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

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

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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