Musculoskeletal and nervous systems

Question 1

Which plants are associated with arthritis, rheumatism and pain?

Answer 1

◦ Willow bark/ salicin: Salix spp., Salicaceae
◦ Meadowsweet: Filipendula ulmaria (L.)
Maxim., Rosaceae
◦ Devil’s claw: Harpagophytum procumbens, Pedaliaceae
◦ Turmeric: Curcuma longa L., Zingiberaceae
◦ Pineapple/ Bromelain: Ananas comosus (L.)
Merr., Bromeliaceae
◦ Papaya/ Papain & Chymopapain: Carica
papaya L., Caricaceae
◦ Rose hips: Rosa canina L., Rosaceae

Question 2

What plant is associated with gout?

Answer 2

Autumn Crocus/ Colchicine: Colchicum autumnale L., Colchicaceae

Question 3

Which plants are Topical Anti-inflammatory Agents?

Answer 3

◦ Wintergreen oil: Gaultheria procumbens L., Ericaceae
◦ Sweet birch: Betula lenta L., Betulaceae
◦ Hot pepper/Capsaicin: Capsicum frutescens
L., Solanaceae

Question 4

Which plants are associated with nocturnal leg cramps?

Answer 4

Quinine tree: Cinchona spp., Rubiaceae

Question 5

Willow bark

Answer 5

Phenolic glycosides (salicin, 15- 18% in extracts), phenolic acids, tannins, flavonoids
The classic NSAID (non-steroidal anti-inflammatory drug), aspirin, was developed as result of studies on salicin
Early uses in Greek medicine – documented in De
Materia Medica
European middle ages – used to treat fever & relieve pain
Native North Americans from Florida to Alaska also used it for fever, headaches, & pain relief
Used in Germany today for pediatric medicine for herbal fever remedy. A tea for influenza contains
◦ 30% willow bark, 40% linden flower, 10% meadowsweet flower, 10% German chamomile flower, & 10% bitter orange peel.

Question 6

Willow and the Gorani

Answer 6

• Cultural keystone species
• Rituals of Giorgidan
• Annual “immunity”
• Sacred baths
• Animal fodder
• Protective amulets for the home and business
• Marriage rituals

Question 7

Salicin & the creation of aspirin

Answer 7

Medicinal effect of willow due to salicin, a glycoside 1st isolated in 19th century from Salix spp.
Today salicin is used as an antirheumatic
Salicylic acid was isolated from Filipendula (Spirea) ulmaria – meadowsweet
◦ In 19th century – this was a top drug for neuralgia, sciatica, myalgia, headaches & fever
◦ Bad side effects – GI discomfort & nausea
1853- derivatives made – one was acetyl- salicylic acid, which was shelved until 1899 when Bayer ‘rediscovered” it
◦ Widely used as: antipyretic, analgesic, antiinflammatory, antirheumatic

Question 8

Devil’s Claw

Answer 8

Bitter iridoids ◦ Harpagide
◦ Harpagoside
Alternative to NSAIDs (which have GI side effects)
MOA: unknown; and still not sure which are the active compounds
◦ Extracts/ supplements are standardizes based on haragide & harpagoside content (>1.2%)
Clinical studies: Placebo controlled, double blind trials demonstrate superiority to placebo for rheumatic conditions & lower back pain
Also used for osteoarthritis as well as other degenerative musculoskeletal conditions
Safety: spasmogenic and uterotonic activity – should not be used by pregnant women

