ArticlePDF Available

Marigold (Calendula officinalis L.)

  • Battelle; Centers for Disease Control and Prevention


Content may be subject to copyright.
Catherine Ulbricht, PharmD, MBA(C), Column Editor
Marigold (Calendula officinalis L.):
An Evidence-Based Systematic
Review by the Natural Standard
Research Collaboration
Ethan Basch, MD, MPhil
Steve Bent, MD
Ivo Foppa, MD, ScD
Sadaf Haskmi, MD, MPH
David Kroll, PhD
Michelle Mele, PharmD
Philippe Szapary, MD
Catherine Ulbricht, PharmD
Mamta Vora, PharmD
Sophanna Yong, PharmD
for the Natural Standard Research Collaboration
Ethan Basch is affiliated with Memorial Sloan-Kettering Cancer Center. Steve Bent
is affiliated with the University of California, San Francisco. Ivo Foppa is affiliated
with the University of South Carolina. Sadaf Haskmi is affiliated with Harvard School
of Public Health. David Kroll is affiliated with Duke University. Michelle Mele is affil
iated with Northeastern University. Philippe Szapary is affiliated with the University
of Pennsylvania. Catherine Ulbricht is affiliated with Massachusetts General Hospital.
Mamta Vora is affiliated with Northeastern University. Sophanna Yong is affiliated with
Massachusetts College of Pharmacy and Health Sciences.
Natural Standard Review ( Copyright © 2006. Re
printed with permission.
Journal of Herbal Pharmacotherapy, Vol. 6(3/4) 2006
Available online at
doi:10.1300/J157v06n03_08 135
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
ABSTRACT. An evidence-based systematic review including written
and statistical analysis of scientific literature, expert opinion, folkloric
precedent, history, pharmacology, kinetics/dynamics, interactions, ad
verse effects, toxicology and dosing.
KEYWORDS. Calendula officinalis L., death-flower, marigold, scotch
marigold, summer’s bride
Search Strategy
To prepare each Natural Standard, electronic searches are conducted
in nine databases, including AMED, CANCERLIT, CINAHL,
CISCOM, the Cochrane Library, EMBASE, HerbMed, International
Pharmaceutical Abstracts, Medline, and NAPRALERT. Search terms
include the common name(s), scientific name(s), and all listed syn-
onyms for each topic. Hand searches are conducted of 20 additional
journals (not indexed in common databases), and of bibliographies
from 50 selected secondary references. No restrictions are placed on
language or quality of publications. Researchers in the field of comple-
mentary and alternative medicine (CAM) are consulted for access to
additional references or ongoing research.
Selection Criteria
All literature is collected pertaining to efficacy in humans (regardless
of study design, quality, or language), dosing, precautions, adverse ef
fects, use in pregnancy/lactation, interactions, alteration of laboratory
assays, and mechanism of action (in vitro, animal research, human data).
Standardized inclusion/exclusion criteria are utilized for selection.
Data Analysis
Data extraction and analysis are performed by health care profes
sionals conducting clinical work and/or research at academic centers,
using standardized instruments that pertain to each review section (de
fining inclusion/exclusion criteria and analytic techniques, including
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
validated measures of study quality). Data are verified by a second re
Review Process
A Blinded review is conducted by multidisciplinary research-clinical
faculty at major academic centers with expertise in epidemiology and
biostatistics, pharmacology, toxicology, complementary and alternative
medicine (CAM) research, and clinical practice. In cases of editorial dis
agreement, a three-member panel of the Editorial Board addresses con
flicts, and consults experts when applicable. Authors of studies are
contacted when clarification is required.
Update Process
Natural Standard regularly monitors scientific literature and industry
warnings. When clinically relevant new data emerge, best efforts are
made to update content immediately. In addition, regular updates with
renewed searches occur every 3-18 months, variable by topic.
Synonyms/Common Names/Related Substances
Asteraceae (family), Bride of the Sun, bull flower, butterwort,
Caltha officinalis, Calendula arvensis L., calendulae flos, calen
dula flower, Calendulae herba, calendula herb, calypso orange
florensis, claveton (Spanish), Compositae (family), cowbloom,
death-flower, drunkard gold, Fiesta gitana Gelb, fior d’ogni (Ital
ian), flaminquillo (Spanish), fleurs de tous les mois (French),
gauche-fer (French), gold bloom, Goldblume (German), golden
flower of Mary, goulans, gouls, holligold, holygold, husband’s
dial, kingscup, maravilla, marybud, marigold, marygold, may or
Natural Standard Review 137
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
ange florensis, poet’s marigold, pot marigold, Mejorana (Span
ish), publican and sinner, Ringelblume (German), ruddles, Scotch
marigold, shining herb, solsequia, souci (French), souci des champs
(French), souci des jardins (French), Summer’s Bride, sun’s bride,
water dragon, yolk of egg. (Note: Not to be confused with the com
mon garden or French marigold (Tagetes spp.), African marigold
(T. erecta), or Inca marigold (T. minuta). Combination products:
Brief Background
Calendula (Calendula officinalis), also known as marigold, has
been widely used topically to treat minor skin wounds, skin infec-
tions, burns, bee stings, sunburn, warts and cancer. Most scientific
evidence regarding its efficacy as a wound-healing agent is based
on animal and in vitro studies.
Preliminary evidence suggesting efficacy of topical calendula oint-
ment in the prevention of dermatitis related to radiation therapy is
reported in one open phase III trial (randomized, non-blinded,
comparison; no placebo arm), conducted in breast cancer patients.
Grades reflect the level of available scientific evidence in support
of the efficacy of a given therapy for a specific indication (Table 1).
Expert opinion and folkloric precedent are not included in this as-
sessment, and are reflected in a separate section of each review
(“Strength of Expert Opinion and Historic/Folkloric Precedent”).
Evidence of harm is considered separately; the below grades apply
only to evidence of benefit (Table 2).
Historical or Theoretical Indications
Which Lack Sufficient Evidence
Abscesses, acne, amenorrhea, analgesia, anemia, antibacterial,
antifungal, anti-inflammatory,
anti-viral, anxiety,
appetite stimulant, atherosclerosis, athlete’s foot, bacterial infec
tions, benign prostatic hypertrophy, bladder irritation, blood puri
fication, blood clots, bowel irritation, bruises, burns, cardiac
disease, cholera, circulation, colitis,
tion, cosmetic, cough, cramps, diaper rash, dizziness, diuresis,
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
dystrophic nervous disturbances, eczema, edema, epididymitis,
epistaxis, eye inflammation, fatigue, fever, frostbite, gastrointesti-
nal tract disorders, gastritis, gingivitis,
gout, headache, heart dis-
ease, hemorrhoids, herpes simplex,
herpes keratitis,
indigestion, immunostimulant,
, insomnia, jaundice,
liver cancer, liver-gallbladder function stimulator, menstrual pe-
riod abnormalities, metabolic disorders, mouth and throat infec-
tions, muscular atrophy, nausea, nosebleed, pain, peptic ulcer
periodontal prophylaxis,
proctitis, prostatitis, purging
agent, skin cancer, sore throat, spasms, spleen disorders, stomach
ulcers, stones, syphilis, thrombophlebitis, tinnitus, toothache, tu-
berculosis, ulcerative colitis, urinary retention, uterine tonic, vari-
cose ulcers,
warts, yeast infections.
