Transcript S2 L9-10 Pro-inflammatory plants Anna Drew

S2 L9-10 Pro-inflammatory
plants
Anna Drew
Plants producing dermatitis….
• = environmental toxicology
• not pollen allergy
• Can result from contact with living, damaged or processed plant
material
• Hazardous in
• Industry: timber, cosmetic/perfume, paint/varnish
• Environment: walks, gardening
• Veterinary: grazing or domestic
– mouth areas inflammed, balding
– scouring – severe diarrhoea – food not utilised properly
• Main clinical problem
• identify cause and remove
• Treatment
• topical corticosteroids
• Dermatitis
• itching -> scratching -> pain
– oedema with blisters that weep. If break can get 2y infection
– OR hyperplasia (thickening) of skin. Dries and breaks
Plants producing contact dermatitis
can be classified into 5 groups:
• Mechanical irritants
• Stinging nettles
• Phototoxic compounds
• Allergenic substances
• Direct or primary irritants
Ref: Evans FJ, Schmidt RJ. Plants and plant products that induce contact dermatitis. Planta Medica 1980: 38(4)
Mechanical irritants
• Caused by:
– Easily detachable rough hairs or bristles on surface of the plant
• break off into skin when touched
• move around the in the skin causing irritation
– or acicular calcium oxalate crystals produced onto plant surface
• Found in:
– Boroginaceae - Borago, Echium, Pentaglottis, Pulmonaria, Symphytum
» Covered with coarse stiff trichomes
» highly lignified or produce silica around the hair
– Cornaceae - Cornus sanguinea
» T shaped trichomes
– Malpighiaceae – Malpighia urens
– Barley (awns) and other cereal grasses
– Cactaceae - Opunta ficus-indica, Opunta cochinillifera (prickly pears)
– Narcissus (daffodil), Hyacinthus (hyacinth family)
» secrete CaOx onto bulb surface
» -> daffodil itch, lily rash which wears off in 12-12 hours
Stinging nettles
• Caused by:
– a defensive trichome which they have evolved
• combination of a spring release mechanism + hypodermic syringe
• silica (glass) or calcium oxalate tip on surface
• when touched tip breaks triggering basal pump mechanism which
releases small amount of toxin into the skin
• (equiv to muscles or contractile tissue!)
tip
wound
hollow
tube
• Causes: mild -> very irritant dermatitis, even
death
– Australia/India
• further evolved with enormous hairs to kill animals
– UK
Tragia
involucrata
• only one species Urtica dioica
• some plants mimic it but do not sting
• varies in form according to nutrient value of soil
• Composition of poison:
– protein peptide material
• large molecule – unusual
• when dried it denatures
• got poison out by dipping leaf in liquid nitrogen and brushing off
trichomes onto paper
• has properties in common with acetylcholine, histamine, 5-HT
• Found in: (over 50 species)
– Urticaceae - Urtica, Giardinia, Gyrotaenia, Laportea, Obetia
– Euphorbiaceae - Acidoton, Cnesmone, Tragia
– (Tragia involucrata – Indian species)
– Loasaceae - Loasa, Evertesia, Eucnide
– Hydrophyllaceae - Wigandia
– lethal ones
– Leguminosae - Mucuna pruriens and other Mucuna sp.
– trichomes on seed pods
– mucunain, a proteinase, on surface responsible for pruritus and mechanical effect for dermatitis
Phytotoxic substances
• Caused by:
– Furanocoumarins (coumarin family)
• harmless – animals and humans can eat plants
• veterinary problem
– photoactivated on skin -> sunburn effect
– red inflammation peels to leave brown pigmented areas
– around muzzle, hair falls out, look in poor condition
– Photoactivated form binds to epidermal DNA and
ribosomal RNA
• -> pigment
1/3 as active
¼ as active
• Found in:
– Umbellifereae – Heracleum mantegazzanium, Pastinacea sativa
– Rutaceae – Dictamnus albus, Phebalium argentium
– Leguminosae – Psoralea sp.
