Lesson 1

Definition, History and Basic

Concepts of Phytotherapy
Asst. Prof Ali Timuçin ATAYOĞLU
What is Phytotherapy?
• Phytotherapy, the use of plant-derived medications in the treatment and prevention of
disease.
• Phytotherapy is a science-based medical practice and is often linked to traditional
knowledge. However, it is distinguished from herbalism, which relies on an empirical
appreciation of herbs .
• Numerous trials and pharmacological studies of specific phytotherapeutic preparations exist
whereas herbalist’s approach generally has not been evaluated in controlled clinical trials or
in rigorous biomedical studies,
• The interpretation and acceptance of such evidence for phytotherapeutic practices varies. In
some countries, it is considered sufficient to license phytotherapeutic products as medicines,
whereas in other countries, phytotherapy is viewed as a form of traditional medicine.

Emprical : originating in or based on observation or experience :relying on experience or observation alone often without due regard for system and theory; :capable of being verified or disproved by
observation or experiment
Examples phytotherapeutic preparations in use

There are a number of phytotherapeutic preparations in use. Examples include :

• preparations derived from the leaves of ginkgo (Ginkgo biloba), which are used
to treat a range of minor cognitive disorders and certain other disorders of the
central nervous system;
• the aerial parts of St. John’s wort (St. Johnswort; Hypericum perforatum), which
typically are used in the treatment of mild to moderate forms of depression;
• the aerial parts and roots of Echinacea angustifolia (and other species of
Echinacea), which are used in the treatment and prevention of the common
cold and other respiratory conditions;
• the root of African devil’s claw (Harpagophytum procumbens), which is used to
treat chronic lower back pain.
Ginkgo biloba
 (St. Johnswort)
Hypericum perforatum
Echinacea angustifolia
 African devil’s claw
(Harpagophytum procumbens)
History Of Phytotherapy

• The concept of phytotherapy originated with French physician Dr.

Henri Leclerc, who first used the term in 1913 and who published
various editions of the Précis de phytothérapie (“Handbook of
Phytotherapy”), the first in 1922.
• Phytotherapy entered the English language with its common
definition in 1934, having been introduced by Eric Frederick William
Powell, who was an English practitioner of herbalism and
homeopathy. The English term, however, did not gain wider
recognition until much later.
• In 1960 German herbalist and physician Dr. Rudolf Fritz Weiss
published Lehrbuch der Phytotherapie (1960; Herbal Medicine),
which became the definitive German textbook on the topic.
• The work initially had been published in a different format in 1944
under the name Die Pflanzenheilkunde in der Ärztlichen Praxis
(“Plant-Based Curative Science in Medical Practice”).
• Both Leclerc’s and Weiss’s approaches shared a strong focus on what
later came to be described as evidence-based medicine.
• Another important landmark in the history of phytotherapy was the
emergence in 1987 of the journal of Phytotherapy Research, edited
by British pharmacognosist Fred Evans.
• In 1997 the book Rational Phytotherapy was published under the
stewardship of American pharmacognosist Varro Tyler. The work was
an English translation of the German book Rationale Phytotherapie:
Ratgeber für die Ärztliche Praxis (3rd ed., 1996), written by Volker
Schulz and Rudolf Hänsel.
Phytotherapy or Herbalism
• The terminology of the various forms of treatment associated with herbal
substances remains confusing. While many consider herbal medicines with a well-
defined use profile (one based on scientific and medical evidence) as
phytotherapeutic products, others consider such products to be food supplements.
• The latter implies that medicines based on herbal substances are unproven
therapies, and in some countries they are treated that way.
• In the United States, for example, all herbal-based products are classified as dietary
supplements.
• To complicate matters, herbalism is sometimes also referred to as phytotherapy,
and both herbalism and phytotherapy are sometimes described as herbal
medicine. Likewise, preparations used in phytotherapy and in herbalism may be
referred to as herbal medicines or phytomedicines.
• The confusion between phytotherapy and herbalism is also reflected in a
complex regulatory situation, where assessments of what can or cannot be
designated a medicine differ vastly.
• The differences often are the result of variations in legal frameworks that
have been implemented by countries or regions, such as the European
Union. For places that have laws or regulations for herbal products,
specific requirements for quality assurance exist.
• The requirements are intended to provide a relatively high level of security
to consumers by regulating the quality of the product through the supply
and value chain, from the collection or wild crafting (harvesting from
nature) of plants to the manufacture and promotion of the final product.
• The products used in phytotherapy generally are produced industrially
by using routine procedures, which differs from herbalism.
• Thus, for phytotherapy, there is a limited difference between the
batches of product sold on the market by an individual company.
• The composition of the same phytotherapeutic product, however,
may differ from one company to the next.
Standardization
• A commonly used but often poorly defined concept in phytotherapy is
standardization, which is the requirement of having a minimum amount of one or
several active compounds or groups of compounds in the plant extract.
• Often a range from a minimum to a maximum amount is given. In the field of
phytotherapy, standardization applies only to extracts and by definition only to
those where the active constituents are fully characterized.
• For example, an extract containing a certain percentage of compound class X
(e.g., flavonoids) must contain one specific compound of the group (e.g., the
flavonoid rutin).
• The quantification often is carried out by using chromatography-based techniques
(e.g., gas chromatography or high-performance liquid chromatography), capillary
electrophoresis, atomic absorption spectroscopy, or mass spectrometry.
• Standardization is intended to ensure a reproducible composition of known
active constituents.
• For example, St. John’s wort (H. perforatum) is used in both phytotherapy
and herbalism.
• In phytotherapy, the preparations often are industrially produced extracts
from the leaves and plant tops that have been standardized according to
hypericin and hyperforin content (or sometimes one or the other). These
two substances are known to be relevant for their pharmacological effects.
The extract is generally formulated as tablets or capsules.
• In herbalism. , herbalists are likely to use a tincture of H. perforatum herb
that is not standardized on its content of any particular constituent.
Phytotherapy and National Health Care
Systems
• The practice of phytotherapy differs widely throughout the world. In
some countries, such as South Korea and Japan, proven phytotherapy
products are integrated into health insurance coverage. Other
countries, including China, India, and Nepal, offer wide health care
coverage for herbal medicines, which fall under traditional medicine
services. In most other parts of the world, however, such products are
not integrated into health care or health insurance programs. They are,
rather, much more a patient’s private choice, and they often are sold
as over-the-counter (OTC) products, though these products may be
recommended or prescribed by a wide range of health care
practitioners, including general practitioners and naturopathic doctors.
• Since phytotherapy is a system of medical practice that is based on
scientific or medical evidence, its products are pharmacologically
active medicines, similar to conventional pharmaceutical drugs.
References:
Michael Heinrich, Phytotherapy, Encyclopædia Britannica, 2017,
https://www.britannica.com/science/phytotherapy (Access date is
October 15, 2020)
 Lesson 2
Phytochemicals and
Drugs Derived from Plants
Asst. Prof. Ali Timuçin ATAYOĞLU
• Long before pure chemicals were manufactured in labs, people
used plants for medicine. Today, there are over 100 active
ingredients derived from plants for use as drugs and medicines.

• This is by no means a comprehensive list of all of the plants,

names of chemicals, or uses for those chemicals, but it should
serve as a useful starting point for further research.

• The common name of a plant is noted next to its

scientific name. Common names are imprecise and often
assigned to completely different plants, so use the scientific
name when looking for additional information concerning a
plant.
Here are some of
the common
drugs that were
derived from or
inspired by
compounds
found in plants.
1. Aspirin
(Salicylic Acid)

• Aspirin is a popular treatment for pain, inflammation, and fever. It works by inhibiting an enzyme
known as cyclooxygenase (COX). The COX-1 enzyme converts arachidonic acid to thromboxanes
and prostaglandins which are responsible for sustaining inflammation and blood clotting.
• The compound was first synthesized in 1890 by a man named Felix Hoffmann.
• Aspirin is modelled after the naturally occurring polyphenol salicylic acid — a compound found
in a handful of plants including Salix alba (white willow), Spireaspp. (wintergreens),
and Betula spp. (birch).
• All of these plants were traditionally used for conditions involving injury, pain, and inflammation.
• The difference Aspirin has to its naturally occurring counterpart is the addition of an acetyl
chemical group, which gives Aspirin its antifibrinolytic effects and improved bioavailability.
2. Quinine
(Qualaquin)

• Quinine is used as a malaria and babesiosis medication. It remains one of the

primary treatments for malaria to this day under the brand name Qualaquin, and
the generic name Quinine.
• It’s an alkaloid taken from the Cinchona calisaya tree from South America. It was a
popular herb used by the local Quechua tribes of the Amazon rainforest, which
eventually caught the attention of the Jesuits who brought it to Europe.
• Although the drug can be synthesised, the most economically viable method of
production is to extract it from the cinchona tree. Unfortunately, there are many
side effects to this medication, including permanent kidney damage.
3. Opiates
(Oxycontin, Morphine, Codeine)

• Opiates are a class of chemicals that target the opioid receptors in the human body that regulate pain and
temperature control.
• Most opiates are classified as benzylisoquinoline alkaloids which can be either naturally occurring, or synthetic.
• These alkaloids were discovered from the Papaveraceae somniferum (Opium poppy), starting with codeine
and morphine. In 1874, a chemist named C.R Alder Wright synthesised a similar compound called
diamorphine, more commonly referred to as heroin.
• For the first 23 years of this discovery, nothing was done.
• It wasn’t until Felix Hoffmann (the producer of aspirin), re-synthesised it that it caught the attention of Bayer
Pharmaceuticals, where it was commercialised as a pain management drug.
• Heroin has since been banned in most countries due to high addiction rates and drug abuse, however, opiates
in general are still widely used in modern medicine. Morphine, codeine, methadone, and Fentanyl are all used
to provide varying potencies of pain management.
4. Myriocin

• Myriocin (aka ISP-1 or thermozymocidin), is an antibiotic and

immunosuppressant derived from the sterile (non-spore-producing)
fungus mycelia sterilia and entomopathogenic (bug-eating) fungus
Isaria sinclairii.
• Scientists modified myriocin to produce a compound known as
fingolimod (compound FTY720), which is used to treat autoimmune
conditions like multiple sclerosis.
5. Digoxin

