Phytomedicine in

pharmacology

Dr Ntsoaki Nyane
PhD (Pharmacology)
Room 6-7, Level 6, Department of Pharmacology,
Basic Medical Sciences Building
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Email: Ntsoaki.nyane@up.ac.za
 Complementary Alternative Medicine

• Encompasses a wide array of healthcare practices,

products and therapies that are distinct from practices,
products and therapies used in conventional or allopathic
medicines
 Complementary
Medicine being used together
with conventional medicine

Alternative
Medicine is used in place of
conventional medicine
WHY A PHYSICIAN SHOULD KNOW ABOUT CAM?

• Physicians are important sources of information and guidance about

health matters
• But patients also rely on a wide range of other sources including
family and friends, cultural traditions, alternative practitioners, and
increasingly the Internet, popular media, and advertising.
• It is essential for physicians to understand what patients are doing to
seek health, as this understanding is important to harness potential
benefits and to help patients avoid harm
 Therapies used world-wide

Acupuncture/Acupressure Alexander Technique Aromatherapy Aryuvedic

Medicine Autogenic training Autologous blood therapy Bach Flower Remedies
Balneotherapy Biofeedback Bioresonance Bonesetting Chelation Chinese
Herbal Medicine Chiropractic Therapy Colonic Irrigation Counter-irritation
Craniosacral therapy crystal therapy Cupping Diets Curanderismo
Electromagnetic therapy Enzyme therapy Folk medicine Healing Circles
Herbal Medicine Homeopathy Hydrotherapy Hypnotherapy Iridology
Kampo Kinesiology Kirlian photography Laser therapy Laying on of hands
Massage Midwifery Native American healing Naturopathy Phytomedicine
Prayer Pulse diagnosis Qi gong Reiki Reflexology Relaxation therapy
Spa therapy Spiritual Healing Tai Chi Thallasotherapy Tongue diagnosis
Transcranial magnetic stimulation Vega testing Water injection Yoga
Reasons for use of CAM
Why do patients not tell their physician about their CAM use?

• 70% of patients see their Physician before or concurrent with their

visits to a CAM provider

• 60% - “My doctor never asked.”

• 60% - “It wasn’t important for my doctor to know.”
• 20% - “My doctor wouldn’t understand.”
• 14% - “My doctor would disapprove.”
Traditional medicine

• Refers to health practices, approaches, knowledge and

beliefs that incorporate the following to treat, diagnose
and prevent illness or maintain well-being
– Plant, animal, and mineral based medicines
– Spiritual therapies
– Manual techniques
– Exercises
Phytopharmacology

• Study of drugs obtained from plants.

• Study of major constituents (active ingredients) and medicinal values
of plants; and toxicity or hazardous components.
• The art or practice of using herbs and herbal preparations to
maintain health and to prevent, alleviate, or cure disease.
• Terms herbal medicine/herbs and phytomedicine will be used throughout
the lecture

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Phytopharmacology

• World Health Organization (WHO) definition:

– Refers to herbs, herbal materials, herbal preparations, and finished herbal
products that contain:
• Whole plants, parts of plants
• Other plant materials: leaves, bark, berries, flowers, and roots
• Plant extracts as active ingredients intended for human therapeutic use or
for other benefits in humans and sometimes animals
• Phytomedicine represent a collection of therapeutic knowledge that is
deeply rooted in a culture
• Formed the basis of early version of pharmacopoeias:
– Which was based in large part on natural products originated from botanicals,
animals, fungi, and minerals

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History of plant based medicine

• Plants have historically served as the most significant source of new leads
for pharmaceutical development
• Currently, it is believed that about one-quarter of allopathic medicines
contain plant derived molecules
– Approximately, 25% of pharmaceutical prescriptions in the United States contain
at least one plant-derived ingredient
• Herbs and herb-derived medicines have played a crucial role in health and
disease management for many centuries
• Use of plants for medicinal purposes is as old as human civilization
• Continuous efforts are being made towards its improvement