Question 9

Turmeric

Answer 9

3 classes of important compounds:
◦**Curcuminoids (curcumin)
◦ Curcumin inhibits iNOS (inducible nitrate oxidase synthesis), it may be a non-specific inhibitor of NF- κB
◦ Curcuminoids are antioxidants & are hepatoprotective against liver damage by toxins
◦Essential oils (sesquiterpene ketones)
◦Polysaccharides (glycans) ◦ Immunostimulant activity
Traditional Uses: Ayurvedic & TCM -> anti-inflammatory, antihepatoxic, digestive, blood purifier, antiseptic, and general tonic.
In West, increasing popularity as antiinflammatory & antihepatotoxic. Popular use in food for curry powders & as coloring agent. It is also important in Hindu & Buddhist religious ceremonies.
Animal & Clinical Studies: hypoglycaemic; immunostimulant; anti- asthmatic; antimutagenic; anticarcinogenic;antirheumatic; low toxicity
Limitations:
◦ poor water solubility and rapid intestinal and hepatic metabolism of curcumin are the major challenges limiting its clinical use
Benefits:
◦ Well tolerated and can be easily incorporated into the diet

Question 10

Bromelain

Answer 10

Mixture of protein-digesting enzymes found in the fruit & stem
MOA: decreases fibrin, promoting circulation & post- traumatic resorption of inflammatory byproducts
Traditional Uses: the root and fruit are either eaten or applied topically as a proteolytic & anti-inflammatory agent. It is also used as an anti-helmintic.
Animal studies: anti-inflammatory
Clinical uses: effective alternative to NSAIDs; used to treat bruising, arthritis, joint stiffness & pain, & to improve post-operative healing

Question 11

Clinical Studies on bromelain

Answer 11

Cardiovascular disease and circulation
◦ Prevents or minimizes severity of angina pectoris and transient ischemic attach (TIA)
◦ Prevention & treatment of thrombophlebitis Osteoarthritis
◦ Combo of bromelain, trypsin & rutin compared to diclofenac for patients with osteoarthritis of knee – saw significant reduction in pain and inflammation
Immunogenecity
◦ Some evidence that oral therapy produces analgesic and anti- inflammatory effects in pt. with rheumatoid arthritis (autoimmune disease)
Blood coagulation and fibrinolysis
◦ Influences blood coagulation by increasing the fibrinolytic activity of serum and inhibiting fibrin synthesis
Surgical recovery
◦ Oral treatment before surgery can reduce avg. # of days for complete disappearance of pain and post-surgical
inflammation
↑
◦May be effective in reducing swelling, bruising and pain for women having an episiotomy during childbirth
◦ Commonly used to treat acute inflammation in sports injuries
Enzymatic burn debridement
◦ Bromelain cream (35% in lipid base) beneficial for debridement of necrotic tissues and accelerated wound healing
Toxicity studies
◦Low toxicity. LD50 >10g/kg in mice, rats, and rabbits
◦1500 mg/kg/day in rats showed no carcinogenic or teratogenic effects

Question 12

Chymopapain

Answer 12

Proteolytic enzyme (protein) found in immature papaya fruit latex
Marketed as Chymodiactin
Injections made into slipped (herniated) lower lumbar discs in spine
◦ Reduces mass of herniated material, reducing pressure on nerve roots
◦ Not available in USA since 1975 – but is used in Canada, Europe & Asia
◦ Risk of severe allergic reaction

Question 13

Colchicine

Answer 13

Source: Autumn Crocus/ Meadow saffron ◦ Colchicum autumnale L., Colchicaceae
1st isolated in 1820
Used as alternative gout treatment for those unable to tolerate NSAIDs
MOA: inhibits deposition of uric acid (urate crystals), raises tissue pH by inhibiting glucose oxidation, reducing production of lactic acid in leukocytes
History
Colchicum autumnale
(Colchicaceae)
Pain of gout
◦ 1st described by Dioscorides as a gout treatment in De Materia Medica ◦ Used in ancient Islamic medicine & in Europe; Benjamin Franklin in USA
used it to treat his gout
◦ 2009 – FDA approved for gout treatment
Utility:
◦ Used to treat the acute phase of gout (pain from formation of needle-like crystals of uric acid in the joint – particularly of thumb and big toe)
Side effects/toxicity:
◦ Plant extract not used because colchicine is highly toxic, and dose must be controlled
◦ Causes GI disturbance, may reduce dose to control side-effects; ◦ colchicine poisoning has similar symptoms as arsenic poisoning