• Digoxin is a heart medication used for heart failure, and cardiac arrhythmias (such as atrial
flutter, or atrial fibrillation). It was isolated from the foxglove plant (Digitalis lanata) in 1930,
however, the first mention of foxglove derivatives for cardiac related conditions goes all the way
back to 1785. It was used to treat a condition known as dropsy, which is an accumulation of fluid
under the skin, often as a result of chronic heart failure.
• The use of digoxin changed how we treated cardiovascular disease for many years, but has since
fallen out of favour due to some of its more dangerous side effects. In fact, in 2003 a nurse
named Charles Cullen killed 40 of his patients with overdoses of digoxin and other heart
medications.
• Digoxin works by inhibiting sodium, potassium, ATP channels in the heart. This causes sodium
levels to build up inside the cells of the heart, which then causes calcium to increase inside the
cell as well. This heightened calcium allows stronger contraction of the heart, while expending
less energy. It also has an effect on the vagus nerve, which is used to control the heart rhythm.
6. Paclitaxel

• Paclitaxel is a chemotherapeutic agent derived from the bark of the Pacific Yew (Taxus brevifolia). When making
the medicine, the yew tree was killed. As demand for the drug increased, the drug became involved in an
ecological controversy. The need for the medication was scrutinised in light of the extensive damage it was
causing to yew populations in North America. Researchers began seeking more sustainable ways to obtain this
compound.
• The drug is now made using semisynthetic methods obtained from liquid plant cultures. Although the plant
tissue is still needed to make the medicine, it poses no threat to wild yew populations because manufactures
now rely on sterile lab-grown cultures of the plant.
• Paclitaxel works by inhibiting a compound called tubulin inside the cells.
• Tubulin is needed during cell division, by inhibiting this compound, Paclitaxel is able to prevent cell division in the
body.
• Since cancer often involves rapidly dividing cells, the drug is used to target these rapidly dividing cells more
specifically, slowing the growth of cancer. Unfortunately, there are also a wide range of side effects, mostly as a
result of the inhibition of rapidly dividing cells.
7. Vincristine & Vinblastine

• Vincristine and vinblastine are alkaloids taken from the Madagascar periwinkle plant
(Catharanthus roseus).
• Both are intravenous chemotherapeutic agents used for cancers like Hodgkin’s disease and
neuroblastoma. Vinblastine was isolated first in 1958, with vincristine to follow in 1961.
• Similarly to Paclitaxel, these alkaloids work by preventing cells from dividing by blocking
tubulin. This has a marked effect on cancers, which are often characteristic in how rapidly they
divide. As a result of this action, both have fairly strong side effects including hair loss,
constipation, nausea & vomiting, neutropenia (low white blood cells), and lung damage.
8. Lysergic Acid
Diethylamide (LSD)

• Lysergic acid was made in 1938 by a man named Albert Hofmann in Switzerland.
• It’s made from a naturally occurring alkaloid called ergotamine found in the fungus
called ergot (Claviceps purpurea). It can now be manufactured synthetically.
• Hofmann didn’t identify the psychoactivity of the extract for another 5 years. Soon
after his discovery, it was picked up by psychologists a treatment for psychiatric
illnesses, and by the United States government in an attempt to use mind control (for
which it was unsuccessful).
• LSD works by stimulating various types of serotonin receptors (5HT2A, and 5HT2B),
as well as the dopamine D2 receptors in the brain.
 Drugs Derived from Plants
Drug/Chemical Action Plant Source
Acetyldigoxin Cardiotonic Digitalis lanata (Grecian foxglove, woolly foxglove)
Adoniside Cardiotonic Adonis vernalis (pheasant's eye, red chamomile)
Aescin Antiinflammatory Aesculus hippocastanum (horse chestnut)
Aesculetin Antidysentery Frazinus rhychophylla
Agrimophol Anthelmintic Agrimonia supatoria
Ajmalicine Treatment for circulatory disorders Rauvolfia sepentina
Allantoin Vulnerary Several plants
Allyl isothiocyanate Rubefacient Brassica nigra (black mustard)
Anabesine Skeletal muscle relaxant Anabasis sphylla
Andrographolide Treatment for baccillary dysentery Andrographis paniculata
Anisodamine Anticholinergic Anisodus tanguticus
Anisodine Anticholinergic Anisodus tanguticus
Arecoline Anthelmintic Areca catechu (betel nut palm)
Asiaticoside Vulnerary Centella asiatica (gotu cola)
Atropine Anticholinergic Atropa belladonna (deadly nightshade)
Benzyl benzoate Scabicide Several plants
Berberine Treatment for bacillary dysentery Berberis vulgaris (common barberry)
Bergenin Antitussive Ardisia japonica (marlberry)
Betulinic acid Anticancerous Betula alba (common birch)
Borneol Antipyretic, analgesic, antiinflammatory Several plants
Bromelain Antiinflammatory, proteolytic Ananas comosus (pineapple)
Caffeine CNS stimulant Camellia sinensis (tea, also coffee, cocoa and other
plants)
Camphor Rubefacient Cinnamomum camphora (camphor tree)
Camptothecin Anticancerous Camptotheca acuminata
(+)-Catechin Hemostatic Potentilla fragarioides
Chymopapain Proteolytic, mucolytic Carica papaya (papaya)
Cissampeline Skeletal muscle relaxant Cissampelos pareira (velvet leaf)
Cocaine Local anaesthetic Erythroxylum coca (coca plant)
Codeine Analgesic, antitussive Papaver somniferum (poppy)
Colchiceine amide Antitumor agent Colchicum autumnale (autumn crocus)
Colchicine Antitumor, antigout Colchicum autumnale (autumn crocus)
Convallatoxin Cardiotonic Convallaria majalis (lily-of-the-valley)
Curcumin Choleretic Curcuma longa (turmeric)
Cynarin Choleretic Cynara scolymus (artichoke)
Danthron Laxative Cassia species
Demecolcine Antitumor agent Colchicum autumnale (autumn crocus)
Deserpidine Antihypertensive, tranquilizer Rauvolfia canescens
Deslanoside Cardiotonic Digitalis lanata (Grecian foxglove, woolly foxglove)
L-Dopa Anti-parkinsonism Mucuna species (nescafe, cowage, velvetbean)
Digitalin Cardiotonic Digitalis purpurea (purple foxglove)
Digitoxin Cardiotonic Digitalis purpurea (purple foxglove)
Digoxin Cardiotonic Digitalis purpurea (purple or common foxglove)
Emetine Amoebicide, emetic Cephaelis ipecacuanha
Ephedrine Sympathomimetic, antihistamine Ephedra sinica (ephedra, ma huang)
Etoposide Antitumor agent Podophyllum peltatum (mayapple)
Galanthamine Cholinesterase inhibitor Lycoris squamigera (magic lily, resurrection lily, naked
lady)
Gitalin Cardiotonic Digitalis purpurea (purple or common foxglove)
Glaucarubin Amoebicide Simarouba glauca (paradise tree)
Glaucine Antitussive Glaucium flavum (yellow hornpoppy, horned poppy, sea
poppy)
Glasiovine Antidepressant Octea glaziovii
Glycyrrhizin Sweetener, treatment for Addison's disease Glycyrrhiza glabra (licorice)
Gossypol Male contraceptive Gossypium species (cotton)
Hemsleyadin Treatment for bacillary dysentery Hemsleya amabilis
Hesperidin Treatment for capillary fragility Citrus species (e.g., oranges)
Hydrastine Hemostatic, astringent Hydrastis canadensis (goldenseal)
Hyoscyamine Anticholinergic Hyoscyamus niger (black henbane, stinking nightshade,
henpin)
Irinotecan Anticancer, antitumor agent Camptotheca acuminata
Kaibic acud Ascaricide Digenea simplex (wireweed)
Kawain Tranquilizer Piper methysticum (kava kava)
Kheltin Bronchodilator Ammi visaga
Lanatosides A, B, C Cardiotonic Digitalis lanata (Grecian foxglove, woolly foxglove)
Lapachol Anticancer, antitumor Tabebuia species (trumpet tree)
a-Lobeline Smoking deterrant, respiratory stimulant Lobelia inflata (Indian tobacco)
Menthol Rubefacient Mentha species (mint)
Methyl salicylate Rubefacient Gaultheria procumbens (wintergreen)
Monocrotaline Topical antitumor agent Crotalaria sessiliflora
Morphine Analgesic Papaver somniferum (poppy)
Neoandrographolide Treatment of dysentery Andrographis paniculata
Nicotine Insecticide Nicotiana tabacum (tobacco)
Nordihydroguaiaretic acid Antioxidant Larrea divaricata (creosote bush)
Noscapine Antitussive Papaver somniferum (poppy)
Ouabain Cardiotonic Strophanthus gratus (ouabain tree)
Pachycarpine Oxytocic Sophora pschycarpa
Palmatine Antipyretic, detoxicant Coptis japonica (Chinese goldenthread, goldthread,
Huang-Lia)
Papain Proteolytic, mucolytic Carica papaya (papaya)
Papavarine Smooth muscle relaxant Papaver somniferum (opium poppy, common poppy)
Phyllodulcin Sweetener Hydrangea macrophylla (bigleaf hydrangea, French
hydrangea)
Physostigmine Cholinesterase inhibitor Physostigma venenosum (Calabar bean)
Picrotoxin Analeptic Anamirta cocculus (fish berry)
Pilocarpine Parasympathomimetic Pilocarpus jaborandi (jaborandi, Indian hemp)
Pinitol Expectorant Several plants (e.g., bougainvillea)
Podophyllotoxin Antitumor, anticancer agent Podophyllum peltatum (mayapple)
Protoveratrines A, B Antihypertensives Veratrum album (white false hellebore)
Pseudoephredrine Sympathomimetic Ephedra sinica (ephedra, ma huang)
nor-pseudoephedrine Sympathomimetic Ephedra sinica (ephedra, ma huang)
Quinidine Antiarrhythmic Cinchona ledgeriana (quinine tree)
Quinine Antimalarial, antipyretic Cinchona ledgeriana (quinine tree)
Qulsqualic acid Anthelmintic Quisqualis indica (Rangoon creeper, drunken sailor)
Rescinnamine Antihypertensive, tranquilizer Rauvolfia serpentina
Reserpine Antihypertensive, tranquilizer Rauvolfia serpentina
Rhomitoxin Antihypertensive, tranquilizer Rhododendron molle (rhododendron)
Rorifone Antitussive Rorippa indica
Rotenone Piscicide, Insecticide Lonchocarpus nicou
Rotundine Analagesic, sedative, traquilizer Stephania sinica
Rutin Treatment for capillary fragility Citrus species (e.g., orange, grapefruit)
Salicin Analgesic Salix alba (white willow)
Sanguinarine Dental plaque inhibitor Sanguinaria canadensis (bloodroot)
Santonin Ascaricide Artemisia maritma (wormwood)
Scillarin A Cardiotonic Urginea maritima (squill)
Scopolamine Sedative Datura species (e.g., Jimsonweed)
Sennosides A, B Laxative Cassia species (cinnamon)
Silymarin Antihepatotoxic Silybum marianum (milk thistle)
Sparteine Oxytocic Cytisus scoparius (scotch broom)
Stevioside Sweetener Stevia rebaudiana (stevia)
Strychnine CNS stimulant Strychnos nux-vomica (poison nut tree)
Taxol Antitumor agent Taxus brevifolia (Pacific yew)
Teniposide Antitumor agent Podophyllum peltatum (mayapple or mandrake)
Tetrahydrocannabinol (THC) Antiemetic, decreases occular tension Cannabis sativa (marijuana)
Tetrahydropalmatine Analgesic, sedative, tranquilizer Corydalis ambigua
Tetrandrine Antihypertensive Stephania tetrandra
Theobromine Diuretic, vasodilator Theobroma cacao (cocoa)
Theophylline Diuretic, bronchodilator Theobroma cacao and others (cocoa, tea)
Thymol Topical antifungal Thymus vulgaris (thyme)
Topotecan Antitumor, anticancer agent Camptotheca acuminata
Trichosanthin Abortifacient Trichosanthes kirilowii (snake gourd)
Tubocurarine Skeletal muscle relaxant Chondodendron tomentosum (curare vine)
Valapotriates Sedative Valeriana officinalis (valerian)
Vasicine Cerebral stimulant Vinca minor (periwinkle)
Vinblastine Antitumor, Antileukemic agent Catharanthus roseus (Madagascar periwinkle)
Vincristine Antitumor, Antileukemic agent Catharanthus roseus (Madagascar periwinkle)
Yohimbine Aphrodisiac Pausinystalia yohimbe (yohimbe)
Yuanhuacine Abortifacient Daphne genkwa (lilac)
Yuanhuadine Abortifacient Daphne genkwa (lilac)
 Lesson 3
Herbal Preparations and
Extraction Methods
Asst. Prof. Ali Timuçin ATAYOĞLU
 INFUSION
• Infusion is the process of extracting chemical
compounds or flavors from plant material in a
solvent such as water or oil, by allowing the
material to remain suspended in the solvent over
time (a process often called steeping).
• An infusion is also the name for the resultant
liquid.
• In common practice, it is boiling water is poured
over the plant, which then rests for 3 to 10
minutes.
• The process of infusion is distinct from both
decoction—a method of extraction involving
boiling the plant material (as in Turkish coffe)—
and percolation, in which water is passed
through the material (as in a coffeemaker).
• The first recorded use of essential oils was in the 10th or 11th century by the Persian
polymath Avicenna, possibly in The Canon of Medicine.
• A common example of an infusion is tea; most varieties of tea call for steeping the leaves
in hot water, although some variants (e.g. Moroccan mint tea) call for decoction instead.
• Many herbal teas are prepared by infusion, as well; lemon, chamomile, senna, apple,
ginger, rooibos, and many other plants are used individually or in combination. Herbal
infusions in water and oil are both commonly used as herbal remedies. Coffee can also be
made through infusion (as in a French press), but is more often made through percolation.
• Plants with desirable flavors may be steeped in an edible oil or vinegar for an extended
period; the infused oil or vinegar is often sold still containing the plant and is then used as
flavoring. Chilis, lemon, garlic, and many other plants may be used. There can be
ambiguity in the labeling of these oils: for example, what is described as sesame oil may
be oil extracted from sesame seeds or another vegetable oil infused with sesame.
 Percolation
•Percolation (from Latin percolare, "to filter" or
"trickle through") refers to the movement and
filtering of fluids through porous materials. It is
described by Darcy's law.
Darcy's law is an equation that describes the
flow of a fluid through a porous medium. The law
was formulated by Henry Darcy based on results
of experiments on the flow of water through beds
of sand, forming the basis of hydrogeology, a
branch of earth sciences.
•Example: Coffee percolation, where the solvent
is water, the permeable substance is the coffee
grounds, and the soluble constituents are the
chemical compounds that give coffee its color,
taste, and aroma.
 DECOCTION
• Decoction is a method of extraction by boiling herbal or plant material to dissolve the chemicals
of the material, which may include stems, roots, bark and rhizomes.
• In herbalism, decoctions are usually made to extract fluids from hard plant materials such as roots
and bark. To achieve this, the plant material is usually boiled in water. It is then strained.
• Decoction involves first mashing the plant material to allow for maximum dissolution, and then
boiling in water to extract oils, volatile organic compounds and other various chemical substances.
• Decoction can be used to make tisanes, tinctures and similar solutions.
• Decoctions and infusions may produce liquids with differing chemical properties as the
temperature and/or preparation difference may result in more oil-soluble chemicals in decoctions
versus infusions.
• The process can also be applied to meats and vegetables to prepare bouillon or stock, though the
term is typically only used to describe boiled plant extracts, usually for medicinal or scientific
purposes.
• Decoction is also the name for the resulting liquid. Although this method of extraction differs from
infusion and percolation, the resultant liquids can sometimes be similar in their effects, or general
appearance and taste.
• Example: Turkish coffee beginning to boil.
Decoction compares to brewing coffee through
percolation.
• The plant is boiled for 5 to 10 minutes, then
cooled and filtered.
MACERATION
• Maceration is a simple extraction method that, although valuable, presents the disadvantage of
long extraction time and low efficiency.
• This procedure consists of soaking the raw material (coarse or powdered) in a selected
solvent(water, oil, alcohol, etc.) at room temperature for at least 3 days, with frequent agitation.
• Before being processed, the plant must be properly washed and separated from foreign material
such as topsoil, pebbles or rocks, weeds, and materials non-suitable for extraction. The plant
material can be used fresh or dry based on the desired product.
• In order to increase contact between the plant material being extracted and the liquid (solvent),
the plant needs to be cut into small pieces.
• The pieces should not be too big, otherwise the solvent will not be able to penetrate the
innermost cells. They also should not be reduced to powder; that would result in losing the
volatile active ingredients (essential oils) contained inside the plant, and also losing the difficult
separation by filtration of the plant material from the liquid used once maceration is completed.
• The solvent must be chosen based upon the chemical nature of the
compounds contained within the plant. Solubility and the desired use of
the extraction should be considered when choosing the solvent. That is,
recognizing their solubility and the desired use of the extraction. One
uses
vegetable oil when one wants to isolate only the lipophilic components, while
water is used to extract only hydrophilic ingredients.

