EFSA Compendium of Botanicals

Draft - work in progress

Piper methysticum G.Forst.

Family:: Piperaceae
Approval state:: Approved
Number of articles retrieved:: 1254
Number of processed references:: 7

Compositions

#1: saponins in leaves #2: alkaloids in leaves #3: tannins in leaves #4: dihydrokavain in roots #5: desmethoxyyangonin in roots #6: kavain in roots #7: dihydromethysticin in roots #8: methysticin in roots #9: yangonin in roots #10: Desmethoxyyangonin in rhizomes #11: Dihydrokavain in rhizomes #12: Methysticin in rhizomes #13: Dihydromethysticin in rhizomes #14: Kavain in rhizomes #15: Yangonin in rhizomes

Endpoint Studies

#1: Kava intoxication in human #2: acute hepatitis in human #3: fulminant hepatic failure in human #4: hepatic necrosis and liver failure in human #5: significant impairment in saccadic and visual attentional function in humans (ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task) #6: Altered mental status ataxia and neurotoxicity in human

Genotoxicity

#1: positive mutagenic activity in the umu-test due to two flavonoid-C-glycodides, (2-O-rhamnosylvitexin and schaftoside)

Composition #1: Lestari, Martina Sri., Himawan, Toto., Abadi, A. Latif., Retnowati, Rurini. Toxicity and phytochemistry test of methanol extract of several plants from papua using Brine Shrimp Lethality Test (BSLT). journal of chemical and pharmaceutical research, 2015, vol. 7, no. 4, p. 866–872. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

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

Phytochemical screening (F604A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

saponins in leaves

Composition #2: Lestari, Martina Sri., Himawan, Toto., Abadi, A. Latif., Retnowati, Rurini. Toxicity and phytochemistry test of methanol extract of several plants from papua using Brine Shrimp Lethality Test (BSLT). journal of chemical and pharmaceutical research, 2015, vol. 7, no. 4, p. 866–872. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

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

Phytochemical screening (F604A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

alkaloids in leaves

Composition #3: Lestari, Martina Sri., Himawan, Toto., Abadi, A. Latif., Retnowati, Rurini. Toxicity and phytochemistry test of methanol extract of several plants from papua using Brine Shrimp Lethality Test (BSLT). journal of chemical and pharmaceutical research, 2015, vol. 7, no. 4, p. 866–872. .

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

Methanol
Substance:

Tannins (RF-00004337-PAR)
Analytical method code:

Phytochemical screening (F604A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

tannins in leaves

Composition #4: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

dihydrokavain (RF-00004275-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

dihydrokavain in roots

Composition #5: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

desmethoxyyangonin (RF-00004270-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

desmethoxyyangonin in roots

Composition #6: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

(+)-kavain (RF-00003463-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

kavain in roots

Composition #7: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

dihydromethysticin (RF-00004276-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

dihydromethysticin in roots

Composition #8: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

(+)-methysticin (RF-00003495-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

methysticin in roots

Composition #9: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Additional extraction description:

unspecified
Substance:

yangonin (RF-00003641-PAR)
Analytical method code:

Unspecified (F598A)
Yes/No Qualitative:

Positive/Present (POS)
Result type:

Qualitative Value (Binary) (BIN)
Internal remarks:

yangonin in roots

Composition #10: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

desmethoxyyangonin (RF-00004270-PAR)
Additional substance description:

Desmethoxyyangonin
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

8.46
Internal remarks:

Desmethoxyyangonin in rhizomes

Composition #11: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

dihydrokavain (RF-00004275-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

13.05
Internal remarks:

Dihydrokavain in rhizomes

Composition #12: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

(+)-methysticin (RF-00003495-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

10.00
Internal remarks:

Methysticin in rhizomes

Composition #13: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

dihydromethysticin (RF-00004276-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

11.36
Internal remarks:

Dihydromethysticin in rhizomes

Composition #14: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

(+)-kavain (RF-00003463-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

11.46
Internal remarks:

Kavain in rhizomes

Composition #15: Lim, Steven T. S., Dragull, Klaus., Tang, Chung-Shih., Bittenbender, Harry C., Efird, Jimmy T., Nerurkar, Pratibha V. Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats . toxicological sciences, 2007, vol. 97, no. 1, p. 214–221. DOI: 10.1093/toxsci/kfm035. [DOI link]

Language:

English (en)
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Extraction/Preparation method:

Solvent extraction (A0BZR)
Additional extraction description:

acetone−water (rhizomes)
Substance:

yangonin (RF-00003641-PAR)
Analytical method code:

GC-FID (F040A)
Result unit:

Percent (G138A)
Result type:

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

8.34
Internal remarks:

Yangonin in rhizomes

Endpoint study #1: Chanwai, L.G. Kava toxicity. emergency medicine, 2000, vol. 12, no. 2, p. 142–145. DOI: 10.1046/j.1442-2026.2000.00107.x. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

16.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

Kava intoxication: feeling unwell, with sore eyes, headache, generalized muscle weakness and abdominal pain, disorientation and hallucinations
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

Kava intoxication in human

Endpoint study #2: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

acute hepatitis
Effect or parameter linked to the endpoint:

no data (CHD002BE)
Internal remarks:

acute hepatitis in human

Endpoint study #3: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male/Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Number of organisms dosed:

6
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

fulminant hepatic failure
Effect or parameter linked to the endpoint:

no data (CHD002BE)
Internal remarks:

fulminant hepatic failure in human

Endpoint study #4: Abdualmjid, R.J., Sergi, C. Hepatotoxic botanicals - An evidence-based systematic review. journal of pharmacy and pharmaceutical sciences, 2013, vol. 16, no. 3, p. 376–404. .

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Female
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

HEPATOTOXICITY (TOX02A)
Target tissue:

digestive: Liver (TT023A)
Effect description:

hepatic necrosis and liver failure
Effect or parameter linked to the endpoint:

no data (CHD002BE)
Internal remarks:

hepatic necrosis and liver failure in human

Endpoint study #5: Cairney, S., Maruff, P., Clough, AR., Collie, A., Currie, J., Currie, BJ. Saccade and cognitive impairment associated with kava intoxication. human psychopharmacology-clinical and experimental, 2003, vol. 18, no. 7, p. 525–533. DOI: 10.1002/hup.532. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

acute toxicity (CHD016TT)
Tested organism:

Human (as organism) (A056J)
Sex:

No data
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

24.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

11
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram (G148A)
Effect concentration:

205
Critical effect:

NONE (TOX14A)
Target tissue:

Neurologic (TT004A)
Effect description:

significant impairment in saccadic and visual attentional function; ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task
Effect or parameter linked to the endpoint:

behaviour (CHD001BE)
Internal remarks:

significant impairment in saccadic and visual attentional function in humans (ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task)

Endpoint study #6: Perez, J., Holmes, JF. Altered mental status and ataxia secondary to acute Kava ingestion. journal of emergency medicine, 2005, vol. 28, no. 1, p. 49–51. DOI: 10.1016/j.jemermed.2004.10.003. [DOI link]

Study relevance:

Human health
Plant part:

Roots and other underground parts used as staple food (as part-nature) (A0F5F)
Type of toxicological test:

case report (CHD060TT)
Limit test:

Not applicable
Tested organism:

Human (as organism) (A056J)
Sex:

Male
Route of exposure:

ORAL: DRINKING WATER (OECD2229PL)
Exposure duration:

1.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

1
Control groups used:

no
Endpoint measured:

Dose not reported (CHD066EP)
Critical effect:

NEUROTOXICITY (TOX04A)
Target tissue:

Neurologic (TT004A)
Effect description:

Altered mental status, leg weakness and severe vertigo, dizziness and vomiting following the ingestion of strong kava tea
Effect or parameter linked to the endpoint:

neurology (CHD027BE)
Internal remarks:

Altered mental status ataxia and neurotoxicity in human

Genotox #1: Jhoo, J. -W., Ang, C. Y. W., Heinze, T. M., Deck, J., Schnackenberg, L. K., Beger, R. D., Dragull, K., Tang, C. -S. Identification of C-glycoside flavonoids as potential mutagenic compounds in kava . journal of food science, 2007, vol. 72, no. 2, p. C120–C125. DOI: 10.1111/j.1750-3841.2007.00278.x. [DOI link]

Study category:

Mutagenicity
Type of toxicological test:

other (CHD008TT)
Method type:

in vitro
Tested organism:

Salmonella typhimurium (as organism) (A0CPZ)
Sex:

No data
Route of exposure:

OTHER (OECD0PL)
Control groups used:

no data
Is genotoxic:

Positive
Remarks on genotox study:

Umu-test revealed 2 mutagenic C-glycoside flavonoids, 2-O-rhamnosylvitexin and schaftoside
Internal remarks:

positive mutagenic activity in the umu-test due to two flavonoid-C-glycodides, (2-O-rhamnosylvitexin and schaftoside)
Internal ID:

WOS:000245079900010