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Current trends

• In many regions of the world, people still rely on traditional plant based
medicines for the primary healthcare
• This is especially true for many rural communities:
– Africa, parts of Asia, and Central and South America
• In other countries, many of these plant based medicines are being
integrated through regulations into mainstream healthcare systems
• For example,
– December 2016, Chinese government announced their aim to integrate
Traditional Chinese Medicine (TCM) into their healthcare system by 2020
– In Europe, a trend towards use herbal medicines alongside pharmaceutical drugs
– Germany, for example, it is estimated that 90% of the population use herbal
medicines

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Traditional medicine around the world

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WHO estimates

• The consumption of herbal medicines is increasing worldwide due to:

– Benefits it offers
– Toxicity and side effects of allopathic medicines
• WHO estimates that 80% of the world's population (4 billion people)
currently use herbal medicines
• This led to sudden increase in the number of herbal drug manufactures
• Some therapies are passed down through generations while others have
emerged more recently
• Use of medicinal plants tends to be underreported, leading to a chronic
ambiguity concerning their therapeutic efficacy but also their acute and
chronic side effects

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Herbal medicine market estimate

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Herbal medicine in SA

• Around 27 million South Africans depend on traditional herbal medicine for

their primary health care needs
• Approximately, 72% Black SA population rely on herbal medicine

• Why do people use herbal medicine?

– Natural is safe/better

– Desperation

– Culture/beliefs

– Easily accessible

– Economical/Cheaper

– Lack of medical facilities

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Why should we know about herbal remedies

• Easily accessible:
• Internet
• Herbal shops
• Informal markets
• Over the counter
• Magazines

• Part of our health care system

• More than third of population uses CAM
• Adverse effects occur and we need to treat patients
Traditional Health Practitioners

Approximately 190 000 THP

• Diviners
• Herbalists
• Prophets
• Sangoma
• Traditional surgeons / birth attendants (midwifery)
• Not to be confused with alternative and complementary
health practitioners
Developing versus developed countries

Drugs

Herbals
Preparations

• Liquids
• Decoctions/teas, infusions
• Tinctures, macerates
• Lotions, salves, balms, poultices
• Inhalations/Vapours
• Enemas
• Snuffs
Value of plants

• Isolate bioactive compounds for direct use as drugs e.g. digoxin,

morphine, taxol, reserpine
• To produce bioactive compounds of novel or known structures as
lead compounds for semisynthesis to produce patentable entities
e.g. metformin, oxycodon, verapamil
• To use agents as pharmacologic tools
• To use as a herbal remedy e.g. echinacea, St. John’s wort
Do plants go out of fashion?

2000 BC “Here, eat this root”

1000 AD “That root is heathen, here say this prayer”

1805 AD “That prayer is superstition, here drink this potion”

1940 AD “That potion is snake oil, here swallow this pill”

1980 AD “That pill is ineffective, here take this antibiotic”

1997 AD “That antibiotic is artificial, here, eat this root

Drug discovery: last 40 years

• Dioscorea spp. – diogenin: anovulatory contraceptive agents

• Rauwolfiia spp. – reserpine: anti-hypertensives, tranquilizing
alkaloids
• Pilocarpus spp. – pilocarpine: glaucoma, dry mouth
• Cassia spp. – laxative agents
• Digitalis spp. – cardiotonic agent, heart failure

070316_0209 • Rauwolfia serpentina

Rauwolfia Cassia Digitalis

Famous African medicinal plants
• Acacia senegal (Gum Arabic): cholesterol, anti-inflammatory
• Agathosma betulina (Buchu): prostatitis
• Aloe ferox/ A. vera (Cape Aloes): purgative, skin
• Artemesia afra (African wormwood): anti-malarial
• Asplanthus linearis (Rooibos tea): antioxidant
• Boswellia sacra (Frankincense): anti-inflammatory, respiratory, digestive
• Catha edulis (Khat): stimulant
• Commiphora myrrha (Myrrh): rheumatism, arthritis
• Harpargophytum procumbens (Devil’s claw): pain, rheumatism
• Hypoxis hemerocallidea (African potato): wasting, immune
• Prunus africana (African cherry): prostate hyperplasia
• Catharanthus roseus (Rosy periwinkle): cancer, diabetes
• Sutherlandia frutescens (Cancer bush): immune, wasting
American/Asian/Indian/Chinese

