EFSA Compendium of Botanicals

Draft - work in progress

Daphne genkwa Siebold & Zucc. // Wikstroemia genkwa (Siebold & Zucc.) Domke

Family:: Thymelaeaceae
Approval state:: Approved
Number of articles retrieved:: 625
Number of processed references:: 10

Compositions

#1: coumarins (umbelliferone, daphnin, daphnoretin, daphnodorin B, and daphnodorin G) from roots #2: coumarins (umbelliferone, daphnoretin, daphnetin, edgeworthin, edgeworin, and umbelliferone-7-O-β-D-glucoside) #3: Elemicin (flowers) #4: Furfural (RF-1009-001-PPP) (flowers) #5: 2, 3-dihydrobenzofuran (flowers) #6: Methyl eugenol (flowers) #7: 20 highly oxygenated novel daphnane-type diterpenoids genkwanines #8: yuanhuacine #9: yuanhuadine (RF-00004105-PAR) #10: yuanhuafine #11: yuanhuatine #12: yuanhuapine #13: lignans (syringaresinol, medioresinol and matairesinol) #14: genkwadaphnin and yuanhuacine (daphnane diterpenes) #15: yuanhuapine #16: genkwadaphnin

Endpoint Studies

#1: mortality in rats #2: mortality at 10 mg/kg yuanhuapine #3: males - serum trigliceride levels increase #4: liver weight increased in both males and females #5: strongly embryotoxic

Genotoxicity

#1: mutation - increase in His+ mutants in TA98 and 1537 at 5000 ug/plate

Composition #1: Shi, Feng., Zheng, Wei-fa. Phenolic constituents from the roots of Daphne genkwa and their immunomodulatory activity. xuzhou shifan daxue xuebao, ziran kexueban, 2004, vol. 22, no. 4, p. 34–40. .

Language:

English (en)
Plant part:

Roots and other underground parts (as part-nature) (A067M)
Additional extraction description:

unspecified
Substance:

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

umbelliferone, daphnin, daphnoretin, daphnodorin B, and daphnodorin G
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

coumarins (umbelliferone, daphnin, daphnoretin, daphnodorin B, and daphnodorin G) from roots

Composition #2: He, Lei., Shi, Qi-rong., Liu, Run-hui., Xu, Xi-ke., Shen, Yun-heng., Li, Hui-liang., Zhang, Wei-dong. Coumarins from the branches of Daphne genkwa. yaoxue shijian zazhi, 2008, vol. 26, no. 6, p. 441–443. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

ethanol
Substance:

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

umbelliferone, daphnoretin, daphnetin, edgeworthin, edgeworin, and umbelliferone-7-O-β-D-glucoside
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

coumarins (umbelliferone, daphnoretin, daphnetin, edgeworthin, edgeworin, and umbelliferone-7-O-β-D-glucoside)

Composition #3: Ueyama, Y., Hashimoto, S., Nii, H., Furukawa, K. The chemical composition of the essential oil of Daphne genkwa sieb. et zucc.. journal of essential oil research, 1990, vol. 2, no. 5, p. 247–250. DOI: 10.1080/10412905.1990.9697875. [DOI link]

Language:

English (en)
Plant part:

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

Essential oil (as part-nature) (A166Q)
Substance:

elemicin (RF-00003787-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

4.5
Internal remarks:

Elemicin (flowers)

Composition #4: Ueyama, Y., Hashimoto, S., Nii, H., Furukawa, K. The chemical composition of the essential oil of Daphne genkwa sieb. et zucc.. journal of essential oil research, 1990, vol. 2, no. 5, p. 247–250. DOI: 10.1080/10412905.1990.9697875. [DOI link]

Language:

English (en)
Plant part:

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

Essential oil (as part-nature) (A166Q)
Substance:

Furfural (RF-1009-001-PPP)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

2.8
Internal remarks:

Furfural (RF-1009-001-PPP) (flowers)

Composition #5: Ueyama, Y., Hashimoto, S., Nii, H., Furukawa, K. The chemical composition of the essential oil of Daphne genkwa sieb. et zucc.. journal of essential oil research, 1990, vol. 2, no. 5, p. 247–250. DOI: 10.1080/10412905.1990.9697875. [DOI link]