– Moraceae – Ficus carica
– Rosaceae
6x as active
Contact allergens
• Most common form of plant dermatitis
= allergenic eczematous contact dermatitis
• dry scaly erythema -> severe papular/vescicular inflammation
with oedema
– 1st exposure -> sensitisation (eg 6-25 days)
– 2nd exposure -> dermatitis (eg 24 hours)
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degree depends on exposure dose
hard to diagnose (patch testing)
population variability: genetically determined (race, gender)
cross sensitization between plants
– compounds of same basic chemical structure can cause
reaction
– elictors – may not be allergenic themselves
Sri Lanka
• Kandy - plant dermatitis accounted for one third of cases
• Clinic incidence affected by:
– industrial development of the area
– pattern of employment
– interest the dermatologist takes in contact dermatitis
Ref: Perera WDH. Special problems and perspectives from Sri Lanka. In: See Ket Ng, Chee Leok Goh (Eds). The Principles and Practice of Contact
and Occupational Dermatology in the Asia-Pacific Region. World Scientific, 2001
Groups of compounds:
• URUSHIOLS = Poison ivy toxins
• typical allergenic compounds
– simple molecules (low MWt, haptens)
– homologous long chain phenolics
• R1 and R3 can be -H, -OH or -COOH
• R2 can be C9 -> C19 saturated or unsaturated
– lipid soluble and will penetrate skin and phenolic groups burn
– mechanism of action unknown (direct irritation, allergenic or
inflammation)
• hard to separate compounds (need GLC) but all work
• cross sensitization takes place
• 150 derivatives have been found in:
– Anacardiaceae
• Toxicodendron (poison ivy)
• Pentaspadon
• Semecarpus (5 species in SL)
– medium-sized forest trees found in the wet zone
– -> itchy vesicular dermatitis in sensitized individuals
– streaks of vesicles correspond to points of contact (face, exposed
areas) with the plant
– reactions often severe requiring treatment with systemic steroids
• Mangifera indica (mango tree)
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-> allergic contact dermatitis
from contact with stem, leaves, skin of unripe fruit
seen on lips and around mouth
climbing a tree can produce dermatitis all over body
• Anacardium occidentale (cashew nut tree)
– -> allergic contact dermatitis
– from handling fruit, nut and also from cashew nut oil
– Ginkgoaceae - Ginkgo biloba (fruit pulp)
– Protaceae - Persiana
• SESQUITERPENE LACTONES
– Mainly found in Compositae
• Allergenic ones also found in: Jubilaceae, Lauraceae
– Concentrated in pollen and trichomes
• distributed by wind over large areas in spring
• distinct from hayfever caused by protein constituents in
pollen exine
– 250+ characterised - 4 main types structurally:
guaiane
pseudoguaiane
eudesmane germacrane
• All essentially have C15 hydrocarbon nuclei
• Not all tested on humans (~50)
• γ-lactone and α-methylene group -> effect
* widely distributed
• Found in:
– Compositae
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Ambrosia
Artemisia*
Chrysanthemum*
Eupatorium*
Helenium
Iva
Parthenium eg Tanacetum parthenium (feverfew)
– Jubilaceae
• Fruillania
– Lauraceae
• Laurus
Parthenolide
• OTHER
– Occupational hazards mainly in timber
industry (sawing -> dusts)
(1) Quinones
• in heartwood are responsible
Primin
Mansenone
• Found in:
– Primulaceae – Primula obconica
Larchol
(2)
• Not present in the plant under normal circumstances
• Formed when plant injured by hydrolysis of tuliposide A ->
tulipalin A (enzyme β-glucosidase)
• = allergenic material (phytoalexin)
• Found in:
– Liliaceae and related families
» Tulipa, Erythronium, Alstroemeria
(3) Volatile oils
• low allergenic sensitizing potential
(4) Many miscellaneous compounds
Primary irritants
• Largest group of all
• Cause most damage
• End up in all kinds of cosmetics, perfumes, soaps, eye makeup –
dermatitis common
• Burn directly (1st and every exposure)
– can be widespread
-> severe erythema, itching, flaking etc
• Have diverse structures
• Not all mechanisms understood
– phorbol esters from croton (Euphorbiaceae) best understood
• activate protein kinase C – inflammation pathway
– some simply acids or phenols which burn
• Time for reaction depends on lipid solubility
– volatile oils worse
– may induce irritation and malignancy at a later stage
• Capsaicins & ginger group
– Capsaicin = irritant principle found in red pepper family
• Solanaceae - Capsicum minimum, C.fructescens
• burning effect on membranes throughout GI tract (curry ingredients)
• externally -> erythema, no blistering
– Gingerols, shagaols
• Zingiberaceae – Zingiber officinalis
• also capsaicin-like compounds -> rubefacient
– Uses:
• Go into “deep heat” products – paraffin-based creams for massage,
counterirritants to increase blood flow to damaged muscle
• Itching powders (mechanical trichome) or chemical irritants
• Some foods
Capsaicin
The gingerols
Shogaol
– Electron dense centre with lipid side chain
• lipophilic, will penetrate cells easily
• Volatile oils
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Thought to be phenols present if they burnt
Now realise terpinoids present
Affect certain types of smooth muscle -> spasm (contraction)
Mechanism unknown – may block Ca2+ channel
– Uses: antibacterial, indigestion preparations
Eugenol
Safrole
Limonene
α-pinene
– Two groups: aromatics, terpinoids
– Beware: cajaput, clove, eucalyptus, nutmeg, pumilopine,
rosemary, thyme, terpentine
• Proteolytic enzymes
– Found in the sap of some plants:
• Papain – Carica sp.
• Ficia – Ficus sp.
• Bromelain – Ananus sp.
• Nepenthin - Nepenthus sp.
– Eg pitcher plant – insectivorous
» insects attracted into modified leaf structure
» contains sugary solution with proteolytic enzyme
» Insects are a source of nitrogen
• On skin -> digestion -> very painful dermatitis
• Use: meat industry
• Sulphur glycosides
– Irritant to mucous membranes
• Eg Allium sp.
– peeling an onion – eye watering (volatile substances)
– when damaged enzymes convert sulphur glycosides ->
propenyl sulphuric acid
• Mustards
– when damaged glucosinolate glycoside ->
isothiocyanates (enzyme myrosinase)
eg isothiocyanate
• Resins
– Found in:
• Berberidaceae
– Podophyllum peltatum
– Podophyllum hexandrum
Podophyllotoxin
– Uses: to burn off worts, (antitumour properties)