Calendula (Calendula officinalis L.)
1. Identity and Botanical Classification
Calendula officinalis Linn., known as pot marigold, is a plant that belongs to the Asteraceae family. The genus Calendula encompasses about 15–20 species of annual and perennial herbaceous plants in the daisy family, Asteraceae, native to Europe, North Africa, Macaronesia, West Asia, and the Western Himalayas, with their center of diversity in the Mediterranean region.
C. officinalis is the most commonly cultivated and used species; popular herbal and cosmetic products named "Calendula" invariably derive from it. It is native to Central, Eastern and Southern Europe, and commercial supplies are obtained largely from Eastern Europe and Egypt.
Nomenclature and Common Names
- Accepted botanical name: Calendula officinalis L.
- The genus name Calendula is a modern Latin diminutive of calendae, meaning "little calendar," "little clock," or possibly "little weather-glass."
- The common name "marigold," a contraction of "Mary's gold" used especially for Calendula officinalis, refers to the Virgin Mary.
- Other vernacular names include: pot marigold, English marigold, gold bloom, holligold, and marybud.
It is not the same as the plant most commonly known as a marigold in the United States, which is in the Tagetes genus. These two genera are frequently confused despite having distinct chemistry and distinct uses.
Plant Description and Used Parts
Calendula flos is an aromatic herb with light green leaves and yellow or orange oblong-spatulate petals; the plant produces curved achenes and has ligulate florets with a tube and protruding style. The World Health Organization monograph on selected medicinal plants provides a detailed description of the plant material, which includes composite flowers and dried ligulate florets. The medicinally used part is primarily the flower head, either as whole dried composite flowers or isolated ligulate (ray) florets, referred to in pharmacopeias as Calendulae flos.
Common Preparations and Dosage Forms
Calendula flowers have been used for centuries to treat a variety of clinical problems in the form of infusions, tinctures, liquid extracts, creams, and ointments. According to the ESCOP and EMA monographs, applicable dosage forms include gels, creams, liquids, ointments, solutions, and sprays. Preparations currently in use also include carophyllenic ointment (containing carotenoids extracted from the flowers) and pot marigold tincture.
The HMPC conclusions cover calendula flower preparations obtained by drying and comminuting the flowers or by putting the plant material in a solvent (such as ethanol or olive oil) to dissolve compounds and form a liquid extract; herbal medicines containing calendula flower preparations are usually available as infusions to be applied to the lining of the mouth or the skin, and in liquid and semi-solid forms to be applied to the skin.
2. Traditional and Historical Use
Ancient and Classical Antiquity
C. officinalis ranks among the oldest cultivated flowers, first described in the third century B.C.; ancient Romans and Greeks used calendula flowers in many rituals and ceremonies, to make crowns or garlands. The nickname "marigold" given to calendula derives from "Mary's Gold," referring to the use of the flowers in early Christian events.
Medieval and Early Modern Europe
The plant has been in cultivation and used for medicinal purposes only since the 12th century and has a long history of use; in the Middle Ages, calendula was used for hepatic disorders, poisoning, and cardiac tonicity. Doctors realized that the plant could stop bleeding and promote wound healing around the 18th century.
Calendula was not a major medicinal herb, but it was used in historic times for headaches, red eye, fever, and toothaches; as late as the 17th century, Nicholas Culpeper claimed calendula benefited the heart, but it was not considered an especially efficacious medicine.
Historically, calendula was known as "poor man's saffron" as it was used to color and flavor foods, specifically butter, cheese, custard, bread, cookies, soups, and rice dishes; calendula petals are also added to salads and used as a dye for fabric and hair.
Traditional Systems of Medicine
Calendula officinalis is extensively used in Homoeopathic, Unani, and Ayurvedic systems of medication as diaphoretic, analgesic, antiseptic, and anti-inflammatory agents, and used to treat gynaecological issues, gastro-intestinal disorders, inflammations of oral and pharyngeal mucosa, eye problems, skin injuries and certain burns, poor eyesight, and menstrual irregularities.
Among the traditionally documented uses, C. officinalis has been traditionally used in the treatment of various skin tumors, dermatological lesions, ulcers, swellings, and nervous disorders, as well as in almost 200 cosmetic formulations, including creams, lotions, and shampoos.
The ESCOP monograph notes that the ESCOP therapeutic tradition also references internal use of calendula flowers for the treatment of cholecystitis, cholangitis, and gastritis, as well as use as a diaphoretic. The German Commission E Monographs approve Calendula officinalis for inflammation of the mouth and pharynx (throat), wounds, and burns.