Generally, alcohol is the most used substance because it is able to extract

a greater part of the molecules (active ingredients) contained within the
plant, including molecules which are hydrophilic (soluble in water), or
lipophilic (soluble in oil) or other organic solvents.
TINCTURE
• Tincture results from the
maceration of the dried plant in
alcohol at 40°, 60°, or 80°.
STANDARDIZED EXTRACT
• Standardized Extract is a concentrate obtained
by concentrating a macerate prepared from the
plant. This makes it possible to extract most of
the useful components and to always control the
content of active ingredients. This method
allows us to always offer the same quality of the
product.
• The extract can be maintained in liquid form:
we speak of fluid extract. Fluid extracts are used
in syrups and creams.
• The extract can also be evaporated and dried:
this results in a dry extract. Dry extracts are
mainly used in capsules and tablets.
TOTAL POWDER
• It is produced by grinding the
dried plant. The powder obtained
is generally put into capsules.
Essential Oil Preperation

• Steam distillation method

Example: Lemon essential oil
https://www.youtube.com/watch?v=IC0qYhQ2XNg
https://www.youtube.com/watch?v=NlgZACkf3Q4

• Extracting the citric acid from lemons

https://www.youtube.com/watch?v=FMtayizdFiw
 Lesson 4
Indications and Contra-
indications in Phytotherapy
Asst. Prof. Ali Timuçin ATAYOĞLU
The olive leaves have a rich history of medicinal uses. There are many
references citing the medicinal use of the plant (Olea europaea) in
ancient times. The plant is cultivated widely in the Mediterranean
region, Arabian Peninsula, the Indian subcontinent and Asia.

Effects of olive leaves like the antioxidant, hypoglycemic,

antihypertensive, antimicrobial, and antiatherosclerotic have been
reported in various studies.
Taxonomy
• Kingdom: Plantae
• Division: Tracheophytes
• Order: Lamiales
• Family: Oleaceae
• Genus: Olea
• Species: O. europaea
Polyphenols in olive leaves
Olive leaves are important for their secondary metabolites such as the
secoiridoid compounds oleacein and oleuropein. They are well known
for their beneficial effects on metabolism when used as a traditional
herbal drug. These properties are attributed to the phenolic
compounds of olive leaves.
Olive leaves have the highest antioxidant and scavenging ability among
the different parts of the olive tree (e.g. oleuropein content in olive oil
ranges between 0.005% and 0.12% while that in olive leaves ranges
between 1% and 14%).
Traditional uses of olive leaves
• Olive leaves used orally for stomach
and intestinal diseases.
• Olive leaves chewed as a mouth
cleanser.
• Infussion of the fresh leaves taken
orally to treat high blood pressure
(hypertension) and to induce urination
(diuresis).
• Infussion of the dried plant taken orally
for bronchial asthma.
• Decoctions of the dried fruit and leaves
taken orally for diarrhea and to treat
urinary tract infections.
Effects of olive-leaves extracts
Oleuropein, the main constituent of olive leaves extract, protects
membrane from lipid oxidation, causes dilatation of coronary blood
vessels, shows antiarrhythmic action, improves lipid metabolism,
protects enzymes from oxidative damage, prevents hypertensive cell
death in cancer patients, and demonstrates antiviral properties.
Hydroxytyrosol, an oleuropein derivative, improves cardiac diseases
and tumor diseases with effects similar to those of oleuropein. In
addition, hydroxytyrosol protects against atherosclerosis and prevents
diabetic neuropathy.
Antioxidant activity of olive leaves Phenolic compounds

