (sesquiterpene)  The leaves are used by the elderly to alleviate memory loss. Ginkolides  The constituents of Ginkgo biloba leaf extract, ginkgolides are known as effective antagonists of platelet-activating factor (PAF).  Ginkgo has been repeatedly evaluated for its ability to reduce anxiety, stress and other symptoms associated with Alzheimer’s disease and cognitive decline associated with aging.Overall, research results are inconsistent in this area.  Some studies show a marked reduction in the rate of cognitive decline in people with dementia using ginkgo, but others fail to replicate this result.  A review of 21 studies revealed that when used in conjunction with conventional medicine, ginkgo extract may increase functional capabilities in those with mild Alzheimer’s.  Another review evaluated four studies and found a significant reduction in a spectrum of symptoms associated with dementia when ginkgo was used for 22–24 weeks.  These positive results could be related to the role that ginkgo may play in improving blood flow to the brain, especially as it relates to vascular types of dementia. Is Ginkgo biloba good for young adults? Ginkgo biloba is reported to enhance cognitive function in patients with selected neural disorders. Its effects in healthy, young adults are less well characterized Ginkgo biloba phytosome may be effective in reducing the number of Raynaud's attacks per week in patients suffering from Raynaud's disease. Interactions Possible interactions include: Alprazolam. Taking ginkgo with this drug used to relieve symptoms of anxiety might reduce the drug's effectiveness. Anticoagulants and anti-platelet drugs, herbs and supplements. These types of drugs, herbs and supplements reduce blood clotting. Taking ginkgo with them might increase your risk of bleeding. Anticonvulsants and seizure threshold lowering drugs, herbs and supplements. Large amounts of ginkgotoxin can cause seizures. Ginkgotoxin is found in ginkgo seeds and, to a lesser extent, ginkgo leaves. It's possible that taking ginkgo could reduce the effectiveness of an anticonvulsant drug. Antidepressants. Taking ginkgo with certain antidepressants, such as fluoxetine (Prozac) and imipramine (Tofranil), might decrease their effectiveness. Certain statins. Taking ginkgo with simvastatin (Zocor) might reduce the drug's effects. Ginkgo also appears to reduce the effects of atorvastatin (Lipitor). Diabetes drugs. Ginkgo might alter your response to these drugs. Ibuprofen. It's possible that combining ginkgo with ibuprofen (Advil, Motrin IB, others) might increase your risk of bleeding.  Triterpinoids Derived from two molecules of farnesyl PP joined together to produce the precursor Squalene The pharmaceutically most important are the pentacyclic triterpinoids (also called saponins) Mevalonic acid Methylerythritol phosphate OPP DMAPP IPP OPP Hemiterpenes (C5) Geraniol Geranyl diphosphate IPP C10 Monoterpenes (C10) OH Farnesol Farnesyl diphosphate C15 Sesquiterpenes (C15) OH IPP Geranylgeraniol Geranylgeranyl diphosphate C20 Diterpenes (C20) OH IPP Sesterpenes (C25) C25 Squalene C30 Triterpenes (C30) Steroids (C18-C30) Phytoene C40 Tetraterpenes (C40) 7  Representative Triterpene tail-to-tail linkage of the two central isoprene units Squalene (shark liver oil)  FPP OPP FPP allylic cation squalene squalene HO lanostterol  Lanatosterol & Cycloartenol H H Oxidation, cyclyzation, alkyl Squalene migration & folding of squalene produce STEROIDS {lanosterol (animals & fungi) and cycloartenol (plants)} 2 HO Cycloartenol 3 Squalene oxide Plants O HO Lanosterol Animals & Fungi Saponin Glycosides - "Sapo" is Latin name for soap (soap-like) - Group of organic compounds that form persistent froth when shaken with water even in dilute solution. -Saponins cause haemolysis of red blood cells. If injected intravenously they cause hemolysis. Use only orally! Destroy the membranes of red blood cells. There are two types of saponins 1- Pentacyclic Triterpenoids 2- Steroidal Saponins. Historically soap was made from the soapwart plant. Saponaria officinalis ‫شرش الحالوة‬ The foaming and emulsifying