Expert Opinion and Folkloric Precedent
Traditionally, calendula has been used topically for treating minor
wounds, burns and other skin problems. Multiple references are
made to calendula as a wound-healing aid and topical anti-infec
tive agent. However, no strong scientific evidence supports these
Powder from the plant’s petals is occasionally used as an inexpen
sive alternative to saffron for coloring and flavoring foods.
Brief Safety Summary
Insufficient data are available to support the safety of these ingre
dients in medicinal or cosmetic formulations.
Natural Standard Review 139
Indication Evidence Grade
Radiation dermatitis
Otitis media
Skin inflammation
Wound healing
TABLE 1. Quality of scientific evidence
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
TABLE 2. Natural Standard Evidence-based validated grading rationale™
Level of Evidence Grade Criteria
A (Strong Scientific Evidence)
Statistically significant evidence of benefit
from 2 properly randomized trials (RCTs),
OR evidence from one properly conducted
RCT AND one properly conducted
meta-analysis, OR evidence from multiple
RCTs with a clear majority of the properly
conducted trials showing statistically
significant evidence of benefit AND with
supporting evidence in basic science,
animal studies, or theory.
B (Good Scientific Evidence)
Statistically significant evidence of benefit
from 1-2 properly randomized trials, OR
evidence of benefit from 1 properly
conducted meta-analysis OR evidence of
benefit from 1 cohort/case-control/
non-randomized trials AND with supporting
evidence in basic science, animal studies,
or theory.
C (Unclear or Conflicting Scientific Evidence)
Evidence of benefit from 1 small RCT(s)
without adequate size, power, statistical
significance, or quality of design by
objective criteria,* OR conflicting evidence
from multiple RCTs without a clear majority
of the properly conducted trials showing
evidence of benefit or ineffectiveness, OR
evidence of benefit from 1 cohort/
case-control/non-randomized trials AND
without supporting evidence in basic
science, animal studies, or theory, OR
evidence of efficacy only from basic
science, animal studies, or theory.
D (Fair Negative Scientific Evidence)
Statistically significant negative evidence
(that is, lack of evidence of benefit) from
cohort/case-control/non-randomized trials,
AND evidence in basic science, animal
studies, or theory suggesting a lack of
F (Strong Negative Scientific Evidence)
Statistically significant negative evidence
(that is, lack of evidence of benefit) from 1
properly randomized adequately powered
trial(s) of high-quality design by objective
Lack of Evidence Unable to evaluate efficacy due to lack of
adequate available human data.
* Objective criteria are derived from
validated instruments for evaluating study quality
, including the 5-point
scale developed by Jadad et al. in which a score below 4 is considered to indicate lesser quality methodologi
cally (
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the
quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clinical Trials 1996;
Listed separately in reviews in the “Historical or Theoretical Uses which Lack Sufficient Evidence” section.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Recommended doses are based on those most commonly used in
available trials, or on historical practice. However, with natural
products it is often not clear what the optimal doses are to balance
efficacy and safety. Preparation of products may vary from manu
facturer to manufacturer, and from batch to batch within one
manufacturer. Because it is often not clear what are the active com
ponents of a product, standardization may not be possible, and the
clinical effects of different brands may not be comparable.
Insufficient evidence available.
Adult Dosing (18 Years and Older)
According to expert panels, the German Commission E and the
European Scientific Cooperative on Phytotherapy, 2-5% ointment
is often used. Topical preparations may be applied 3-4 times daily
as needed. According to these sources, a 1:1 tincture in 40% alco-
hol or 1:5 in 90% alcohol may be diluted at least 1:3 with freshly
boiled water for compresses.
Otic (Ear Drops)
5 drops of Otikon Otic® Solution, instilled into affected ear three
times a day has been used.
5 drops of NHED® solution (which contains garlic [Allium
sativum], Verbascum thapsus, Calendula flores, St. John’s wort
[Hypericum perfoliatum], lavender [Lavandula angustifolia], and
vitamin E in olive oil) has been instilled into affected ears three
times daily in one study.
Children (Younger Than 18 Years)
Insufficient evidence to recommend.
Natural Standard Review 141
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
In vitro, some calendula saponins have cytotoxic properties.
Genotoxicity has been described from calendula extract.
relevance of these findings is unclear.
of 375 mg/kg and a LD
of 580 mg/kg has been deter
mined in mice by intravenous and intraperitoneal administration of
aqueous extracts. In hydro-alcoholic extracts a LD
of 45mg/
mouse (sub-cutaneous) and LD
of 526 mg/100 g in rats (intrave
nous) has been reported.
Calendula officinalis extract is reported to be used in almost 200
cosmetic formulations, over a wide range of product categories.
Acute toxicity studies in rats and mice suggest that the extract is
relatively nontoxic. Animal tests have demonstrated minimal skin
irritation, and no sensitization or phototoxicity. Minimal ocular
irritation was seen with one formulation and no irritation with
others. Six saponins isolated from C. officinalis flowers were not
mutagenic in an Ames test, and a tea derived from C. officinalis
was not genotoxic in Drosophila melanogaster. Clinical testing of
cosmetic formulations containing the extract elicited little irrita-
tion or sensitization. Published accounts assert that until more data
are available, there is insufficient evidence to support the safety of
these ingredients in cosmetic formulations.
Known allergy/hypersensitivity to members of the Aster/Compo
sitae family such as ragweed, chrysanthemums, marigolds and
Anaphylactic shock after gargling with a calendula infu
sion has been reported, and one patient had a positive skin patch-
test to calendula 10% tincture.
Reider et al. tested 443 consecutive patients with Compositae mix,
sesquiterpene lactone mix, arnica, calendula, and propolis.
subjects (1.13%) reacted to arnica, and 9 (2.03%) to calendula.
The Compositae mix elicited a reaction in 18 cases (approximately
4.06%). Sensitization to arnica and calendula was often accompa
nied by reactions to nickel, Myroxylon Pereirae resin, propolis,
and colophonium.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
A case report exists of a 35-year-old woman who experienced
recalcitrant atopic dermatitis with a positive patch-test reaction to
Compositae mix.