3. Key Constituents and Active Compounds
Flavonoids, triterpenoids, essential oil, and polysaccharides are the principal constituents of calendula flowers, and all groups have been shown to exhibit pharmacological activity.
Triterpenoids
The ligulate flowers are rich in triterpene alcohols, triterpene saponins, fatty acid esters, flavonoids, carotenoids, coumarins, hydrocarbons, essential oils, and fatty acids. These include oleanolic acid saponins (glucosides or glucuronides), α-amyrin, β-amyrin, lupeol, and triterpene fatty acid esters (TFAEs), of which faradiol myristate and faradiol palmitate are the most abundant.
In vivo pharmacological testing has determined that the triterpenoid fatty acid esters are responsible for the anti-inflammatory effects of calendula flowers; the lauryl, myristoyl, and palmitoyl esters of faradiol are the most prevalent, demonstrating that flower extract of C. officinalis was much more effective for treating both acute (caused by dextran and carrageenan) and chronic (caused by formalin) swelling in mice.
Flavonoids
The flower oil contains several bioactive compounds including flavonoids, mainly quercetin, isorhamnetin, and kaempferol aglycones. Flavonoids are understood to contribute to the plant's antioxidant and anti-inflammatory properties. The major constituents also include triterpene saponins (2–10%) based on oleanolic acid.
Carotenoids
Carotenoids, which are pre-eminently found in plant flowers, majorly consist of lycopene, beta carotene, lutein, flavoxanthin, and zeaxanthin; other carotenoids found in petals and pollens include luteoxanthin, neoxanthin, violaxanthin, auroxanthin, mutatoxanthin, α-cryptoxanthin, β-cryptoxanthin, and related geometrical isomers.
Essential Oil Constituents
The flower oil also contains terpenoids and terpenes (mainly bisabolol, faradiol, chamazulene, arnidiol, and esters), and polyunsaturated fatty acids, mainly calendic acid.
Other Compounds
Phytochemical screening has revealed the existence of several other groups of compounds, including coumarins, quinones, volatile oil, and amino acids.
4. Established Mechanisms of Action
Anti-Inflammatory Mechanisms
Pot marigold flower extracts stimulate fibroblast proliferation and migration; they also inhibit production of the pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumour necrosis factor-alpha (TNF-α) in response to lipopolysaccharide (LPS) in macrophages in vitro and in vivo.
Early studies observed that extracts of pot marigold, as well as triterpenoids present in those extracts, could reduce oedema in mouse ear inflammation models; further studies showed that the triterpene diols faradiol and arnidiol had more anti-oedematous activity than the less-polar Ψ-taraxasterol, taraxasterol, and their fatty acid esters.
An anti-inflammatory study on the plant extract revealed that a combination of carotenoids, flavonoids, and triterpenoids was capable of mediating acute and chronic inflammation in a mouse model via cytokine and macrophage suppression.
Wound Healing Mechanisms
The n-hexanic and ethanolic extracts from calendula flowers influence the inflammatory phase by activating the transcription factor NF-κB and by increasing the amount of the chemokine IL-8, both at the transcriptional and protein level, in human immortalized keratinocytes; the migration of keratinocytes during the new tissue formation phase was only marginally influenced in the scratch assay; however, the ethanolic extract inhibited the activity of collagenase in vitro and enhanced the amount of collagen in the supernatant of human dermal fibroblasts.
Antioxidant Mechanisms
Secondary metabolites including terpenoids, flavonoids, coumarins, quinones, essential oils, carotenoids, and amino acids exhibit anti-inflammatory, hepatoprotective, renoprotective, anti-edematous, antioxidant, antibacterial, antifungal, and immunostimulant properties.
Antimicrobial Activity
The plant is reported to present several biological activities, namely angiogenic, vascular regeneration, analgesic, antimicrobial, antioxidant, and immunomodulatory activities. The antimicrobial effects have been attributed to multiple compound classes, particularly the essential oil fraction and phenolic compounds, though most evidence remains from in vitro studies.
5. Scientific Evidence by Area of Use
5.1 Skin Inflammation and Wound Healing
Calendula officinalis flower extracts have a long-lasting tradition in ethnopharmacology, and the European Medicines Agency (EMA) has approved its lipophilic and aqueous alcoholic extracts as traditional medicinal products for the treatment of minor inflammation of the skin and as an aid in the healing of minor wounds.
