Calendula

1. Calendula Calendula officinalis L. By Emily Gupta and Stephen Vickery

2. Botanical Description • “small, bushy, • cool-weather • Grows annually • Light green, lance-shaped leaves • yellow-orange flowers that can grow up to 3 inches in diameter [1,2].” http://bp1.blogger.com/_9d3eviT3TsM/RdcSXP2IQBI/AAAAAAAAAPA/ZR0aTFMjdV8/s320/Calendula1.JPG

3. Scientific Classification • Kingdom: Plantae • Division: Magnoliophyta –(Flowering plants) • Class: Magnoliopsida –(Dicots) • Order: Asterales • Family: Asteraceae –(Aster) • Genus: Calendula L. –(marigold) • Species: Calendula officinalis L. –(pot marigold) http://plants.usda.gov/java/profile?symbol=CAOF

4. Nomenclature Cont’d • Common Names • calendula   • marigold • pot-marigold • ruddles • Scottish-marigold • Scotch-marigold

5. Native of the Mediterranean Used as an additive in foods, specifically butter, cheese, bread, and soups [2,6]. petals color butter and cheese dry petals in soup for flavor ‘Calendula’ comes from the Latin word ‘kalendae’ for ‘first day of the month,’ “the plant starts blooming in the beginning months of the year [5,6].” Nowadays, it can pretty much be cultivated anywhere in the United States. History of Calendula

6. Processing/Preparations • Dried, whole or fully cut open flowers, with petals removed from the receptacle [3,4]. • Used in lotions, poultices, extracts, and ointments.

7. Calendula On the Market PRODUCT NAME MANUFACTURER TYPE Horsechestnut Pro MMS Pro Soft gel capsules Calendula Extract Herb Pharm Liquid extract Calendula Plus Cream NF Formulas, Inc. Cream Calendula Flower Oil Gaia Herbs, Inc. Oil Calendula Oil Trinity Alps Botanicals Oil Calendula Gel VitaminUSA Gel Calendula Ointment VitaminUSA Ointment

8. On the Market Cont’d • Traumeel®: anti-inflammatory and and analgesic • Organic lip balms • Weleda, Inc.: all sorts of products http://www.nutritiondynamics.com/ featured_product/traumeel.jpg http://www.ecolips.com/Products.aspx • Diaper Care • Face Cream • Oil • Ointment • Shampoo • Soap • Tooth Gel • Body Lotion • Wound Care http://shop.weleda.com/images/items/large/8816.jpg

9. Standard Dose • 5 ear drops placed in affected ear 3x daily (Otikon Otic® and NHED® [19]) • 2% to 5% ointment 3-4 times daily as needed(German Commission E and the European Scientific Cooperative on Phytotherapy) • 1:1 tincture in 40% alcohol • 1:5 tincture in 90% alcohol • diluted at least 1:3 with freshly boiled water, apply to skin as a compress 3-4 times daily http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-calendula.html

10. Medicinal Properties • Used as a lotion to alleviate sprains and wounds, and for inflamed eyes [8] • Folk healers used it to induce menstrual flow and cure jaundice [7,9] • 19th century American physicians used it to treat liver problems and conjunctivitis [9]

11. Medicinal Properties Cont’d • “Demonstrates astringent and anti-inflammatory activity [10,11].” • Some herbalists recommend the plants oils as a treatment of yeast infections [6]. • Preparations have been used for “skin and mucous membrane inflammations (such as pharyngitis and leg ulcers) [4,6].”

12. Calendula Constituents • Polysaccharides, • Proteins, • Fatty acids, • Flavonoids, • Triterpenoids, • Saponins [20] • Carotenoids [17] • Main pigments: • flavoxanthin • Lutein • Rubixanthin • β-carotene • γ-carotene • lycopene.

13. Adulterants • No found adulterants, but… • Used as an adulterant in saffron [21]

14. Pharmacology • Calendic acid is the omega-6 fatty acid chain present in Calendula which is one of the factors that gives Calendula officinalis its medicinal properties.

15. Pharmacodynamics • Laser activated Calendula extract shows inhibition of cell proliferation in G phases of cell cycle [20] • High levels of enzyme activity (especially naphthol-AS-BI-phosphohydrolase and acidic phosphatase) found in fresh juices of the plant [22] • “therapeutic effect might be directly related to the quantity and activity of plant enzymes” • Pharmacokinetics: Couldn’t find any studies on ADME (absorption, distribution, metabolism, and excretion)

16. Contraindications • Very few concerns and warnings in regards to Calendula, however: • “Internal use of Calendula preparations should be avoided during early pregnancy due to its ability to cause menstruation [12].” • “Allergic hypersensitivity may be an issue for persons sensitive to Calendula or to other members of the Asteraceae family [12].’