Reactive oxygen and nitrogen species are essential in normal physiological

mechanisms of energy supply, detoxification, chemical signaling, and
immune function.
They are continuously produced in the human body and are controlled by
endogenous enzymes such as superoxide dismutase, glutathione
peroxidase, and catalase.
When there is an overproduction of these reactive species, due to
exposure to external oxidant substances, or a failure in the defense
mechanisms, damage to valuable bio-molecules (DNA, lipids and proteins)
may occur. This damage has been associated with an increased risk of
cardiovascular disease, cancer, and other chronic diseases.
Anti-atherosclerotic effect of olive leaves
The phenolic compounds of olive leaves and olive oils in the
Mediterranean diet have been associated with a reduced incidence of
heart disease. Accordingly, these antioxidant-rich diets might prevent the
deleterious effects of oxidative metabolism by scavenging free radicals,
thus inhibiting oxidation and delaying atherosclerosis. The process may
involve phospholipase C activation and arachidonic acid metabolism, and
is thought to reduce hydrogen peroxide. The cardiovascular effects of
olive-leaf extracts have been well studied and attributed to the main
components of the European cultivar leaves, oleuropein and oleacein. The
secoiridoid derivatives (oleuropeoside) in olive leaves are responsible for
the vaso-dilating and relaxing properties of their extracts.
Cardioprotective effects of olive-leaves polyphenols

Oleuropein, which was found to be completely nontoxic in several animal species, has
antitumor activity. Doxorubicin (DXR), an anthracycline antibiotic clinically known as
adriamycin, is an anti- neoplastic drug that is highly effective against many malignant
diseases. It was reported that the clinical use of DXR is often limited because of its
undesirable serious cardiotoxic side effects, which frequently lead to congestive heart
failure.
The effect of oleuropein on cardiotoxicity induced by acute DXR treatment in rats has
been investigated. It was found that all groups treated with oleuropein had very low
cytoplasmic vacuolization in cardiomyocytes compared to the DXR group, indicating
that oleuropein protects against DXR-induced cardiotoxicity. Oleuropein successfully
attenuated DXR-induced cardiotoxicity by inhibiting lipid peroxidation products, by
decreasing oxidative stress, and by reducing nitric oxide species in cardiomyocytes. For
this reason, acute DXR cardiotoxicity might be successfully treated with oleuropein.
Anti-inflammatory activity
Oleuropein and hydroxytyrosol, inhibit leukotriene B4 generation
involved in a wide range of pro-inflammatory pathways as well as
eicosanoid production. Luteolin is also a key component, which showed
anti-inflammatory activity in animal models and anti allergic effects in
test-tube studies. Apigenin, also in the leaf, inhibits the inflammatory
mediator's nitric oxide and prostaglandin E2.
Antimicrobial activity
Both Oleuropein and hydroxytyrosol showed antimicrobial (Bacillus
subtilis, B. cereus, Staphylococcus aureus, Salmonella typhi, Vibrio
cholerae, V. parahemolyticus and Micrococcus sp.), anti-protozoal and
antiviral activity. Oleuropein acts through elenolic acid, a hydrolysis
products.
The olive leaf extract is proved to have anti-fungal properties. It is
especially useful in cases of candida overgrowth, also known as a yeast
infection. This fungal excess may cause a variety of symptoms, including
digestive upset, fatigue, and respiratory concerns.
Hypoglycemic effect of olive leaves
Olive-tree leaves are well known as a traditional anti-diabetic and
antihypertensive herbal drug. Olive leaves have also been used as a medical herb
to treat diabetic hyperglycemia, hypertension, and infectious diseases. They are
especially widely recognized as a traditional remedy for diabetes and hypertension
in Europe.
Mechanisms suggested for explaining the hypoglycemic effect of oleuropein in
diabetes:
1. Glucose-induced insulin release.
2. Increase peripheral uptake of glucose.
The results demonstrated that oleuropein may be beneficial in inhibiting
hyperglycemia and oxidative stress induced by diabetes, and they suggest that
administration of oleuropein may be helpful in the prevention of diabetic
complications associated with oxidative stress.
Anti-Rheumatoid Arthritis effect
Oleuropein has been found to help prevent and treat symptoms of
rheumatoid arthritis. When administered at the earliest sign of arthritis
in animal models, oleuropein prevented symptoms from developing
and also produced marked improvement in the microscopic appearance
of joint tissue from affected animals. When administered after arthritis
was fully developed, there was significant improvement in
inflammatory changes to joints, compared with untreated animals.
Oleuropein had similar benefits on osteoarthritis. In animal models of
this degenerative joint disease, olive leaf extract improved joint
swelling, improved the microscopic appearance of joint tissue, and
prevented the production of inflammatory cytokines.
Anti-Osteoporosis
The plant is useful in both stimulation of osteoblasts,the cells involved
in bone growth as well as in inhibition of osteoclasts, the cells involved
in bone removal. These studies are grund-breaking and may lead to
additional studies in the near future.
Immune system modulation
Olive leaf extracts are able to in vitro modify healthy human immune response by
increasing IFN-γ production which seems to be associated to the higher absolute
numbers of CD8+ and NK cells and this may suggest a reinforcement of the anti-
tumor activity.
Furthermore, increased levels of NO may indicate the potential cardioprotective
effects exerted by olive leaf extracts in virtue of their vasodilation dependent activity.
Olive leaf extracts are able to maintain the equilibrium between T regulatory cells
and Th17 cells as evidenced by unmodified levels of interleukin (IL)-IL-10 and IL-17,
respectively.
In the light of these results, olive leaf extracts are potential therapeutic compounds
for the treatment of chronic inflammatory disease, also preventing cardiovascular
event outcome.f the flavonoids in olive leaf extract have anti-microbial activity.
Against Chronic Fatigue
Chronic fatigue syndrome (CFS) is associated with immune dysfunction,
which allows infections with a variety of opportunistic microbes from
herpes-viruses, retro viruses, fungi and parasites.
In the U.S.A the use of olive leaf extract has become very popular with
doctors, naturopaths and the general public where it is being
prescribed for the symptoms of CFS.
Skin & Topical uses
Olive leaf extracts are rich in antioxidants and skin softening properties.
Olive leaf helps skin with the presence of flavonoids and oleanolic acid,
which stimulate the components of the connective tissue and
regularize the tissue - thereby boosting the health of the skin protecting
it from aging.
Anti-warts
Most common warts show up on knees, hands, feet, and elbows.
However, there are also some types that establish a colony on mouth,
nail beds and even the genital area. Since warts are caused by viruses,
particularly the human papiloma virus, olive leaf is an effective agent in
this type of skin diseases.
 Anti-Cancer effect
Olive leaves extract and oleuropein significantly inhibited increases in skin thickness
and reductions in skin elasticity, and skin carcinogenesis and tumor growth.
Dried olive leaf extract (DOLE) significantly inhibited proliferation and subsequently
restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late
phase tumor treatment with dried olive leaf extract significantly reduced tumor
volume in a syngeneic strain of mice. dried olive leaf extract-treated B16 cells were
blocked in the G(0) /G(1) phase of the cell cycle, underwent early apoptosis and died
by late necrosis. At the molecular level, the dying process started as caspase
dependent, but finalized as caspase independent. In concordance, over expression of
anti-apoptotic members of the Bcl-2 family, Bcl-2 and Bcl-XL, and diminished
expression of their natural antagonists, Bim and p53, were observed.
Olive leaves extract is effective in reducing IL-1β and TNF-α levels after chemotherapy
and exert a therapeutic effect and prevent development of severe oral mucositis.
Antithrombotic effect
Oral pre-treatment of rabbits with 100 mg or 200 mg/kg OLE for 8
weeks had no effect on Activated Partial Thromboplastin Time (APTT).
However, the same doses produced a significant prolongation of PT
(extrinsic coagulation pathway). The prolongation of PT was more
prominent with the higher dose of 200 mg/kg than the smaller dose
(p<0.01). This antithrombic activity of OLE might be due to modification
of the extrinsic but not the intrinsic coagulation system.
Anti-Neurodegenerative diseases
Olive extracts protect central nervous system from the destruction
brought on by age-related degenerative conditions such as Alzheimer’s
and Parkinson’s diseases. They suppress inflammation and reduce the
damage done by oxidative stress.
 Conclusion
Olive leaves extracts can be applied safely for treating variety of health
problems like microbial infections, inflammatory diseases, oxidative
stress, hypertension, hypercholestermeae, type II diabetes, thrombosis,
enuresis and cancer.
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Black seed
(Nigella sativa)
Out of the medicinal plants, black seed (Nigella sativa), which is native to
southwest Asia and has a rich historical and cultural heritage, due to a wide
range of medicinal properties.
N. sativa seeds have been used to promote health and fight diseases,
especially in the Middle East and Southeast Asia. N. sativa in South Asia is
known as Kalonji, in Arabic as Habbat-uL-Sauda, and commonly referred as
black cumin in English.
 Botanical characteristics
N. sativa belongs to Ranunculaceae family and is an
annual herbaceous plant which mainly grows in various
parts of southern Europe and some parts of Asia,
including Syria, Turkey, Saudi Arabia, Pakistan and India.
Flowers are elegant predominantly white, yellow, pink,
light blue or lavender and have 5−10 petals. The fruits
of this plant are large and swollen capsule, which
contain numerous black seeds with aromatic and bitter
taste.
N. sativa cultivation time is usually between November
and April and germination lasts for about 10−15 days
after sowing seeds. The flowering and fruiting times of
the plant are generally from January to April.
Scientific classification of the plant

• Kingdom: Plantae
• Division: Magnoliophyt
• Order: Ranunculales
• Family: Ranunculacea
• Genus: Nigella
• Species: N. sativa
Chemical composition of N. sativa
So far, several chemical compounds have been extracted and identified from different
species of Nigella. N. sativa contains 216 g protein, 406 g fat, 45 g ash, 84 g fiber, 249
g free nitrogen extract, 38 g moisture, 105 mg iron, 18 mg copper, 60 mg zinc, 527
mg phosphorus, 1860 mg calcium, 15.4 mg thiamin, 57 mg niacin and 160 μg folic
acid per kg. Also, studies have shown the presence of different active pharmaceutical
ingredients in the N. sativa seeds, including thymoquinone, thymol, limonene,
carvacrol, p-cymene, alpha-pinene, 4-terpineol, longifolene, and t-anethole
benzene.
Moreover, other phytochemical studies have revealed that the plant seeds contain
two classes of alkaloids, including isoquinoline alkaloids such as nigellimine-N-oxide,
and pyrazole alkaloids such as nigellidine and nigellicine. N. sativa seeds are also rich
in unsaturated fatty acid such as linoleic acid, oleic acid, and palmitic acid. Other
components of the seeds include saponins, flavonoids, indazole-type alkaloids, cardiac
glycosides, vitamins, and some important minerals like calcium, phosphorus and iron.
Use of N. sativa in traditional medicine
Food and therapeutic uses of N. sativa oil (NSO) and seeds
have a long history in Indian and Arabic culture. N. sativa
has been traditionally used for treatment of various
diseases (e.g., asthma, bronchitis, rheumatism, headaches,
and dysentery) in Southeast Asia, Northern Africa and
Middle East. According to recent reports the grain’s syrup
was beneficial for digestion, appetite loss, amenorrhea,
and dysmenorrheal and treatment of worms and skin rash.
Avicenna in his famous book, Canon of Medicine, has
pointed out several black cumin properties, such as fatigue
improvement and energy recovery. Islamic medicine also
has enlisted health effects for this plant.
Pharmacological potentials
Anti-microbial