A 2019 systematic review published in Wound Repair and Regeneration (Givol et al.) conducted a comprehensive analysis: searches were conducted in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus (up to April 2018) with 14 studies meeting inclusion criteria, comprising 7 animal experiments and 7 clinical trials; findings from the review on acute wound healing showed faster resolution of the inflammation phase with increased production of granulation tissue in the test groups treated with extract, and these findings were consistent in five animal studies and one randomized clinical trial; chronic wound healing studies were varied.
Two clinical control studies on venous ulcers demonstrated decreased ulcer surface area compared to controls. Two animal studies demonstrated a prophylactic effect for the administration of calendula extract prior to burn injury; however, a randomized clinical trial of patients suffering from partial to full thickness burns demonstrated no benefit for topical application of calendula extract compared to controls.
The authors of the systematic review concluded: "Calendula officinalis possesses a number of properties that are conducive to wound healing. Clinical data support several of these properties, but such evidence is weak and warrants further investigation using more rigorous clinical trials."
In the past, several clinical trials with calendula preparations have been conducted, but most often they encountered some limitations; critical points include the small number of patients, the clinical design, evaluation, and statistics.
A randomized clinical study (Buzzi et al., PMC 2021) examined the use of a standardized extract of Calendula officinalis for acute wounds of the hand and fingers in patients presenting at an emergency room: the objective was to analyze the progression and speed of the healing process by secondary intention in acute wounds of the hand and fingers using the standardized extract of Calendula officinalis (SEC), assessed by photo planimetry; control and intervention groups were formed by patients seen at the emergency room who presented acute trauma in the hand and fingers, mainly with skin loss or wounds in which primary healing was not possible.
In a clinical trial, calendula ointment was shown to speed up caesarean wound healing.
Evidence strength: Moderate for acute wound healing (supported by animal data and some clinical trials), weak-to-moderate for chronic wounds (inconsistent human trial results). The EMA and ESCOP recognize its use on the basis of traditional use rather than on the basis of sufficient clinical evidence alone.
5.2 Radiation-Induced Dermatitis (Radiodermatitis)
One of the most robust human clinical trials for calendula involves its use in preventing radiation-induced skin damage. A landmark Phase III randomized controlled trial (Pommier et al., Journal of Clinical Oncology, 2004) compared calendula ointment against trolamine (the then-standard reference topical agent) for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma: between July 1999 and June 2001, 254 patients who had been operated on for breast cancer and were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session.
The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% vs. 63%; P < 0.001) with the use of calendula than with trolamine; moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain; calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater.
A second randomized clinical trial also assessed the potential for extract to prevent acute post-radiation dermatitis, with this study finding no improvement compared to aqua gel cream. The conflicting results across trials mean that evidence in this area, though promising, remains mixed and further large-scale confirmatory research is needed.
Evidence strength: One large, well-designed Phase III RCT (n=254) found significant benefit over trolamine; one RCT found no benefit over aqua gel cream. Evidence is promising but not yet consistent across trials.
5.3 Radiation-Induced Oral Mucositis
A randomized controlled clinical study (Babaee et al., PMC 2013) evaluated calendula extract mouthwash in head-and-neck cancer patients: 40 patients with head and neck cancers under radiotherapy or concurrent chemoradiotherapy protocols were randomly assigned to receive either 2% calendula extract mouthwash or placebo (20 patients in each group); patients were treated with telecobalt radiotherapy at conventional fractionation (200 cGy/fraction, five fractions weekly, 30–35 fractions within 4–7 weeks).
Calendula mouthwash significantly decreased the intensity of oral mucositis (OM) compared to placebo at week 2 (score: 5.5 vs. 6.8, p = 0.019), week 3 (score: 8.25 vs. 10.95, p < 0.0001), and week 6 (score: 11.4 vs. 13.35, p = 0.031).
Using the World Health Organization mucositis scale, the researchers reported that only 15% of patients in the calendula group developed grade 3 mucositis, compared to 65% in the placebo group (p < 0.001). Laboratory testing supported these clinical findings: calendula extract demonstrated strong antioxidant activity, suggesting that its protective effects may stem from reducing oxidative stress and inflammation in oral tissues exposed to radiation; no adverse effects from calendula were reported.
Evidence strength: Positive results from one small RCT (n=40); the small sample size limits definitive conclusions. Further confirmatory trials are needed.
