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Calendula

Scientific Name(s): Calendula officinalis L.
Common Name(s): Calendola, Calendula, Garden marigold, Gold bloom, Goudsbloem, Holligold, Maravilla, Marigold, Marybud, Marygold, Nagotki, Neven, Pot marigold, Ringelblume, Souci

Clinical Overview

Use

Potential uses for calendula include the treatment of inflammatory skin disorders, wound healing, and the treatment of other skin conditions. It may also be ingested for its anti-inflammatory and antispasmolytic effects. However, clinical trials to support these uses are limited. Use of calendula for dental purposes is increasing.

Dosing

A preparation can be made by steeping 5 to 10 mL of the herb in 1 cup of boiling water for 10 minutes and then gargled as a mouthwash for oral sores, consumed for its antispasmodic effects, or applied topically for skin conditions. Topical products typically contain 2 to 5 g of the herb per 100 g of the product.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. A study in rats demonstrated a reduction in maternal weight gain when administered during pregnancy.

Interactions

None well documented.

Adverse Reactions

Allergic reactions, contact sensitization, and 1 case of anaphylaxis have been reported.

Toxicology

Calendula appears to have a low potential for toxicity.

Scientific Family

  • Asteraceae (daisies)

Botany

Calendula is believed to be native to Egypt and has almost worldwide distribution. There are numerous varieties of this species, differing primarily in flower shape and color. Calendula grows to about 0.7 m tall, and the wild form has small, bright yellow-orange flowers that bloom from May to October. The ligulate florets of the plant have been used medicinally. Calendula plant should not be confused with other members of the marigold family.1, 2

History

Calendula plant has been grown in European gardens since the 12th century. Tinctures and extracts of the florets were used topically to promote wound healing and to reduce inflammation; systemically, they have been used to reduce fever, control dysmenorrhea, and treat cancer. The plant is listed in the German Commission E Monographs for wound healing and anti-inflammatory actions.2

The dried petals have been used as a seasoning and have been used to adulterate saffron.3 The pungent odor of the marigold has been used as an effective pesticide. Marigolds are often interspersed among plants in vegetable gardens to repel insects.4

Chemistry

Calendula plant contains a number of oleanolic acid glycosides.5 Flavonol and triterpene glycosides have been isolated from C. officinalis via high-pressure liquid chromatography.6, 7 Calendulin (also known as bassorin), a mucilage found in the plant, contains sterols and fatty acids, including calendic acid.8, 9, 10 The plant also contains triterpenoid in free and ester forms,11, 12, 13 tocopherols,14 mucilage, and a volatile oil.2 Enzymatic activity of calendula extracts has been described.15 The carotenoid pigments have been used as coloring agents in cosmetics, and the volatile oil has been used in perfumes.2, 16, 17

Uses and Pharmacology

Despite the history of calendula use and the detailed studies of its chemistry, clinical studies are lacking.

Anti-inflammatory

The anti-inflammatory properties of calendula are attributed to triterpenoids.18

Animal/In vitro data

Triterpenoid-containing extracts of calendula have been investigated in chemically induced inflammation in mice.7, 12 Calendula extracts alleviated signs of chronic conjunctivitis and other chronic ocular inflammatory conditions in rats19; the extracts also had a systemic anti-inflammatory effect. A study of dogs with experimentally induced ulcerative colitis found that when given at 3 mL/day for 30 days, calendula 40% was associated with statistically significant healing of the mucosa at 30 and 45 days after induction.20

Clinical data

A case report described calendula tincture as an effective treatment for anal fissures. A 52-year-old woman with chronic anal fissures was treated with nonpharmacological, pharmacological, and surgical options. Following surgery, her fissures returned, and she began using a calendula tincture applied to the area 3 times daily with a cotton ball for 4.5 months. She reported improvement in pain with no rectal bleeding.21

