S2 L9-10 Pro-inflammatory plants

1. S2 L9-10 Pro-inflammatory plants Anna Drew

2. 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

3. 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)

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

5. 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!) wound hollow tube tip

6. Causes: mild -> very irritant dermatitis, even death • Australia/India • further evolved with enormous hairs to kill animals • UK • only one species Urtica dioica • some plants mimic it but do not sting • varies in form according to nutrient value of soil Tragia involucrata

7. 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

8. 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

9. 1/3 as active • Found in: • Umbellifereae – Heracleum mantegazzanium, Pastinacea sativa • Rutaceae – Dictamnus albus, Phebalium argentium • Leguminosae – Psoralea sp. • Moraceae – Ficus carica • Rosaceae ¼ as active 6x as active

10. 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) • 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

11. 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

12. 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

13. 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) • -> 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

14. 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: • All essentially have C15 hydrocarbon nuclei • Not all tested on humans (~50) • γ-lactone and α-methylene group -> effect guaiane pseudoguaiane eudesmane germacrane

15. * widely distributed • Found in: • Compositae • Ambrosia • Artemisia* • Chrysanthemum* • Eupatorium* • Helenium • Iva • Parthenium eg Tanacetum parthenium (feverfew) • Jubilaceae • Fruillania • Lauraceae • Laurus Parthenolide

16. OTHER • Occupational hazards mainly in timber industry (sawing -> dusts) (1) Quinones • in heartwood are responsible • Found in: • Primulaceae – Primula obconica Primin Mansenone Larchol

17. (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

18. 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

19. 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

20. Capsaicin • Electron dense centre with lipid side chain • lipophilic, will penetrate cells easily Shogaol The gingerols

21. Volatile oils • 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 • Two groups: aromatics, terpinoids • Beware: cajaput, clove, eucalyptus, nutmeg, pumilopine, rosemary, thyme, terpentine Eugenol Safrole Limonene α-pinene

22. 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

23. Sulphur glycosides • Irritant to mucous membranes • Eg Allium sp. • peeling an onion – eye watering (volatile substances) • when damaged enzymes convert sulphur glycosides -> • Mustards • when damaged glucosinolate glycoside -> isothiocyanates (enzyme myrosinase) propenyl sulphuric acid eg isothiocyanate

24. Resins • Found in: • Berberidaceae • Podophyllum peltatum • Podophyllum hexandrum • Uses: to burn off worts, (antitumour properties) Podophyllotoxin