5.4 Oral Health: Anti-Plaque and Anti-Gingivitis
In a clinical study, 240 subjects were randomly assigned into two groups (test group n=120, control group n=120); all test group patients were advised to dilute 2 ml of tincture of calendula with 6 ml of distilled water and rinse their mouths once in the morning and once in the evening for six months. This study found that the calendula-based preparation was more effective at controlling plaque and had a more pleasing taste than the chlorhexidine comparator.
Evidence strength: Preliminary; single study; further replication required before firm conclusions can be drawn.
5.5 Diaper Dermatitis
A randomized comparative trial (Panahi et al., The Scientific World Journal, 2012; PMID: 22606064) compared topical aloe vera to calendula officinalis cream in children with diaper dermatitis. This trial is frequently cited in systematic reviews of calendula's topical uses, though its sample size and the limited number of follow-up studies again constrain broader conclusions.
Evidence strength: Preliminary; single pediatric RCT; evidence insufficient for firm recommendations.
5.6 Antimicrobial and Antifungal Activity
Being rich in secondary metabolites, C. officinalis has been proven to have antibacterial and antifungal activities. However, the large majority of antimicrobial evidence comes from in vitro laboratory studies rather than clinical trials in human subjects. These chemical constituents also confer anti-helminthic and antiviral activities.
Evidence strength: Predominantly in vitro; no robust human clinical evidence for infectious diseases as a primary indication.
5.7 Antioxidant and Hepatoprotective Activity
Animal and in vitro studies have examined calendula's potential for hepatoprotection. One study was conducted to evaluate the total phenolic compounds, the antioxidant properties, and the hepatorenoprotective potential of Calendula officinalis extract against aflatoxin-induced liver damage in rats; six groups of male Sprague-Dawley rats were treated for 6 weeks with the control, aflatoxin-contaminated diet (2.5 mg/kg diet), or groups treated orally with calendula extract at low and high doses (500 and 1000 mg/kg body weight). These results are animal-based and cannot be extrapolated directly to human use.
Evidence strength: Animal/in vitro only; no controlled human clinical trials confirming hepatoprotective effects in humans.
5.8 Anticancer Activity
Human clinical trials have been used to assess the effectiveness of calendula in breast cancer patients, primarily in the context of managing treatment-related side effects (radiodermatitis) rather than as a direct anticancer agent. In vitro, the plant has been observed to have cytotoxic effects on tumor cell lines, and anticancer activity in vivo in animal models. No clinical trials have established calendula as an effective treatment for cancer itself.
Evidence strength: In vitro and animal studies show cytotoxic properties; clinical use in oncology is limited to managing radiation side effects. No human evidence supports an anti-tumor claim.
6. Body Systems and Health Areas
- Integumentary system (skin): The primary therapeutic indications recognized by ESCOP are minor inflammations of the skin and mucosa, and as an aid to the healing of minor wounds.
- Oral mucosa and oropharynx: The Committee on Herbal Medicinal Products (HMPC) of the EMA recommends using calendula flower medicines for skin inflammations, minor wounds, and mouth or throat inflammation based on their traditional use.
- Gastrointestinal system: Traditional use for stomach and duodenal ulcers, gastritis, and promotion of bile secretion; no current human clinical trial data to support efficacy.
- Gynecological system: Traditional use includes treatment of gynaecological issues and menstrual irregularities.
- Immune system: Polysaccharides extracted from C. officinalis have been studied for immunostimulant activity in preclinical models.
- Musculoskeletal system: Calendula is one of the constituents of the proprietary homoeopathic medicine Traumeel®, used for treating the symptoms associated with acute musculoskeletal injuries including pain and swelling.
- Ear (otological): Otikon otic solution and naturopathic herbal extract ear drops solution, ear drop formulations of naturopathic origin containing calendula flowers, have been reported to be effective for the management of otalgia associated with acute otitis media in children.
7. Dosage Forms and Reported Dosages
The following dosages are drawn from official monograph sources and clinical study protocols. They are reported for reference purposes and reflect ranges documented in published studies and regulatory documents.
Topical Use (as reported in EMA Assessment Report)
- For treatment of minor skin inflammations: in impregnated dressing, use diluted 1:3 with water, 30–60 minutes, 2–4 times per day.
- The DAC (German Drug Codex) references a liquid extract at a concentration equivalent to 4–10% herbal substance in semi-solid preparations; dosage is in semi-solid preparation at concentration equivalent to 4–10% herbal substance.
- Ointments containing liquid extract in a concentration of 10% have been on the Austrian market for more than 30 years, and at 4% concentration on the German market.
