[2][3] Although these compounds are widely associated with kidney problems, liver and urothelial cancers, the use of AA-containing plants for medicinal purposes has a long history.

Birthwort plants, and the aristolochic acids they contain, were quite common in ancient Greek and Roman medical texts, well-established as an herb there by the fifth century BC.

In the early first century, in Roman texts, Aristolochia is first mentioned as a component of frequently ingested medicines to treat things such as asthma, hiccups, spasms, pains, and expulsion of afterbirth.

[6] A similar condition previously known as Balkan endemic nephropathy (BEN), first characterized in the 1950s in southeastern Europe, was later discovered to be also the result of aristolochic acid (AA) consumption.

BEN is more slowly progressive than the nephritis that is seen in CHN, but is likely caused by low-level AA exposure, possibly from contamination of wheat flour seeds by a plant of the birthwort family, Aristolochia clematitis.

Degradation studies of the isolated 14C-labeled AA-I demonstrated that the carbon atom at ring position C4 of the benzyltetrahydroisoquinoline norlaudanosoline was incorporated exclusively in the carboxylic acid moiety of AAI.

When this study was repeated but using [4‑14C]-tetrahydropapaverine no labeled AAI was isolated; this observation established that a phenol oxidative reaction was required for the biosynthesis of AA-I from norlaudanosoline, further supporting the intermediacy of aporphine intermediates.

[15] A potential role for CYP80G2, a cytochrome P450 that has been demonstrated to catalyze the intramolecular C-C phenol coupling of several benzyltetrahydroisoquinolines, in this orientaline (7) to prestephanine (10) transformation has been suggested.

[14] This final transformation, that is stephanine (11) to AA-I (12), involves an uncommon oxidative cleavage of the B ring of the aporphine structure to give a nitro substituted phenanthrene carboxylic acid.

One study estimated, on average, detectable cancer develops ten years from the start of daily aristolochic acid consumption.

[6] A patient thought to have AAN can be confirmed through phytochemical analysis of plant products consumed and detection of aristolactam DNA adducts in the renal cells.

[6][7][22] Aristolactam I adducts that are bound to DNA are extremely stable; they have been detected in patient biopsy samples taken 20 years after exposure to plants containing aristolochic acid.