Question 14

Methyl salicylate

Answer 14

Topical antirheumatic
◦ Rubifacient that acts by counter- irritation; useful in treating localized pain (included in liniments like Bengay)
Sources: Betula lenta (Betulaceae) or Gaultheria procumbens (Ericaceae)
◦ Oil contains methyl salicylate (98%) ◦ Anti-inflammatory & antirheumatic
Indications:
Toxicity:
◦ can cause irritation; should not be used by children, pregnant or breastfeeding women
◦ do not apply to open wounds, broken skin, or mucous membranes (near eyes)
◦Linament or rehumatism, sprains, sciatica, neuralgia
◦Muscular pains

Question 15

Capsaicin

Answer 15

Pungent oleo-resin from chili pepper fruits
◦ Capsicum frutescens L. & some varieties of C. annuum L. (Solanaceae)
MOA:
◦ acts on vanilloid receptors, causing inflammation and
◦ Desensitizes sensory nerve endings to pain stimulation by depleting the neuropeptide substance P from local C-type nerve fibers
Used as a local analgesic for:
Formulation:
◦ Cream containing 0.025%, 0.075% or 0.75% capsaicin
◦ Patch (8% capsaicin)
◦ Postherpetic neuralgia (shingles), diabetic neuropathy, osteoarthritis, pruritis, and other forms of intractable pain
◦ Patch for shingles marketed as Qutenza Toxicology:
◦ Can produce severe irritation; burning upon initial application; do not apply near mucous membranes or broken skin; children & pregnant or breastfeeding women should not use

Question 16

Quinine

Answer 16

Alklaoid extracted from bark of Cinchona spp.
Quinine salts used in doses of 200-300 mg at bedtime in ambulatory patients for treatment of nocturnal leg cramps (common in elderly)
◦ FDA has recalled drugs containing quinine for this use
Toxicology
◦ Cardiac effects – can be toxic in overdose

Question 17

Rose hips (Rosa canina L., Rosaceae)

Answer 17

Source of Vitamin C, pseudofruits made into syrups
Anti-inflammatory constituents in rose hip extract:
◦ Triterpene acids, Oleanolic acid, Betulinic acid, Ursolic acid, lineoleic acid, alpha-lineoleic acid, galactolipids
Double-blind placebo controlled trial of pt. w/ rheumatoid arthritis: 5 g daily capsules of rose hip powder showed pain reduction
MOA and active/responsible constituent(s) still not elucidated

Question 18

Plant Drugs for the Peripheral Nervous System

Answer 18

Physostigma venenosum Balf. f., Fabaceae
Chondrodendron tomentosum Ruiz & Pav., Menispermiaceae Nicotiana tabacum L., Solanaceae
Lobelia inflata L., Campanulaceae
Pilocarpus jaborandi Holmes, Rutaceae
Atropa belladonna L., Solanaceae
Ephedra sinica Stapf, Ephedraceae
Erythroxylum coca Lam., Erythroxylaceae
Rauvolfia serpentina (L.) Benth. ex Kurz, Apocynaceae

Question 19

Physostigma venenosum

Answer 19

Calabar bean
◦ Historical ‘ordeal’ bean in the Calabar area of Nigeria
◦ Given to people on trial – if died, were guilty, if vomit & live, not guilty
Physostigmine
◦ Alkaloid
◦ Reversible cholinesterase inhibitor
◦ Interferes with metabolism of acetylcholine
◦ Stimulates both nicotinic & muscarinic receptors
◦ Used for: myasthenia gravis, glaucoma, Alzheimer’s disease and delayed gastric emptying
◦ antidote of choice for Datura stramonium & Atropa belladonna poisoning

Question 20

Dart Poisons

Answer 20

Neuromuscular blocking agents
◦ Isoquinoline & indole alkaloids
◦ (+)-tubocurarine leading agent
◦ Competes with acetylcholine for cholinergic receptors at the motor endplate, preventing formation of action potential
◦ Causes death by paralyzing the respiratory system, causing asphyxiation
Loganiaceae & Menispermiaceae families are primary plant sources
◦ Strychnos spp. (Loganiaceae)
◦ Chondrodendron tomentosum Ruiz & Pav., Menispermiaceae (curare plant)

