ARISTOLOCHIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H11NO7
Molecular Weight	341.2717
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C2C=C(C3=C(C4=C(OCO4)C=C3C(O)=O)C2=CC=C1)[N+]([O-])=O

InChI

InChIKey=BBFQZRXNYIEMAW-UHFFFAOYSA-N

InChI=1S/C17H11NO7/c1-23-12-4-2-3-8-9(12)5-11(18(21)22)14-10(17(19)20)6-13-16(15(8)14)25-7-24-13/h2-6H,7H2,1H3,(H,19,20)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27080942 | Pharmaceuticals. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100A. retrieved from https://www.ncbi.nlm.nih.gov/books/NBK304331

Aristolochic acid (AA-I), a naturally occurring nitrophenanthrene carboxylic acid, commonly found in the plant family Aristolochiaceae, that are used in traditional Chinese medicine. Aristolochic acid exhibits nephrotoxic, carcinogenic, and mutagenic activities and can cause aristolochic acid nephropathy, and urothelial malignancies. The FDA has issued a strong warning to consumers to avoid herbs containing the chemical aristolochic acid. The mechanisms underlying AA-I toxicity in the kidneys are poorly understood. However, was found a protein α-actinin-4 that is inhibited by AA-I, resulting in kidney disease.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ATP-binding cassette sub-family G member 2 16 Target ID: Q9UNQ0\|\|\|Q86V64 Gene ID: 9429.0 Gene Symbol: ABCG2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26183576	Substrate 661
Alpha-actinin-4 2 Target ID: O43707 Gene ID: 81.0 Gene Symbol: ACTN4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27080942	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
[Current status of injury caused by Chinese herbal medicine and its counter measure].	2001 Jan	12577382
Contribution of different taste cells and signaling pathways to the discrimination of "bitter" taste stimuli by an insect.	2002 Aug 15	12177223
Antithrombin activity of some constituents from Origanum vulgare.	2002 Dec	12490231
[Comparison among families of Mutong].	2002 Jun	12774628
[Influence of long-term use of low dose caulis Aristolochiae manshuriensis on partial nephrectomized rats].	2002 Jun	12585193
Enzymatic activity and inhibition of the neurotoxic complex vipoxin from the venom of Vipera ammodytes meridionalis.	2002 Nov-Dec	12562098
Determination of aristolochic acid I and II in North American species of Asarum and Aristolochia.	2002 Oct	12426949
Mechanism of endothelin-1-induced cytosolic Ca(2+) mobility in cultured H9c2 myocardiac ventricular cells.	2002 Oct	12135702
Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer?	2002 Oct 10	12216081
Bradykinin increases permeability by calcium and 5-lipoxygenase in the ECV304/C6 cell culture model of the blood-brain barrier.	2002 Oct 25	12384249
[Aristolochic acid induced transdifferentiation and apoptosis in human tubular epithelial cells in vitro].	2002 Sep	12411187
An LC/DAD-UV/MS method for the rapid detection of aristolochic acid in plant preparations.	2002 Sep	12357407
Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure.	2002 Sep 10	12206661
Involvement of phosphatidic acid in both degranulation and oxidative activity in fMet-Leu-Phe stimulated polymorphonuclear leukocytes.	2003	12876387
Aristolochic acid and 'Chinese herbs nephropathy': a review of the evidence to date.	2003	12495362
Effects of dexfenfluramine on aristolochic acid nephrotoxicity in a rat model for Chinese-herb nephropathy.	2003 Apr	12698237
Transgene-derived hepatocyte growth factor attenuates reactive renal fibrosis in aristolochic acid nephrotoxicity.	2003 Dec	14605273
The importance of a histology-based diagnosis of interstitial nephropathy in two patients with renal insufficiency.	2003 Feb	12543907
Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristolochic acid may occur without severe renal failure.	2003 Feb	12543902
Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens.	2003 Jan	12453725
[Clinical analysis of two children with aristolochic acid nephropathy].	2003 Jul	14746690
The role of phospholipases A2 in the stimulation of neutrophil motility by cobra venoms.	2003 Mar	12657315
Zona pellucida induces activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa.	2003 Mar	12604641
[A comparative study of manchurian Dutchmanspipe and antibiotics induced acute tubular necrosis in renal cellular biological features].	2003 May	12800411
[Provide against possible trouble--on knowledge, prevention and treatment of adverse drug reactions].	2003 May	12800410
Determination of aristolochic acids by capillary electrophoresis.	2003 May-Aug	14596334
H2O2-induced platelet aggregation and increase in intracellular Ca2+ concentration are blocked by inhibitors of intracellular signaling.	2003 Nov	14640963
Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies.	2003 Nov	14531824
Analysis of aristolochic acid in nine sources of Xixin, a traditional Chinese medicine, by liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry.	2003 Nov 24	14623612
Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase.	2003 Oct	12869422
Effect of indomethacin on force responses and sarcoplasmic reticulum function in skinned skeletal muscle fibers and cytosolic [Ca2+] in myotubes.	2003 Oct	12814911
Aristolochic acid, an herbal carcinogen, sold on the Web after FDA alert.	2003 Oct 16	14561805
The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids.	2003 Sep	14586714
Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement.	2003 Sep	12949730
Arachidonic acid regulates surface expression of epithelial sodium channels.	2003 Sep 19	12837767
Role of phospholipase A2 activation and calcium in CYP2E1-dependent toxicity in HepG2 cells.	2003 Sep 5	12813050
Insecticidal activity of chemical constituents from Aristolochia pubescens against Anticarsia gemmatalis larvae.	2004 Apr	15119605
Transcriptional activation of Igl, the gene for indole formation in Zea mays: a structure-activity study with elicitor-active N-acyl glutamines from insects.	2004 Apr	15110684
DNA adducts and p53 mutations in a patient with aristolochic acid-associated nephropathy.	2004 Apr	15042566
[Cellular mechanism of renal proximal tubular epithelial cell injury induced by aristolochic acid I and aristololactam I].	2004 Feb	14970885
Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts.	2004 Feb 1	14743397
Phospholipase C, but not InsP3 or DAG, -dependent activation of the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle cells.	2004 Jan	14662735
An easy and rapid method to determine aristolochic acids I and II with high sensitivity.	2004 Jan	13680054
Herbal bioactivation: the good, the bad and the ugly.	2004 Jan 9	14672753
Fanconi's syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acid.	2004 Jun	15189173
Aristolochic acid nephropathy: what we know and what we have to do.	2004 Jun	15189168
Regulation of Na+ transport by aldosterone: signaling convergence and cross talk between the PI3-K and MAPK1/2 cascades.	2004 Jun	15039143
Arachidonic acid released by phospholipase A(2) activation triggers Ca(2+)-dependent apoptosis through the mitochondrial pathway.	2004 Jun 11	15070903
Purification of a Class B1 platelet aggregation inhibitor phospholipase A2 from Indian cobra (Naja Naja) venom.	2004 Mar	15134835
NMR regulatory analysis: determination and characterization of Chinese-herb aristolochic acids.	2004 Mar	15074585