Language:

English (en)
Plant part:

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

Essential oil (as part-nature) (A166Q)
Substance:

Benzofurans (RF-00010791-PAR)
Additional substance description:

2, 3-dihydrobenzofuran
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

2.7
Internal remarks:

2, 3-dihydrobenzofuran (flowers)

Composition #6: Ueyama, Y., Hashimoto, S., Nii, H., Furukawa, K. The chemical composition of the essential oil of Daphne genkwa sieb. et zucc.. journal of essential oil research, 1990, vol. 2, no. 5, p. 247–250. DOI: 10.1080/10412905.1990.9697875. [DOI link]

Language:

English (en)
Plant part:

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

Essential oil (as part-nature) (A166Q)
Substance:

methyleugenol (RF-00003931-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

4.6
Internal remarks:

Methyl eugenol (flowers)

Composition #7: Zhan, ZJ., Fan, CQ., Ding, J., Yue, HM. Novel diterpenoids with potent inhibitory activity against endothelium cell HMEC and cytotoxic activities from a well-known TCM plant Daphne genkwa . bioorganic & medicinal chemistry, 2005, vol. 13, no. 3, p. 645–655. DOI: 10.1016/j.bmc.2004.10.054. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

95% ethanol
Substance:

daphnane diterpenes (RF-00004330-PAR)
Additional substance description:

20 highly oxygenated novel daphnane-type diterpenoids genkwanines
Analytical method code:

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

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

20 highly oxygenated novel daphnane-type diterpenoids genkwanines

Composition #8: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petrolium, ethanol
Substance:

yuanhuacine (RF-00004104-PAR)
Analytical method code:

LC-MS (F026A)
Result unit:

Milligram/gram (G060A)
Result type:

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

7.4
Internal remarks:

yuanhuacine

Composition #9: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petrolium, ethanol
Substance:

yuanhuadine (RF-00004105-PAR)
Analytical method code:

LC-MS (F026A)
Result unit:

Milligram/gram (G060A)
Result type:

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

10.7
Internal remarks:

yuanhuadine (RF-00004105-PAR)

Composition #10: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petrolium, ethanol
Substance:

Yuanhuafin (RF-00013687-PAR)
Additional substance description:

yuanhuafine
Analytical method code:

LC-MS (F026A)
Result unit:

Milligram/gram (G060A)
Result type:

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

1.97
Internal remarks:

yuanhuafine

Composition #11: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petrolium, ethanol
Substance:

Yuanhuatine (RF-00013686-PAR)
Analytical method code:

LC-MS (F026A)
Result unit:

Milligram/gram (G060A)
Result type:

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

1.04
Internal remarks:

yuanhuatine

Composition #12: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

petrolium, ethanol
Substance:

Yuanhuapine (RF-00013688-PAR)
Analytical method code:

LC-MS (F026A)
Result unit:

Milligram/gram (G060A)
Result type:

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

1.31
Internal remarks:

yuanhuapine

Composition #13: Zhang, Yuanyuan., Zhang, Ruowen., Yuan, Yang., Geng, Lulu., Zhao, Xu., Meng, Xia., Zhuang, Hefei., Bi, Kaishun., Chen, Xiaohui. Simultaneous determination of eight active components in chloroform extracts from raw and vinegar-processed Genkwa flos using HPLC-MS and identification of the hepatotoxic ingredients with an HL-7702 cell . analytical methods, 2014, vol. 6, no. 17, p. 7022–7029. DOI: 10.1039/c4ay01241k. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Powder (A06JD)
Additional extraction description:

methanol and water/chloroform extraction
Substance:

lignans (RF-00004361-PAR)
Additional substance description:

syringaresinol, medioresinol and matairesinol
Analytical method code:

LC-MS (F026A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

lignans (syringaresinol, medioresinol and matairesinol)

