EFSA Compendium of Botanicals

Draft - work in progress

Liquorice (as plant) // Glycyrrhiza glabra L.

Family:: Fabaceae
Approval state:: Approved
Number of articles retrieved:: 5992
Number of processed references:: 5

Compositions

#1: Umbelliferone in roots #2: Glycyrrhizin in roots #3: Herniarin in roots #4: Formononetin in roots

Endpoint Studies

#1: Behavioral/neurologic changes in rats (acute tox) #2: Endocrine effects in rats (sub-acute toxicity) with mineralocorticoid excess syndrome accompanied with systemic hypertension, water retention, hypernatremia, and hypokalemia. #3: Reproductive effects in rats (sub-chronic) #4: Mortality in black molly fish (chronic)

Genotoxicity

#1: Aqueous extract of root was mutagenic in Ames assay

Composition #1: Kaur, Prabhjit., Kumar, Manish., Singh, Bikram., Kumar, Subodh., Kaur, Satwinderjeet. Amelioration of oxidative stress induced by oxidative mutagens and COX-2 inhibitory activity of umbelliferone isolated from Glycyrrhiza glabra L. asian pacific journal of tropical biomedicine, 2012, vol. 2, no. Suppl. 1, p. S120–S126. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

methanol
Substance:

umbelliferone (RF-00004096-PAR)
Analytical method code:

Standard Chromatographic tests (paper- thin layer- and column chromatography) (F016A)
Analytical method - additional description:

Thin-layer chromatography followed by H1 and C13 NMR
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Umbelliferone in roots

Composition #2: Paolini, M., Pozzetti, L., Sapone, A., Cantelli-Forti, G. Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases. life sciences, 1998, vol. 62, no. 6, p. 571–582. DOI: 10.1016/S0024-3205(97)01154-5. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

aqueous
Substance:

glycyrrhizin (RF-00003721-PAR)
Analytical method code:

High Performance Liquid Chromatography (HPLC)/Liquid Chromatography (LC) (F018A)
Result unit:

Percent (G138A)
Result type:

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

7.64
Internal remarks:

Glycyrrhizin in roots

Composition #3: Paolini, M., Pozzetti, L., Sapone, A., Cantelli-Forti, G. Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases. life sciences, 1998, vol. 62, no. 6, p. 571–582. DOI: 10.1016/S0024-3205(97)01154-5. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

aqueous
Substance:

herniarin (RF-00010991-PAR)
Analytical method - additional description:

(Mentioned in review portion of paper without details)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Herniarin in roots

Composition #4: Kim, Chulwon., Lee, Seok-Geun., Yang, Woong Mo., Arfuso, Frank., Um, Jae-Young., Kumar, Alan Prem., Bian, Jinsong., Sethi, Gautam., Ahn, Kwang Seok. Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. cancer letters, 2018, vol. 431, p. 123–141. DOI: 10.1016/j.canlet.2018.05.038. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Substance:

formononetin (RF-00000291-NTR)
Analytical method code:

Unspecified (F598A)
Analytical method - additional description:

Article mentions that compounds comes from roots, but no details given (introduction/review)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Formononetin in roots

Endpoint study #1: Nazari, Somayeh., Rameshrad, Maryam., Hosseinzadeh, Hossein. Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review. phytotherapy research, 2017, vol. 31, no. 11, p. 1635–1650. DOI: 10.1002/ptr.5893. [DOI link]

Study relevance:

Human health
Substance:

glycyrrhizin (RF-00003721-PAR)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

aqueous and ethanol
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

1.0
Unit of exposure duration:

Unit (G005A)
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight (G225A)
Effect concentration:

1000
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

Behavioral assessment showed that the animal’s alertness, spontaneous locomotor activity, and reactivity to touch behavior were decreased by all doses up to 3 h.
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

Behavioral/neurologic changes in rats (acute tox)

Endpoint study #2: Nazari, Somayeh., Rameshrad, Maryam., Hosseinzadeh, Hossein. Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review. phytotherapy research, 2017, vol. 31, no. 11, p. 1635–1650. DOI: 10.1002/ptr.5893. [DOI link]

Study relevance:

Human health
Substance:

glycyrrhizin (RF-00003721-PAR)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

aqueous
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Wistar (CHD013ST)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

15.0
Unit of exposure duration:

Day (G134A)
Control groups used:

no data
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight per day (G211A)
Effect concentration:

100-500
Critical effect:

ENDOCRINE (TOX12A)
Target tissue:

Glandular (TT003A)
Effect description:

Strong inhibitory effects on adrenal-pituitary axis.
Effect or parameter linked to the endpoint:

other (CHD003BE)
Internal remarks:

Endocrine effects in rats (sub-acute toxicity) with mineralocorticoid excess syndrome accompanied with systemic hypertension, water retention, hypernatremia, and hypokalemia.

Endpoint study #3: Nazari, Somayeh., Rameshrad, Maryam., Hosseinzadeh, Hossein. Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review. phytotherapy research, 2017, vol. 31, no. 11, p. 1635–1650. DOI: 10.1002/ptr.5893. [DOI link]

Study relevance:

Human health
Substance:

glycyrrhizin (RF-00003721-PAR)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

aqueous
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

9.0
Unit of exposure duration:

Week (G205A)
Control groups used:

no data
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligrams per kilogram body weight per day (G211A)
Effect concentration:

500-2000
Critical effect:

REPRODUCTIVE (TOX05A)
Target tissue:

urogenital: Prostrate (TT048A)
Effect description:

Decreased prostate weight and daily sperm production.
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

Reproductive effects in rats (sub-chronic)

Endpoint study #4: Nazari, Somayeh., Rameshrad, Maryam., Hosseinzadeh, Hossein. Toxicological Effects of Glycyrrhiza glabra (Licorice): A Review. phytotherapy research, 2017, vol. 31, no. 11, p. 1635–1650. DOI: 10.1002/ptr.5893. [DOI link]

Study relevance:

Human health
Substance:

glycyrrhizin (RF-00003721-PAR)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

propylene glycol
Type of toxicological test:

chronic/long term toxicity (CHD004TT)
Tested organism:

Animals (as animal) (A04SF)
Sex:

Male
Route of exposure:

ORAL: FEED (OECD2230PL)
Exposure duration:

45.0
Unit of exposure duration:

Day (G134A)
Control groups used:

no data
Endpoint measured:

Concentration level (CHD013EP)
Concentration unit:

Milligram/litre (G062A)
Effect concentration:

1-4
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

Mortality. Also decreased appetite, decreased body weight, and liver toxicity.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Mortality in black molly fish (chronic)

Genotox #1: Martinez, A., Ikken, Y., Cambero, MI., Marin, ML., Haza, AI., Casas, C., Morales, P. Mutagenicity and cytotoxicity of fruits and vegetables evaluated by the Ames test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. food science and technology international, 1999, vol. 5, no. 5, p. 431–437. DOI: 10.1177/108201329900500509. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

bacterial gene mutation assay (CHD027TT)
Method type:

in vitro
Tested organism:

Salmonella typhimurium (as organism) (A0CPZ)
Strain of test organism:

TA 100 (CHD024ST)
Exogenous metabolic activation applied:

with and without
Control groups used:

yes
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

Aqueous extract of root was mutagenic in Ames assay
Internal remarks:

Aqueous extract of root was mutagenic in Ames assay
Internal ID:

WOS:000089270500009