17. Calendula has shown promise in numerous arenas such as antimicrobial, anti-HIV, and wound healing [4,7]. One in vitro study stated that B-calendic acid showed anti-cancer properties against malignant colon cells [13]. Research

18. In vitro Studies • Antioxidant Properties [15] • possessed better scavenging and antioxidant activity than Calendula arvensis • Water extracts had the best antioxidant properties; 0.75 mg/ml extracts completely eliminated hydroxyl radical • Genotoxic and Chemopreventive properties [16] • Aqueous and ethanol extracts of Calendula officinalis showed reversion of diethylnitrosamine unscheduled DNA synthesis (DEN effect) • “Concentrations producing genotoxic damage were three orders of magnitude above concentrations that conferred total protection [from DEN effect]” • Anti-tumor therapeutic effect: cytotoxic tumor cell activity and lymphocyte activation [20] • 70-100% inhibition of tumor cell proliferation when tested on a wide variety of human and mouse tumor cell lines • Non-Laser Activated Calendula Extract only produced slight tumor inhibition (they think it’s excited carotenoids)

19. Animal Studies • Anti-tumor & Anti-Inflammatory Properties[14] • Triterpenes are thought to be the reason for these properties • taraxastanes and helianol levels lead to inhibitory effects of inflammation of mouse ears

20. Clinical Trials • Highly effective for the prevention of acute dermatitis of grade 2 or higher [18] • Single blind study • occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P .001) using calendula instead of trolamine. • less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. • more difficult to apply, but self-assessed satisfaction was greater • should be proposed for patients undergoing postoperative irradiation for breast cancer.

21. Clinical Trials Cont’d • Reduces pain of acute infection and inflammation of the middle ear in children [19] • Concluded “an herbal extract solution may be beneficial” in treatment of ear pain • Administered to 180 children, double blind • Best effects were the [calendula officinalis flores (28%), hypericum perforatum herba tota (30%), and verbascum thapsus flores (25%) in olive oil and the essential oils allium sativum in 0.05% in olive oil (10%), lavandulla officinalis (5%), and tocoferol acetate oil (2%)] with amoxicillin • Concludes that the findings did not account for a lot of the pain resolution and best idea for physicians is to prescribe 3 days to give the body “a chance to repair itself”

22. Conclusions • There is definite proof that ointment containing Calendula officinalis helps prevent skin irritation, redness, and pain • Pain-relieving properties may be present, but more studies are needed to investigate this possibility • There hasn’t been many animal studies to prove that it really does reduce skin inflammation • There need to be clinical trials to determine if it helps with wound and burn healing

23. Works Cited • 1. Bown D. The Herb Society of America’s New Encyclopedia of Herbs and Their Uses. London: Dorling Kindersley Limited, 2001. • 2. Tucker AO, Debaggio T. The Big Book of Herbs. Loveland, CO: Interweave Press; 2000. • 3. European Scientific Cooperative on Phytotherapy. ESCOP Monographs. 2nd ed. New York: Thieme New York; 2003 • 4. Wichtl M, ed. Brinckmann JA, Lindenmaier MP, trans. Herbal Drugs and Phytopharmaceuticals. 3rd ed. Stuttgart: Medpharm GmbH Scientific Publishers; 2004 • 5. Talbert R. What’s in a Name! In: Calendula: An Herb Society of America Guide. Kirtland, OH: Herb Society of America; 2007 • 6. Foster S, Johnson RL. National Geographic Desk Reference to Nature’s Medicine. Washington, DC: National Geographic; 2006 • 7. Blumenthal M, Goldberg A, Brinckmann J, editors. Herbal Medicine: Expanded Commission E Monograph. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communications; 2000

24. 8. Grieve M. A Modern Herbal. Vol. 2. New York: Dover Books; 1971 • 9. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2nd ed. New York: Wiley-Interscience; 1996 • 10. Foster S. 101 Medicinal Herbs: An Illustrated Guide. Loveland, CO: Interweave Press; 1993 • 11. Tyler VE. Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York: Pharmaceutical Products Press; 1994 • 12. Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy, OR: Eclectic Medical Publications; 2001. Plus online updates and additions, August 26, 2007. • 13. Yasui Y, Hosokawa M, Kohno H, Tanaka T, Miyashita K. “Growth inhibition by all-trans-conjugated linolenic acids on human colon cancer cells.” Anticancer Res 26 (3A): 1855- 60. • 14. Akihisa, T. et al., Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects, Phytochemistry 1996; 43(6): 1255-60. • 15. Ćetković, G. S. et al., Antioxidant properties of marigold extracts, Food Research International 2004, Vol. 37(7): 643-650.

25. 16. Pérez-Carreón, J. I. et al., Genotoxic and anti-genotoxic properties of Calendula officinalis extracts in rat liver cell cultures treated with diethylnitrosamine, Toxicology in Vitro 2002, 16(3): 253-258. • 17. Pintea, A., et al., HPLC analysis of carotenoids in four varieties of Calendula officinalis L. flowers, Acta Biol. Szeged. 2003, 47: 37–40. • 18. Pommier P, et al., Phase III Randomized Trial of Calendula Officinalis Compared With Trolamine for the Prevention of Acute Dermatitis During Irradiation for Breast Cancer, J Clin Oncol 2004. • 19. Sarrell EM, Cohen HA, Kahan E., Naturopathic treatment for ear pain in children, Pediatrics 2003, 111: e574-e579. • 20. Jimenez-Medina E., A new extract of the plant Calendula officinalis produces a dual in vitro effect: cytotoxic antitumor activity and lymphocyte activation, BMC Cancer 2006; 5: 119 • 21. Kafi, M., Saffron (Crocus Sativus) Production and Processing, Science Publishers 2006, 209. • 22. Chudnicka, A. and Matysik, G., Research of enzymatic activities of fresh juice and water infusions from dry herbs, Journal of Ethnopharmacology 2005, 99(2): 281-286.