Wound healing Anti-oxidant

Immuno- Anti-
protective inflammatory

Neuro- Anti-
protective hyperlipidemic

Hepatoprotectiv
Anti-cancer
e

Nephro-
Anti-diabetic
protective

Gastro- Cardiovascular-
protective protective
Anti-microbial activity
Experimental studies have reported that NSO and N. sativa extracts have
anti-microbial activity against a wide range of microbes, especially multiple-
antibiotic resistant bacteria. Anti-microbial effects of the plant extracts have
been determined in Gram-positive bacteria (Staphylococcus aureus), Gram-
negative bacteria (Pseudomonas aeruginosa and Escherichia coli) and the
pathogenic fungus Candida albicans. It is found that anti-microbial
properties of N. sativa are due to its active compounds such as
thymohydroquinone and melanin. Evaluation of in vitro antibacterial activity
of NSO on pathogenic bacteria species consisting of three gram-positive,
eleven gram-negative and C. albicans yeast has indicated strong sensitivity
in all species. Researchers have shown that N. sativa extract could
effectively eradicate non-lethal staphylococcal infection in mice after
subcutaneous injection.
Anti-oxidant activity
In several studies, anti-oxidant activity of N. sativa seeds has been reported. N. sativa could
be a useful compound for preventing and treating cerebral ischemic and
neurodegenerative diseases, due to its anti-oxidant property. Co-administration of NSO
with cisplatin in male rats improves oxidative stress induced by cisplatin in testicles. Also in
a study to determine the anti-oxidative properties of N. sativa, 64 healthy subjects received
3 g N. sativa daily for two weeks. The results indicated a significant reduction in lipid
peroxidation after consumption, and therefore the anti-oxidant activity of N. sativa was
confirmed in that study.
N. sativa extract consists of numerous anti-oxidant compounds, including TQ, carvacrol, t-
anethole and 4-terpineol. TQ with powerful anti-oxidant properties indirectly reduces the
production of reactive oxygen species and causes the inhibition of lipid peroxidation. NSO
or TQ injection in ischemia phase causes reperfusion and improves the performance and
level of glutathione peroxidase and superoxide dismutase in rats. TQ improves
nonenzymatic (GSH and vitamin C) and enzymatic activities (SOD, CAT, GPX, and GST) of
anti-oxidants. It also reduces malondialdehyde (MDA) to normal in mouse brain.
Other compounds of NSO like quinone, carvacrol and 4-terpineol are
wonderful in connecting free radicals to each other for neutralization.
These compounds have been evaluated in many in vitro anti-oxidant
tests.
The results indicate that different combinations of N. sativa have
synergistic effects. The combination of N. sativa with iron prevents
oxidation. In many diseases, such as cirrhosis or liver damage, N.
sativa anti-oxidant activity could eliminate free radicals.
Anti-inflammatory activity
In traditional medicine, fixed oil of N. sativa seed is widely used to treat
skin rashes, back pain, rheumatism, and related inflammatory diseases.
Studies have shown that fixed oil of black cumin seed and TQ exert
their anti-inflammatory properties by inhibiting the production of these
compounds. Eosinophils, oxidants, cytokine, and inflammatory
macrophages and neutrophils are responsible for creating inflammation
condition in body. It is found that administration of aqueous extract of
N. sativa or TQ in calcium ionophore-stimulated neutrophils inhibits
production of 5-lipooxigenase.
Anti-hyperlipidemic activity
N. sativa has significantly improved the lipid profiles in menopausal
women [decreased total cholesterol, low density lipoprotein
cholesterol (LDL-c) and triglyceride (TG), and increased high density
lipoprotein cholesterol (HDL-c)] more than the placebo treatment
within two-month intervention. One month after discontinuation of
treatment, the lipid profiles in the N. sativa-treated group have
changed towards the pretreatment levels.
Anti-cancer activity
N. sativa seed, its essential oil and some of its active compounds,
especially TQ and α-hederin, have been shown to exert significant anti-
cancer effects on a variety of neoplasms. For N. sativa anti-cancer
effects, different mechanisms such as utilization of free radicals, effects
on enzyme activity, inhibition of cell proliferation, changes in
intracellular glutathione, anti-oxidant activity, trapping free radicals and
induction of apoptosis in cancer cells through a pathway dependent
and independent of p53 have been proposed.
Also for TQ anti-cancer mechanism, its effects on colon cancer cells are
growth inhibition, morphological changes and increased apoptosis of
cancer cells. TQ induces apoptosis by increasing the expression of the
target gene mRNAs of P53 and p21WAF1 and inhibition of anti-
apoptotic proteins (BCL-2).
Anti-diabetic activity
N. sativa has been recommended by many traditional medicine experts to treat
diabetes. Significant effects of N. sativa on blood sugar reduction have been
confirmed, which is probably due to the presence of essential oil. It is thought that
the anti-diabetic properties of N. sativa are induced by activation of adenosine
monophosphate kinase (AMPK), affecting cellular uptake of proteins with
hypolipidemic and anti-diabetic properties. Oral administration of volatile oil of
black cumin (2 mg·kg−1·BW−1) shows a significant reduction in blood glucose in
Balb/c mice. Intraperitoneal injection of NSO (50 mg·kg−1) caused con- siderable
hypoglycemic effect in fasting normal rabbits and alloxan-diabetic rabbits. Because
of no change in basal insulin levels in all groups, it appears that N. sativa reduces
blood glucose by an insulin-independent mechanism. N. sativa extract show an
insulin-sensitizing action by enhancing ACC phosphorylation, a major component
of the insulin-independent AMPK signaling pathway, and by enhancing muscle
Glut4 content.
Cardiovascular-protective activity
In a study, the protective effect of N. sativa on the thoracic aorta
contractile response is evaluated in an experimental model of diabetes
mellitus in rat. The results show that treatment of diabetic rats with this
plant causes maximum reduction in contractile response to non-specific
KCL agonist and specific noradrenaline agonist.
Gastro-protective activity
In an experiment the anti-ulcer potential of N. sativa aqueous suspension is
assessed on induced gastric ulcers and basal gastric secretion in rats and the
results show that an aqueous suspension of N. sativa inhibits induced gastric ulcer
formation. This extract also significantly ameliorates the ulcer severity and basal
gastric acid secretion in pylorus-ligated Shay rats. The anti-ulcer effect of N. sativa
is possibly because of prostaglandin-mediated and through its anti-oxidant and
anti-secretory activities. It is also reported that N. sativa aqueous extract reduces
indexes to 36% in aspirin-induced stomach ulcer in rats. The use of NSO at a dose
of 0/88 g·kg−1·d−1 for two weeks increases mucin and glutathione levels in
stomach and decreases the amount of histamine. The protective effects of
hydroalcoholic extract on the gastric mucosa have been demonstrated. In a study,
TQ (doses of 50 and 100 mg·kg−1) and N. sativa are shown to have protective
effects on gastric ulcer in Wistar rats, via their anti-oxidant effects, decreasing
induced ischemia-reperfusion and gastric ulcer.
Nephro-protective acivity
A study has been carried out to show the possible benefi- cial effects of
TQ in STZ-induced diabetic rats and to determine the predictive value of
mesenchymal and epithelial markers in the response of diabetic
nephropathy to TQ. TQ shows protective effects on experimental
diabetic nephropathy.
Hepatoprotective activity
It has been reported that N. sativa (0.2 mL·kg−1) intraperitoneally relieves
the detrimental effects of ischemia- reperfusion injury on liver. N. sativa
treatment protects the rat liver against hepatic ischemia-reperfusion
injury. TQ protective role in the hepatotoxicity of Cd++ especially with
regards to its protection against perturbation of non-enzymatic and
enzymatic anti-oxidants has been investigated. Pretreatment with TQ (10
μmol·L−1) demonstrates a significant protection by decrease in protein
oxidation and the depleted anti-oxidants rejuvenation of cellular fraction .
Another study was undertaken to explore and validate N. sativa fixed oil
(NSFO) and essential oil (NSEO) in diabetes mellitus treatment and the
results supported the traditional use of N. sativa and its derived products
as a treatment for hyperglycemia and associated abnormalities.
Neuro-protective activity
Effects of NSO on the central nervous system have been sedating and
weakening. The TQ derived from N. sativa extract causes a reduction in
neuronal degeneration. Research has shown that TQ has an effective
analgesic effect and exerts these effects through stimulation of opioid
receptors in the central nervous system. In another study, administration of
intracranial TQ blocked PTZ-induced seizures and probably mediated this
effect by increasing the gabaergic system tone and opioid receptors. It is
reported that N. sativa (200−400 mg·kg−1) causes loss of depression in the
forced swim test and open field test in the LPS-induced depression model.
Abdul Zahir et al. have reported that NSO can protect mice in the tolerance
and dependence caused by tramadol. NSO has therapeutic potential
through blocking the overproduction of drug-induced nitric oxide and
oxidative stress.
Immuno-protective activity
Many studies have demonstrated the effect of N. sativa and TQ on the immune
system. In one of these studies N. sativa products lead to a reduction in B cell-
mediated immunity in vitro. Some other studies have indicated that α-linolenic
acid, estearidonic acid and other compounds of the plant seed boost the
immune response, particularly T lymphocytes. N. sativa increases the
proportion of helper T cells to suppressor T cells and increases the activity of
natural killer cells. Additionally, this herb stimulates interleukin-3 secretion by
T cells. Moreover, the plant’s positive stimulatory effect on macrophages has
been reported. N. sativa (2 g) supplementation with immunotherapy for 30
days results in an increase in phagocytic activity of macrophages in comparison
to immunotherapy alone. A research has demonstrated that the use of NSO for
six weeks, increases phagocytic activity of peritoneal macrophages and
increases the number of peripheral blood lymphocytes in diabetic rats.
Wound healing activity
N. sativa seeds and oil have been found to promote wound healing in farm
animals. Moreover, ether extract of N. sativa seed applied topically onto
staphylococcal-infected skin in mice improves healing by reducing total and
absolute differential WBC counts, local infection and inflammation, bacterial
expansion, and tissue impairment. Durmus and Ceribasi have compared the
effects of N. sativa and silver sulfadiazine (SSD) cream on healing of burn
wounds in an animal model. Histopatological evaluations on the 4th, 9th and
14th days showed that burn healing was better in the N. sativa and SSD
groups compared with the control group. Wound healing was significantly
different among the groups at 4th, 9th, and 14th days. In another study, the
contracting ability of the wounds treated by NSO is similar to antibiotic
(Baneocin). However, there is some retardation in wound treated with NSO.
The closure time of the wounds for both is similar to some extent.
Effects on reproductive system
N. sativa seeds increase the weight of reproductive organs, sperm
motility and count in cauda epidydimides and testicular ducts.
Spermatogenesis is increased at primary and secondary spermatocyte.
And there is an increase in number of female pregnant rats. In another
study to assess the effect of NSO on sperm parameters and testes in
comparison with nicotine in rats, nicotine reduced sperm motility and
morphology of normal and live sperms and also affected the testes
histology, while NSO increased sperm quality and exhibited better
testes histological features.
Potential mechanisms of action
Conclusion
N. sativa has been considered worldwide as an important
medicinal herb.
Its use in pharmaceutical, food and ornamental industries displays
considerable commercial value. N. sativa and its compounds, particularly TQ,
have various pharmacological effects on different body parts.
Available reports show antiinflammatory, anti-microbial, anti-cancer, anti-
oxidant, antidiabetic, and anti-hypertensive activities of the plant. Also, its
effects on digestive, immune, and central nervous system have been
demonstrated in various studies. The plant composition and medicinal
properties necessitate further research on other useful and unknown features,
so it can be used as a plant-derived medicine to treat various diseases.
 Turmeric
(Curcuma longa)
The spice turmeric is a botanical
that is used widely in the Middle
East and Asia, not only to impart a
distinctive flavor to foods, but also
purportedly to provide health
benefits as a component of
traditional medicines.
Recently, it has been added to
nutraceuticals, beverages, and
processed foods. Turmeric is
obtained from the rhizome of
Curcuma longa L.
Taxonomic Tree