Initially, sensitization appeared to be due to her
past use of calendula, although it was later determined that her diet
consisted largely of food products of the Compositae family,
which may cross-react. Her skin condition improved quickly upon
exclusion of these food products.
Adverse Effects/Post Market Surveillance
There is limited evidence other than reports of hypersensitivity re
actions. In one small animal study, calendula was associated with a
fatal reduction in blood glucose, accompanied by decreased serum
lipids and protein. Skin and eye irritation have been reported.
Use cautiously in patients with allergy/hypersensitivity to mem-
bers of the Aster/Compositae family.
Pregnancy and Lactation
In vitro, calendula has exhibited moderate “uterotonic” effects in
isolated rabbit and guinea pig uterine tissues.
Anecdotal reports
indicate that calendula may possess spermatocide and abortifacient
Use during pregnancy and lactation has not been shown
safe, and systemic effects from topical use are not clear.
Calendula/Drug Interactions
Sedative Drugs: In early animal studies, high doses of ingested ca
lendula preparations were reported to act as sedatives.
combination use with sedative agents may lead to additive effects.
In rats, calendula was shown to increase hexobarbital sleeping
Systemic effects after topical use of calendula in humans is
not clear.
Antihypertensive Drugs: In early animal studies, high doses of
calendula preparations were reported to possess hypotensive ef
Natural Standard Review 143
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Therefore, combination use with hypotensive agents may
lead to additive effects. Systemic effects after topical use of calen
dula in humans is not clear.
Hypoglycemic Drugs: Calendula may increase the activity of hypo
glycemic medications or insulin.
Cholesterol-Lowering Drugs: Calendula may have an additive ef
fect with agents that decrease lipids and triglycerides.
Calendula/Herb/Supplement Interactions
Sedative Herbs and Supplements: In early animal studies, high
doses of ingested calendula preparations were reported to act as
Therefore, combination use with sedative agents may
lead to additive effects. In rats, calendula was shown to increase
hexobarbital sleeping time.
Systemic effects after topical use of
calendula in humans is not clear.
Hypotensive Herbs: In early animal studies, high doses of calen-
dula preparations were reported to possess hypotensive effects.
Therefore, combination use with hypotensive agents may lead to
additive effects. Systemic effects after topical use of calendula in
humans is not clear.
Hypoglycemic Herbs and Supplements: Calendula may increase
the activity of hypoglycemic agents.
Cholesterol-Lowering Herbs and Supplements: Agents that de-
crease lipids and triglycerides may have additive effects with ca-
Lutein and Beta-Carotene: Since the stem and leaves of calendula
contain lutein and beta-carotene, a possible supplement interaction
exists with products that contain these ingredients.
Constituents: The principal identified constituents of calendula are
triterpenoids and flavonoids,
with at least eight bioactive
triterpendiol monoesters identified in the extracts of dried calendula
flowers: faradiol-3-O-palmitate, faradiol-3-O-myristate, faradiol-
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
3-O-laurate, arnidiol-3-O-palmitate, arnidiol-3-O-myristate, arnidiol-
3-O-laurate, calenduladiol-3-O-palmitate, and calenduladiol-3-O-
Various pharmacological properties have been attrib
uted in preclinical research to various constituents, including
anti-inflammatory, immuno-stimulating, anti-bacterial, anti-viral,
anti-protozoal, and anti-neoplastic. The mechanisms underlying
these possible effects are poorly understood. Hypoglycemic, gas
tric emptying inhibitory, and gastroprotective properties have
been attributed to calendasaponins A, B, C, and D; two additional
ionone glucosides (officinosides A and B), and two sesquiterpene
oligoglycosides (officinosides C and D), have been isolated from
the flowers of Egyptian Calendula officinalis.
Two homologous
cDNAs, CoFad2 and CoFac2, were isolated from a Calendula
officinalis developing seed by polymerase chain reaction.
sequences share similarity to FAD2 desaturases and FAD2-related
enzymes. In C. officinalis plants, CoFad2 was expressed in all tis-
sues tested, whereas CoFac2 expression was specific to develop-
ing seeds. Expression of CoFad2 cDNA in yeast (Saccharomyces
cerevisiae) indicated it encodes a Delta12 desaturase that intro-
duces a double bond at the 12 position of 16:1(9Z) and 18:1(9Z).
Expression of CoFac2 in yeast revealed that the encoded enzyme
acts as a fatty acid conjugase converting 18:2(9Z, 12Z) to calendic
acid 18:3(8E, 10E, 12Z). The enzyme also has weak activity on the
mono-unsaturates 16:1(9Z) and 18:1(9Z) producing compounds
with the properties of 8,10 conjugated dienes.
Anti-Inflammatory Effects: The active components of calendula’s
anti-inflammatory activity are thought to be the triterpenoids, par
ticularly faradiol monoester. Free ester faradiol is the most active
and exhibits the same effects as an equimolar dose of indometha
Calendula’s glycosides have also inhibited lipoxygen
ase activity in vitro.
Wound Healing Effects: Rao et al. observed a reduction of epi
thelization time, an increase in wound strength, and improvement
of wound contraction in rats with experimental incision wounds
that were topically treated with calendula.
Effects may also be
mediated by stimulation of phagocytosis and increased granula
and via effects on metabolism of glycoproteins, nucleo
proteins, and collagen proteins in tissue regeneration.
Anti-Viral Effects: Anti-HIV activity of calendula has been dem
onstrated in vitro,
specifically involving inhibition of HIV-1
(IIIB) induced cytopathogenicity in CD4 lymphocytic Molt-4
Natural Standard Review 145
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
clone 8 cells. Triterpenoid saponins from Calendula arvensis have
inhibited multiplication of vesicular stomatitis virus and rhinovirus
in vitro.
Anti-Bacterial Effects: Hydroacetonic extract from fresh plants in
hibits the growth of Staphylococcus aureus at a concentration of
1mg/mL in vitro.
Calendula extract was tested on biofilms of
infant dentifrices and did not demonstrate antimicrobial effects
against A. viscosus, C. albicans, L. casei, S. mitis, S. mutans, S.
oralis, S. sanguis, S. sobrinus.
Anti-Protozoal Effects: Oxygenated terpene alcohols and terpene
lactones from calendula have been observed to possess tricho
monacidal activity.
Anti-Proliferative Effects: In a mouse model, dietary lutein de
rived from calendula extract has been found to suppress mammary
tumor growth, increase tumor latency, and enhance lymphocyte
Saponins isolated from calendula express in vitro
antimutagenic and tumor cell cytotoxic activity.