properties of saponins are because of their amphipathic nature, i.e., hydrophobic aglycone backbone and hydrophilic glycan moiety. The pentacyclic triterpenoid skeleton exemplified by lupeol, α- amyrin and β-amyrin are encountered in the form of triterpenes saponins structure. HO HO β-amyrin α-amyrin Lupeol b-amyrin a-amyrin Liquorice (licorice), which is the dried, unpeeled root of the herb Glycyrrhiza glabra ‫(عرق السوس‬Fabaceae). Glycyrrhizic acid is the major triterpenoid saponin in licorice root and the main sweetener of the herb. Glycyrrhizic (or glycyrrhizinic) acid is a diglucuronide of the aglycone glycyrrhetic (glycyrrhetinic) acid. The bright yellow colour of liquorice root is provided by flavonoids (1- 1.5%), including liquiritin and isoliquiritin, and their corresponding aglycones. Glycyrrhizin is reported to be 50-150 times as sweet as sucrose, and liquorice has thus long been used in pharmacy to mask the taste of bitter drugs.  Glycyrrhiza licorice appears to have modest glucocorticoid activity and may act synergistically with cortisol. (Glycyrrhizin, which is structurally similar to corticoids) can bind to glucocorticoid and mineralocorticoid receptors, weakly mimicking the role of endogenous steroid hormones.  The structure of glycyrrhetinic acid is close to that of cortisone.  Both molecules are flat and similar at position 3 and 11.  This might be the basis for licorice's anti-inflammatory action. The active components of licorice G exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2 Licorice-Induced Hypertension and Hypokalemia: Consuming large amounts of licorice has been associated with hypertension and hypokalemia Glycyrrhizin Mechanism: Glycyrrhetinic acid, the active component of licorice, inhibits renal IIbeta-hydroxy- steroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid receptors, which can lead to hyperten-sion and hypokalemia Licorice extract improves hyperpigmentation by dispersing the melanin, inhibition of melanin biosynthesis and inhibition of cyclooxygenase activity thereby decreasing free radical production. Glabridin, a polyphenolic flavonoid is the main component of licorice. It inhibits the production of melanin. Liquiritin is the other important ingredient of licorice extract with whitening effect extract Glabridin Liquiritin Consumption of large amounts of licorice during pregnancy may increase the risk of miscarriage or preterm labor. Studies have shown that children born to pregnant women taking 250 mg of licorice root have a higher likelihood of developing brain impairments later in life. Pregnant and breastfeeding women should avoid licorice Licorice might interfere with blood pressure control during and after surgery. Stop taking licorice at least 2 weeks before a scheduled surgery. There are no universal guidelines for the proper use of licorice root. Doses of 5 to 15 grams a day are considered safe for short-term use Liquorice is contraindicated in patient with hypertension( especially in large doses)  Steroidal saponins The steroidal saponins are much less widely distributed in nature than the pentacyclic triterpenoid saponins. Plant steroidal sapogenins (aglycones) are often used as starting materials for the synthesis of the sex hormones (testosterone, oestrogen, progesterone), corticosteroids and mineralocorticoids Diosgenin, obtained from the tubers of the vine-like Yams or Dioscorea. An important food in many countries (like potatoes) A variety of species exist, including Dioscorea alata (water yam), Dioscorea batatas (Chinese yam), Dioscorea villosa (Wild Yam). Wild yam is believed to influence hormone balances in a way that can benefits conditions like morning sickness, premenstrual syndrome (PMS), hot flashes, menstrual cramps, vaginal dryness, low libido, and osteoporosis Cucurbitacins are tetracyclic terpenes with steroidal structures that are isolated from plants of the family Cucurbitaceae such as pumpkins, cucumbers, etc. Ancient peoples used cucurbits medicinally, but they also recognized their toxic properties Cucurbits ‫قثاء الحمار‬ Ecballium elaterium Cucurbitacins