Dermatitis/Skin conditions

Animal data/In vitro data

Calendula extracts have been used topically to promote wound healing, and experiments in rats have confirmed a measurable effect. An ointment containing 5% flower extract in combination with allantoin markedly stimulated epithelialization in surgically induced wounds. On the basis of histological examination of wound tissue, it was concluded that the ointment increased glycoprotein, nucleoprotein, and collagen metabolism at the site.22 Calendula may help enhance blood flow to the affected area.21 Also, calendula 4% and 5% creams applied for 1 month produced alterations in the levels of antioxidants found in the skin of rats that received ultraviolet-B radiation. Specifically, malonyldialdehyde levels decreased, whereas catalase, glutathione, superoxide dismutase, ascorbic acid, and total protein levels increased.23

Calendula extract given in doses of 20, 100, and 200 mg/kg were all effective in the treatment of thermal burns. There were higher amounts of hydroxyproline in the granuloma tissue of those treated with calendula compared with the controls. Treatment with calendula 200 mg/kg was also found to reduce acute phase protein levels.24

In a murine model, wound closure on day 8 of healing was approximately 90% in rats receiving oral calendula 20 or 100 mg/kg, or topical calendula, compared with 51.5% of those in the control group. The period of re-epithelization following wound infliction was 17.7 ± 0.8 days compared with 14 ± 1.1, 3 ± 0.6, and 16.1 ± 0.4 days with oral calendula 20 or 100 mg/kg, or topical calendula, respectively.25 In another murine model, topically applied calendula cream following tendon transection resulted in elevated hydroxyproline and noncollagenous proteins.26

Clinical data

A single-blind, randomized trial investigating the efficacy of a calendula preparation in preventing grade 2 or higher radiation therapy–associated acute dermatitis in breast cancer has been published.27 A decrease in grade 2 or higher dermatitis was found with the calendula preparation containing 4 g of fresh plant in 20 g of petroleum jelly; however, application of the preparation proved difficult in 30% of the participants. A reduction in pain was also reported for patients treated with calendula.27, 28, 29 In a randomized, blinded, phase 3 trial, 411 women with breast cancer undergoing adjuvant radiotherapy received either calendula cream or an aqueous cream applied twice daily, starting on the day of initial radiotherapy and continuing until 2 weeks after the last radiotherapy session or until the acute radiation skin reaction healed. No statistically significant differences existed between treatment groups with regard to acute radiation skin reactions (incidence of 23% with calendula vs 19% with the aqueous cream). In general, patients reported low levels of skin symptoms. The authors concluded that acute radiation skin reactions may be influenced more by treatment factors than by selection of skin products.30

A randomized, double-blind study was conducted in 66 infants and children with diaper dermatitis. The participants received either calendula ointment or aloe cream applied 3 times daily for 10 days. Both treatments significantly reduced the severity of diaper dermatitis (P < 0.001); however, calendula ointment was associated with a significantly greater rate of reduction compared with aloe cream (P = 0.001). 31

In a study of primiparous women who underwent an episiotomy, calendula ointment applied every 8 hours to the perineal area was associated with improvements in redness, edema, approximation, and ecchymosis compared with standard treatment with betadine.18

Dental conditions

Animal/In vitro data

In a study of human gingival fibroblasts, calendula 1% to 3% completely inhibited collagen degradation, and calendula 2% to 3% completely inhibited pro-matrix metalloproteinase–2 activity. The authors suggest that calendula be further investigated for in vivo use in periodontal disease.32

In a study of hamsters with 5-fluorouracil (5-FU)–induced oral mucositis, administration of C. officinalis 5% and 10% gel reduced both microscopic and macroscopic mucositis scores.33

Clinical data

A case report described an 18-year-old man with exfoliative cheilitis who experienced continuous symptoms with corticosteroid treatment. He was switched to calendula 10% ointment and experienced complete healing after 15 days with complete resolution thereafter.34

Case reports describe successful treatment of 2 patients with desquamative gingivitis who received topical gel containing calendula 3%, clobetasol 0.05%, nystatin 100,000 units/mL, and pectin 5% three times a day.35

In a randomized, controlled clinical study, 38 patients with head and neck cancer received a calendula 2% mouthwash as a gel formulation (5 mL twice daily) or placebo. Statistically significant reductions in intensity of oropharyngeal mucositis were noted at all time points (weeks 2, 3, and 6) for patients treated with calendula compared with placebo.36