Composition #14: Zhang, Yuanyuan., Zhang, Ruowen., Yuan, Yang., Geng, Lulu., Zhao, Xu., Meng, Xia., Zhuang, Hefei., Bi, Kaishun., Chen, Xiaohui. Simultaneous determination of eight active components in chloroform extracts from raw and vinegar-processed Genkwa flos using HPLC-MS and identification of the hepatotoxic ingredients with an HL-7702 cell . analytical methods, 2014, vol. 6, no. 17, p. 7022–7029. DOI: 10.1039/c4ay01241k. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

methanol and water/chloroform extraction
Substance:

daphnane diterpenes (RF-00004330-PAR)
Additional substance description:

genkwadaphnin, yuanhuacine
Analytical method code:

LC-MS (F026A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

genkwadaphnin and yuanhuacine (daphnane diterpenes)

Composition #15: Chen, Yanyan., Guo, Jianming., Tang, Yuping., Wu, Liang., Tao, Weiwei., Qian, Yefei., Duan, Jin-ao. Pharmacokinetic profile and metabolite identification of yuanhuapine, a bioactive component in Daphne genkwa by ultra-high performance liquid chromatography coupled with tandem mass spectrometry . journal of pharmaceutical and biomedical analysis, 2015, vol. 112, p. 60–69. DOI: 10.1016/j.jpba.2015.04.023. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Additional extraction description:

unspecified
Substance:

Yuanhuapine (RF-00013688-PAR)
Analytical method code:

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

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

yuanhuapine

Composition #16: Kang, Ho-Bum., Lee, Ha-Reum., Jee, Da Jung., Shin, Su-Hyun., Nah, Seong-Su., Yoon, Sun Young., Kim, Jae Wha. PRDM1, a Tumor-Suppressor Gene, is Induced by Genkwadaphnin in Human Colon Cancer SW620 Cells . journal of cellular biochemistry, 2016, vol. 117, no. 1, p. 172–179. DOI: 10.1002/jcb.25262. [DOI link]

Language:

English (en)
Plant part:

Bud (as part-nature) (A066Z)
Substance:

daphnane diterpenes (RF-00004330-PAR)
Additional substance description:

genkwadaphnin
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

genkwadaphnin

Endpoint study #1: Chen, Yan-Yan., Guo, Jian-Ming., Qian, Ye-Fei., Guo, Sheng., Ma, Chun-Hua., Duan, Jin-Ao. Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat . phytomedicine, 2013, vol. 21, no. 1, p. 82–89. DOI: 10.1016/j.phymed.2013.06.012. [DOI link]

Study relevance:

Human health
Substance:

daphnane diterpenes (RF-00004330-PAR)
Plant part:

Bud (as part-nature) (A066Z)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

dried flowers bud extracted in petroleum
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

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

Sprague-Dawley (CHD012ST)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

24.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

24
Control groups used:

no
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram/kilogram (G015A)
Effect concentration:

0.25-1
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

Respiratory (TT005A)
Effect description:

decreased motor activity, immobility, respiratory distress, abdominal breathing, convulsions, death of all the animals after 5 minutes of administration of a dose of 1g/kg
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

mortality in rats

Endpoint study #2: Chen, Yanyan., Guo, Jianming., Tang, Yuping., Wu, Liang., Tao, Weiwei., Qian, Yefei., Duan, Jin-ao. Pharmacokinetic profile and metabolite identification of yuanhuapine, a bioactive component in Daphne genkwa by ultra-high performance liquid chromatography coupled with tandem mass spectrometry . journal of pharmaceutical and biomedical analysis, 2015, vol. 112, p. 60–69. DOI: 10.1016/j.jpba.2015.04.023. [DOI link]

Study relevance:

Human health
Substance:

Yuanhuapine (RF-00013688-PAR)
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

House mouse (as animal) (A0CNT)
Sex:

No data
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Control groups used:

no data
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Milligram/kilogram (G061A)
Effect concentration:

10
Critical effect:

SYSTEMIC (TOX01A)
Effect description:

mice became completely immobile with pronounced respiratory distress and marked abdominal breathing, and pronounced convulsions were observed shortly before death
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

mortality at 10 mg/kg yuanhuapine

Endpoint study #3: Yun, Jun-Won., Kim, Seung-Hyun., Kim, Yun-Soon., You, Ji-Ran., Kwon, Euna., Jang, Ja-June., Park, In Ae., Kim, Hee Chan., Kim, Hyeon Hoe., Che, Jeong-Hwan., Kang, Byeong-Cheol. Evaluation of subchronic (13 week) toxicity and genotoxicity potential of vinegar-processed Genkwa Flos . regulatory toxicology and pharmacology, 2015, vol. 72, no. 2, p. 386–393. DOI: 10.1016/j.yrtph.2015.04.008. [DOI link]