C. officinalis
does not exert a direct mitogenic effect on human lymphocytes in
vitro, and exhibits inhibitory effects on lymphocyte proliferation.
A preparation of several herbs (Calendula officinalis, Echinacea
purpurea, Scorzonera humilis, Aconitum moldavicum) has been
associated with “normalization” of pathologic enzyme activity by
rat hepatocytes affected by carcinoma.
Other Effects: In vitro, calendula exhibited moderate “uterotonic”
effects in isolated rabbit and guinea pig uterine tissues.
In early
(1964) animal studies, high doses of calendula preparations were
reported to act as sedatives and hypotensive agents.
Insufficient available evidence.
Calendula (Calendula officinalis L.), commonly known as mari
gold, is an annual flower in the daisy family that grows to a height
of 12-18 inches and is native to Asia and southern Europe. Calen
dula has been cultivated for centuries in ornamental gardens,
where it readily grows in poor soils.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Calendula has been used medicinally since the 12th century
throughout central Europe and the Mediterranean. The name ca
lendula is derived from the Latin word “calends” meaning the first
day of each month, when the flowers bloom. Calendula has also
been called the “herb of the sun,” because it’s flowers bloom in the
morning and close in the evening. According to Greek mythology,
calendula was named after four wood nymphs that fell in love with
Refers to the medical condition or disease targeted by a therapy.
Study Design
Common Types Include
Randomized Controlled Trial (RCT): An experimental trial in
which participants are assigned randomly to receive either an in-
tervention being tested or placebo. Note that Natural Standard de-
fines RCTs as being placebo-controlled, while studies using active
controls are classified as equivalence trials (See the following para-
graph). In RCTs, participants and researchers are often blinded
(that is, unaware of group assignments), although unblinded and
quasi-blinded RCTs are also often performed. True random alloca-
tion to trial arms, proper blinding, and sufficient sample size are
the basis for an adequate RCT.
Equivalence Trial: An RCT which compares two active agents.
Equivalence trials often compare new treatments to usual (stan
dard) care, and may not include a placebo arm.
Before and After Comparison: A study that reports only the change
in outcome in each group of a study, and does not report between-
group comparisons. This is a common error in studies that claim to
be RCTs.
Case Series: A description of a group of patients with a condition,
treatment, or outcome (for example, 20 patients with migraine head
ache underwent acupuncture and 17 reported feeling better after
wards). Case series are considered weak evidence of efficacy.
Case-Control Study: A study in which patients with a certain out
come are selected and compared to similar patients (without the
outcome) to see if certain risk factors/predictors are more common
Natural Standard Review 147
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
in patients with that outcome. This study design is not common in
the complementary and alternative medicine literature.
Cohort Study: A study which assembles a group of patients with
certain baseline characteristics (for example, use of a drug), and
follows them forward in time for outcomes. This study design is
not common in the complementary and alternative medicine litera
Meta-Analysis: A pooling of multiple trials to increase statistical
power (often used to pool data from a number of RCTs with small
sample sizes, none which demonstrates significance alone but in
aggregate can achieve significance). Multiple difficulties are en
countered when designing/reviewing these analyses; in particular,
outcomes measures or therapies may differ from study to study,
hindering direct comparison.
Review: An author’s description of his or her opinion based on per-
sonal, non-systematic review of the evidence.
Systematic Review: A review conducted according to pre-speci-
fied criteria in an attempt to limit bias from the investigators. Sys-
tematic reviews often include a meta-analysis of data from the
included studies.
P: Pending verification.
Author, Year
Identifies the study being described in a row of the table.
The total number of subjects included in a study (treatment group
plus placebo group). Some studies recruit a larger number of subjects
initially, but do not use them all because they do not meet the study’s en
try criteria. In this case, it is the second, smaller number that qualifies as
N. N includes all subjects that are part of a study at the start date, even if
they drop out, are lost to follow-up, or are deemed unsuitable for analy
sis by the authors. Trials with a large number of drop-outs that are not
included in the analysis are considered to be weaker evidence for effi
cacy. (For systematic reviews the number of studies included is re
ported. For meta-analyses, the number of total subjects included in the
analysis or the number of studies may be reported.) P = Pending
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Statistically Significant
Results are noted as being statistically significant if a study’s authors re
port statistical significance, or if quantitative evidence of significance is
present (such as p values). P = Pending verification.
Quality of Study
A numerical score between 0-5 is assigned as a rough measure of
study design/reporting quality (0 being weakest and 5 being strongest).
This number is based on a well-established, validated scale developed
by Jadad et al. (Jadad AR, Moore RA, Carroll D, et al. Assessing the
quality of reports of randomized clinical trials: is blinding necessary?
Controlled Clinical Trials 1996;17[1]:1-12). This calculation does not
account for all study elements that may be used to assess quality (other
aspects of study design/reporting are addressed in the “Evidence Dis-
cussion” sections of reviews).
A Jadad score is calculated using the seven items in the table. The
first five items are indications of good quality, and each counts as
one point towards an overall quality score. The final two items in-
dicate poor quality, and a point is subtracted for each if its criteria
met. The range of possible scores is 0 to 5.
Natural Standard Review 149
Jadad Score Calculation
Item Score
Was the study described as randomized (This includes words such
as randomly, random, and randomization)?
Was the method used to generate the sequence of randomization described
and appropriate (Table of random numbers and computer-generated, etc.)?
Was the study described as double blind? 0/1
Was the method of double blinding described and appropriate
(Identical placebo, active placebo, dummy, etc.)?
Was there a description of withdrawals and dropouts? 0/1
Deduct one point if the method used to generate the sequence of
randomization was described and it was inappropriate (patients were
allocated alternately, or according to date of birth, and hospital number, etc.).
Deduct one point if the study was described as double blind but the
method of blinding was inappropriate (for example, comparison
of tablet vs. injection with no double dummy).
P = Pending verification.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Magnitude of Benefit
This summarizes how strong a benefit is: small, medium, large, or
none. If results are not statistically significant “NA” for “not applica
ble” is entered. In order to be consistent in defining small, medium, and
large benefits across different studies and reviews, Natural Standard de
fines the magnitude of benefit in terms of the standard deviation (SD) of
the outcome measure. Specifically, the benefit is considered:
Large: if >1 SD
Medium: if 0.5 to 0.9 SD
Small: if 0.2 to 0.4 SD
In many cases, studies do not report the standard deviation of change
of the outcome measure. However, the change in the standard deviation
of the outcome measure (also known as effect size) can be calculated,
and is derived by subtracting the mean (or mean difference) in the pla-
cebo/control group from the mean (or mean difference) in the treatment
group, and dividing that quantity by the pooled standard deviation
(Effect size = [Mean Treatment – Mean Placebo]/SDp).