In a randomized, controlled clinical study of 240 patients with gingivitis with reported bleeding, calendula mouthwash (calendula tincture 2 mL plus 6 mL of water) rinsed twice daily for 6 months significantly reduced the plaque index, gingival index, and sulcus bleeding index in the absence of scaling between the first and second visit (P < 0.05). Controls did not have reductions in any of these parameters. Statistically significant findings with calendula mouthwash were also demonstrated after scaling was performed, between the third and sixth month. Controls experienced reductions in these parameters; however, a larger reduction was noted with calendula.37

Other uses

Calendula extracts have demonstrated in vitro antibacterial, antiviral, antifungal,7, 38, 39, 40, 41 and immunostimulating properties.42, 43 Cytotoxic, hepatoprotective, spasmogenic, and spasmolytic properties have been demonstrated in in vitro experiments.7, 43, 44, 45 In an animal model, calendula provided protective effects against hepatotoxicity and cisplastin-induced nephrotoxicity.46 Angiogenic activity due to induction of neovascularization was reported with an ethanolic extract and dichloromethane and hexanoic fractions of calendula.47

In a study of mice with B16F-10 melanoma allografts, the antimetastatic effects of calendula were assessed. Administration of calendula 250 mg/kg orally for 10 days was found to decrease lung tumor nodules by 74%, increasing life span by 43.3%. Mice receiving calendula also had lower levels of uronic acid, serum sialic acid, and gamma-glutamyl transpeptidase.48

One study showed mild mosquito repellent properties, conferring protection for 2.15 hours. However, it was not as effective when compared with DEET or myrtle.49

In rats, calendula was cardioprotective through stimulation of left ventricular pressure and aortic flow, and through reduction in myocardial infarct size (41.45% ± 2% in the control versus 20.5% ± 1.61% treatment groups). Tumor necrosis factor-alpha levels were also reduced in calendula-treated rats.50

In a murine model of 3-nitropropionic acid–induced Huntington disease, an extract of C. officinalis flower attenuated reductions in body weight due to 3-nitropropionic acid; improved behavioral changes; increased locomotor counts; and improved memory performance, motor coordination, hind limb function, and grip strength.51

In a murine model, C. officinalis 100 mg/kg twice daily given 1 hour before cigarette exposure conferred some protection against cell injury. Specifically, rats treated with calendula had reduced levels of malondialdehyde and protein carbonyl content in the lungs and brain, compared with increased levels for those exposed to cigarette smoke only.52

Dosing

A preparation can be made by steeping 5 to 10 mL of the herb in 1 cup of boiling water for 10 minutes and then gargled as a mouthwash for oral sores, consumed for its antispasmodic effects, or applied topically for skin conditions.53 Commercial topical preparations are also available.27 An ointment containing 2% to 5% of the flower extract has been used for topical wound healing.54

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. A study in rats demonstrated that a hydroalcohol extract of C. officinalis did not possess toxic effects on male fertility or during the early and midpregnancy periods in females. However, during the fetal period of pregnancy (ie, after the tenth week), a reduction in maternal weight gain was noted in rats receiving the extract.55

Interactions

None well documented.

Adverse Reactions

There are few reports describing serious reactions, despite the widespread use of calendula preparations.

Allergic reactions, contact sensitization, and 1 case of anaphylaxis to other members of the Asteraceae family have been described.56, 57

Toxicology

The Cosmetic Ingredient Review Expert Panel concluded that C. officinalis extract, flower, flower extract, flower, oil, and seed oil are safe for use in cosmetics.58 In a study of Wistar rates, 2,000 mg/kg given as 1 dose was not associated with any acute toxicity. Calendula 50, 250, and 1,000 mg/kg/day for 90 days was assessed for toxicity in the subchronic toxicity arm of this study. Following 90 days of treatment, differences were noted in hemoglobin, erythrocytes, leukocytes, blood clotting time, AST, ALT, and alkaline phosphatase that were gender-specific in some cases. Slight abnormalities in the hepatic parenchyma were also noted.59 Saponin extracts of C. officinalis are not mutagenic.60 The median lethal dose of calendula flower extract in rats was more than 4.64 g/kg.58