- Applicable dosage forms for topical application include infusion or tincture of 1–2 g/150 mL for topical application, a 40% alcohol extract for external use, and a 2–5% ointment for treatment of wounds and compresses.
Oromucosal Use (as reported in EMA Assessment Report)
- For oromucosal use: 2–3 g dried flower as an infusion in 150 ml water; liquid extract 1:1 in ethanol 40%, 0.5–1 ml; tincture 1:5 in 90% ethanol, 0.3–1.2 ml.
- The ESCOP monograph (2003) references infusion for cutaneous application: 1–2 g dried flower per 150 ml water.
Dosages in Specific Clinical Trials
- Oral mucositis trial (Babaee et al.): A 2% calendula extract mouthwash was used; 20 patients per group, rinsing throughout the radiotherapy course.
- Anti-plaque/gingivitis trial: Test group patients diluted 2 ml of calendula tincture with 6 ml of distilled water and rinsed their mouths once in the morning and once in the evening for six months.
8. Safety Considerations and Interactions
General Tolerability
Despite the widespread use of calendula preparations, there are few reports describing serious reactions. The dried flowers have been used as a spice and are considered to be generally recognized as safe.
Allergic Reactions and Contact Sensitization
Allergic reactions, contact sensitization, and one case of anaphylaxis have been reported. The exact allergens present in Calendula officinalis are unknown, but the flowers reportedly contain a variety of phenolic acids and phenylpropanoids that have elicited contact dermatitis; anecdotal case reports of accidental exposure/sensitization and experimental studies provide sufficient evidence to confirm the causal relationship between contact dermatitis and Calendula officinalis.
Because calendula belongs to the Asteraceae (Compositae) family, cross-reactivity with other Asteraceae species (such as ragweed, chrysanthemums, and arnica) is a documented concern. Even though it is not considered toxic, adequate safety data for use in children do not exist; pediatric use of these extracts should be very careful, especially in subjects allergic to Asteraceae.
A Reported Pediatric Case
A case of a 12-year-old girl presenting at hospital for an acute bilateral periocular erythema and eczema after two days of Calendula officinalis compresses on the eyes for treatment of an episode of conjunctivitis has been described in the medical literature.
Pregnancy and Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking; in a study in rats, a hydroalcoholic extract of C. officinalis did not demonstrate toxic effects on male fertility or during the early and mid-pregnancy periods in females; however, during the fetal period of pregnancy (after the 10th week), a reduction in maternal weight gain was noted in rats receiving the extract.
Toxicological Data
In two clinical studies of patients with bacterial vaginosis or vaginal candidiasis, itching was reported more frequently with vaginally applied calendula cream than with comparator creams; saponin extracts of C. officinalis are not mutagenic; the median lethal dose of calendula flower extract in rats was more than 4.64 g/kg.
Although data on dermal irritation and sensitization are available, the risk of subchronic systemic toxicity following dermal application of Calendula officinalis preparations has not been fully evaluated.
Drug Interactions
Formally documented pharmacokinetic or pharmacodynamic drug–drug interactions with calendula are not well established in the scientific literature. No drug interactions are well documented. Theoretical concern has been raised about potential additive sedative effects if calendula is taken orally alongside sedative medications, based on observed sedative and hypotensive properties of some preparations in early pharmacological studies.
Cosmetic Safety Assessment
Calendula officinalis extract is reported to be used in almost 200 cosmetic formulations, over a wide range of product categories. The Cosmetic Ingredient Review Expert Panel published an amended safety assessment of Calendula officinalis-derived cosmetic ingredients (International Journal of Toxicology, 2010), finding the ingredient safe for cosmetic use at the concentrations evaluated. In cosmetic products, calendula is used in formulations for sensitive skin and soothing products, among a variety of presentations, including skin, eye, hair, and bath products, with recognized safety for use in cosmetics.
9. Regulatory Status
The European Union herbal monograph on Calendula officinalis L., flos stipulates that, to obtain a licence for calendula flower medicines, national authorities must assess an application and consider the HMPC's scientific conclusions. The British Herbal Pharmacopoeia also contains indications for calendula's use as a herbal medicine, including swollen or inflamed lymphatic nodes, sebaceous cysts, duodenal ulcers, and acute and chronic inflammatory skin lesions. The German Commission E, ESCOP (2019 monograph), WHO, and the EMA HMPC all provide monographs for Calendulae flos. The EMA classification is as a "traditional herbal medicinal product," reflecting documented traditional use rather than established clinical efficacy according to the standards required for conventional medicines.
References
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