• Chinese: > 5000 years old

– Spread to all continents
– Panax ginseng: stimulant, aphrodisiac, DM II
– Ephedra sinica: decongestant + bronchiodilator (asthma)
– Gingko biloba: dementia, cerebral deficiencies

• Europe: originated with Hippocrates (460-377 BC)

– Herbal teas
– Hypericum perforatum (St John’s Wort) depression
– Echinacea: immune system modulator st johns wort
Plants and common uses

• Cocaine from Coca plants: anaesthetics

• Chondrodendron tomentosum: alkaloid D-tubocurarine: muscle
relaxant in surgery
• Papaver somniferum: morphine: analgesic, narcotic
• Salix spp.- salicylic acid: aspirin – fever, anti-platelet, anti-
inflammatory
Common herbs

• Caraway – bloating
• Coriander – carminative
• Fennel – mildly carminative
• Anis – expectorant, spasmolytic, carminative
• Ginger – motion sickness
• Thyme and mint – bronchiolytics and expectorants
ginger-263x300
Anti-cancer drugs

• Catharanthus roseus (Rosy periwinkle)– vincristine, vinblastine: childhood

leukaemia, Hodgkin’s disease, breast ca (Velbe: Eli Lilly)
• Asimina spp (Papaw) – ovarian cancer
• Taxus brevifolia (Pacific Yew) -Taxol: ovarian cancer (Paclitaxel). Analogs -
Docetaxel
• Podophyllum peltatum (May Apple) – podophyllotoxin: leukemia, lymphoma,
lung, testicular cancer (Etoposide/Vepesid)
Anti-cancer drugs

Catharanthus roseus (Madagascar Periwinkle)

• Alkaloids: vincristine + vinblastine
• Inhibit mitosis by binding to tubulin → prevents cell from making
spindles
• Side-effects: hair loss, nausea

Catharanthus roseus
Bronchiodialator

Ephedra sinica (Ephedra)

• Decongestant, bronchiodilator, asthma, hay fever, CNS and cardiac
stimulator
• Main component is alkaloid ephedrine, less pseudoepinephrine
• Stimulates α1, ß1 and ß2 adrenoreceptors
• Ephedrine excites sympathetic NS, causing vasoconstriction +
cardiac stimulation
• BP by elevating both systolic and diastolic pressures and pulse rates
• Bad publicity – weight reduction + fat burning products
Diabetes

Syzygium cumini (Java plum)

• Hypoglycaemic effect
• 50% reduction of blood glucose
• ~ 10-fold increase in cathepsin B activity (proteolytic conversion of pro-
insulin to insulin)
• Inhibits insulinase activity: liver and kidney

Syzygium_cumini.jpg
 070316_0209 • Rauwolfia serpentina

Cardiovascular
Rauwolfia serpentina (Snake-root) Seva Aushadhi.com

• Alkaloid reserpine
• Hypotensive
• Lowers high blood pressure by depleting tissue stores or catecholamines
(epinephrine and norepinephrine) from peripheral sites
• Sedative properties related to the depletion of catecholamines and serotonin
from the brain
• Once absorbed from GIT, active alkaloids concentrate in tissues with high
lipid content
• Pass BBB and placenta
• Slow onset of action, sustained effect
• CNS and CVS effects persist after withdrawing the drug
• Interacts with/potentiated by some drugs
CNS

Hypericum perforatum (St. John’s Wort)

• Nervous disorders (such as depression)
• Hypericin
• Inhibits synaptosomal uptake of neurotransmitters: serotonin,
dopamine, noradrenaline and GABA
• Interactions – oral contraceptives, anticonvulsants, cyclosporins,
digoxin, HIV protease inhibitors, selective serotonin reuptake
inhibitors, etc. st johns wort
Phytomedicine Toxicity
Potential hazards

• Medicinal plants contain mixtures of different chemical compounds:

- act individually
- additively
- synergy
• Modern allopathic – patentable single compound
• Today – used together
More problems