References

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2. Hamburger M, Adler S, Baumann D, Förg A, Weinreich B. Preparative purification of the major anti-inflammatory triterpenoid esters from Marigold (Calendula officinalis). Fitoterapia. 2003;74(4):328-338. 12781802
3. Duke JA. Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985.
4. Lewis WH, Elvin-Lewis MP. Medical Botany: Plants Affecting Man's Health. New York, NY: John Wiley & Sons; 1977.
5. Kasprzky Z, Janiszowska W, Sobczyk E. Metabolism of a new series of oleanolic acid glycoside in Calendula officinalis shoots. Acta Biochim Pol. 1973;20(3):231-235.4749664
6. Pietta P, Bruno A, Mauri P, Rava A. Separation of flavonol-2–O-glycosides from Calendula officinalis and Sambucus nigra by high-performance liquid and micellar electrokinetic capillary chromatography. J Chromatogr. 1992;593(1-2):165-170.1639901
7. Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, Kimura Y. Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers. J Nat Prod. 2006;69(12):1692-1696.17190444
8. Chisholm MJ, Hopkins CY. Calendic acid in seed oils of the genus Calendula. Can J Biochem. 1967;45(2):251-254.6021179
9. Badami RC, Morris LJ. The oxygenated fatty acid of Calendula seed oil. J Am Oil Chem Soc. 1965;42(12):1119-1121.5845654
10. Szakiel A, Kasprzyk Z. Distribution of oleanolic acid glycosides in vacuoles and cell walls isolated from protoplasts and cells of Calendula officinalis leaves. Steroids. 1989;53(3-5):501-511.2799856
11. Auguścińska E, Kasprzyk K. Studies on the labelling of terpenoids in shoots and cells or protoplasts from Calendula officinalis leaves. Acta Biochim Pol. 1982;29(1-2):7-15.6817567
12. Neukirch H, D'Ambrosio M, Sosa S, Altinier G, Della Loggia R, Guerriero A. Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modifications, from the abundant triterpenes of the flowery plant Calendula officinalis. Chem Biodivers. 2005;2(5):657-671.17192009
13. Neukirch H, D'Ambrosio M, Dalla Via J, Guerriero A. Simultaneous quantitative determination of eight triterpenoid monoesters from flowers of 10 varieties of Calendula officinalis L. and characterisation of a new triterpenoid monoester. Phytochem Anal. 2004;15(1):30-35.14979524
14. Janiszowska W, Jasinska R. Intracellular localization of labelling of tocopherols with [U-14C] tyrosine in Calendula officinalis leaves. Acta Biochim Pol. 1982;29(1-2):37-44.7180325
15. Chudnicka A, Matysik G. Research of enzymatic activities of fresh juice and water infusions from dry herbs. J Ethnopharmacol. 2005;99(2):281-286.15894139
16. Tyler VE. The New Honest Herbal. Philadelphia PA: G.F. Stickly Co; 1987.
17. Kishimoto S, Maoka T, Sumitomo K, Ohmiya A. Analysis of carotenoid composition in petals of calendula (Calendula officinalis L.). Biosci Biotechnol Biochem. 2005;69(11):2122-2128.16306694
18. Eghdampour F, Jahdi F, Kheyrkhah M, Taghizadeh M, Naghizadeh S, Hagani H. The impact of Aloe vera and Calendula on perineal healing after episiotomy in primparous women: a randomized clinical trial. J Caring Sci. 2013;2(4):279-286.25276736
19. Marinchev VN, Bychkova LN, Balvanovich NY, Giraev AN. Use of calendula for therapy of chronic inflammatory diseases of eyelids and conjunctiva [in Russian]. Oftalmol Zh. 1971;26(3):196-198.5565187
20. Mehrabani D, Ziaei M, Hosseini SV, et al. The effect of Calendula officinalis in therapy of acetic acid induced ulcerative colitis in dog as an animal model. Iran Red Crescent Med J. 2011;13(12):884-890.22737434
21. Naseer S, Lorenzo-Rivero S. Role of calendula extract in treatment of anal fissures. Am Surg. 2012;78(8):E377-E378.22856483