Patents

Sample Use Guides

In Vivo Use Guide

The FDA has issued a strong warning to consumers to avoid herbs containing the chemical aristolochic acid

Route of Administration: Oral

In Vitro Use Guide

It was studied the mechanism of aristolochic acid I (AA-I) nephrotoxicity by analyzing the uptake, subcellular distribution, and intracellular targets of AA-I in the human kidney cell line HK-2 using immunocytochemistry, immunoprecipitation, and LC-MS/MS. In HK-2 cells incubated with 20 ug/mL AA-I for different periods of time (up to 12 h). AA-I was detected by a specific monoclonal antibody (MAb) against AA-I, both in the cytoplasm and nuclei. Nuclear localization depended on the exposure time. A protein with the molecular weight of 100 kDa was immunoprecipitated with the anti-AA-I MAb from the AA-I-treated cell lysates and was identified by LC-MS/MS as alpha-actinin-4

Name

Type

Language

ARISTOLOCHIC ACID

Common Name

English

ARISTOLOCHINE

Common Name

English

3,4-METHYLENEDIOXY-8-METHOXY-10-NITRO-1-PHENANTHRENECARBOXYLIC ACID

Systematic Name

English

ARISTOLOCHIC ACID [IARC]

Common Name

English

ARISTOLOCHIC ACID-I

Common Name

English

NSC-11926

Code

English

ARISTOLOCHIC ACID, PLANTS CONTAINING [IARC]

Common Name

English

Aristolochic acid [WHO-DD]

Common Name

English

8-METHOXY-6-NITROPHENANTHRO(3,4-D)-1,3-DIOXOLE-5-CARBOXYLIC ACID

Systematic Name

English

8-METHOXY-3,4-METHYLENEDIOXY-10-NITROPHENANTHRENE-1-CARBOXYLIC ACID

Systematic Name

English

ARISTOLOCHIA A

Common Name

English

ARISTOLOCHIC ACID A

Common Name

English

ARISTOLOCHIC ACID I

Common Name

English

ARISTOLOCHIC ACID [MI]

Common Name

English

PHENANTHRO(3,4-D)-1,3-DIOXOLE-5-CARBOXYLIC ACID, 8-METHOXY-6-NITRO-

Common Name

English

TARDOLYT

Brand Name

English

TR 1736

Code

English

TR-1736

Code

English

NSC-50413

Code

English

Code System Code Type Description

MESH

C000228