Wasp sting: Inflammation & Relief by Topical Natural Phytochemicals

Wasp sting, wasp venom composition, immune response, local reactions, severe reactions, anaphylaxis, treatment with home remedies and OTC products, rational treatment with topical phytochemicals.

1. WASP STING:
INFLAMMATION & RELIEF BY TOPICAL
NATURAL PHYTOCHEMICALS
By
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, FL, USA
Email: [email protected]
Presented at HealthCare provider Seminar 2018

2. Lecture Outline
▪Introduction: what is a wasp? What is wasp sting?
▪Statistics: incidence of wasp stings and deaths
▪Composition of wasp venom
▪Reactions to wasp sting by immune system
▪Acute inflammation: mediators
▪Treatment of wasp stings: Local reaction
Systemic reaction or anaphylaxis
▪Anti-inflammatory phytochemicals
▪Effect of topical anti-inflammatory phytochemicals
▪Summary and future directions.
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3. Modified taxonomic tree of stinging insects
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517515/
waswasp
Vespula
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4. Background of Wasp Stings
▪More than 25,000 species of wasps exist worldwide. They include yellow jackets,
paper wasps and hornets of the genus Vespula.
▪Stings by members of the order Hymenoptera is a major cause of morbidity and
mortality and accounts for more fatalities than any other venomous animal.
▪The skin is the most commonly affected organ system.
▪The result of a wasp sting can vary from a single area of localized inflammation
to a generalized urticarial rash.
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5. Hymenoptera (wasp, hornets, yellow jackets) Stings in USA
▪Annual number of stings by Hymenoptera
• more than1 million stings annually
• 3% of general population
▪Systemic reactions
• 0.4-0.8 % of children
• 3 % of adults
https://emedicine.medscape.com/article/768764-overview#a6
Deaths from 2003-2010
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6. Incidence of Reactions to Wasp Stings in Emergency Room
n = 2606 patients in 2015
https://emedicine.medscape.com/article/169324-overview#a6
Under
reported
Hymenoptera stings and wasp stings
have increased over the last 60 years
and now account for over 79 deaths
each year.
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7. Fatal occupational injuries involving insects 2003-2013
http://blogs.marketwatch.com/capitolreport/2014/08/11/bee-stings-are-behind-most-insect-related-deaths-for-workers/
number
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8. Anatomy of a Common Wasp (Vespula Vulgaris)
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9. Features of an adult female worker wasp
▪Length: 0.5-1.0 inch
▪Stinger: 2.5 mm/0.1 inch
▪Narrow waist
▪Black and yellow stripes in abdomen
▪Only worker wasp (sterile female) has stinger
▪Fly with legs hanging down
▪Feed on flower nectar, ripen fruits and insectshttps://www.confirmakill.co.uk/services/wasp-nest-removal/
stinger 2.5 mm
0.5-1.0 inch
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10. Wasp sting and the stinger apparatus
http://www.vapaguide.info/page/23https://www.healthline.com/health/wasp-sting
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11. Only female (sterile) adult worker wasp stings
▪Only female worker wasp has stinger
▪It stings when threatened
▪It does not pollinate
▪It does not make honey
▪It feeds on other insects and human food
▪It’s average life span is 12-22 days
▪The queen has an average lifespan of 12 months
http://www.stepin2mygreenworld.com/healthyliving/around-the-home/wasp-repellent/
https://www.landcareresearch.co.nz/science/plants-animals-fungi/animals/.../wasps/faq
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12. Which insect gives the most painful sting?
Adapted from www.bbc.com/earth/story/20150312-the-worlds-most-painful-insect-sting
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13. Reactions to a wasp sting
▪A local reaction: Pain, swelling and redness lasting 30
minutes to 3 hours
▪A large local reaction causes swelling beyond the sting
site. The large local reactions peak at about 48 hours
and last 5 to10 days
▪The most serous reaction is an allergic response to the
sting. It needs to be treated immediately with Epi-pen
and followed up at Emergency Room
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14. What happens when a wasp stings ?
(1 sting contains 2 –15 µg venom)
Acute Inflammation
to 10 days
to 5 days
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15. Chemical mediators of inflammation
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16. Chemical mediators of inflammation
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17. 17

18. Pain Swelling Heat Redness
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The body’s immune response to toxin and tissue injury

