Musculoskeletal and nervous systems Flashcards
Which plants are associated with arthritis, rheumatism and pain?
◦ 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
What plant is associated with gout?
Autumn Crocus/ Colchicine: Colchicum autumnale L., Colchicaceae
Which plants are Topical Anti-inflammatory Agents?
◦ Wintergreen oil: Gaultheria procumbens L., Ericaceae
◦ Sweet birch: Betula lenta L., Betulaceae
◦ Hot pepper/Capsaicin: Capsicum frutescens
L., Solanaceae
Which plants are associated with nocturnal leg cramps?
Quinine tree: Cinchona spp., Rubiaceae
Willow bark
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.
Willow and the Gorani
- Cultural keystone species
- Rituals of Giorgidan
- Annual “immunity”
- Sacred baths
- Animal fodder
- Protective amulets for the home and business
- Marriage rituals
Salicin & the creation of aspirin
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
Devil’s Claw
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
Turmeric
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
Bromelain
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
Clinical Studies on bromelain
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
Chymopapain
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
Colchicine
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
Methyl salicylate
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
Capsaicin
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