• Failure to follow preparation method/s

• Secrecy and denial
• Laboratory tests non existent
• Dosage: Overdosing, over duration (seasonal variation)
Frequency/ Period of use
• Unknown precautions, contraindications, adverse effects
• Pharmacological activity
• Active compounds
Yet other problems

• Plant compounds themselves + part of plant used

• Adulteration
• Contamination (Microbial etc.)
• Misidentification/substitution
• Concentrations of compounds not standardized
(quality issues)
• Lack clinical trials
• Lack of laws: supplements
• Self-prescription
Patients presenting with poisonings

• Deny use/think not important to mention (use not

disclosed)/not asked
• Herbals exported – not familiar with signs and symptoms
• No information on content
• Area bound
• Acute versus chronic toxic effects
 ANd9GcRYB2Tb3NWfKz3n-Bv_yykUfjeLaHQQhExhSWi-NZkPSI7xaloE8Y2SzA

Herbal remedy toxicity

Extrinsic factors Intrinsic factors

(Not plant associated) (Inherent phytochemicals)

Misidentification Pharmacodynamic
Contamination Pharmacokinetic
Substitution
Adulteration
INTRINSIC TOXICITY
Examples of plant toxicity
Toxin Species Effects

Digoxin-like Oleander Cardiac arrhythmias

glycosides
Hallucinogens Mushrooms Delirium
Datura spp.
Ricin Castor oil plant Haemagglutination
Pyrrolizidines Senecio spp. Veno-occlusive liver
disease
Solanins Solanum spp. Circulatory collapse
Strychnine Red bitter berry Convulsions
Examples of plant toxicity

Toxin Species Effects

Amphetamine Catha edulis Delirium, convulsions
(Bushman’s tea)
Amanatins Mushrooms Hepatic and renal failure
Atractyloside Callilepis laureola Mitochondrial toxin
Colchicine Crocus Diarrhoea and vomiting
Shock, renal failure

Azoglycosides Cycads Neurotoxicity,

carcinogenesis
Cyanogenic Cassava, Apricots Shock, metabolic failure
glycosides
Indirect indices of poisoning

• Prothrombin time (coumarins)

• Glucose
• Alanine aminotransferase (ALT) (hepatotoxins)
• Myoglobinuria (myotoxins)
• Haemoglobinuria (haemolytic toxins)
• Methaemoglobin (oxidising agents)
• Hypocalcaemia (+ acidosis)(oxalates)
Callilepis laureola DC.
Ox-eye daisy
Impila

• Decongestant
• Induce fertility
• Ward off “evil spirits”
Callilepis laureola DC poisoning
Patient Presentation:

• 80% confused/coma
• 95% hypoglycaemia
• 87% metabolic acidosis
• Hepatocellular failure
• Nephrotoxicity
 Atractyloside
Carboxyatractyloside

Inhibits transport of
ADP into mitochondria
(No synthesis of ATP)

ADP ATP

Cell death
Callilepis laureola DC poisoning
Patient Management:

Treatment:
• Supportive
• No antidote

Outcome:
• Survival rates low
• 91% admitted die
Senecio latifolius DC.
Ragwort, groundsel

• Induce abortion
• Skin eruptions
• Chest pains
• Palpitations
Human Senecio poisonings are accidental:

• Ingestion of grain contaminated with seeds of

Pyrrolizidine alkaloids (PA) containing weeds
• Consumption of herbal/bush teas
• Herbal infusions for medicinal purposes
Senecio latifolius DC Poisoning
Patient Presentation

• 96% ascites - fluid build-up in the abdomen

• 85% hepatomegaly - enlarged live
• 92% liver enzymes - high Liver Enzyme Concentrations
 Retrorsine
(pyrrolizidine alkaloid)

Damages vascular
endothelium

Hepatic veno-occlusive
disease (VOD)
Senecio latifolius DC Poisoning
Patient Management

Treatment:
• Supportive
• No antidote
• Counteract thrombosis

Outcome:
• 33% mortality in children < 2 years
Urginea sanguinea Shinz.
Squill (slangkop)