19. Wasp
sting
venom
Skin
Inflamation
Pain
Warmth
Redness
Swelling
Itch
Interaction of wasp sting and skin
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20. Major components of Wasp Toxin
https://en.wikipedia.org/wiki/Stinger
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21. Components of the immune system
▪White blood cells
▪Platelets
▪Plasma
▪Endothelium
▪Nerves
▪Fibroblasts
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22. Release of chemical mediators by wasp venom
Chemical mediators
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23. Actions of inflammatory chemical mediators
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24. Activation of Mast Cell
https://www.frontiersin.org/articles/10.3389/fimmu.2012.00143/full
Mediators Release
Normal cell Activated cell
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25. The effect of chemical mediators on skin
Inflammation
Inflammation
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26. Wasp venom allergens
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517515/
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27. Pathophysiology (local reaction)
▪Wasp does not leave the stinger behind.
▪Wasp venom contains up to 13 different antigens.
▪The venom causes an intense stinging sensation that is mediated by acetylcholine
and serotonin, which make up to 5% of the dry weight of the venom
▪The acetylcholine stimulates nociceptors within the dermis. The serotonin causes
multiple effects through the 5-hydroxytryptamine (5-HT) receptors,
▪The wasp venom also contains phospholipase A2 , phospholipase B, as well as
mastoparan peptide, which can cause direct mast cell degranulation with the release
of histamine.
https://emedicine.medscape.com/article/169324-overview#a5
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28. Pathophysiology (Systemic reaction)
▪For individuals who have been sensitized to the venom by a past exposure to
Hymenoptera venom, symptoms may progress
▪This progression involves elements of both cellular and humoral immunity.
▪The cellular components consist of lymphocytes, both T cells (CD4+ and CD8+) and B
cells, macrophages, and mast cells
▪The humoral factors include immunoglobulin E (IgE) and cytokines.
▪An immediate type of hypersensitivity occurs when the sensitized mast cells contact the
offending allergen.
▪This is followed by degranulation with the release of chemical mediators: histamine,
heparinand tumor necrosis factor (TNF).
▪Mast cell activation also initiates generation of bioactive products through lipid
metabolism of arachidonic acid and the production of cytokines such as TNF, interleukin
(IL)–6, IL-4, and IL-5.
▪Mast cells are located in the connective tissue of the dermis, intestinal tract, airway, and
lungs and around the vascular system, thus producing the symptoms of urticaria,
vomiting, abdominal cramp, diarrhea, dyspnea and wheezing.
https://emedicine.medscape.com/article/169324-overview#a5
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29. Signs and symptoms of Severe Wasp Sting or
Anaphylaxis
https://en.wikipedia.org/wiki/Anaphylaxis
Treatment
●Epi-Pen
●Call 911 or
go to Emergency Room
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30. Pathophysiology: severe systemic or anaphylactic reaction
▪Anaphylactic shock is an immediate-type hypersensitivity reaction that occurs when
mast cells are activated within multiple organ systems.
▪The explosive of histamine and cytokines cause vascular collapse.
▪This is an IgE-mediated reaction to the sting.
▪Most fatalities occur within 1 hour, with most severe reactions occurring within 10
minutes of the wasp sting.
▪In one study of postmortem sera from patients with sudden death, 23% had
elevated levels to Hymenoptera venom
https://emedicine.medscape.com/article/169324-overview#a5
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31. Requirements for rational treatment of
local reaction to wasp sting
▪Knowledge of the severity of reaction to wasp sting
▪Knowledge of potency of wasp venom
▪Knowledge of components of wasp venom
▪Knowledge of the immune response to wasp venom
▪Knowledge of the natural history of wasp sting
▪Knowledge of pharmacology of anti-inflammatory drugs and phytochemicals.
▪Combination of these knowledges help to formulate a natural topical product based
on anti-inflammatory phytochemicals,
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32. Potency of Hymenopteran Venom
(1/lethal dose x 1000)
Source: Schmidt, J.O. (1983) Hymenoptera envenomation
Potency
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33. Lethality of Hymenopteran Stings
http://www.artasaweapon.info/pages/bullet-ant-sting-pain-scale.awp
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34. Wasp Sting: My Story from July 17–July 24 2018.
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35. Natural history of wasp sting
wasp toxin mediators Inflammation
Tissue repair & resolution
Resolution
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36. Mechanism of inflammation: chemical mediators
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mastoparan
(cell penetrating peptide)
Release of preformed mediators
Newly synthesized mediators
Phospholipase A₂
COX-2
5-LOX