Question 21

Chondrodendron tomentosum

Answer 21

Curare plant
◦ Source of dart/arrow poison
tubocurarine
◦ Alkaloid
◦ neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation
◦ long-duration, non-depolarizing neuromuscular blocking agent that is a competitive antagonist of nicotinic neuromuscular acetylcholine receptors
◦ rarely used as an adjunct for clinical anesthesia because safer alternatives such as cisatracurium and rocuronium are available.

Question 22

Nicotiana tabacum

Answer 22

Tobacco
◦ Tobacco has been used as an antispasmodic, a diuretic, an emetic, an expectorant, a sedative, and a sialagogue, and in homeopathy
◦ Solanaceae family
Nicotine
◦ Alkaloid
◦ activates the sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream

Question 23

Lobelia inflata

Answer 23

Indian Tobacco
◦ plant was widely used by the Penobscots in New England
Lobeline
◦ Alkaloid
◦ mixed agonist-antagonist at nicotinic acetylcholine receptors

Question 24

Atropa belladonna

Answer 24

Used in traditional treatments for centuries for an assortment of conditions including
◦ headache
◦ menstrual symptoms
◦ peptic ulcer disease
◦ histaminic reaction
◦ Inflammation
◦ motion sickness
◦ Mydriatic (pupil dilator)
Occasionally used as a recreational drug because of the vivid hallucinations and delirium that it produces.
◦ These hallucinations are most commonly described as very unpleasant, however, and recreational use is considered extremely dangerous because of the high risk of unintentional fatal overdose.
◦ In addition, the CNS effects of atropine include memory disruption, which may lead to severe confusion
Atropine can be used as antidote for cholinergic crisis (such as induced by physostigmine)

Question 25

Tropane Alkaloids

Answer 25

Atropine is used as the sulphate as a mydriatic and cycloplegic for eye examinations. It is also used as an antidote to organophosphate and carbamate poisoning and is loaded in an autoinjector for use in case of a nerve gas attack.
Hyoscamine is used as the sulphate or hydrobromide for GI problems and Parkinson’s Disease. Its side effect profile is intermediate betwixt that of atropine and scopolamine, and can also be used to combat the toxic effects of organophosphates

Question 26

Cocaine – local anesthetic

Answer 26

Alkaloid from Erythroxylum coca or E.
nonogranatense
MOA: blocks somatic motor neurons & synapses & diminishes the responsiveness of skeletal muscle neurons to acetylcholine
Topical anesthetic for nose, throat, larynx & eye
◦ Toxicology: intense vasoconstrictor & potential cardiovascular toxicity
◦ Less toxic alternatives include lignocaine, procaine, benzocaine, lidocaine

Question 27

Coca Plant

Answer 27

Traces of coca on mummies >3,000 years old
Evidence of using coca leaves as topical anesthetic in ancient cranial surgeries (trepanning)
When chewed with alkali, coca acts as a mild stimulant and suppresses hunger, thirst, pain, and fatigue
Part of religious cosmology of Andean people from pre-Inca period to present

Question 28

Rauvolfia serpentina

Answer 28

snakeroot
◦ Alexander the Great administered this plant to cure his general Ptolemy of a poisoned arrow. It was reported that Mahatma Gandhi took it as a tranquilizer during his lifetime
◦ Alkaloids: yohimbine, reserpine, ajmaline, deserpidine, rescinnamine, serpentinine
Reserpine
◦ Indole alkaloid
◦ antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, rarely used today
◦ Reserpine almost irreversibly blocks the uptake (and storage) of norepinephrine (i.e. noradrenaline) and dopamine into synaptic vesicles by inhibiting the Vesicular Monoamine Transporters (VMAT)