• Veneral diseases
• Blood purifier
Urginea sanguinea Shinz poising
Patient Presentation

• Gastrointestinal symptoms
• Nausea
• Vomiting
 Scillaren A

Digitalis-like effect

AV block
Rhythm disturbance
Aloe ferox Mill.
(Cape aloe)

T: Laxative
Arthritis
Eczema
Conjuctivitis
Hypertension
Stress
Wounds
 Aloin
Aloeresin

Aloe-emodin anthrone

Laxative action

Adverse effects: allergy, intraoperative bleeding,

acute renal failure, melanosis coli
 Harpagophytum
procumbens DC.
(Devil’s claw)

T: Rheumatism, arthritis
 Harpagoside

Harpagide

Analgesic
Anti-inflammatory

Anticoagulant
Solanum spp.
Thorn apple
“Gifappel”
Solanum spp poisoning
Patient Presentation:
• Headache
• Salivation
• Nausea
• Vomiting
• Diarrhoea
• Fever
• Coma
Solanins - Solasonine, Solasodine

Circulatory collapse
Cycads
Azoglycosides

Cycasin
Macrozamin

Neurotoxicity
Carcinogenic
Liver damage
Datura stramonium
(Thorn apple) “Malpitte”
(Jimson weed)

T: Asthma
Reduce pain
Headaches
Datura stramonium poisoning
Patient Presentation:

• Blurred vision
• Suppressed salivation
• Vasodilation
• Delirium
 Tropane alkaloids

Atropine
Scopolamine

Anticholinergic activity
Datura stramonium poisoning
Patient Management:

Treatment:
• Fluids
• Gastric decontamination: charcoal

Outcome:
• Poisonings sporadic
• No deaths
 Extrinsic toxicity

• Substitution
• Misidentification
Contamination

• Micro-organisms
– Moulds
– Yeasts
– Bacteria

• Heavy metals
– Concentrate - mushrooms
– Soil uptake
– Environment - pollution
Adulteration

• Definition: substitution/addition of another closely related plant species or

foreign substance in order to increase weight, potency, decrease its cost

Detected in herbal remedy mixtures:

• Steroids: Prednisolone, hydrocortisone, triamcinolone, methyltestosterone
• Benzodiazepines: Diazepam, estazolam, chlordiazepoxide
• Heavy metals: Mercury, lead, arsenic, antimony, cadmium
• Analgesics and NSIADs: Acetaminophen, aspirin, indomethacin
• Other drugs and chemicals
– Hydrochlorothiazide, caffeine, scopolamine, atropine, strychnine, carbamazepine,
phenytoin, valproic acid
Other mechanisms/
implications
Drug-Herb interactions

• Borage - lower seizure threshold with anticonvulsants

• Valerian - excessive sedation with barbiturates
• Garlic, gingko, ginseng, ginger – with warfarin additive
anticoagulation effect
• Digitalis spp. – potentiate digoxin
• Liquorice – potentiate corticosteroids
Drug-Herb interactions

➢ St. John’s Wort induces cytochrome P450

➢ Displacement of strongly protein bound drug by herb
- Interferes with immunoassays i.e. [ ] drug in serum/plasma incorrect
- Cyclosporin plasma [ ] leading to kidney transplant rejection
- Decrease in serum level: oral contraceptives, methadone, warfarin
Pharmacological interference

➢ Haematology: increase warfarin’s action: ( platelet aggregation)

• Ginseng, Danshen, Garlic, Ginkgo Biloba, Ginger,
Devil’s Claw, Red Clover, Dong Qui and Horse-Chestnut
➢ Potassium
• Licorice [ ]
➢ Glucose
• Licorice
• Garlic, ginger, nettle, sage
Other problems

• Scientific botanical name unknown

• Plant part used and country of origin
• Type of extract
• Standardised constituents and concentrations
• Specific lot number
Safety and efficacy

Limited scientific evidence about phytomedicine’s safety and efficacy

The following are still required:

• Formulate national policy and regulation for use

• Establish regulatory mechanisms to control its safety and quality

• Create awareness among consumers