37. How drugs or chemical mediators work?
https://hubpages.com/education/How-drugs-act-tyrosine-kinase-receptors-hormone-receptors
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38. Mechanism of receptor blockade
Antagonist (drug)
Agonist (chemical mediator)
receptor
response No response
cell membrane
cell membrane
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39. Mechanism of Anti-inflammation
steroids
Aspirin; NSAIDS
*zileuton
*=discontinued 2008
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Thromboxane synthase inhibitor ?
Receptor blocker
?

40. Remedies for Local Reaction to Wasp Sting
Home remedy
▪Ice
▪Garlic
▪Onion
▪Cucumber
▪Lemon
▪Baking soda ?
▪Honey
OTC product
▪Antihistamine cream
▪Hydrocortisone cream
▪Ibuprofen
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41. Disadvantages of Current Topical Renedies
▪Low concentration of active ingredients.
▪Water-based formulations.
▪Inefficient and slow absorption.
▪Actions limited to 2 out of 14 mediators.
▪Many mediators act unopposed.
▪Therefore treatment is incomplete.
▪This prompted us to search for anti-inflammatory
phytochemicals among food, spices and herbs.
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42. What are phytochemicals?
▪Phytochemicals are bioactive substances
found in plants.
▪Phytochemicals are found in roots, barks, stems,
leaves, flowers, fruits.
▪Phytochemicals are beneficial for health.
▪Phytochemicals are not vitamins.
▪Phytochemicals can be extracted by water,
alcohol or massage oils.
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43. Bioactive functions of phytochemicals
Anti-inflammatory
Anti-oxidant
Anti-aging
Anti-cancer
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44. Examples of anti-inflammatory phytochemicals
in food, spices and herbs
Product Variety Active ingredient
Fruit Grape Resveratrol
Apple Quercetin
Chili pepper Capsaicin
Leaf Green tea EGCG
Aloe Salicylic acid, emodin
Bark White willow Salicylic acid
Magnolia Honokiol
Root Ginseng Ginsenosides
Galagal Galagin
Tumeric Cucumin
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45. Synthetic blockers on 15inflammatory mediators
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46. Phytochemical Molecular Targets
Ginger
Aloe
Cayenne
Green tea
Lemon grass
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47. 15 Molecular targets of synthetic drugs and phytochemicals
Food
Spices
Herbs
Synthetic
drugs
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48. A phytochemical formula L35 made from spices and herbs for
Itch, Pain and Swelling caused by wasp sting
chemical mediators
Spices
Herbs
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49. Preparation of extracts of phytochemicals with
alcohol and olive oil
Botanical materials + extraction solvent
Temperature controlled treatment
Homogenization
Differential centrifugation
Residue removal
Recovery of filtrate
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50. Effects of extracts of spices or herbs on
itch & swelling caused by wasp sting
▪Oil extract with one anti-inflammatory herb: no relief
▪Oil extract with two anti-inflammatory herbs: slight relief
▪Oil extract with three anti-inflammatory herbs: moderate relief
▪Oil extract with four or more anti-inflammatory herbs : significant relief
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51. Effect of L35 on symptoms of wasp sting:
significant relief
Pain
Redness
Swelling
Itch
●Control data based on family exposure
●L35 Rx based on personal experience
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52. Summary
▪Only female (sterile) adult worker wasp stings.
▪Wasp venom contains allergens, proteins, peptides, enzymes, etc.
▪Exposure of the skin to wasp venoms results in the release of multiple
chemical mediators which cause a local reaction, severe systemic
reaction or anaphylaxis.
▪Local reactions are self-limiting, whereas severe systemic and toxic
reaction require immediate medical intervention.
▪Home remedies and OTC products for local reactions are generally
not effective as they target only a few chemical mediators.
▪A combination of phytochemicals target most of the chemical
mediators and provide a rational local treatment of wasp stings.
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53. ANY QUESTION?
Contact
Kevin KF Ng, MD, PhD
Email: [email protected]
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