Radiation therapy kills tumor cells, yet has acute side effects that may include: dermatitis, diarrhea, dry mouth, fatigue, hair loss, immune suppression, incontinence, mucositis, nausea, shortness of breath and sexual problems. This slide presentation summarizes clinical and non-clinical studies on Calendula studied in laboratories around the world, and its' benefits on protecting the skin from the harmful effects of radiation therapy.
The Benefits of Calendula Officinalis on Protecting the Skin from the Harmful Effects of Radiation by Kevin Leach Ph.D. DABT
1. The Benefits of Calendula Officianalis
on Protecting the Skin from the
Harmful Effects of Radiation
Kevin Leach Ph.D. DABT
2. Radiation Therapy is an
important modality in
cancer treatment
• Approximately 50% of all cancer patients
receive radiation therapy
Delaney G, Jacob S, Featherstone C, Barton M. The role
of radiotherapy in cancer treatment: estimating optimal utilization
from a review of evidence-based clinical
guidelines. Cancer. 2005;104:1129-1137
Begg AC, Stewart FA, Vens C. Strategies to improve
radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11:239-253
• Radiation contributes to approximately 40% of
the total therapeutic value of the entire
course of cancer treatments
Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE,
Pharoah PD, Burnet NG. Normal tissue reactions to radiotherapy:
towards tailoring treatment dose by genotype. Nat Rev
Cancer. 2009;9:134-142
Multiple
Treatment
Modalities
Surgery Immunotherapy
Chemotherapy Radiation
Multiple
Treatment
Modalities
3. Radiation Therapy Kills Tumor Cells
Leads to the death
of tumor cells
Acute Molecular
Effects of Radiation
Cell Damage and Death
• DNA breaks
• Oxidative damage to cellular components
• Lipid peroxidation
• Protein malfunction
Inflammation
• Gene expression of pro-inflammatory genes
• Secretion of pro-inflammatory proteins
• Immune cell activation
Acute Tissue Side
Effects
4. Radiation Therapy
has acute side effects
• Dermatitis
• Fatigue
• Dry mouth
• Nausea
• Diarrhea
• Shortness of breath
• Incontinence
• Sexual problems
• Immune suppression
• Hair loss
• Mucositis
5. Radiation Dermatitis Grade 1
• Erythema
• Dry desquamation
• Swelling
• Pigment changes
• Hair loss
• Scaling
Grade 2
• Brisk erythema
• Focal sloughing
• Moist desquamation
• Pain
• High chance of infection
Grade 3
• Extensive moist
desquamation outside of
skin folds
Grade 4
• Ulcerations
• Hemorrhage
• Skin ulceration
• Skin necrosis
• 95% of patients who receive radiation
therapy experience radiation
dermatitis
• 23% experience Grade 2 or higher
• Grade 3 or higher is associated with
discontinuation of therapy
McQuestion M. Semin Oncol Nurs. 2011; 27e1-17
Salvo N. et al. Curr Oncol. 2010; 17;94-112
Severity Scoring of Radiation Dermatitis
6. Calendula has been
studied in laboratories
around the world • The individual components and/or the extract of calendula
have been tested for activity against
• Oxidants
• Inflammation
• Microbial growth
• Cellular proliferation
• Pain
• Water loss from the skin
• Wound healing
• Protection from the sun
• Radiation dermatitis
7. Calendula Extract Has
A Complex Mixture
of Phytochemicals
Calendula
Tocopherols
They include:
• Flavinoids
• Carotenoids
• Tocopherols
• Sesquiterpenes
• Coumarins
• Andersen F.A. Et al. 2010. Int. J. Tox. 29 (suppl 4) 221S-243S
9. Radiation reacts with water inside the cell to
form oxygen radicals
• Oxygen radicals cause-
• DNA damage
• Protein disfunction
• Lipid membrane damage
• Activate the inflammation machinery in the cell
Oxidants and Radiation
Dermatitis
Reactive Oxygen
Species
DNA Damage
Cell DeathLipid Peroxidation
Cell Leakage
Protein disfunction
Inflammation
Loss of
Water
Radiation Therapy
11. Anti-Oxidant
Activity
Non-Clinical Studies Show Calendula Extract
Components Block the Cellular Effects of Oxidants
ROS
DNA Damage
Cell DeathLipid Peroxidation
Cell Leakage
Protein Oxidation
Inflammation
Loss of
Water
Calendula extract components
block the harmful effects of
oxidants
• Cordova CA. et al. Redox Rep. 2002; 7(2):95-102
• Abdel-Azlem SH. Et al. Cytotechnology May 2014, Vol
66(3) 457-470
• Fonseca YM et al. J. Ethnopharmacol. 2010, 127:596-
601
12. Inflammation and
Radiation Dermatitis
Radiation induced oxidants leads
to activation of inflammatory
pathways in the irradiated pathway
• Activates inflammatory cell signaling
pathways
• Cytokines, NFkB, p38 MAPK
