The old herbal drug aristolochic acid (AA), derived from Aristolochia spp., has been associated with the development of a novel nephropathy, designated aristolochic acid nephropathy (AAN), and urothelial cancer in AAN patients. There is clear evidence that the major components of the plant extract AA, aristolochic acid I (AAI) and aristolochic acid II (AAII), both nitrophenanthrene carboxylic acids, are genotoxic mutagens forming DNA adducts after metabolic activation through simple reduction of the nitro group. Several mammalian enzymes have been shown to be capable of activating both AAI and AAII in vitro and in cells. The activating metabolism has been elucidated and is consistent with the formation of a cyclic nitrenium ion with delocalized charge leading to the preferential formation of purine adducts bound to the exocyclic amino groups of deoxyadenosine and deoxyguanosine. The predominant DNA adduct in vivo, 7-(deoxyadenosin-N(6)-yl)aristolactam I (dA-AAI), which is the most persistent of the adducts in target tissue, is a mutagenic lesion leading to AT-->TA transversions in vitro. This transversion mutation is found at high frequency in codon 61 of the H-ras oncogene in tumours of rodents induced by AAI, suggesting that dA-AAI might be the critical lesion in the carcinogenic process in rodents. DNA-binding studies confirmed that both AAs bind to the adenines of codon 61 in the H-ras mouse gene and preferentially to purines in the human p53 gene. In contrast, the molecular mechanism of renal interstitial fibrosis in humans after chronic administration of AA remains to be explored. However, preliminary findings suggest that DNA damage by AA is not only responsible for the tumour development but also for the destructive fibrotic process in the kidney. It is concluded that there is significant evidence that AA is a powerful nephrotoxic and carcinogenic substance with an extremely short latency period, not only in animals but also in humans. In particular, the highly similar metabolic pathway of activation and resultant DNA adducts of AA allows the extrapolation of carcinogenesis data from laboratory animals to the human situation. Therefore, all products containing botanicals known to or suspected of containing AA should be banned from the market world wide.

Aristolochic acid as a probable human cancer hazard in herbal remedies a review

Publisher Summary The polymers are embedded in or associated with a complex mixture of relatively nonpolar lipids that are collectively called wax because of the similarity of their physical properties to those of the honeycomb material. In most plants, wax can be found on the surface and the crystalline structure of this wax is a rather unique characteristic of each species. The most widespread site of occurrence of wax is the cuticle, and the abundance of production of cuticular waxes by some aerial parts of plants allows easy removal of the most familiar and widely utilized plant waxes such as carnauba wax. Internal organs usually contain little wax, except in rare plants such as jojoba in which large amounts of wax esters are stored as the major energy reserve. This chapter presents a methodology that is useful for examining waxes and polymerized lipids. It discusses the types of compounds found in plant waxes and in lipid-derived polymers and explains their biosynthesis, degradation, and possible functions.

Cutin, suberin, and waxes

Local uses of Aristolochia species and content of nephrotoxic aristolochic acid 1 and 2—A global assessment based on bibliographic sources

Naturally occurring aristolactams, aristolochic acids and dioxoaporphines and their biological activities

https://www.kidney-international.org/article/S0085-2538(15)50657-1/pdf

Horacio A. Priestap

Papers

Seven aristololactams from Aristolochia argentina

Volatile constituents of Aristolochia argentina.

Minor aristolochic acids from Aristolochia argentina and mass spectral analysis of aristolochic acids

Aristololactams of Aristolochia argentina

Volatile constituents of leaves, roots and stems from Aristolochia elegans