EFSA Compendium of Botanicals

Draft - work in progress

Croton tiglium L.

Family:: Euphorbiaceae
Approval state:: Approved
Number of articles retrieved:: 418
Number of processed references:: 11

Compositions

#1: Crotin I and II #2: Phorbol and deoxyphorbol derivatives (in seed oil) #3: Saponins (seeds) #4: Alkaloids (seeds) #5: phorbol ester derivatives (seeds) #6: phorbol ester (seeds) #7: crotocaudin #8: Tigliane-type diterpenoids derivative: Crotignoid A - Crotignoid K (leaves and twigs) #9: Tigliane diterpene esters (leaves)

Endpoint Studies

#1: Oral administration of seed oil caused tachypnea and decreased motor activity leading to mortality in mice. #2: Croton proteins caused gastrointestinal damage with edema, diarrhea and inflammation leading to mortality in mice.

Genotoxicity

#1: 1. Seed extract showed mutagenic effects in Ames test in S. typhimurium; 2. Negative results in in vitro chromosomal aberration assay and in vivo micronucleus assay.

Composition #1: Chen, Minghuang., Pan, Kezhen. Isolation, characterization, and crystallization of crotin toxin from the seeds of Croton tiglium L. shengwu huaxue zazhi, 1993, vol. 9, no. 1, p. 104–8. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

PBS buffer
Substance:

Crotin I (RF-00000337-TOX)
Additional substance description:

crotin I and II
Analytical method code:

Electrophoretic tests (F578A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Crotin I and II

Composition #2: Vogg, G., Achatz, S., Kettrup, A., Sandermann, H. Fast, sensitive and selective liquid chromatographic-tandem mass spectrometric determination of tumor-promoting diterpene esters. journal of chromatography a, 1999, vol. 855, no. 2, p. 563–573. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

Seed oil used as a starting material - extracted with methanol
Substance:

phorbol (RF-00003989-PAR)
Additional substance description:

Phorbol and deoxyphorbol derivatives
Analytical method code:

LC-MS/MS (F027A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Phorbol and deoxyphorbol derivatives (in seed oil)

Composition #3: Abbas, Mazhar., Shahid, Muhammad., Iqbal, Munawar., Anjum, Fozia., Sharif, Sumaira., Ahmed, Sohail., Pirzada, Tajnees. Antitermitic activity and phytochemical analysis of fifteen medicinal plant seeds. journal of medicinal plants research, 2013, vol. 7, no. 22, p. 1608–1617. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

absolute EtOH
Substance:

Saponins (RF-00004333-PAR)
Analytical method code:

Phytochemical screening (F604A)
Result unit:

Percent (G138A)
Result type:

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

2.51-2.57
Internal remarks:

Saponins (seeds)

Composition #4: Abbas, Mazhar., Shahid, Muhammad., Iqbal, Munawar., Anjum, Fozia., Sharif, Sumaira., Ahmed, Sohail., Pirzada, Tajnees. Antitermitic activity and phytochemical analysis of fifteen medicinal plant seeds. journal of medicinal plants research, 2013, vol. 7, no. 22, p. 1608–1617. .

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

absolute EtOH
Substance:

Alkaloids (RF-00004360-PAR)
Analytical method code:

Phytochemical screening (F604A)
Result unit:

Percent (G138A)
Result type:

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

9.14-9.66
Internal remarks:

Alkaloids (seeds)

Composition #5: Du, Qizhen., Zhao, Yongchun., Liu, Hongchun., Tang, Chunping., Zhang, Minmin., Ke, Changqiang., Ye, Yang. Isolation and Structure Characterization of Cytotoxic Phorbol Esters from the Seeds of Croton tiglium. . planta medica, 2017 . DOI: 10.1055/s-0043-110227. [DOI link]

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone
Substance:

Phorbol esters (RF-00004310-PAR)
Additional substance description:

PE derivatives: 7-Keto-12-O-tiglylphorbol-13-acetate, 7-Keto-phorbol-12-tiglate, 7-Keto-phorbol-12-(2-methyl)butyrate, 20-Formylphorbol-12-tiglate, 20-Formylphorbol-13-dodecanoate, 20-Formylphorbol-13-decanoate, Phorbol-12-isobutyrate
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:

phorbol ester derivatives (seeds)

Composition #6: Pal, Prince Kumar., Nandi, Manmath Kumar., Singh, Narendra Kumar. Detoxification of Croton tiglium L. seeds by Ayurvedic process of Sodhana. . ancient science of life, 2014, vol. 33, no. 3, p. 157–61. DOI: 10.4103/0257-7941.144619. [DOI link]

Language:

English (en)
Plant part:

Seed (as part-nature) (A066P)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

methanol
Substance:

Phorbol esters (RF-00004310-PAR)
Substance used for equivalence:

Tetradecanoylphorbol acetate (RF-00008921-PAR)
Analytical method code:

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

Milligram/100 gram (G057A)
Result expression:

Dry matter (B002A)
Result type:

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

1.8-5.2
Internal remarks:

phorbol ester (seeds)

Composition #7: Yadav, Ram P., Singh, Ajay. Toxic Effects of Crotocaudin Extracted from the Medicinal Plant Croton tiglium . zeitschrift fur naturforschung section c-a journal of biosciences, 2010, vol. 65, no. 5-6, p. 327–336. .