• Increased activity of enzymes that
mediate inflammation
• Cyclooxygenase, Prostaglandin
synthase
• Leading to
• Edema
• Erythema
• Pain
Oxidative Stress
Expression of inflammatory genes
Gene activating
factors
Activates
Ras
Raf
Mek1/2
MAPK
Cell Signaling Events
IL-1b
TNFa
PGES
MMP1
COX
14. Blocks Edema
Faradiol esters are sesquiterpenes present in abundance in Calendula
Officianalis
• Faradiol myristic ester
• Faradiol palmitic ester
Calendula Extract Components Stop
Inflammation
Calendula Component Potency
Faradiol myristic ester IC45=240mg/cm2
Faradiol palmitic ester IC45=240mg/cm2
In Experiments - Calendula extract components
block induced edema in mice
• Della Loggia R. Et al. 1994. Planta Med. 60; 516-520
• Zitterl-Eglseer K. Et al. 1997. J. Ethnopharmacology. 57; 139-144
15. Reduces
Molecular
Markers of
Inflammation
Calendula Extracts Stop Inflammation
• Coumarins are found in abundance in Calendula Officianalis
• Esculetin
• Scopoletin
• 7-hydroxy coumarin
• P Coumaric acid
In experiments of inflammation - calendula extract components reduce
markers of inflammatory signaling
Calendula
component
NFkB nuclear
localization
p38 MAPK
phosphorylation
Nitric
oxide
levels
TNFa
levels
IL-1b
levels
PGE2
levels
MMP1
levels
Scopoletin
Esculetin
7-HC
P-CA
• Zhao Y. Et al. 2016. Med Chem 6:5 327-330
• Chen T. Et al. 2015 Free Radical Research; 49(12); 1459-1468
• Nascimento MVPdS Et al. 2016. Immunopharmacology and
Immunotoxicology; Vol 38, No.5, 344-352
• Sim MO Et al. 2015 Nutrition Research and Practice. 9(4):364-
369
16. Blocks
Activation of
Inflammatory
Enzymes
Calendula Extracts Stop Inflammation
• Flavinoids are found in abundance in Calendula Officianalis
• Quercetin
• Isorhamnetin
In studies - Calendula extract components inhibit COX2 and PGES enzymes
which play a role in inflammation-erythema and collagen breakdown
following injury to the skin
COX2
PGESROS ErythemaInflammation
Collagen Breakdown
Pain
Quercetin
Quercetin
Isorhamnetin
Isorhamnetin
• Li Y. Et al. 2016. Nutrients. 8, 167; 1-14
• Han X. Et al. 2015. Biomol Ther 23(4), 357-366
17. Radiation Therapy and
Skin Infections
• Skin infections are common in patients
with radiation dermatitis
• Altoparlak U. etal. The Eurasian Journal
of Medicine 2011 Dec 43(3) 177-181
• Infection can exacerbate dermatitis and
delays healing
• Hill A. etal. Am J Clin Oncol. 2004 Aug
27(4) 381-3
Wet Desquamation
Dry Desquamation
19. Radiation Dermatitis is a
type of wound
• Calendula extract has been shown experimentally
to accelerate wound healing
Wet Desquamation
20. Wound
Healing
Non-Clinical Studies Show That Calendula
accelerates wound healing
Increased local angiogenesis
• New blood vessels bring growth factors to
stimulate repair and immune cells to clear
debris
Increased epithelialization
• Fibroblasts proliferate to create the new
skin over the wound
Wound closure times decreased
• Naeini AT. Et al. 2012. Comp Clin Pathol; 21: 253
21. Radiation Therapy Leads to
Impaired Barrier Function
and Dry Skin
• Skin dryness can be measured clinically by
Transepidermal Water Loss (TEWL)
• In clinical studies of patients receiving radiation therapy -
TEWL increases were predictive of radiation dermatitis
severity and duration
• Schmuth M. etal. Arch Dermatol Vol 137 Aug 2001 p1019-1023
• Due to the known effects of radiation therapy on the
skin, clinical guidelines stress the need to hydrate the
skin during radiation therapy
Wet Desquamation
Dry Desquamation
22. Hydrating
Activity
Clinical Studies Show that Calendula Hydrates
Skin
• Calendula hydrates skin
• A clinical study showed that
the skin hydration increased
as with calendula application
to skin
Calendula
• Provides moisture to skin cells
• Akhtar N. Acta Polonicae Pharm-Drug Research Vol 68 No5
p693-701, 2011
23. Calendula Containing
Products for Damaged Skin
• My Girls™ Skin Care cream
• My Guys™ Skin Care cream
• California Baby Calendula Cream
• Weleda baby Calendula Cream
• Miaderm Radiation Relief Lotion
• Boiron Calendula Ointment
• Calendula extracts have been used for skin
ailments since antiquity and it is acknowledged
as a traditional medicine by the European
Medical Agency
• Currently there are several topical products for
skin conditions available over the counter that
include calendula
• Examples include:
Editor's Notes
I would delete the image of the radiation source – it is low Def and might refer to a specific product