• Kingdom: Plantae
• Phylum: Spermatophyta
• Subphylum: Angiospermae
• Class: Monocotyledonae
• Order: Zingiberales
• Family: Zingiberaceae
• Genus: Curcuma
• Species: Curcuma longa
Bioactive ingredients
Three curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin,
of which curcumin is the most prevalent, are among many bioactive ingredients in
turmeric. The yellow pigment curcumin or diferuloylmethane makes up 60% to 70%
of crude turmeric extracts and is the principal curcuminoid evaluated for health-
promoting activities. In addition, turmeric contains sugars, proteins, resins, and
volatile oils, such as turmerone, atlantone, and zingiberene, some of which may
have bioactivity as well. Numerous preclinical investigations identified a variety of
potential health benefits, including treatment for cancer, heart disease, arthritis,
Alzheimer's disease, gastrointestinal disorders, and the metabolic syndrome
(MetS).
Initial human trials examining the biological
actions of oral curcumin given as raw turmeric
powder were confronted with its poor water
solubility, low intestinal absorption, and rapid
metabolic degradation, which limited its
systemic distribution and bioavailability.
Consumption of gram quantities of curcumin
powder by human subjects was needed to
obtain measurable amounts of circulating
curcumin from which discernable biological
actions were inconsistently observed. Over the
previous decade, considerable research led to
improvements in curcumin's bioavailability,
which has contributed to the appearance of
numerous clinical studies evaluating various
possible health benefits of both turmeric and
curcuminoids using these new delivery
approaches.
Such methods include inclusion of piperine, a phytochemical
that enhances intestinal uptake of curcumin, and use of novel
delivery systems that complex curcuminoids within diverse
matrices. For example, curcumin can be incorporated into
micelles, microemulsions, liposomes, nanoparticles, and in
other lipid and biopolymer particles. Curcuminoids
encapsulated with turmeric essential oils, particularly with
turmerone, which enhances intestinal permeability, also have
been prepared. Noticeable improvements in oral bioavailability
in human subjects were reported using these novel formulations,
and comparative efficacies have been reported for some
strategies.
Potential Health Benefits
The effects of curcumin, having a polyphenol structure, on certain cytokines, kinases, enzymes,
transcription factors, growth factors and receptors have been studied, and it has shown some
antimicrobial, antiinflammatory, antioxidant, immunomodulatory, renoprotective,
hepatoprotective and hypoglycaemic effects. The fact that its antiinflammatory effect has been
shown in some studies, and that inflammation is one of the factors for cancer development
suggested that curcumin could be used for the prevention and treatment of cancer.
Since 1987, the U.S. National Cancer Institute tested more than 1,000 agents for
chemopreventive purposes. Among them, approximately 40 promising agents were moved to
clinical trials. Curcumin is one of these agents. However, its poor bioavailability and high
potential to interfere with other drugs, combined with lack of evidence showing its efficacy,
constitute barriers at this point.
Human investigations into the effects of turmeric and its extracts and novel formulations on
subjects with signs and symptoms of arthritis, type 2 diabetes mellitus (T2DM) and MetS are
avalable. It may provide new insights into emerging potential health benefits of turmeric from
the recent and growing number of human studies.
Cancer
Some anticancer properties of curcumin, in terms of both treatment and
chemoprevention, are to be found in many laboratory studies and there have
been efforts to describe them with different mechanisms. In one study, it was
alleged to be an interaction with the arachidonic acid metabolism and association
with its antiangiogenic characteristics; in another study, it was attributed to the
inhibition of STAT-3 (signal transducer and activator of transcription-3) pathway .
Then, there are some other studies in which it was associated with various
mechanisms such as matrix metalloproteinase, vascular endothelial growth
factor, and caspase and mitochondria-dependent apoptosis. Moreover, in various
laboratory studies, curcumin inhibited cyclooxygenase-2, lipoxygenase, ornithine,
c-Jun/AP- 1, nuclear factor-kappa B, c-Jun N-terminal kinase, protein kinase C,
and epidermal growth factor activities in a variety of tumor cells .
 Most of these trials evaluated patients with knee
osteoarthritis, and the patients enrolled were
predominantly females (75%). Patient populations
Arthritis were derived primarily from the Middle East and
Asia. The trials measured both intensity of pain
and improvements in physical functioning using
several indices. The Western Ontario and
McMaster Universities Osteoarthritis Index, the
Lequesne's Pain Functional Index, and the
Japanese Knee Osteoarthritis Measure evaluate
improvements in pain and functionality, whereas
the visual analog scale measures severity of pain.
The Clinician Global Impression of Change
measures joint tenderness, crepitus, alignment,
movement, and muscle wasting.
MetS and T2DM
Prior to 2009, only 6 trials were identified. Today, novel delivery systems increase
the bioavailability of curcumin. Because of this, in the last 10 years, more than 50
reports have been published of trials investigating the impact of different forms
and doses of oral turmeric and curcuminoids in healthy adults, as well as in those
with T2DM and those with MetS.
In healthy adults, 6 studies evaluated curcuminoids at doses as high as 6 g/d for
periods as long as 6 months. Outcomes were inconsistent for measurements of
blood glucose levels and lipid profiles. Similar disparate effects were observed in
healthy adults when curcuminoids were provided in bioavailability-enhanced forms
such as in solid lipid particles or as a phosphatidylcholinephytosome complex.
Mechanisms of Action
The mechanisms of action of curcumin in humans are not well understood.
Inflammatory cytokines and biochemical markers of oxidative status were
measured in some arthritis trials, and there is preliminary evidence from meta-
analyses that curcuminoids may decrease biomarkers of systematic inflammation
and increase serum adiponectin levels. For trials of T2DM and MetS, there is
preliminary evidence from meta-analyses that curcuminoids may reduce serum
levels of CRP and leptin.
Preclinical experiments indicate that changes in cellular inflammatory responses,
oxidative stress, chondrocyte destruction and renewal, and in osteoclastogenesis
contribute to the antiarthritic action of curcuminoids. Preclinical studies of glucose
and lipid homeostasis indicate that curcuminoids can modulate insulin action,
lipolysis, adipogenesis, lipoprotein function, and nutrient absorption.
Conclusion
Results obtained from animal studies and other laboratory studies indicate that curcumin may have
antiinflammatory, antioxidant and anticancer properties, in particular. However, since there is a
limited number of clinical studies, its effects on humans are not known clearly. Although no serious
side effects associated with the use of curcumin and curcumin-containing products have been
reported, there are data on drug interactions, particularly with chemotherapeutic agents.
In light of the evidence that the small amounts of curcuminoids in turmeric powder are very poorly
bioavailable, culinary quantities of turmeric powder added to foods for sensory purposes are
unlikely to provide meaningful health benefits for the conditions reviewed. Based on current,
preliminary evidence from human trials, curcuminoid extracts and other novel formulations may
have potential to help manage symptoms of T2DM, MetS, and especially arthritis. Yet, due to
inconsistent findings from trials that differ substantially in quality, and due to incomplete
understanding of curcuminoids' effective doses and duration and of their safety and their
interactions with comedications, it is premature to recommend their supplemental use to improve
health in a clinical setting or in the general population.
Future larger, longer, high-quality RCTs are needed to better characterize any potential health
benefits of this spice's bioactive constituents.
Ginkgo