Language:

English (en)
Plant part:

Stem / stalk (as part-nature) (A067S)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petroleum ether
Substance:

labdane diterpenes (RF-00004392-PAR)
Additional substance description:

crotocaudin
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

crotocaudin

Composition #8: Zhang, Dong-Dong., Zhou, Bin., Yu, Jin-Hai., Xu, Cheng-Hui., Ding, Jian., Zhang, Hua., Yue, Jian-Min. Cytotoxic tigliane-type diterpenoids from Croton tiglium. tetrahedron, 2015, vol. 71, no. 52, p. 9638–9644. DOI: 10.1016/j.tet.2015.10.070. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

ethanol
Substance:

Diterpene esters (RF-00010831-PAR)
Additional substance description:

tigliane-type diterpenoids derivative: Crotignoid A - Crotignoid K
Analytical method code:

Chromatography hyphenated to element spectrometry (F355A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Tigliane-type diterpenoids derivative: Crotignoid A - Crotignoid K (leaves and twigs)

Composition #9: Zhao, Bi-Qing., Peng, Shuai., He, Wei-Jun., Liu, Yong-Hong., Wang, Jun-Feng., Zhou, Xiao-Jiang. Antitubercular and cytotoxic tigliane-type diterpenoids from Croton tiglium . bioorganic & medicinal chemistry letters, 2016, vol. 26, no. 20, p. 4996–4999. DOI: 10.1016/j.bmcl.2016.09.002. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

80% methanol
Substance:

Diterpene esters (RF-00010831-PAR)
Additional substance description:

tigliane diterpene esters
Analytical method code:

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

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

Tigliane diterpene esters (leaves)

Endpoint study #1: Anika, S.M., Shetty, S.N. Investigations on croton penduliflorus hutch.: III. Estimation of the acute toxicity in frogs and mice and the irritant activity in mice. pharmaceutical biology, 1984, vol. 22, no. 4, p. 173–176. DOI: 10.3109/13880208409070671. [DOI link]

Study relevance:

Human health
Plant part:

Seed (as part-nature) (A066P)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

petroleum ether
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

House mouse (as animal) (A0CNT)
Strain of test organism:

Swiss (CHD005ST)
Sex:

Male/Female
Route of exposure:

ORAL: FEED (OECD2230PL)
Number of organisms dosed:

70
Control groups used:

yes
Endpoint measured:

Dose producing lethality in 50% of experimental organisms (CHD024EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

1096
Critical effect:

PULMONARY AND CARDIAC (TOX08A)
Target tissue:

respiratory: Lung (TT041A)
Effect description:

Tachypnea and decreased motor activity in mice orally administered with seed oil (LD50 = 1096 mg/kg).
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Oral administration of seed oil caused tachypnea and decreased motor activity leading to mortality in mice.

Endpoint study #2: Liu, Liping., Yu, Hongli., Wu, Hao., Yang, Xiaolin., Pan, Yaozong., Chen, Yeqing., Wang, Kuilong., Wang, Wei., Zhang, Wenying., Jin, Yangping., Zhang, Chengchao., Jiang, Ai., Xia, Chunyan. Toxic proteins from Croton tiglium L. exert a proinflammatory effect by inducing release of proinflammatory cytokines and activating the p38-MAPK signaling pathway . molecular medicine reports, 2017, vol. 16, no. 1, p. 631–638. DOI: 10.3892/mmr.2017.6617. [DOI link]

Study relevance:

Human health
Plant part:

Seed (as part-nature) (A066P)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

Toxic proteins from seed extracted in PBS buffer
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

House mouse (as animal) (A0CNT)
Strain of test organism:

ICR (CHD044ST)
Sex:

Male/Female
Number of organisms dosed:

60
Control groups used:

yes
Endpoint measured:

Dose producing lethality in 50% of experimental organisms (CHD024EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

2752-3407
Critical effect:

Digestive (TOX18A)
Target tissue:

Digestive (TT002A)
Effect description:

Croton proteins caused significant gastrointestinal damage with edema and diarrhea. The toxic reactions of the crude protein were associated with inflammation.
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Croton proteins caused gastrointestinal damage with edema, diarrhea and inflammation leading to mortality in mice.

Genotox #1: Kim, Ji-Young., Yun, Jun-Won., Kim, Yun-Soon., Kwon, Euna., Choi, Hyung Jun., Yeom, Su-Cheong., Kang, Byeong-Cheol. Mutagenicity and tumor-promoting effects of Tiglium seed extract via PKC and MAPK signaling pathways . bioscience biotechnology and biochemistry, 2015, vol. 79, no. 3, p. 374–383. DOI: 10.1080/09168451.2014.980217. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

bacterial reverse mutation assay (CHD028TT)
Method type:

in vitro
Guideline used:

According to
Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay) (OECD1287PL)
Tested organism:

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

TA 98 (CHD029ST)
Sex:

No data
Exogenous metabolic activation applied:

no data
Control groups used:

yes
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

The Tiglium seed extract significantly produced His+ mutants at the highest concentration 16.8 mg/plate in S. typhimurium TA98.
Internal remarks:

1. Seed extract showed mutagenic effects in Ames test in S. typhimurium; 2. Negative results in in vitro chromosomal aberration assay and in vivo micronucleus assay.
Internal ID:

WOS:000350470400005