Cucurbitacins are also known as “bitter principles Citrullus colocynthis ‫الحنظل‬ Cucumber Pumpkins Ginseng The roots of the herbaceous plants Panax ginseng (Araliaceae) from China, Korea and Russia, and related Panax species have been widely used for the treatment of a number of diseases. It contains a large number of triterpenoid saponins Studies have shown that ginseng extracts can increase sperm count in humans. The use of Panax ginseng has demonstrated an increase in sperm mortality and density. Using ginseng boosts nitric oxide synthase and nitric oxide productions, which are closely related to the healthy functioning of the sperm. Ginseng is classified as an 'adaptogen', helping the body to adapt to stress, ginseng may strengthen the immune system, enhance brain function, fight fatigue and improve symptoms of erectile dysfunction.  Long-term use of ginseng can lead to symptoms similar to those of corticosteroid poisoning, including hypertension, nervousness and sleeplessness in some subjects "Auto-immune diseases" such as multiple sclerosis (MS), lupus (systemic lupus erythematosus, SLE), rheumatoid arthritis (RA), or other conditions: Panax ginseng seems to increase the activity of the immune system. Bleeding conditions: Panax ginseng seems to interfere with blood clotting. Heart conditions: Panax ginseng can affect heart rhythm and blood pressure slightly on the first day it is used. Trouble sleeping (insomnia): High doses of Panax ginseng have been linked with insomnia. Tetraterpenes are terpenes consisting of eight isoprene units and have the molecular formula C40H64. Carotenoids are naturally occurring pigments. Structurally, carotenoids are tetraterpenes. They have 40 carbons. Two C20 units are linked in a head- to-tail fashion. Examples are lycopene and carotene.  Lycopene (tomatoes) -Carotene (carrots)  CAROTENOIDS Among this important group, the numerous compounds consist of C40 chains with conjugated double bonds, they show strong light absorption and often are brightly colored (red, orange). They occur as pigments in bacteria, algae and higher plants.  Vitamin A is a fat-soluble vitamin found only in the animal kingdom, particularly in fish oils They are converted to vitamin A in the small intestine by body flora. Hence very small children have a very limited capacity to effect this conversion. Antioxidants like beta carotene might be very helpful in reducing the symptoms of Alzheimer's disease and age- related cognitive decline. Research has shown that antioxidants, including beta carotene, can help maintain skin health and appearance, and may protect the skin against UV radiation from the sun. Beta-carotene, the main ingredient in TanCare, is responsible for what is known as the 'carrot effect'. The body converts beta-carotene into vitamin A, but only in the amount it needs. Excess beta-carotene is stored in the skin. This gives the skin a golden glow that resembles a natural tan Carrots are the food most associated with tanning, and the reason for this is that they encourage the production of melanin, which is what gives our skin a tan through melanocytes. These are activated after exposure to the sun and at the same time protect our skin from ultraviolet rays Eating too many carrots can bring in too much beta-carotene. This can lead to excess blood carotene which can discolor the skin. Known as carotenemia, the condition occurs because carotene is a fat-soluble molecule  Adding olive oil to diced tomatoes during cooking greatly increases the absorption of lycopene and augments the health benefits of lycopene Research results indicated a significant drop in vitamin C, but in contrast, a substantial increase in lycopene. Steaming or boiling tomatoes is the preferred method of cooking to bring out more lycopene for optimal nutrition. Lycopene is a powerful antioxidant with many health benefits, including sun protection, improved heart health and a lower risk of certain types of cancer. Though it can be found as a supplement, it may be most effective when consumed from lycopene-rich foods like tomatoes and other red or pink fruits