Ginkgo biloba
• Definition
Folium Ginkgo consists of the dried
whole leaf of Ginkgo biloba L.
(Ginkgoaceae).
• Synonyms
Pterophyllus salisburiensis Nelson,
Salisburia adiantifolia Smith,
Salisburia macrophylla C. Koch.
• Selected vernacular names
Eun-haeng, gin-nan, ginkgo, ginkgo
balm, ginkgo leaves, ginkyo, ginan,
icho, ityo, kew tree, maidenhair tree,
pei-wen, temple balm, yin guo,
yinhsing.
Taxonomy
• Kingdom: Plantae
• Clade: Tracheophytes
• Division: Ginkgophyta
• Class: Ginkgoopsida
• Order: Ginkgoales
• Family: Ginkgoaceae
• Genus: Ginkgo
• Species: G. biloba
• Plant material of interest: dried leaf
The kernel (nut, seed) is used in Chinese medicine.
• General appearance
The leaves are green, grey-yellow, brown or blackish;
the upper side of a leaf may be somewhat darker
than the underside. The leaves are fan-shaped, long-
petioled and have two lobes with forked veins
radiating from the petiole end.
• Organoleptic properties
Ginkgo leaves have a weak characteristic odour.
 • Microscopic characteristics
Young leaves have abundant trichomes that become
confined to the petiole base as the leaf ages. While the
leaves have no midrib, dichotomous venation with regular,
numerous branching parallel veins arises from two vascular
strands within the petiole. Stomata occur almost exclusively
on the lower surface of the leaf. The epidermis of the upper
and underside of the leaf consists of undulated, irregular,
mostly long extended cells. In the cross-section, the
epidermal cells appear nearly isodiametric and from above
appear to be slightly undulated, with the upper cells
appearing larger. The outer walls of the epidermal cells are
covered with a more or less thin layer of cuticle. In the area
of vascular bundles there are remarkable long extended
narrow cells with slightly undulated walls. Numerous druses
of calcium oxalate occur near the vascular bundles.
Figure: Ginkgo biloba L., leaf, Asian specimens: A. Face view of the adaxial side of the epidermis in LM (Beijing), B.
Face view of the abaxial side of the epidermis in LM (Hiroshima), C, D. Adaxial and abaxial surfaces of the epidermis
in SEM (Hiroshima), E, G, H. Detail of epidermis, druse and minor vascular bundle (E: Tokyo, G: Beijing, H:
Hiroshima), F. A secretory cavity in the mesophyll (Beijing); ct, cuticle, dr: druse, ep: epidermis, LM: light
microscopy, phc: phenolic compounds, plp: plicate parenchyma, sc: secretory cavity, SEM: scanning electron
microscopy, sp: spongy parenchyma, st: stomatum, vb: vascular bundle. Bar = 20 m
• Powdered plant material
The colour of the powder agrees with that of the leaves. The powder
shows fragments of the epidermis with wavelike indentations irregular
in form with generally elongated cells; large stomal openings of the
anisocytic type; markedly elongated, narrow cells with only weakly
undulated walls in the vascular areas and without marked indentations.
The equifacial mesophyll comprises excretory vesicles, secretory cells,
and idioblasts, as well as intermittent calcium oxalate druses, in the
region of the vascular fascicles.
• Geographical distribution
Native to China, but grown as an ornamental shade tree in Australia,
south-east Asia, Europe, Japan, and the United States of America. It is
commercially cultivated in France and the United States of America.
• Dosage forms
Standardized extracts (dry extracts from dried
leaves, extracted with acetone and water,
drug:extract ratio 35–67:1) contain 22–27%
flavone glycosides and 5–7% terpene
lactones, of which approximately 2.8–3.4%
consists of ginkgolides A, B, and C and 2.6–
3.2% bilobalide. The level of ginkgolic acids is
below 5 mg/kg. Coated tablets and solution
for oral administration are prepared from
standardized purified extracts.
Medicinal uses
• Uses supported by clinical data
Extracts as described above (Dosage forms) have been used for symptomatic
treatment of mild to moderate cerebrovascular insufficiency (demential
syndromes in primary degenerative dementia, vascular dementia, and mixed
forms of both) with the following symptoms: memory deficit, disturbance in
concentration, depressive emotional condition, dizziness, tinnitus, and
headache. Such extracts are also used to improve pain-free walking distance in
people with peripheral arterial occlusive disease such as intermittent
claudication, Raynaud disease, acrocyanosis, and post-phlebitis syndrome, and
to treat inner ear disorders such as tinnitus and vertigo of vascular and
involutive origin. Extracts and doses other than those described in Dosage
forms and Posology are used for similar but milder indications.
• Uses described in pharmacopoeias and in traditional systems of
medicine
None.
• Uses described in folk medicine, not supported by experimental or
clinical data
As a vermifuge, to induce labour, for the treatment of bronchitis,
chronic rhinitis, chilblains, arthritis, and oedema.
Pharmacology
Experimental pharmacology
• Cerebrovascular insufficiency and peripheral vascular diseases
In vitro studies. A standardized extract of Ginkgo biloba (100μg/ml) did
not produce isometrically recordable contractions in isolated rabbit aorta
but did potentiate the contractile effect of norepinephrine. Higher
concentrations (EC50 1.0 mg/ml) produced a concentration-dependent
contraction that could be antagonized by the α-adrenoceptor-blocking
agent phentolamine. Both cocaine and desipramine, inhibitors of
catecholamine re-uptake, potentiated the contractile effect of
norepinephrine but inhibited the contractile effects of a standardized
extract of G. biloba and tyramine. The results of these experiments
indicate that the contractile action of G. biloba may be due to the release
of catecholamines from endogenous tissue reserves, and this activity may
explain some of the therapeutic effects of the drug in humans (e.g.
improvement in cerebrovascular and peripheral vascular insufficiency).
• Vestibular and auditory effects
Ginkgo biloba extract improved the sum of action potentials in the cochlea
and acoustic nerve in cases of acoustically produced sound trauma in guinea-
pigs. The mechanism reduced the metabolic damage to the cochlea. Oral or
parenteral administration of a standardized G. biloba extract to mice
(2mg/kg) improved the ultrastructure qualities of vestibular sensory
epithelia when the tissue was fixed by vascular perfusion. Improvement was
due to the effects of the drug on capillary permeability and general
microcirculation.
• Antagonism of platelet-activating factor (PAF)
The ginkgolides, and in particular ginkgolide B, are known antagonists
of PAF. PAF is a potent inducer of platelet aggregation, neutrophil
degranulation, and oxygen radical production leading to increased
microvascular permeability and bronchoconstriction. Intravenous
injections of PAF induced transient thrombocytopenia in guinea-pigs,
which was accompanied by nonhistamine-dependent bronchospasm.
Ginkgolide B has been shown to be a potent inhibitor of PAF-induced
thrombocytopenia and bronchoconstriction. PAF or ovalbumin-induced
bronchoconstriction in sensitized guinea-pigs was inhibited by an
intravenous injection of ginkgolide B (1–3 mg/ kg) 5 minutes prior to
challenge.
Clinical pharmacology
• Cerebral insufficiency
Cerebral insufficiency is an inexact term to describe a collection of
symptoms associated with dementia. In dementia owing to
degeneration with neuronal loss and impaired neurotransmission,
decline of intellectual function is associated with disturbances in the
supply of oxygen and glucose. In clinical studies G. biloba effectively
managed symptoms of cerebral insufficiency including difficulty in
concentration and memory, absent-mindedness, confusion, lack of
energy, tiredness, decreased physical performance, depressive
mood, anxiety, dizziness, tinnitus, and headache. Several
mechanisms of action of G. biloba have been described: effects on
blood circulation such as the vasoregulating activity of arteries,
capillaries, veins (increased blood flow); rheological effects
(decreased viscosity, by PAF-receptor antagonism); metabolic
changes such as increased tolerance to anoxia; beneficial influence
on neurotransmitter disturbances; and prevention of damage to
membranes by free radicals.
• Peripheral arterial occlusive disease
The effectiveness of G. biloba extract in the
treatment of intermittent claudication
(peripheral arterial occlusive disease Fontaine
stage II), as compared with a placebo, was
demonstrated in placebo-controlled, double-
blind clinical trials by a statistically significant
increase in walking distance. Sixty patients
with peripheral arterial occlusive disease in
Fontaine stage IIb who were treated with the
drug (120–160mg for 24 weeks) and
underwent physical training also clearly
increased their walking distance.
• Vertigo and tinnitus
Ginkgo biloba extracts have been used clinically in the treatment of
inner ear disorders such as hearing loss, vertigo, and tinnitus. In a
placebo-controlled, double-blind study of 68 patients with vertiginous
syndrome of recent onset, treatment with G. biloba extract (120–160mg
daily, for 4–12 weeks) produced a statistically significant improvement as
compared with the placebo group.
• Contraindications
Hypersensitivity to G. biloba preparations.
• Warnings
No information available.

Precautions
• Carcinogenesis, mutagenesis, impairment of fertility
Investigations with G. biloba extracts have shown no effects that were mutagenic,
carcinogenic, or toxic to reproduction.
• Pregnancy: non-teratogenic effects
The safety of Folium Ginkgo for use during pregnancy has not been established.
• Nursing mothers
Excretion of Folium Ginkgo into breast milk and its effects on the newborn have not
been established.
• Other precautions
No information is available concerning general precautions or drug interactions, drug
and laboratory test interactions, teratogenic effects on pregnancy, or paediatric use.
Lavender
Lavandula angustifolia
Introduction
Lavender (Lavandula angustifolia) is a plant with a number of beneficial
properties for the human body. Besides its application in herbal
treatment, lavender is widely used in the cosmetic, perfume, food, and
aromatherapeutic industries.
The active compounds present in herbs exhibit multidirectional
phytotherapeutic activity and are used in the treatment of
gastrointestinal, cardiovascular, respiratory, and urinary infections, as
well as in chronic diseases of children and elderly people.
Furthermore, they exhibit antibacterial, antifungal, antispasmodic, and
antioxidant activity, and also regulate digestive activity. Due to the
biologically active substances present in them, herbs have antimicrobial,
antioxidant, and therapeutic properties, and may be extensively used, as
they are effective as synthetic drugs.
Taxonomy
Domain: Eukaryota
Kingdom: Plantae
Phylum: Spermatophyta
Subphylum: Angiospermae
Class: Dicotyledonae
Order: Lamiales
Family: Lamiaceae
Genus: Lavandula
Species: Lavandula angustifolia
Lavender oil is essential oil distilled
from lavender flower, it has an anti-
inflammatory, antiseptic,
antibacterial, antifungal
antimicrobial, antidepressant
properties.
This herb stimulates urine
production and improves digestion,
reduce emotional stress and
anxiety, this herb heal burn and
wound and improve sleep,
improves eczema and psoriasis,
reduce acne and store skin
complexion. Lavender is also used
in aromatherapy.
CHEMICAL COMPOSITION OF LAVENDER
Lavender (L. angustifolia) contains essential oil,
anthocyanins, phytosterols, sugars, minerals,
coumaric acid, glycolic acid, valeric acid, ursolic
acid, herniarin, coumarin and tannins
Main components linalool (26.73%-57.48%) and
linalyl acetate (4.01%-35.39%) , Borneol (17.69%),
Champhor (14.31%)and Eucalyptol (1,8-Cineol)
(7.60%)
Essential oil (EO) of lavender (LEO; Lavandula
angustifolia) is purported to be antibacterial,
antifungal, anxiolytic, antidepressant, analgesic,
carminative (smooth-muscle relaxant), as well as to
have beneficial immunomodulatory effects on
wound healing.
Folkloric claims of benefit in anxiety have been
supported recently by clinical data, while other
studies have produced inconclusive or equivocal
results. Although whole-plant formulations may not
provide adequate concentrations of active ingredients
for effect, EOs are concentrated lipophilic extracts of
aromatic terpenoid constituents. They are able to
pass cell membranes and exhibit pharmacologic
effects at nanomolar concentrations, making them
druglike and increasing suitability for potential
pharmaceutical application.
Lavender Oil Constituents

