Calendula Preparations to Treat Cutaneous Infections
December 1998; Volume 1: 140-142
By Vance Dietz, MD, MPH, TM
Scratches, bruises, and minor cuts! most parents have had to deal with them for their children and themselves. Since Ambroise Pare substituted egg whites for boiling water to treat war wounds in the 16th century, the search for wound healing compounds has been ongoing and it will continue.1 Many unguents are available to prevent or treat infection. In addition, nature has provided numerous anti-inflammatory and antiviral herbs that have been used through the years. One of the most common of these is derived from Calendula officinalis, the marigold.
History of Calendula
Calendula officinalis, also called pot marigold or simply calendula, originated in the Mediterranean and is a member of the aster or daisy family. An annual, calendula’s flowers bloom in the summer. Since medieval times this remarkably hardy herb has been grown in gardens, where it will sprout in poor soil, stone piles, and similar areas. Although its flowers are also bright orange and yellow, calendula should not be confused with the common garden marigold (Tagetes sp.).
Folklore
Calendula has been widely used as an anti-inflammatory and as a remedy for skin infections, burns, and numerous other conditions. It is a folk remedy for warts and, when combined with milk, for cancer.2 Calendula is aid to be good for bee stings when rubbed on the skin. It is said to be effective as an "analgesic, anthelmintic, anti-spasmodic, astringent, bactericide, carminative, ... diaphoretic, diuretic ... laxative, stimulant."2 In addi-tion, the "tincture of flowers has been used to heal amenorrhea, bruises, cholera, cramps, syphilis, tubercu-losis, ulcers, and wounds." When boiled together with honey and ground ivy, calendula is said to stop the spread of cancers or ulcers, although this remains unproven. In addition, powder from the plant’s petals is used like saffron to season and color seafood, chowders, soups, stews, sauces, and more.
Mechanism of Action
Calendula’s mechanism of action in wound healing is not completely clear. The main compounds of calendula flower extracts include triterpenoids and flavonoids, especially flavonol glycosides.3 Among the triterpenoids, the faradiol monoester appears to be most related to calendula’s anti-inflammatory activity.4 However, laboratory studies demonstrate an anti-inflammatory effect of more than one compound in the plant.4-8 Bactericidal activity against Staphylococcus aureus has also been reported.9
Animal Studies
Della Loggia et al assessed the ability of a CO2-induced extract of calendula containing triterpenes to reduce inflammation in mice using the croton oil ear test. In this induced otodermatitis test,4 the irritant croton oil was injected on the inner surface of the ear canal. Varying doses of calendula extract were applied topically to the same areas. Controls received only the irritant. Small plugs were placed in each ear and after six hours the plugs were removed. The difference in weight between the two plugs was taken as a measure of the edematous response.
The authors also conducted the experiment using indomethacin in place of the calendula extract. Both the CO2 extracts and the triterpenes fractions were found to reduce the edema when compared with the controls (P < 0.01). In addition, a dose-dependent response to both types of extracts was observed. The extracts were shown to inhibit edema to a greater degree than seen in mice treated with indomethacin. The authors demonstrated that the faradiol monoester content in the CO2 extract was the best index of its anti-inflammatory activity.
Zitterl-Eglseer and colleagues also assessed the anti-inflammatory activity of calendula using the croton oil-induced test.6 The authors demonstrated a statistically significant reduction in edema in mice treated with a calendula preparation as compared to the controls. The anti-inflammatory effect of calendula in animals has been studied using other established laboratory models of artificially induced inflammation, including the tetradecanoylphorbol-13-acetate (TPA) induced inflammatory test7 and the carragheenin-induced inflammatory test.8 In both studies, the calendula preparation demonstrated an anti-inflammatory effect similar to that of the commercially approved medication indomethacin and, in Belgium, acetylsalicyclate de lysine.
Clinical Studies
Although numerous laboratory-based studies on the anti-inflammatory effect of calendula were found, few studies have been conducted in humans. French researchers assessed the ability of calendula ointment to promote healing in second- and third-degree burns.10 Calendula was compared to pure vaseline and a commercial proteolytic ointment indicated in the management of burns. Approximately 50 people with second- or third-degree burns were treated for 12 days in each group. Assessment of success was conducted at eight and 12 days and was defined as the absence of an eschar or local infection. In total, 70% of the calendula group were classified as successes compared to 66% of those treated with the commercial product (P > 0.05) and only 54% of those receiving vaseline (P = 0.05). In addition, 35% of those treated with the calendula ointment denied an adverse effect and 60% denied pain, but only 10% of those treated with the commercial product denied any adverse effects (P < 0.05) and 21% denied any pain (P < 0.05).
