Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions. The plants rhizome contains several alkaloids that individually target multiple molecular processes. These bioactive compounds, mechanistically correlate with the plant’s history of ethnobotanical use. Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents. Instead, they have been associated with clinical toxicities ranging from mouthwash induced leukoplakia to cancer salve necrosis and treatment failure. This review explores the historical use of S. canadensis, the molecular actions of the benzophenanthridine and protopin alkaloids it contains, and explores natural alkaloid variation as a possible rationale for the inconsistent efficacy and toxicities encountered by S. canadensis therapies. Current veterinary and medicinal uses of the plant are studied with an assessment of obstacles to the pharmaceutical development of S. canadensis alkaloid based therapeutics.
Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.
Black salve is a topical escharotic used for the treatment of skin cancer. Although promoted as a safe and effective alternative to conventional management by its proponents, limited clinical research has been undertaken to assess its efficacy and potential toxicities. Patients are increasingly utilizing the Internet as a source of health information. As a minimally regulated space, the quality and accuracy of this information vary considerably. This review explores four health claims made by black salve vendors, investigating its natural therapy credentials, tumour specificity, and equivalence to orthodox medicine in relation to skin cancer cure rates and cosmesis. Based upon an analysis of in vitro constituent cytotoxicity, in vivo post black salve histology, and experience with Mohs paste, black salve is likely to possess normal tissue toxicity with some cancer cell lines being relatively resistant to its effects. This may explain the incongruous case study reports of excessive scarring, deformity, and treatment failure.
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