EFSA Compendium of Botanicals

Draft - work in progress

Marigold (as plant) // Calendula officinalis L.

Family:: Asteraceae
Approval state:: Approved
Number of articles retrieved:: 2372
Number of processed references:: 9

Compositions

#1: coumarins (umbelliferone, esculetln) in inflorescences #2: Triterpene saponins in leaves #3: saponins in flowers, Calendula glycosides A, B, C, D, D2 #4: coumaric acid in herb #5: epigallocatechin gallate in herb #6: gallic acid in herb #7: Total alkaloids in herb #8: gallocatechin-gallate in herb #9: Total saponins in herb #10: epigallocatechin in aerial parts #11: epigallocatechin gallate in aerial parts

Endpoint Studies

#1: Calendula officinalis Extract in soybean oil for rats; LD50: >4640 mg/kg

Genotoxicity

#1: genotoxicity (both mitotic crossing-over and chromosome malsegregation being observed) to Aspergillus #2: unscheduled DNA synthesis in rat liver cells #3: DNA damage in brain and liver rat cells.

Composition #1: Derkach, A. I., Komissarenko, N. F., Chernobai, V. T. Coumarins from inflorescences of Calendula officinalis and Helichrysum arenarium. khimiya prirodnykh soedinenii, 1986, vol. (6), p. 777. .

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol (inflorescences)
Substance:

coumarins (RF-00004351-PAR)
Additional substance description:

umbelliferone, esculetln
Analytical method code:

Standard Chromatographic tests (paper- thin layer- and column chromatography) (F016A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

coumarins (umbelliferone, esculetln) in inflorescences

Composition #2: Mohamed, Mona., Sterner, Olov., Bergquistt, Karl-Erik. Phytochemical and cytotoxic studies on Calendula officinalis. life science journal, 2015, vol. 12, no. 1), 194-20, p. 8 pp. .

Language:

English (en)
Plant part:

Leaves (as part-nature) (A0EKT)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

CHCl3, EtOAc and MeOH extracts
Substance:

Triterpene saponins Triterpene saponins (RF-00004338-PAR)
Analytical method code:

Nuclear Magnetic Resonance (NMR) (F061A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Triterpene saponins in leaves

Composition #3: Balsevich, J. John., Bishop, Greg G., Deibert, Leah K. Use of Digitoxin and Digoxin as Internal Standards in HPLC Analysis of Triterpene Saponin-Containing Extracts . phytochemical analysis, 2009, vol. 20, no. 1, p. 38–49. DOI: 10.1002/pca.1095. [DOI link]

Language:

English (en)
Plant part:

Flower (as part-nature) (A067B)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

methanol
Substance:

Saponins (RF-00004333-PAR)
Additional substance description:

Calendula glycosides A, B, C, D, D2
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Analytical method - additional description:

HPLC-PAD-MS analysis
Result unit:

Percent (G138A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

8.8
Internal remarks:

saponins in flowers, Calendula glycosides A, B, C, D, D2

Composition #4: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

p-coumaric acid (RF-00010717-PAR)
Additional substance description:

coumaric acid
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Nanogram/millilitre (G079A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.5
Internal remarks:

coumaric acid in herb

Composition #5: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

epigallocatechin gallate (RF-00003802-PAR)
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Nanogram/millilitre (G079A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

2.6
Internal remarks:

epigallocatechin gallate in herb

Composition #6: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

gallic acid (RF-00003821-PAR)
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Nanogram/millilitre (G079A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.8
Internal remarks:

gallic acid in herb

Composition #7: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

Alkaloids (RF-00004360-PAR)
Additional substance description:

gallocatechin-gallate
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Microgram/millilitre (G052A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

13.4
Internal remarks:

Total alkaloids in herb

Composition #8: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

gallocatechin (RF-00003822-PAR)
Additional substance description:

gallocatechin-gallate
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Nanogram/millilitre (G079A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

0.9
Internal remarks:

gallocatechin-gallate in herb

Composition #9: Hernandez-Saavedra, Diego., Perez-Ramirez, Iza F., Ramos-Gomez, Minerva., Mendoza-Diaz, Sandra., Loarca-Pina, Guadalupe., Reynoso-Camacho, Rosalia. Phytochemical characterization and effect of Calendula officinalis, Hypericum perforatum, and Salvia officinalis infusions on obesity-associated cardiovascular risk . medicinal chemistry research, 2016, vol. 25, no. 1, p. 163–172. DOI: 10.1007/s00044-015-1454-1. [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

boiled water (herb)
Substance:

Saponins (RF-00004333-PAR)
Additional substance description:

gallocatechin-gallate
Analytical method code:

HPLC-DAD (F587A)
Analytical method - additional description:

HPLC–DAD–MSD
Result unit:

Microgram/millilitre (G052A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

17.6
Internal remarks:

Total saponins in herb

Composition #10: Matei, Alina Oana., Gatea, Florentina., Teodor, Eugenia Dumitra., Radu, Gabriel Lucian. Tannins analysis from different medicinal plants extracts using MALDI-TOF and MEKC . chemical papers, 2016, vol. 70, no. 4, p. 515–522. DOI: 10.1515/chempap-2015-0222. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol / acetone
Substance:

