Aristolochic acid

Aristolochic acid is a carcinogenic, aromatic compound found in hundreds of Aristolochia species of plants found worldwide as a 1:1 mixture of two compounds, denoted AA1 and AA2. Despite links to endemic (Balkan) nephropathy (1,2), which leads to kidney failure and often death, Aristolochic acid is still used in some herbal supplements. Due to kidney failure and renal carcinoma associated with herbal diet supplements, its use is banned in several countries.

Aristolochia species have been used for centuries in traditional medicines (3). A. clematitus (birthwort) was used to induce labor, expel the placenta and abort pregnancies. Other Aristolochia-based recipes were used to treat asthma, gout and bladder stones in Greek and Roman regions. In North America, Native Americans used A. serpentaria (Virginia Snakeroot) to treat snake bites. Presently, Aristolochia extracts are still used in weight loss supplements (A. fangchi), as diuretics (A. manshuriensis), for the treatment of asthma (A. heterophylla) and to suppress coughs (A. debillis). The seeds, leaves, roots and stalks of all Aristolochic plants are poisonous.

Renal Carcinoma
Aristolochic acid causes cancer in the kidneys by forming adducts with DNA (1). Specificially, aristolochic acid bonds to either adenine or guanine bases to make either dA-aristolactam or dG-aristolactam, respectively. These adducts can then, for example, mutate an A:T DNA base pair to a T:A base pair in the p53 tumor suppressor protein.

Referencess
1. A. P. Grollman et al. "Aristolochic acid and the etiology of endemic (Balkan) nephropathy", Proc. Natl. Acac. Sci. U.S.A., 104:12129-34, 2007.

2. J. C. Mead, "Manna from Hell", The Scientist 21(11):44-51, 2007.

3. K. M. Wu, et al. "Complexities of the herbal nomenclature system in traditional Chinese medicine (TCM): Lessons learned from the misuse of Aristolochia-related species and the importance of the pharmaceutrical name during botanical drug product development", Phytomedicine, 14:273-9, 2007.