22. Klouchek-Popava E, Popov A, Pavlova N, Krusteva S. Influence of the physiological regeneration and epithelialization using factions isolated from Calendula officinalis. Acta Physiol Pharmacol Bulg. 1982;8(4):63-67.7185264
23. Mishra AK, Mishra A, Verma A, Chattopadhyay P. Effects of Calendula essential oil-based cream on biochemical parameters of skin of albino rats against ultraviolet B radiation. Sci Pharm. 2012;80(3):669-683.23008814
24. Chandran PK, Kuttan R. Effect of Calendula officinalis flower extract on acute phase proteins, antioxidant defense mechanism and granuloma formation during thermal burns. J Clin Biochem Nutr. 2008;43(2):58-64.18818737
25. Preethi KC, Kuttan R. Wound healing activity of flower extract of Calendula officinalis. J Basic Clin Physiol Pharmacol. 2009;20(1):73-79.19601397
26. Aro AA, Perez MO, Vieira CP, et al. Effect of Calendula officinalis cream on Achilles tendon healing. Anat Rec. 2014;298(2):428-435.25266273
27. Pommier P, Gomez F, Sunyach MP, D'Hombres A, Carrie C, Montbarbon X. 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;22(8):1447-1453.15084618
28. McQuestion M. Evidence-based skin care management in radiation therapy. Semin Oncol Nurs. 2006;22(3):163-173.16893745
29. Bolderston A, Lloyd NS, Wong RK, Holden L, Robb-Blenderman L; Supportive Care Guidelines Group of Cancer Care Ontario Program in Evidenced-Based Care. The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Cancer. 2006;14(8):802-817.16758176
30. Sharp L, Finnila K, Johansson H, Abrahamsson M, Hatschek T, Bergenmar M. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions – results from a randomised blinded trial. Eur J Oncol Nurs. 2013;17:429-435.23245940
31. Panahi Y, Sharif MR, Sharif A, et al. A randomized comparative trial on the therapeutic efficacy of topical aloe vera and Calendula officinalis on diaper dermatitis in children [published online April 19, 2012]. ScientificWorldJournal.10.1100/2012/810234
32. Saini P, Al-Shibani N, Sun J, et al. Effects of Calendula officinalis on human gingival fibroblasts. Homeopathy. 2012;101(2):92-98.22487368
33. Tanideh N, Tavakoli P, Ali Saghiri M, et al. Healing acceleration in hamsters of oral mucositis induced by 5-fluorouracil with topical Calendula officinalis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(3):332-338.23182376
34. Roveroni-Favaretto LHD, Lodi KB, Almeida JD. Topical Calendula officinalis L. successfully treated exfoliative chelitis: a case report. Cases J. 2009:9;9077.20062714
35. Machado MA, Contar CM, Brustolim JA, et al. Management of two cases of desquamative gingivitis with clobestasol and Calendula officinalis gel. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154(4):335-338.21293545
36. Babaee N, Moslemi D, Khalilpour M, et al. Antioxidant capacity of Calendula officinalis flowers extract and prevention of radiation induced oropharyngeal mucositis in patients with head and neck cancers: a randomized controlled clinical study. DARU. 2013;21(1):18.23497687
37. Khairnar MS, Pawar B, Marawar PP, Mani A. Evaluation of Calendula officinalis as an anti-plaque and anti-gingivitis agent. J Indian Soc Periodontol. 2013;17(6):741-747.24554883
38. Dumenil G, Chemli R, Balansard C, Guraud H, Lallemand M. Evaluation of antibacterial properties of marigold flowers (Calendula officinalis L.) and mother homeopathic tinctures of C. officinalis L. and C. arvensis L [in French]. Ann Pharm Fr. 1980;38(6):493-499.7283346
39. De Tommasi N, Pizza C, Conti C, Orsi N, Stein ML. Structure and in vitro antiviral activity of sesquiterpene glycosides from Calendula arvensis. J Nat Prod. 1990;53(4):830-835.1965654
40. Iauk L, Lo Bue AM, Milazzo I, Rapisarda A, Blandino G. Antibacterial activity of medicinal plant extracts against periodontopathic bacteria. Phytother Res. 2003;17(6):599-604.12820224
