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Attention, Aristolochia!

We use herbs daily, let it be in the kitchen or the medicine. After all, a little dash of herbs can´t hurt… right? Well, not really. Aristolochic acids are a group of chemical substances produced by the Aristolochiaceae family. They are very dangerous to human health, so much so that they are classified as Group I carcinogens. You wouldn´t expect such compounds in medicinal products. However, they are still contained in many traditional medicines, which are distributed worldwide without any supervision. How exactly are aristolochic acids dangerous and how could we prevent their detrimental consequences to human health? The group of Dr. Jiří Zavadil from the International Agency for Cancer Research in Lyon, France focused on exactly that in their new review published in the prestigious scientific journal Nature Reviews Cancer. The review was co-authored by Shefali Thakur, who graduated from the Faculty of Science, Charles University.

The first mention of the use of aristolochic acids dates to the 4th century BC. The application of these substances is well documented in ancient Greece and Rome and even in 18th century Europe. Even today, Aristolochia is part of traditional Chinese medicine. The first modern records of their toxicity can´t be found earlier than in the 1960s when they were attributed to ten cases of acute renal failure. Detailed research dates even later, specifically to the turn of the millennia. In 2001, the American Food and Drug Administration (FDA) issued a warning about the danger posed by products containing aristolochic acids. It wasn´t until 11 years later that they were classified as Group I carcinogens.

Aristolochia clematitis.
source: Wikipedia, author: Radio Tonreg

Before the year 2003 herbal products containing Aristolochia were very popular in Taiwan. A study of data from that period shows an increased risk of developing urinary tract or renal cancer and renal failure. Aristolochic acids leave a specific mutational signature in cancer cells. It is a unique pattern of mutations that can be connected to the cause of the mutation. Similarly, lung cancer cells have a mutational signature if the disease is caused by smoking or skin cancer caused by UV rays. Mutational signatures of aristolochic acids have been found in tumors of the urinary tract, liver, hepatobiliary tract, and occasionally in the gastrointestinal tract. However, the carcinogenic effect is not the only problem of the compounds in question. As early as 1969, it was hypothesized that aristolochic acids are connected to Balkan endemic nephropathy (BEN) which manifests itself by progressive unreversible renal failure. The disease probably arises when bread made from flour contaminated by seeds of Aristolochia clematitis is consumed. Aristolochic acids thus have strong nephropathic effects which means that they are very dangerous to the kidneys of affected people. Such damage can but doesn´t have to lead to cancer.

Many countries have banned the import of herbal products containing these acids as soon as the beginning of the millennium. However, it is still possible to buy these products in the USA, China, and several European countries without any limitations, and buying them on the Internet is possible worldwide. Unrelenting demand for these products probably stems from the trust people have in traditional medicine due to its use for a very long time.

Aristolochia gigantea
source: Wikipedia, author: Nevit Dilmen

Aristolochic acids can get into our bodies not only from herbal medicine but also directly from our environment. The Aristolochiaceae family grows as uncontrolled weeds in southeast Asia, tropical Africa, Oceania, and both Americas. In these areas, its toxins can leak into the soil from where they get into underground water and into crops planted in such soil, thus getting another way into the food chain.

Early detection of aristolochic acids in herbal products, live plants, and humans is crucial to preventing the consequences of exposure. The widely applied method of analysis of plant material is high-performance liquid chromatography (HPLC) which can separate individual chemicals in the extract so they can be identified one by one. To determine the extent of exposure scientists, detect chemical changes in DNA or subsequent mutational signatures typical for aristolochic acids.

Looking at current data, there is no doubt about the toxicity and carcinogenicity of aristolochic acids. However, well-thought-out programs for the elimination of exposure to these substances are still missing. Scientists think it is caused by several factors. Firstly, the perseverance of aristolochic acids in the environment is unknown, and secondly, the situation concerning the extent of exposure is very chaotic. Even in countries, where the distribution of herbal products is strictly under control, over half of all sales happen outside of system control. On top of that, it is very hard to determine the amount of aristolochic acids in herbal products without specialized equipment and knowledge. Lastly, the complete extent of dangers that these compounds can pose is still unknown. The list of cancers that can be caused by Aristolochia is still growing and other problems are recorded worldwide. Thus, it is still very much needed to strengthen the knowledge about the dangers that these plants pose.

Das, S., Thakur, S., Korenjak, M. et al. Aristolochic acid-associated cancers: a public health risk in need of global action. Nat Rev Cancer (2022)

Magda Křelinová

Published: Sep 15, 2022 09:40 PM

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