EFSA Compendium of Botanicals

Draft - work in progress

Aristolochia manshuriensis Kom.

Family:: Aristolochiaceae
Approval state:: Approved
Number of articles retrieved:: 268
Number of processed references:: 5

Compositions

#1: aristolochic acid C in unspecified plant part #2: aristolochic acid D in unspecified plant part #3: aristolochic acid II in unspecified plant part #4: aristolochic acid I in unspecified plant part #5: aristolochic acid I in stem/stalk #6: aristolochic acid II in stem/stalk

Endpoint Studies

#1: Nephrotoxicity in rats after oral intake of decoction of stem #2: acute renal failture - acute tubular necrosis, and increased serum levels of urea and creatine #3: carcinogenic effect observed 6 months after dosing with decoct in rats. Renal tumors but also tumours in breast, thyroid and skin #4: Dose-dependent behavioural changes, reduced body weights, reduced organ weights and histopathological changes in kidneys (nepropathy)

Genotoxicity

#1: Positive (mutagen) in Salmonella typhimurium strains TA98, TA100 and TA1537 #2: positive (clastogenic) effect of a methanolic extract of stems in the Bone Marrow Micronucleus test in mice

Composition #1: Yuan, Jinbin., Liu, Qian., Zhu, Weifeng., Ding, Li., Tang, Fei., Yao, Shouzhuo. Simultaneous analysis of six aristolochic acids and five aristolactams in herbal plants and their preparations by high-performance liquid chromatography-diode array detection-fluorescence detection. journal of chromatography a, 2008, vol. 1182, no. 1, p. 85–92. . [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Powder (A06JD)
Additional extraction description:

methanol extraction
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid C
Analytical method code:

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

HPLC-DAD-FLD
Result unit:

Milligram/gram (G060A)
Result type:

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

0.521
Internal remarks:

aristolochic acid C in unspecified plant part

Composition #2: Yuan, Jinbin., Liu, Qian., Zhu, Weifeng., Ding, Li., Tang, Fei., Yao, Shouzhuo. Simultaneous analysis of six aristolochic acids and five aristolactams in herbal plants and their preparations by high-performance liquid chromatography-diode array detection-fluorescence detection. journal of chromatography a, 2008, vol. 1182, no. 1, p. 85–92. . [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Powder (A06JD)
Additional extraction description:

methanol extraction
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid D
Analytical method code:

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

HPLC-DAD-FLD
Result unit:

Milligram/gram (G060A)
Result type:

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

0.854
Internal remarks:

aristolochic acid D in unspecified plant part

Composition #3: Yuan, Jinbin., Liu, Qian., Zhu, Weifeng., Ding, Li., Tang, Fei., Yao, Shouzhuo. Simultaneous analysis of six aristolochic acids and five aristolactams in herbal plants and their preparations by high-performance liquid chromatography-diode array detection-fluorescence detection. journal of chromatography a, 2008, vol. 1182, no. 1, p. 85–92. . [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Powder (A06JD)
Additional extraction description:

methanol extraction
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid II
Analytical method code:

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

HPLC-DAD-FLD
Result unit:

Milligram/gram (G060A)
Result type:

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

1.04
Internal remarks:

aristolochic acid II in unspecified plant part

Composition #4: Yuan, Jinbin., Liu, Qian., Zhu, Weifeng., Ding, Li., Tang, Fei., Yao, Shouzhuo. Simultaneous analysis of six aristolochic acids and five aristolactams in herbal plants and their preparations by high-performance liquid chromatography-diode array detection-fluorescence detection. journal of chromatography a, 2008, vol. 1182, no. 1, p. 85–92. . [DOI link]

Language:

English (en)
Plant part:

Unspecified (A07XD)
Extraction/Preparation method:

Powder (A06JD)
Additional extraction description:

methanol extraction
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid I
Analytical method code:

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

HPLC-DAD-FLD
Result unit:

Milligram/gram (G060A)
Result type:

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

3.25
Internal remarks:

aristolochic acid I in unspecified plant part

Composition #5: Hwang, Youn-Hwan., Kim, Taesoo., Cho, Won-Kyung., Yang, Hye Jin., Kwak, Dong Hoon., Ha, Hyunil., Song, Kwang Hoon., Ma, Jin Yeul. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom. . evidence-based complementary and alternative medicine : ecam, 2012, vol. 2012, p. 412736–412736. DOI: 10.1155/2012/412736. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

methanol-water extraction
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid I
Analytical method code:

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

Milligram/gram (G060A)
Result type:

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

2.85
Internal remarks:

aristolochic acid I in stem/stalk

Composition #6: Hwang, Youn-Hwan., Kim, Taesoo., Cho, Won-Kyung., Yang, Hye Jin., Kwak, Dong Hoon., Ha, Hyunil., Song, Kwang Hoon., Ma, Jin Yeul. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom. . evidence-based complementary and alternative medicine : ecam, 2012, vol. 2012, p. 412736–412736. DOI: 10.1155/2012/412736. [DOI link]

Language:

English (en)
Plant part:

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

Solvent extraction (A0BZR)
Additional extraction description:

methanol and water
Substance:

Aristolochia (RF-00000498-VET)
Additional substance description:

aristolochic acid II
Analytical method code:

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

Milligram/gram (G060A)
Result type:

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

0.50
Internal remarks:

aristolochic acid II in stem/stalk

Endpoint study #1: Liu, Man-Chang., Maruyama, Shoichi., Mizuno, Masashi., Morita, Yoshiki., Hanaki, Shigeru., Yuzawa, Yukio., Matsuo, Seiichi. The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids. . clinical and experimental nephrology, 2003, vol. 7, no. 3, p. 186–94. DOI: 10.1007/s10157-003-0229-z. [DOI link]

Study relevance:

Human health
Substance:

Aristolochia (RF-00000498-VET)
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

decoction, Aristolochic acids I and II
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Wistar (CHD013ST)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

5.0
Unit of exposure duration:

Day (G134A)
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram (G148A)
Effect concentration:

4
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

death (acute renal failure), tubular damage, decreased renal function, transient elevated serum creatinine, BUN and urinary proteinNe
Effect or parameter linked to the endpoint:

mortality (CHD010BE)
Internal remarks:

Nephrotoxicity in rats after oral intake of decoction of stem

Endpoint study #2: Qiu, Q., Liu, ZH., Chen, HP., Yin, HL., Li, LS. Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats . acta pharmacologica sinica, 2000, vol. 21, no. 12, p. 1129–1135. .

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

decoction
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Sprague-Dawley (CHD012ST)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

7.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

30
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram/kilogram (G015A)
Effect concentration:

20-50
Critical effect:

NEPHROTOXICITY (TOX03A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

acute renal failure - acute tubular necrosis, proteinuria, glycosuria, increased levels of creatine and urea in serum
Effect or parameter linked to the endpoint:

urinalysis (CHD029BE)
Internal remarks:

acute renal failture - acute tubular necrosis, and increased serum levels of urea and creatine

Endpoint study #3: Qiu, Q., Liu, ZH., Chen, HP., Yin, HL., Li, LS. Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats . acta pharmacologica sinica, 2000, vol. 21, no. 12, p. 1129–1135. .

Study relevance:

Human health
Plant part:

Unspecified (A07XD)
Preparation/Extraction method:

Solvent extraction (A0BZR)
Additional plant/substance description:

water - decoction
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

Sprague-Dawley (CHD012ST)
Sex:

Female
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

7.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

30
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Gram/kilogram (G015A)
Effect concentration:

20-50
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

Urogenital (TT006A)
Effect description:

carcinogenic effect observed 6 months after dosing with decoction - renal tumors but also tumors in breast, thyroid and skin.
Effect or parameter linked to the endpoint:

Carcinogenic (CHD036BE)
Internal remarks:

carcinogenic effect observed 6 months after dosing with decoct in rats. Renal tumors but also tumours in breast, thyroid and skin