In Brazil, Neto et al also demonstrated the ability of calendula to promote burn healing. They studied the impact of calendula and a combination of calendula and barbatimao (derived from Stryphnodendron barbadetiman) on three groups: individuals with burns (both sunburns and domestic burns, such as hot oil); with varicose ulcers; and with cuts and dermatitis.11 The authors stated that all individuals had been treated by conventional therapy without success. Each group had 5-8 patients. Fifteen individuals with burns who were treated with calendula alone or in combination with barbatimao reportedly had complete healing within 2-6 days. Of the 12 individuals treated with a calendula preparation for varicose ulcers, eight reported complete healing within 30 days. Finally, seven of the 11 individuals with cuts or chronic dermatitis reportedly were healed within 10 days. Thus, calendula appeared to have greater efficacy in the management of burns than when used for ulcers, cuts or dermatitis.
Kartikeyan et al compared the effect of calendula cream in a homeopathic preparation to antibiotic topical ointment for trophic ulcers in leprosy patients.12 After 3-4 weeks, patients using calendula ointment showed a 30-40% reduction in depth and diameter of the ulcers and the absence of any secondary infections. Although the authors did not comment on the outcome of those treated with an antibiotic ointment, they did point out that, in general, trophic ulcers do not heal without immobilization of the affected extremity. None of the patients in the study had affected extremities immobilized.
Extracts of calendula combined with other herbal preparations were also shown to accelerate healing of artificially induced skin abrasions in five healthy subjects.13 Compared to controls, the preparation accelerated healing by an average of 3.4 days.
Adverse Effects
No adverse effects of calendula ointment were found in the literature. However, a case of severe allergy to calendula tea was reported from Russia. Individuals allergic to other members of the aster family, such as ragweed, should exercise caution when ingesting calendula.
Drug Interaction
No drug interactions have been reported.
Formulation
Calendula extract generally is prepared from the flower as a tincture, lotion, or cream that usually is applied directly or as a cool compress. Calendula tea preparations have been gargled or taken internally to treat oral and gastric ulceration. Calendula is also prepared and available as a homeopathic remedy, fluid extract, and oil.
Dosage
Herbal ointments are often used 3-4 times a day. Commission E lists the calendula flower as an approved substance in ointments equivalent to 2-5 g of crude drug in 100 g of ointment. The calendula herb, comprised of an extract of the whole plant, is not approved.
Conclusion
Medicinal preparations of calendula have been used since medieval times. Calendula has a strong history as a folk remedy for skin infections, particularly in Europe. Numerous laboratory-based studies have demonstrated a significant anti-inflammatory effect of calendula extracts on induced inflammation in mice. Data from human studies are limited and the studies conducted were not rigorous. Nevertheless, they suggest that calen-dula can promote the healing of burns and that it has an anti-inflammatory effect.
Recommendation
When questioned by their patients about the use of calendula, clinicians could advise that laboratory studies using animal models suggest an anti-inflammatory effect. Although clinical studies are limited in number and in scope, they do suggest a benefit of using calendula to treat and manage skin inflammation, particularly burns. Clinicians can also feel confident that the use of calendula preparations is safe.
References
1. Srinivasan H. Do we need trials of agents alleged to improve healing of plantar ulcers? Lepr Rev 1989;60:278-282.
2. Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press, Inc.; 1985.
3. Kalvatchev Z, et al. Anti-HIV activity of extracts from Calendula officinalis flowers. Biomed Pharmacother 1997;51:176-180.
4. Della Loggia R, et al. The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers. Planta Med 1994;60:516-520.
5. Della Loggia R, et al. Topical anti-inflammatory activity of Calendula officinalis extracts. Planta Med 1990;56:658.
6. Zitterl-Eglseer K, et al. Anti-oedematous activities of the main triterpenoil esters of marigold (Calendula officinalis L.). J Ethnopharmocol 1997;57:139-144.
7. Akihisa T, et al. Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry 1996;1255-1260.
8. Chemli R, et al. Calendula arvensis L. Impact des saponines sur la toxicité, le pouvoir hémolytique et l’activité anti-inflammatoire. J Pharm Belg 1990;45:12-16.
9. Dumenil G, et al. Etude des propriétés antibactériennes des fleurs de Souci Calendula officinalis L. et des teintures meres homéopathiques de C. officinalis L. et C. arvensis L. Ann Pharm Fr (French) 1980;38: 493-499.
10. Lievre M, et al. Controlled study of three ointments for the local management of 2nd and 3rd degree burns. Clinical trials and meta-analysis 1992;28:9-12.
11. Neto JJ, et al. Tratamento de ulcera varicosa e lesoes de pele com Calendula officinalis L. E/OU com Stryphnodendron barbadetiman (vellozo) Martius. Rev Cienc Farm Sao Paulo 1996;17:181-186.
12. Kartikeyan S, et al. Effect of calendula on trophic ulcers. Lepr Rev 1990;61:399.
13. Gasiorowska I, et al. [The use of Calendula officinalis]. Cosmet Toilet 1985;100:45-58.
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