title: LC-MS- and (1)H NMR-Based Metabolomic Analysis and in Vitro Toxicological Assessment of 43 Aristolochia Species.
abstract: Species of Aristolochia are used as herbal medicines worldwide. They cause aristolochic acid nephropathy (AAN), a devastating disease associated with kidney failure and renal cancer. Aristolochic acids I and II (1 and 2) are considered to be responsible for these nephrotoxic and carcinogenic effects. A wide range of other aristolochic acid analogues (AAAs) exist, and their implication in AAN may have been overlooked. An LC-MS- and (1)H NMR-based metabolomic analysis was carried out on 43 medicinally used Aristolochia species. The cytotoxicity and genotoxicity of 28 Aristolochia extracts were measured in human kidney (HK-2) cells. Compounds 1 and 2 were found to be the most common AAAs. However, AA IV (3), aristolactam I (4), and aristolactam BI (5) were also widespread. No correlation was found between the amounts of 1 or 2 and extract cytotoxicity against HK-2 cells. The genotoxicity and cytotoxicity of the extracts could be linked to their contents of 5, AA D (8), and AA IIIa (10). These results undermine the assumption that 1 and 2 are exclusively responsible for the toxicity of Aristolochia species. Other analogues are likely to contribute to their toxicity and need to be considered as nephrotoxic agents. These findings facilitate understanding of the nephrotoxic mechanisms of Aristolochia and have significance for the regulation of herbal medicines.
authors.affiliation: Research Cluster Biodiversity and Medicines/Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy , 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
authors.forename: Johanna
authors.initials: J
authors.lastname: Michl
authors.affiliation: Royal Botanic Gardens , Kew, Richmond, Surrey, TW9 3AB, United Kingdom.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Kite
authors.forename: Stefan
authors.initials: S
authors.lastname: Wanke
authors.forename: Oliver
authors.initials: O
authors.lastname: Zierau
authors.forename: Guenter
authors.initials: G
authors.lastname: Vollmer
authors.forename: Christoph
authors.initials: C
authors.lastname: Neinhuis
authors.affiliation: Royal Botanic Gardens , Kew, Richmond, Surrey, TW9 3AB, United Kingdom.
authors.forename: Monique S J
authors.initials: MS
authors.lastname: Simmonds
authors.affiliation: Research Cluster Biodiversity and Medicines/Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy , 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Heinrich
mesh_terms: D030022:Aristolochia / Q000737:chemistry* / Q000235:genetics; D034341:Aristolochic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D055432:Metabolomics; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; C121135:aristolactam I; C000228:aristolochic acid I