Absolute Risk Reduction
This describes the difference between the percent of people in the
control/placebo group experiencing a specific outcome (control event
rate), and the percent of people in the experimental/therapy group expe
riencing that same outcome (experimental event rate). Mathematically,
Absolute Risk Reduction (ARR) equals experimental event rate minus
control event rate. ARR is better able to discriminate between large and
small treatment effects than relative risk reduction (RRR), a calculation
that is often cited in studies ([control event rate experimental event
rate]/control event rate). Many studies do not include adequate data to
calculate the ARR, in which cases “NA” is entered into this column.
P = pending verification.
Number Needed to Treat
This is the number of patients who would need to use the therapy un
der investigation, for the period of time described in the study, in order
for one person to experience the specified benefit. It is calculated by di
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
viding the Absolute Risk Reduction into 1 (1/ARR). P = pending
When appropriate, this brief section may comment on design flaws
(inadequately described subjects, lack of blinding, brief follow-up, not
intention-to treat), notable study design elements (crossover), dosing,
and/or specifics of study group/sub-groups (age, gender). More detailed
description of studies is found in the “Evidence Discussion” section that
follows the “Evidence Table” in Natural Standard reviews.
Radiation Dermatitis
Summary: Evidence from one open phase III trial suggests that
topical calendula may be beneficial for the prevention of dermati-
tis pain and erythema during radiation therapy, and may be worth
trying in patients who experience radiation dermatitis that is not
responsive to other agents. However, due to methodological limi-
tations, these results can only be considered preliminary. Addi-
tional evaluation in a double-blind placebo controlled trial is
necessary before a firm conclusion can be reached.
Evidence: An open phase III trial was conducted in 254 women re-
ceiving radiation therapy to the breast at a cancer center in Lyon,
Patients were randomly assigned to use a topical oint
ment consisting of either a Calendula officinalis extract in petro
leum jelly (Pommade au Calendula par Digestion; Boiron Ltd.,
Levallois-Perrte, France) or trolamine, a non-steroid sometimes
used for radiation dermatitis prevention (with unclear efficacy).
Patients were instructed to use their assigned ointment at least
twice daily starting on the day of radiation, continuing until the
completion of therapy. Those with greater amounts of pain or
redness (erythema) used more frequent dosing. Overall, fewer pa
tients reported grade 2-3 skin toxicity with calendula versus trol
amine, using the well-established criteria developed by RTOG
(Radiation Therapy Oncology Group): 41% versus 63% respec
tively (p < 0.001). This corresponded to an ARR of 22% and num
ber needed to treat (NNT) of approximately five patients, meaning
Natural Standard Review 151
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
that five patients would need to be treated in order to see reduced
toxicity in one patient. No allergic reactions occurred with calen
dula. However, using calendula was considered to be “difficult” to
use by more patients than trolamine (30% vs. 5%), and more phy
sicians felt that compliance was less good with calendula than
trolamine (84% vs. 92%). Two patients stopped using calendula
because of “difficulty,” whereas no patients stopped using trol
Limitations: This study was non-blinded (open): both patients and
clinicians knew which ointment was being used. The authors
stated that this approach was unavoidable because of the different
texture, color, and smell of the two agents. This design may have
biased the results (particularly because there have been recent re
ports of questionable efficacy of trolamine, of which clinician
might have been aware). The calendula preparation contained pe-
troleum jelly, which itself may have beneficial effects. No placebo
arm was used. Comparison to placebo would have provided a
clearer view of the effects of calendula. Use of a placebo arm
would not have been unethical since there is currently no standard
of care in this area. Notably, prior RTOG studies have reported
grade 3 breast dermatitis in approximately 40% of patients-sug-
gesting the possibility (however unlikely based on prior studies)
that trolamine may have worsened dermatitis and calendula may
have had no effects (without a placebo arm, this cannot be ruled
out). Finally, it remains unknown if calendula is comparable to
other approaches such as steroid creams, hyaluronic acid cream, or
topical sucralfate. More patients reported “difficulty” using calen
dula than trolamine, although the nature of that difficulty was not
described in detail.
Otitis Media
Summary: There is insufficient human evidence to recommend ca
lendula for the treatment of otitis media or for pain associated with
otitis media (Table 3).
Evidence: Sarrell et al. compared Otikon Otic® solution, a nat
uropathic herbal solution containing Allium sativum, Verbascum
thapsus, Calendula flores, and Hypericum perforatum, with anes
thetic eardrops as a symptomatic treatment of otalgia in 110 chil
dren with acute otitis media.
Subjects were randomized to
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
TABLE 3. Evidence table
Condition Study
N Statistically
Quality of Study
0-2 = Poor
3-4 = Good
5 = Excellent
of Benefit
ARR NNT Comments
Open phase
III trial
no placebo
254 Yes 3 Medium 22% 5 Topical calendula extract
in petroleum jelly reduced
the incidence of RTOG
grade 2-3 skin toxicity
compared to trolamine
(an unproven topical
171 Yes 2 Small NA NA Comparison of
NHED ® (multi-
ingredient “Naturopathic
Herbal Extract Ear
Drops”), with or without
amoxicillin as manage-
ment of otalgia associ-
ated with acute otitis
media in children.
110 Yes 1 Small NA NA Comparison of Otikon
Otic® solution,
Allium sativum
Verbascum thapsus
Calendula flores
Hypericum perforatum
with anesthetic eardrops
as a symptomatic treat-
ment of otalgia in children
with acute otitis media.
ARR = Absolute Risk Reduction, NNT = Number Needed to Treat
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
receive either five drops of Otikon Otic® or anesthetic ear drops in
the affected ear three times daily. Pain was measured using a sub
jective pain scale.
Throughout the study, mean pain levels re
mained lower in the Otikon Otic® group, although this difference
was only statistically significant during the first day, 30 minutes
after application. Although this study is suggestive, the lack of pla
cebo group limits the distinction between pain relief due to the nat
ural history of otitis pain versus analgesia due to therapeutic
intervention. In addition, inadequate blinding may have allowed
for the introduction of bias. The simple 1-10 pain scale may not
have been sensitive enough to detect between-group differences.
The effects of Calendula flores monotherapy cannot be extrapo
lated from this study of a combination product.
In a subsequent study, Sarrell et al. compared NHED, a natu-
ropathic solution containing Calendula flores as well as garlic
(Allium sativum), mullien (Verbascum thapsus), St. John’s wort
(Hypericum perfoliatum), lavender, and vitamin E in olive oil,
with anesthetic ear drops, with or without amoxicillin 80 mg/kg/d
(maximum of 500 mg/dose divided three times a day), adminis-
tered as a treatment for otalgia associated with acute otitis media
in 171 children.