41. Efstratiou E, Hussain A, Nigam PS, Moore JE, Ayub MA, Rao JR. Antimicrobial activity of Calendula officinalis petal extracts against fungi, as well as Gram-negative and Gram-positive clinical pathogens. Complement Ther Clin Pract. 2012;18(3):173-176.22789794
42. Wagner H, Proksch A, Riess-Maurer I, et al. Immunostimulating action of polysaccharides (heteroglycans) from higher plants [in German]. Arzneimittelforschung. 1985;35(7):1069-1075.4052142
43. Jiménez-Medina E, Garcia-Lora A, Paco L, Algarra I, Collado A, Garrido F. A new extract of the plant Calendula officinalis produces a dual in vitro effect: cytotoxic anti-tumor activity and lymphocyte activation. BMC Cancer. 2006 May 5;6:119.16677386
44. Bashir S, Janbaz KH, Jabeen Q, Gilani AH. Studies on spasmogenic and spasmolytic activities of Calendula officinalis flowers. Phytother Res. 2006;20(10):906-910.16906636
45. Rusu MA, Tamas M, Puica C, Roman I, Sabadas M. The hepatoprotective action of ten herbal extracts in CCl4 intoxicated liver. Phytother Res. 2005;19(9):744-749.16220565
46. Preethi KC, Kuttan R. Hepato and reno protective action of Calendula officinalis L. flower extract. Indian J Exp Biol. 2009;47(3):163-168.19405380
47. Parente LML, Andrade MA, Brito LAB, et al. Angiogenic activity of Calendula officinalis flowers L. in rats. Acta Cirurgica Brasileira. 2011;26(1):19-24.21271199
48. Preethi KC, Siveen KS, Kuttan R, Kuttan G. Inhibition of metastasis of B16F-10 melanoma cells in C57BL/6 mice by an extract of Calendula officinalis. L. flowers. Asian Pac J Cancer Prev. 2010;11(6):1773-1779.21338232
49. Tavassoli M. Shayeghi M, Rafi F. Repellency effects of essential oils of myrtle (Myrtus communis), marigold (Calendula officinalis) compared with DEET against Anopheles stephension human volunteers. Iran J Arthropod Borne Dis. 2011;5(2):10-22.22808414
50. Ray D, Mukherjee S, Falchi M, Bertelli A, Braga PC, Das DK. Amelioration of myocardial ischemic reperfusion injury with Calendula officinalis. Curr Pharm Biotechnol. 2010;11(8):849-854.
51. Shivasharan BD, Nagakanna P, Shivanandappa Thippeswamy B, Prabakar Veerapur V, Bansal P, Unnikirshnan MK. Protective effect of Calendula officinalis Linn. flowers against 3-nitropropionic acid induced experimental Huntington's disease in rats. Drug Chem Toxicol. 2013;36(4):466-473.23590827
52. Ozkol H, Tuluce Y, Koyuncu I. Subacute effect of cigarette smoke exposure in rats: protection by pot marigold (Calendula officinalis L.) extract. Toxicol Ind Health. 2012;28(1):3-9.21505008
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55. Silva EJ, Costa-Silva JH, Evencio LB, Fraga Mdo C, Coelho MC, Wanderley AG. Reproductive assessment of hydroalcohol extract of Calendula officinalis L. in Wistar rats. Phytother Res. 2009;23(10):1392-1398.19288530
56. Wintzen M, Donker AS, van Zuuren EJ. Recalcitrant atopic dermatitis due to allergy to Compositae. Contact Dermatitis. 2003;48(2):87-88.12694211
57. Reider N, Komericki P, Hausen BM, Fritsch P, Aberer W. The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.). Contact Dermatitis. 2001;45(5):269-272.11722485
58. Andersen FA, Bergfeld WF, Belsito DV, et al. Final report of the Cosmetic Ingredient Review Expert Panel amended safety assessment of Calendula officinalis-derived cosmetic ingredients. Int J Toxicol. 2010;29(6 suppl):221S-243S.21164072
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60. Elias R, De Méo M, Vidal-Ollivier E, Laget M, Balansard G, Dumenil G. Antimutagenic activity of some saponins isolated from Calendula officinalis L., C. arvensis L. and Hedera helix L. Mutagenesis. 1990;5(4):327-331.2204784

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