Flowers of the English or Pot Marigold (Calendula officinalis), have long been recommended and used for minor cuts, grazes, and slow healing wounds. However despite this popularity, and it being approved by the European Medicines Agency as a traditional medicinal product⁽¹⁾, clinical trials involving calendula have been few and far between until recently. Now though, results from at least 10 clinical trials involving use of topical dosage forms of calendula for a range of clinical conditions, have been published.

Preventive effects against radiation-induced dermatitis were reported by French oncologists in a study involving 254 breast cancer patients in 2004. Only 41% of patients who received calendula ointment treatment after each radiotherapy session subsequently developed acute dermatitis, compared to 63% of those given topical trolamine treatment. Reduced radiation-induced pain, and less frequent interruption of the radiotherapy treatment regimen, were other positive outcomes associated with calendula ointment application^(2,3).

A more recent Australian trial involving 81 women undergoing breast cancer radiotherapy compared topical calendula with the standard sorbolene treatment. The prevalence of radiation-induced dermatitis was 53% in the calendula group and 62% in the sorbolene group. While this difference was not statistically significant, the study was underpowered due to less than half the recruitment target of 178 patients, being achieved⁽⁴⁾. Use of a calendula mouthwash has also been reported to reduce the intensity of radiation-induced oropharyngeal mucositis in patients with head and neck cancers undergoing radiotherapy⁽⁵⁾.

Other trials have evaluated calendula in the management of venous leg ulcers. The first of these compared twice daily application of calendula ointment with saline solution dressings, in a group of 34 patients over a 3 week period⁽⁶⁾. After the third week, the total surface of the ulcers decreased by an average of 41.7% in the calendula group, but only 14.5% in the group treated with saline dressings. In four calendula treated patients, complete wound closure was achieved. 

A Brazilian clinical trial evaluated the effectiveness of a spray application of calendula extract on the healing rate of 38 non-healing diabetic leg ulcers⁽⁷⁾. Treatment entailed twice daily application of calendula or standard hospital procedure, consisting of the enzyme collagenase, the antibiotic chloramphenicol, and 1% silver sulfadiazine cream for a period of 30 weeks or until ulcers healed.

After 12 weeks of treatment, 39% of wounds treated with calendula were completely closed, but none in the standard treatment control group. After 30 weeks treatment, 72% achieved complete wound closure, compared to only 32% in the control group. Average healing times were 12 weeks in the calendula treatment group, versus 25 weeks in the control group. No adverse events were observed during calendula treatment.

While confirmation of these benefits through a trial involving greater patient numbers is needed, these studies suggest a significant acceleration of venous ulcer healing through twice daily application of topical calendula products.

A shortened duration of caesarian wound healing, has also been recently reported by another Iranian trial involving 72 women, through twice daily application of calendula ointment versus the standard hospital post surgical routine⁽⁸⁾. Faster wound healing after episiotomy, has also been reported from an Italian trial recently⁽⁹⁾. Women who received calendula ointment compared to standard care benefited from a significantly lower pain level starting from day two after episiotomy, as well as improved wound healing in terms of redness and oedema.

Several mechanisms of action are likely to be responsible for these effects of calendula on wound healing or dermatitis prevention. Beneficial effects on granulation tissue and new tissue formation during acute wound healing have been observed in vitro using human immortalised keratinocytes and human dermal fibroblasts⁽¹⁰⁾. A recent review of calendula’s effects on acute wounds which incorporated 7 animal and 7 clinical studies, reported faster resolution of the inflammation phase and increased production of granulation tissue, in acute wounds treated with calendula⁽¹¹⁾.

Another traditional application of calendula is for the treatment of fungal infections, and findings from another Iranian trial comparing a 7 day treatment of calendula or clotrimazole cream for the treatment of vaginal candidiasis in a group of 150 women aged 18–45 years, are of interest⁽¹²⁾. While a higher rate of negative testing for candidiasis was measured at 10-15 days post treatment in the clotrimazole than in the calendula group (74% vs 49% negative tests for candidiasis), when further testing was undertaken at 30-35 days after treatment, calendula treatment was associated with 77% testing negative for candidiasis, versus only 34% in the clotrimazole group. Signs and symptoms were similar in both groups at 10-15 days post treatment, but significantly less in the calendula group, at the later follow-up. Thus vaginal administration of calendula cream was effective in treating vaginal candidiasis, and while the onset of effect was delayed compared to clotrimazole, a greater and longer term effect was seen following calendula treatment⁽¹²⁾. 

With antibiotic resistance becoming an increasing problem, not to mention the high and rising costs of wound care management associated with aging populations and the impact of diabetes, investigation into plant-based alternative wound treatment agents, is gaining more research attention.

The orange-yellow flowers of calendula have a convincing reputation for helping to enhance wound healing in traditional herbal medicine. Encouragingly, its potential usefulness in wound care management and fungal infections such as candidiasis, is being increasingly validated by a growing number of clinical studies published in recent years.

References:

1. https://www.ema.europa.eu/en/medicines/herbal/calendulae-flos.
2. Pommier P et al, J Clin Oncol. 2004 Apr 15;22(8):1447-53.
3. Rasmussen PL, Calendula for radiotherapy-induced skin damage. Phytonews 20, published by Phytomed Medicinal Herbs Ltd, Dec 2004.ISSN 1175-0251.
4. Siddiquee S et al, Australas J Dermatol 2020 Sep 23. doi: 10.1111/ajd.13434. Online ahead of print.
5. Babaee B et al, Daru. 2013 Mar 7;21(1):18.
6. Duran V et al, Int J Tissue React. 2005;27(3):101-6.
7. Buzzi M et al, Ostomy/wound Management 2016; 62(3):8-24.
8. Jahdi F et al, J Family Med Prim Care. Sep-Oct 2018;7(5):893-897.
9. De Angelis CD et al,  Matern Fetal Neonatal Med. 2020 May 27;1-5. doi: 10.1080/14767058.2020.1770219. Online ahead of print.
10. Nicolaus C et al, J Ethnopharmacol. 2017 Jan 20;196:94-103.
11. Givol O et al,Wound Repair Regen 2019 Sep;27(5):548-561.
12. Saffari E et al, Women Health Nov-Dec 2017;57(10):1145-1160.