The children were randomly assigned to receive
either NHED (five drops three times daily alone or with
amoxicillin, or anesthetic ear drops alone or with amoxicillin). The
presence or absence of ear pain was assessed over three days with a
visual analog scale. Baseline characteristics were similar between
groups. Over the course of three days, there was statistically sig
nificant improvement in ear pain in each group. Children who
were given ear drops alone had a better response than patients who
were given ear drops with amoxicillin; the NHED (group report
edly did better than the other group. However, the results sug
gested that the pain was largely self-limited (80%) and could be
explained by the time elapsed. The authors concluded that con
comitant antibiotic treatment was not contributory and that an
herbal solution may be an option to consider instead of a few days
of waiting. The herbal solution was well-absorbed and well-toler
ated. There were no side effects reported.
A 1979 study assessing the efficacy of multiple herbal products in
the treatment of chronic otitis media found calendula to be “mini
mally effective.”
Additional details are limited.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
Skin Inflammation
Summary: Limited animal research suggests that calendula ex
tracts may possess anti-inflammatory properties when applied top
ically to the skin. Human studies are limited in this area.
Evidence: Della-Loggia et al. reported that hydro-alcoholic ex
tracts of calendula exhibit mild anti-inflammatory activity with
dose-dependent effects in mice with experimental inflammation of
the ear canal.
A carbon dioxide extract appeared to be more ac
tive with a dose-dependent effect. In a subsequent study, the most
active anti-inflammatory component of the carbon dioxide extract
was found to be free faradiol, which demonstrated a dose-depend
ent effect equal to indomethacin.
The authors suggested that
esterified faradiol may be the main active constituent, due to its
quantitative prevalence.
Wound Healing
Summary: Although minor skin wounds are a common indication
for topical treatment with calendula, few scientific studies have
been conducted in this area. Limited evidence from animal and in
vitro studies lend support to the use of calendula to promote
wound-healing, and have observed a reduction of epithelialization
time, an increase in wound strength, and an improvement of
wound contraction of experimental incisions treated with topical
However, high-quality human evidence is lacking.
Evidence: In a poorly described case series, Neto el al. studied ca
lendula’s effects on burn healing.
Calendula or a combination of
calendula with barbatimao (derived from Stryphnodendron
barbadetiman) was administered to 15 patients with burns, vari
cose ulcers, abrasions, or dermatitis. All subjects had been “unre
sponsive” to conventional therapy. The authors reported that all
patients with burns experienced complete healing in two-to-six
days, eight of 12 patients with varicose ulcers experienced com
plete healing within 30 days, and seven of 11 patients with abra
sions or chronic dermatitis were healed within 10 days. The method
of evaluating wound-healing was not described in detail, and sta
tistical analysis was not provided.
In a poorly designed and described comparison study, a group of
patients with second or third degree burns was treated topically
Natural Standard Review 155
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
with calendula, pure Vaseline®, or a commercial “proteolytic
A successful outcome was defined as the absence of
eschar or local infection, as evaluated by subjective criteria. After
12 days of therapy, the authors reported that 70% of the calendula
group was considered a “success” as compared to 66% of the
proteolytic ointment group (p 0.05) and 54% of the Vaseline®
group (p 0.05). Analgesia was reported by 60% of calendula pa
tients versus 21% receiving the proteolytic ointment. This study
was not randomized or blinded, allowing for the possible introduc
tion of confounders or bias. The lack of placebo arm leaves open
the question of whether improvements were due to the natural
course of wound healing, rather than to therapeutic interven
Brands Used in Statistically Significant Clinical Trials
NHED solution (combination product).
Otikon Otic® solution (combination product).
Topical: Pommade au Calendula par Digestion; Boiron Ltd.,
Levallois-Perrte, France.
1. Hamburger M, Adler S, Baumann D, et al. Preparative purification of the major
anti-inflammatory triterpenoid esters from Marigold (Calendula officinalis). Fito
terapia 2003;74(4):328-338.
2. Cordova CA, Siqueira IR, Netto CA, et al. Protective properties of butanolic ex
tract of the Calendula officinalis L. (marigold) against lipid peroxidation of rat liver
microsomes and action as free radical scavenger. Redox Rep 2002;7(2):95-102.
3. Chaparzadeh N, D’Amico ML, Khavari-Nejad RA, et al. Antioxidative responses
of Calendula officinalis under salinity conditions. Plant Physiol Biochem 2004;42(9):
4. Chakurski I, Matev M, Stefanov G, et al. [Treatment of duodenal ulcers and
gastroduodenitis with a herbal combination of Symphitum officinalis and Calendula
officinalis with and without antacids]. Vutr Boles 1981;20(6):44-47.
5. Chakurski I, Matev M, Koichev A, et al. [Treatment of chronic colitis with an
herbal combination of Taraxacum officinale, Hipericum perforatum, Melissa
officinaliss, Calendula officinalis and Foeniculum vulgare]. Vutr Boles 1981; 20(6):
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
6. Marinchev VN, Bychkova LN, Balvanovich NV, et al. [Use of calendula for ther
apy of chronic inflammatory diseases of eyelids and conjunctiva]. Oftal’mologicheskii
Zhurnal 1971;26(3):196-198.
7. Mozherenkov VP, Shubina LF. [Treatment of chronic conjunctivitis with Calen
dula]. Med Sestra 1976;35(4):33-34.
8. Krazhan IA, Garazha NN. [Treatment of chronic catarrhal gingivitis with po
lysorb-immobilized calendula]. Stomatologiia (Mosk) 2001;80(5):11-13.
9. Bogdanova NS, Nikolaeva IS, Shcherbakova LI, et al. [Study of anti-viral proper
ties of Calendula officinalis]. Farmakol Toksikol 1970;33(3):349-355.
10. Corina P, Dimitris S, Emanuil T, et al. [Treatment with acyclovir combined with
a new Romanian product from plants]. Oftalmologia 1999;46(1):55-57.
11. Barbour EK, Sagherian V, Talhouk S, et al. Evaluation of homeopathy in broiler
chickens exposed to live viral vaccines and administered Calendula officinalis extract.
Med Sci Monit 2004;10(8):BR281-BR285.
12. Matev M, Chakurski I, Stefanov G, et al. [Use of an herbal combination with
laxative action on duodenal peptic ulcer and gastroduodenitis patients with a concomi
tant obstipation syndrome]. Vutr Boles 1981;20(6):48-51.