Endpoint study #4: Xue, Xiang., Xiao, Ying., Gong, Likun., Guan, Shuhong., Liu, Yongzhen., Lu, Henglei., Qi, Xinming., Zhang, Yunhai., Li, Yan., Wua, Xiongfei., Ren, Jin. Comparative 28-day repeated oral toxicity of Longdan Xieganwan, Akebia trifoliate (Thunb.) koidz., Akebia quinata (Thunb.) Decne. and Caulis aristolochiae manshuriensis in mice . journal of ethnopharmacology, 2008, vol. 119, no. 1, p. 87–93. DOI: 10.1016/j.jep.2008.05.037. [DOI link]

Study relevance:

Human health
Plant part:

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

Solvent extraction (A0BZR)
Additional plant/substance description:

water
Type of toxicological test:

short-term toxicity (CHD017TT)
Tested organism:

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

C57BL (CHD061ST)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration:

28.0
Unit of exposure duration:

Day (G134A)
Number of organisms dosed:

10
Control groups used:

yes
Endpoint measured:

Dose level (CHD014EP)
Concentration unit:

Grams per kilogram body weight per day (G212A)
Effect concentration:

>=0.24
Critical effect:

SYSTEMIC (TOX01A)
Target tissue:

urogenital: Kidneys (TT046A)
Effect description:

Dose-dependent behavioural changes, reduced body weights, reduced organ weights and histopathological changes in kidneys (nepropathy)
Effect or parameter linked to the endpoint:

histopathology non neoplastic (CHD025BE)
Internal remarks:

Dose-dependent behavioural changes, reduced body weights, reduced organ weights and histopathological changes in kidneys (nepropathy)

Genotox #1: Hwang, Youn-Hwan., Kim, Taesoo., Cho, Won-Kyung., Yang, Hye Jin., Kwak, Dong Hoon., Ha, Hyunil., Song, Kwang Hoon., Ma, Jin Yeul. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom. . evidence-based complementary and alternative medicine : ecam, 2012, vol. 2012, p. 412736–412736. DOI: 10.1155/2012/412736. [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)
Sex:

No data
Exogenous metabolic activation applied:

with and without
Route of exposure:

OTHER (OECD0PL)
Control groups used:

yes, concurrent vehicle
Endpoint measured:

gene mutation
Is genotoxic:

Positive
Remarks on genotox study:

Mutagen in Salmonella typhimurium strains TA98, TA100 and TA1537
Internal remarks:

Positive (mutagen) in Salmonella typhimurium strains TA98, TA100 and TA1537
Internal ID:

MEDLINE:22844332

Genotox #2: Hwang, Youn-Hwan., Kim, Taesoo., Cho, Won-Kyung., Yang, Hye Jin., Kwak, Dong Hoon., Ha, Hyunil., Song, Kwang Hoon., Ma, Jin Yeul. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom. . evidence-based complementary and alternative medicine : ecam, 2012, vol. 2012, p. 412736–412736. DOI: 10.1155/2012/412736. [DOI link]

Study category:

Genotoxicity
Type of toxicological test:

Mammalian erythrocyte micronucleus test (CHD057TT)
Method type:

in vivo
Guideline used:

According to
Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test) (OECD1290PL)
Tested organism:

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

ICR (CHD044ST)
Sex:

Male
Route of exposure:

ORAL: UNSPECIFIED (OECD2234PL)
Exposure duration for in vivo:

48.0
Unit of exposure duration:

Hour (G099A)
Number of organisms dosed:

30
Control groups used:

yes, concurrent vehicle
Endpoint measured:

DNA damage and/or repair
Is genotoxic:

Positive
Remarks on genotox study:

Increased the incidence (%) of Bone Marrow Micronucleute after a single dose of 1250–5000 mg/kg body weight
Internal remarks:

positive (clastogenic) effect of a methanolic extract of stems in the Bone Marrow Micronucleus test in mice
Internal ID:

MEDLINE:22844332