• Gas chromatography–mass spectrometry has aided in untangling

which constituents occur most frequently, allowed insight into
variability among LEOs, and given clues about which constituents may
be primarily active. For example, one analytic study found varying
concentrations of linalool (26.73%-57.48%) and linalyl acetate
(4.01%-35.39%) among 9 different LEO samples. This concentration
variability leads to significant heterogeneity in products used in
different studies and adds to the difficulty in delineating results.
Pharmacokinetics

• Linalool is metabolized primarily through conjugation with glucuronic

acid and is oxidized by cytochrome P450 enzymes (CYP450). Linalool
is excreted primarily in urine but is also excreted via feces and in
expired air.
• Linalyl acetate is a carboxylated ester and metabolized to linalool by
β-esterases, which are mostly found in hepatocytes but are also found
in the periphery.
Review of Literature
Lavender essential oil is used in medicines and cosmetics products.
Lavender oil has been used for centuries as a therapeutic agent and the
oil derived from these plants has been widely used as an antibacterial.
The lavender oil is believed to have sedative, carminative, anti-
depressive, and anti-inflammatory properties in addition it has
antimicrobial effect also. Lavender oil is active against many species of
bacteria, including those resistance to antibiotic such as methicillin
resistance staphylococcus aureus and vancomycin resistance
enterococcus.
Lavender Oil and Aromatherapy

• Historically, EOs have been delivered as aromatherapy via inhalation

or topical routes. Essential oils delivered via inhalation route may
exert psychologic effects, because the olfactory bulb has limbic inputs
in the amygdala and hippocampus that are associated with emotion
and memory. It is hypothesized that smell-triggered emotional
memory may be the etiologic root of situational anxiety in some
circumstances. This form of emotional memory is exemplified by state
anxiety associated with the characteristic smell of the dentist's office,
which has been reduced with LEO. Conversely, particular smells may
be associated with positive emotions and mood, which is a core tenet
of hypothesized benefits in aromatherapy.
Conclusion
Lavender essential oil is an herb which is used in our daily life for many
purposes. It has many health benefits also. Besides having the
medicinal properties lavender is also very healthy for glowing skin and
it protect skin from acne and other skin problems. Lavender have also
some medical benefit also such as inhaling of lavender oil helps to
improve sleep duration, sleep quality, and it provide relaxation.
Lavender also reduces the symptoms of diabetes. Lavender helps to
slow down the ageing process. Lavender also have antifungal,
antimicrobial, antibacterial effects also.
• The SLO product exhibits many desirable properties of an anxiolytic
agent, including a calming effect without sedation, as well as a lack of
dependence, tolerance, or withdrawal. SLO has a relatively benign
side effect profile in short-term studies, and its onset of efficacy is
more rapid than current first-line agents. Evidence from multiple high-
quality randomized trials suggests a role for SLO in the treatment of
anxiety disorders. The favorable safety and efficacy profile of SLO
makes it a reasonable alternative to consider in patients with anxiety
disorders. Clinicians should exercise caution given limitations of the
current evidence base and lack of Food and Drug Administration
endorsement in the management of anxiety disorders.
 Lesson 5
Complications, Interactions
and Safety in Phytotherapy
Asst. Prof. Ali Timuçin ATAYOĞLU
Purity tests
• Microbiology
The test for Salmonella spp. in Folium Ginkgo should be negative. The maximum
acceptable limits of other microorganisms are as follows. For preparation of
decoction: aerobic bacteria not more than 107/g; fungi not more than 105/g;
Escherichia coli not more than 102/g. Preparations for internal use: aerobic bacteria
not more than 105/g or ml; fungi not more than 104/g or ml; enterobacteria and
certain Gram-negative bacteria not more than 103/g or ml; Escherichia coli 0/g or ml.
• Foreign organic matter
Not more than 5% of twigs and not more than 2% of other foreign matter.
• Total ash
Not more than 11%.
• Pesticide residues
To be established in accordance with national requirements. Normally, the
maximum residue limit of aldrin and dieldrin in Folium Ginkgo is not more than
0.05mg/kg. For other pesticides, see WHO guidelines on quality control methods for
medicinal plants, and guidelines for predicting dietary intake of pesticide residues.
• Heavy metals
Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg,
respectively, in the final dosage form of the plant material.
• Radioactive residues
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-
239, see WHO guidelines on quality control methods for medicinal plants.
• Other purity tests
Acid-insoluble ash, acid-insoluble extractive, chemical, and moisture tests to be
established in accordance with national requirements.
• Chemical assays
Flavonoids not less than 0.5% calculated as flavonol glycosides or 0.2–
0.4% calculated as aglycones; also contains ginkgolides (0.06–0.23%)
and bilobalide (up to 0.26%).
Qualitative and quantitative determination of flavonoid glycosides is
carried out after hydrolysis to the aglycones kaempferol, quercetin, and
isorhamnetin. The qualitative presence or absence of biflavones is
determined by high- performance liquid chromatography; and
qualitative and quantitative determination of the diterpene ginkgolides
and sesquiterpene bilobalide by high-performance liquid
chromatography or gas–liquid chromatography.
Certain commercial products used for clinical and experimental
biological studies, e.g. EGb 761 and LI 1370, do not contain biflavones.
• Major chemical constituents
Folium Ginkgo contains a wide variety of phytochemicals, including
alkanes, lipids, sterols, benzenoids, carotenoids, phenylpropanoids,
carbohydrates, flavonoids, and terpenoids.
Olive leaves are safe, non-toxic and well-tolerated by the majority of
the population. No adverse reactions or toxicity reports have been
documented, and no drug interactions are yet known. Olive leaf may
stimulate the thyroid, so if one suffers from hyperthyroid conditions or
goiter he/she should use olive leaf with care. Olive leaf decreases blood
sugar and may interact with diabetic medications.
Headache, gastrointestinal disturbances, and allergic skin reactions are
possible adverse effects of Ginko.
Potential side effects and drug interactions
Jarisch-Herxheimer or Herxheimers reaction
It is an immune response to the release of toxins from pathogens which have been destroyed, in
this case by the olive leaf extract. The reaction proceeds as follows: Olive leaf compounds attack
and damage the cells cause release of toxins, break down and are absorbed by surrounding tissues,
which were already displaying symptoms caused by the infection of the pathogens. This increase in
the concentration of toxins worsens the original symptoms and elicits a further immune response
from the body causing histamine release, swelling and pain the body ramps up its detoxification
and cleansing processes which may result in other undesirable symptoms. As the overload of dead
organisms is reduced and removed from the body, healing and a surge of energy and feeling of
Health improvement follows drinking 4-6 glasses of purified water daily helps the body eliminate
these toxins more quickly. The tissue surfaces where most discomfort may be felt are the mucous
membranes of the mouth, esophagus, stomach, intestines, sexual and urinary organs, ears, lungs
and membranes surrounding the brain and synovial linings of the joints. These can give rise to the
following olive leaf side effects: dull headaches, muscle and joint pain, feverishness and sweating,
nausea, sore throat and nasal passages, vaginal irritation especially in the case of yeast/fungal
infections. Olive leaf side effects may also include dizziness in people who have low blood-pressure,
by lowering it further.
Stomach irritation
This can be caused in some people by very strong olive leaves extracts
or tinctures. Olive leaves extracts can be taken with food to minimize
irritation
Diarrhea
This may be caused by stomach irritation described above but the cases
involved people with candida overgrowth in the gut. When it turns
parasitic, candida albicans forms filaments which embed themselves in
the gut lining in place of the beneficial probiotic bacteria. When olive
leaf extract damages these filaments, a Herxheimer reaction may occur
as described above causing a loose stool.
Acid reflux/Heartburn
This is experienced after taking olive leaf tinctures (Jacob et. al. 2010).
It appears to happen mostly to acid reflux sufferers after taking
peppermint-flavored glycerine tinctures, although it has occasionally
been reported. As peppermint relaxes smooth muscle, it can relax the
lower esophageal or cardiac sphincter (valve) entering the stomach,
already loose in an acid reflux sufferer, causing reflux and heartburn. It
can sometimes be overcomed by taking an unflavored tincture, or by
diluting it in tea or water.
Attention to Herb-Drug Interaction !
• The possibility of drug interactions, direct toxicities, and contamination with active pharmaceutical agents
are among the safety concerns about dietary and herbal supplements. Although there is a widespread
public perception that herbs and botanical products in dietary supplements are safe, research has
demonstrated that these products carry the same dangers as other pharmacologically active compounds.
Interactions may occur between prescription drugs, over-the-counter drugs, dietary supplements, and
even small molecules in food—making it a daunting challenge to identify all interactions that are of
clinical concern.

• Concerns about herb-drug interactions are often not based on rigorous research. Most herb-drug
interactions identified in current sources are hypothetical, inferred from animal studies, cellular assays, or
based on other indirect means; however, attention to this issue is needed for drugs with a narrow
therapeutic index, such as cancer chemotherapeutic agents, warfarin, and digoxin.

• To date, well-designed clinical studies evaluating herbal supplement-drug interactions are limited and
sometimes inconclusive. This issue of the Digest provides information about several herbs and their
potential interactions with other agents.
a. Due to its ability to lower blood pressure, olive leaf increases the
effects of drugs that lower blood pressure. Some of the blood pressure-
lowering drugs:
b. Due to a possible decrease in blood sugar levels, taking olive leaf
may increase the effects of insulin and oral drugs for diabetes, such as:
Actos, Amaryl, Avandia, glipizide, glyburide, Glynase, Glyset, metformin
(Glucophage), Prandin and Precose. Because olive leaf may decrease
blood sugar levels, taking it with other blood sugar-lowering herbal
products may result in hypoglycemia. Eleuthero, Fenugreek, Ginger (in
high amounts) & Kudzu.
c. Olive leaf extract may increase the effect of blood thinners such as
Warfarin as it tends to prevent blood platelets from sticking together.
 Lesson 6
Scientific Studies in
Phytotherapy
Asst. Prof. Ali Timuçin ATAYOĞLU