13. Iauk L, Lo Bue AM, Milazzo I, et al. Antibacterial activity of medicinal plant
extracts against periodontopathic bacteria. Phytother Res 2003;17(6):599-604.
14. Neto JJ, Fracasso JF, Neves MDCLC, et al. Treatment of varicose ulcer and skin
lesions with calendula. Revista de Ciencias Farm Sao Paulo 1996;17:181-186.
15. Anonymous. Final report on the safety assessment of Calendula officinalis ex-
tract and Calendula officinalis. Int J Toxicol 2001;20 Suppl 2:13-20.
16. Sarrell EM, Mandelberg A, Cohen HA. Efficacy of naturopathic extracts in the
management of ear pain associated with acute otitis media. Arch Pediatr Adolesc Med
17. Sarrell EM, Cohen HA, Kahan E. Naturopathic treatment for ear pain in chil-
dren. Pediatrics 2003;111(5 Pt 1):e574-e579.
18. Quetin-Leclercq J, Elias R, Balansard G, et al. Cytotoxic activity of some
triterpenoid saponins. Planta Med 1992;58(3):279-281.
19. Ramos A, Edreira A, Vizoso A, et al. Genotoxicity of an extract of Calendula
officinalis L. J Ethnopharmacol 1998;61(1):49-55.
20. Dietz V. Calendula preparations to treat cutaneous infections. Alt Med Alert
21. Bruynzeel DP, van Ketel WG, Young E, et al. Contact sensitization by alterna
tive topical medicaments containing plant extracts. The Dutch Contact Dermatoses
Group. Contact Dermatitis 1992;27(4):278-279.
22. Reider N, Komericki P, Hausen BM, et al. 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.
23. Wintzen M, Donker AS, Van Zuuren EJ. Recalcitrant atopic dermatitis due to
allergy to Compositae. Contact Dermatitis 2003;48(2):87-88.
24. Shipochliev T. [Uterotonic action of extracts from a group of medicinal plants].
Vet Med Nauki 1981;18(4):94-98.
25. Brinker F. Herb Contraindications and Drug Interactions. Sandy: Eclectic Med
ical Publications, 1998: 46.
Natural Standard Review 157
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
26. Bojadjiev C. On the sedative and hypotensive effect of preparations from the
plant Calendula officinalis. Nauch Trud Visshi Med Inst Sof 1964;43:15-20.
27. Samochowiec L. Pharmacological study of saponosides from Aralia mand
shurica Rupr. et Maxim and Calendula officinalis L. Herba Pol 1983;29:151-155.
28. Yoshikawa M, Murakami T, Kishi A, et al. Medicinal flowers. III. Marigold.
(1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and
new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from
Egyptian Calendula officinalis. Chem Pharm Bull (Tokyo) 2001;49(7):863-870.
29. Vidal-Ollivier E, Elias R, Faure F, et al. Flavonol glycosides from Calendula
officinalis flowers. Planta Med 1989;55:73-74.
30. Neukirch H, D’Ambrosio M, Dalla VJ, et al. Simultaneous quantitative determi
nation of eight triterpenoid monoesters from flowers of 10 varieties of Calendula
officinalis L. and characterisation of a new triterpenoid monoester. Phytochem Anal
31. Marukami T, Kishi A, Yoshikawa M. Medicinal flowers. IV. Marigold. (2):
Structures of new ionone and sesquiterpene glycosides from Egyptian Calendula
officinalis. Chem Pharm Bull (Tokyo) 2001;49(8):974-978.
32. Qiu X, Reed DW, Hong H, et al. Identification and analysis of a gene from Ca-
lendula officinalis encoding a fatty acid conjugase. Plant Physiol 2001; 125(2):
33. Della Loggia R., et al. Topical anti-inflammatory activity of Calendula offi-
cinalis extracts. Planta Med 1990;56:658.
34. Della LR, Tubaro A, Sosa S, et al. The role of triterpenoids in the topical anti-in-
flammatory activity of Calendula officinalis flowers. Planta Med 1994;60(6):516-520.
35. Zitterl-Eglseer K, Sosa S, Jurenitsch J, et al. Anti-oedematous activities of the
main triterpendiol esters of marigold (Calendula officinalis L.). J Ethnopharmacol
36. Bezakova L, Masterova I, Paulikova I, et al. Inhibitory activity of isorhamnetin
glycosides from Calendula officinalis L. on the activity of lipoxygenase. Pharmazie
37. Rao S, Udupa A, Udupa SL, et al. Calendula and Hypericum: Two homeopathic
drugs promoting wound healing in rats. Fitoterapia 1991;62(6):508-510.
38. Klouchek-Popova E, Popov A, Pavlova N, et al. Influence of the physiological
regeneration and epithelialization using fractions isolated from Calendula officinalis.
Acta Physiol Pharmacol Bulg 1982;8(4):63-67.
39. Kalvatchev Z, Walder R, Garzaro D. Anti-HIV activity of extracts from Calen
dula officinalis flowers. Biomed Pharmacother 1997;51(4):176-180.
40. De Tommasi N, Conti C, Stein ML, et al. Structure and in vitro antiviral activity
of triterpenoid saponins from Calendula arvensis. Planta Med 1991;57(3):250-253.
41. Dumenil G, Chemli R, Balansard C, et al. [Evaluation of antibacterial properties
of marigold flowers (Calendula officinalis L.) and other homeopathic tinctures of
C. officinalis L. and C. arvensis L. (author’s transl)]. Ann Pharm Fr 1980;38(6):493-499.
42. Modesto A, Lima KC, de Uzeda M. Effects of three different infant dentifrices
on biofilms and oral microorganisms. J Clin Pediatr Dent 2000;24(3):237-243.
43. Gracza L. Oxygen-containing terpene derivatives from Calendula officinalis.
Planta Med 1987;53:227.
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
44. Chew BP, Wong MW, Wong TS. Effects of lutein from marigold extract on
immunity and growth of mammary tumors in mice. Anticancer Res 1996;16(6B):
45. Elias R, De Meo M, Vidal-Ollivier E, et al. Antimutagenic activity of some
saponins isolated from Calendula officinalis L., C. arvensis L. and Hedera helix L.
Mutagenesis 1990;5(4):327-331.
46. Amirghofran Z, Azadbakht M, Karimi MH. Evaluation of the immunomo
dulatory effects of five herbal plants. J Ethnopharmacol 2000;72(1-2): 167-172.
47. Marchenko MM, Kopyl’chuk HP, Hrygor’ieva OV. [Activity of cytoplasmic
proteinases from rat liver in Heren’s carcinoma during tumor growth and treatment
with medicinal herbs]. Ukr Biokhim Zh 2000;72(3):91-94.