Study relevance:

Human health
Plant part:

Bud (as part-nature) (A066Z)
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

13.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

120
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Micrograms per kilogram body weight (G224A)
Effect concentration:

222-2000
Critical effect:

SYSTEMIC (TOX01A)
Effect description:

males - serum trigliceride levels increase
Effect or parameter linked to the endpoint:

haematology (CHD023BE)
Internal remarks:

males - serum trigliceride levels increase

Endpoint study #4: Yun, Jun-Won., Kim, Seung-Hyun., Kim, Yun-Soon., You, Ji-Ran., Kwon, Euna., Jang, Ja-June., Park, In Ae., Kim, Hee Chan., Kim, Hyeon Hoe., Che, Jeong-Hwan., Kang, Byeong-Cheol. Evaluation of subchronic (13 week) toxicity and genotoxicity potential of vinegar-processed Genkwa Flos . regulatory toxicology and pharmacology, 2015, vol. 72, no. 2, p. 386–393. DOI: 10.1016/j.yrtph.2015.04.008. [DOI link]

Study relevance:

Human health
Plant part:

Bud (as part-nature) (A066Z)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

vinegar + water
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Rat (as animal) (A0CNV)
Sex:

Male/Female
Route of exposure:

ORAL: GAVAGE (OECD2231PL)
Exposure duration:

13.0
Unit of exposure duration:

Week (G205A)
Number of organisms dosed:

120
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Micrograms per kilogram body weight (G224A)
Effect concentration:

74-2000
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

liver weight increased
Effect or parameter linked to the endpoint:

organ weights (CHD012BE)
Internal remarks:

liver weight increased in both males and females

Endpoint study #5: Li, Lin-Yan., Cao, Fen-Fang., Su, Zhi-Jian., Zhang, Qi-Hao., Dai, Xiao-Yong., Xiao, Xue., Huang, Ya-Dong., Zheng, Qing., Xu, Hua. Assessment of the embryotoxicity of four Chinese herbal extracts using the embryonic stem cell test . molecular medicine reports, 2015, vol. 12, no. 2, p. 2348–2354. DOI: 10.3892/mmr.2015.3598. [DOI link]

Study relevance:

Human health
Plant part:

Bud (as part-nature) (A066Z)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

water
Type of toxicological test:

in vitro (CHD061TT)
Control groups used:

yes, concurrent vehicle
Endpoint measured:

Half maximal inhibitory concentration (CHD021EP)
Concentration unit:

Milligram/millilitre (G191A)
Effect concentration:

1
Critical effect:

REPRODUCTIVE (TOX05A)
Target tissue:

Urogenital (TT006A)
Effect description:

strongly embryotoxic
Effect or parameter linked to the endpoint:

reproduction (CHD014BE)
Internal remarks:

strongly embryotoxic

Genotox #1: Yun, Jun-Won., Kim, Seung-Hyun., Kim, Yun-Soon., You, Ji-Ran., Kwon, Euna., Jang, Ja-June., Park, In Ae., Kim, Hee Chan., Kim, Hyeon Hoe., Che, Jeong-Hwan., Kang, Byeong-Cheol. Evaluation of subchronic (13 week) toxicity and genotoxicity potential of vinegar-processed Genkwa Flos . regulatory toxicology and pharmacology, 2015, vol. 72, no. 2, p. 386–393. DOI: 10.1016/j.yrtph.2015.04.008. [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 1535, TA 1537, TA 98 and TA 100 (CHD037ST)
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

mutation - increase in His+ mutants in TA98 and 1537 at 5000 ug/plate
Internal remarks:

mutation - increase in His+ mutants in TA98 and 1537 at 5000 ug/plate
Internal ID:

WOS:000356902900024