Epigallocatechin (RF-00010399-PAR)
Analytical method code:

MALDI-TOFMS (F065A)
Analytical method - additional description:

MALDI-TOF spectra
Result unit:

Microgram/gram (G049A)
Result expression:

Dry matter (B002A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

230.01
Internal remarks:

epigallocatechin in aerial parts

Composition #11: Matei, Alina Oana., Gatea, Florentina., Teodor, Eugenia Dumitra., Radu, Gabriel Lucian. Tannins analysis from different medicinal plants extracts using MALDI-TOF and MEKC . chemical papers, 2016, vol. 70, no. 4, p. 515–522. DOI: 10.1515/chempap-2015-0222. [DOI link]

Language:

English (en)
Plant part:

Aerial part of plants (as part-nature) (A166F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

ethanol / acetone
Substance:

epigallocatechin gallate (RF-00003802-PAR)
Analytical method code:

MALDI-TOFMS (F065A)
Analytical method - additional description:

MALDI-TOF spectra
Result unit:

Microgram/gram (G049A)
Result expression:

Dry matter (B002A)
Result type:

Numerical Value (VAL)
Value (concentration, content):

132.70 - 370.43
Internal remarks:

epigallocatechin gallate in aerial parts

Endpoint study #1: [Anonymous]. Final report on the safety assessment of Calendula officinalis extract and Calendula officinalis. . international journal of toxicology, 2001, vol. 20 Suppl 2, p. 13–20. .

Study relevance:

Human health
Plant part:

Flower (as part-nature) (A067B)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

soybean oil
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

No data
Route of exposure:

ORAL: FEED (OECD2230PL)
Control groups used:

no data
Endpoint measured:

Lethal dose rate in 50% of experimental organisms (CHD029EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

>4640
Effect description:

no data
Effect or parameter linked to the endpoint:

no data (CHD002BE)
Internal remarks:

Calendula officinalis Extract in soybean oil for rats; LD50: >4640 mg/kg

Genotox #1: Ramos, A., Edreira, A., Vizoso, A., Betancourt, J., Lopez, M., Decalo, M. Genotoxicity of an extract of Caldendula officinalis L.. journal of ethnopharmacology, 1998, vol. 61, no. 1, p. 49–55. DOI: 10.1016/S0378-8741(98)00017-8. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

in vitro gene mutation assay in fungi (CHD029TT)
Method type:

in vitro
Tested organism:

Other (A07XE)
Strain of test organism:

Strain P Aspergillus nidulans (CHD119ST)
Sex:

No data
Exogenous metabolic activation applied:

no data
Endpoint measured:

chromosome aberration
Is genotoxic:

Positive
Remarks on genotox study:

The extract of Calendula exhibited dose-dependent toxicity and genotoxicity (both mitotic crossing-over and chromosome malsegregation being observed) to Aspergillus in the range of five plate concentrations from 0.1 to 1.0 mg of solids/ml assayed
Internal remarks:

genotoxicity (both mitotic crossing-over and chromosome malsegregation being observed) to Aspergillus
Internal ID:

WOS:000074288600006

Genotox #2: Perez-Carreon, JI., Cruz-Jimenez, G., Licea-Vega, JA., Popoca, EA., Fazenda, SF., Villa-Trevino, S. Genotoxic and anti-genotoxic properties of Calendula officinalis extracts in rat liver cell cultures treated with diethylnitrosamine . toxicology in vitro, 2002, vol. 16, no. 3, p. 253–258. DOI: 10.1016/S0887-2333(02)00005-X. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

unscheduled DNA synthesis (CHD059TT)
Method type:

in vitro
Tested organism:

Rat (as animal) (A0CNV)
Control groups used:

no
Is genotoxic:

Positive
Remarks on genotox study:

aqueous or water-ethanol extracts, at ng of solid material per ml concentrations, protect completely against diethylnitrosamine (DEN)-induced unscheduled DNA synthesis; however, concentrations three orders of magnitude higher are genotoxic.
Internal remarks:

unscheduled DNA synthesis in rat liver cells
Internal ID:

WOS:000176538700006

Genotox #3: Sabir, Syed Mubashar., Khan, Muhammad Fareed., Rocha, Joao Batista Texeira., Boligon, Aline Augusti., Athayde, Margareth Linde. Phenolic Profile, Antioxidant Activities and Genotoxic Evaluations of Calendula officinalis . journal of food biochemistry, 2015, vol. 39, no. 3, p. 316–324. DOI: 10.1111/jfbc.12132. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro (CHD038TT)
Method type:

in vitro
Tested organism:

Rat (as animal) (A0CNV)
Strain of test organism:

RL1 cell line (rat) (epithelial-like rat liver cell line) (CHD142ST)
Sex:

No data
Exogenous metabolic activation applied:

no data
Is genotoxic:

Positive
Remarks on genotox study:

A small but significant increase (P < 0.05) in DNA damage frequency at levels 1 and 4 using 400 μg/mL concentration of extract in brain and liver rat cells.
Internal remarks:

DNA damage in brain and liver rat cells.
Internal ID:

WOS:000355981100012