48. Pommier P, Gomez F, Sunyach MP, et al. Phase III randomized trial of Calen
dula officinalis compared with trolamine for the prevention of acute dermatitis during
irradiation for breast cancer. J Clin Oncol 2004;22(8):1447-1453.
49. Shaparenko BA, Slivko AB, Bazarova OV, et al. On use of medicinal plants for
treatment of patients with chronic suppurative otitis. Zh Ushn Gorl Bolezn 1979;39:
50. Lievre M, Marichy J, Baux S, et al. Controlled study of three ointments for the
local management of 2nd and 3rd degree burns. Clin Trials Meta-Analysis 1992;28:
Natural Standard Review 159
J Herb Pharmacother Downloaded from by University of North Carolina on 06/20/14
For personal use only.
... It is considered one the best herbs for the treatment of local skin aliments, external bleeding, contusions and burns. It is also considered to have a notable anti-fungal property (Basch et al., 2007). Already in the 12th century it was observed, that "even looking at the golden flowers of the garden marigold improves the sight, cleanses the brain and mends the spirit" (Nikitidis, Papiomytoglou, 2011). ...
Full-text available
The following is a compilation of information on a collection of herbs donated to Dr. Mokler by a now closed company in Sebago, Maine. According to the Eli Lilly museum in Indianapolis, Indiana, these samples were used to identify herbs that were sent to Eli Lilly from around the world in the early 1900s. Many of the herbs that were received were either not labeled or mislabeled. These samples were used to try to correctly identify the herbs. The herbs are in the original bottles and have not been opened. Most of these herbs will be familiar to current day herbalists. We have placed a photograph of the bottle and the information given on the bottle label, then added information from current herbal sources as to the medicinal uses of the herb.
Full-text available
Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries. Graphical Abstract To develop biological skin dresses with improved performance in the treatment of chronic skin wounds, gelatin-collagen microparticles were mixed with collagen suspensions and the resulting mixtures lyophilized to make porous scaffolds. Scaffolds were then loaded with a hydroglycolic extract of C. officinalis flowers and fully characterized in vitro.
Calendula officinalis, a member of the Asteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood. Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K-dependent pathway. The increase in phosphorylation of FAK (Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC-ESI MS revealed the presence of flavonol glycosides as the major compounds of CDOT. Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K-dependent pathway, and the identified compounds are likely to be responsible for wound healing activity. Copyright © 2015 John Wiley & Sons, Ltd.
The present mini-review actualizes the pharmacy of botanical, animal, and fungal sources of potential value in the management of burns wounds. It also highlights the importance of applying contemporary imaged-based sciences such as radiology in the assessment and prognosis of wounds and burns.
This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.
Full-text available
In patients with ulcerative colitis (UC), the repeated cycle of injury and repair of intestinal mucosa has been reported to increase the risk of colon cancer. So, a safe and efficient therapy is required for the treatment and prophylaxis for the disease.This study aims to investigate the efficacy of Calendula officinalis extract in treatment of experimentally induced ulcerative colitis in dog animal model. During fall 2010, 10 out-bred female German dogs (1-2 years old; weighs of 20-25 kg) were enrolled. Ulcerative colitis was induced with 6% acetic acid as enema and method of treatment was retrograde (via enema) too by C. officinalis. Loose stools, diarrhea, gross bleeding and loss of body weight happened after administration of acetic acid and crypt damage, loss of epithelium, infiltration of inflammatory cells and depletion of goblet cells were noticed histologically. C. officinalis could successfully resolve the damages of UC. Treatment with C. officinalis can broaden the current therapy options for UC.
Objectives: The aim of this overview of systematic reviews (SRs) is to evaluate critically the evidence regarding interactions between herbal medicinal products (HMPs) and synthetic drugs. Methods: Four electronic databases were searched to identify relevant SRs. Results: Forty-six SRs of 46 different HMPs met our inclusion criteria. The vast majority of SRs were of poor methodological quality. The majority of these HMPs were not associated with severe herb-drug interactions. Serious herb-drug interactions were noted for Hypericum perforatum and Viscum album. The most severe interactions resulted in transplant rejection, delayed emergence from anaesthesia, cardiovascular collapse, renal and liver toxicity, cardiotoxicity, bradycardia, hypovolaemic shock, inflammatory reactions with organ fibrosis and death. Moderately severe interactions were noted for Ginkgo biloba, Panax ginseng, Piper methysticum, Serenoa repens and Camellia sinensis. The most commonly interacting drugs were antiplatelet agents and anticoagulants. Conclusion: The majority of the HMPs evaluated in SRs were not associated with drug interactions with serious consequences. However, the poor quality and the scarcity of the primary data prevent firm conclusions.
The effects of three ointments (Pommade au calendula par digestion® = Calendula, Elase® and vaseline) on the management of 2nd and 3rd degree burns were compared in a randomized, open, parallel study in 156 patients. A marginally significant difference in favor of Calendula over vaseline was observed. Calendula was significantly better tolerated than the other treatments.
A reinvestigation of the aerial parts of Calendula arvensis afforded, in addition to the oleanolic acid glycosides 1-4 (4), the new glycoside 5 whose structure was elucidated by spectral and chemical studies and determined as 3-O-(beta-D-galactopyranosyl-(1----3) [beta-D-glucopyranosyl-(1----4)]-beta-D-glucopyranosyl) oleanolic acid (28----1)-beta-D-glucopyranosyl ester. Furthermore, some antiviral tests were performed on glycosides 1-5 and on 5a, the hydrolysis product of 5, towards vesicular stomatitis virus (VSV) and rhinovirus (HRV) infection in cell cultures. An inhibitory effect against VSV multiplication was observed for all the compounds tested while HRV replication was significantly affected only by compound 3.
Thirteen saponins were isolated and identified from Calendula oficinalis, C. arvensis and Hedera helix. Mutagenic and antimutagenic activities of these products were investigated using a modified liquid incubation technique of the Salmonella/microsomal assay. The Salmonella tester strain TA98 ± S9 mix was used. Screening of the antimutagenic activity was performed with a known promutagen: benzo-[a]pyrene (BaP) and a mutagenic urine concentrate from a smoker (SU). Antimutagenic activities were also compared with the activity of chlorophyllin. All the saponins were found to be non-toxic and non-mutagenic for doses of 400 μg. Chlorophyllin inhibited the mutagenic activities of BaP (1 μg) and SU (5 μl) in a dose-dependent manner. The four saponins from C. arvensis and the three saponins from H. helix showed antimutagenic activity against BaP (1 μg) and SU (5 μl) with a dose—response relationship. The possible mechanism of the antimutagenic activity of saponins is discussed.