Solvent extracts of an herbal formula containing <i>Petasites hybridus</i> and <i>Tanacetum parthenium</i> inhibited the lung development in zebrafish embryos and demonstrated cytotoxicity in human lung cancer cell lines

Butterbur is an herbal formula made from parts of the Petasites hybridus and Tanacetum parthenium medicinal plants, which are traditionally used to treat inflammatory disorders. They are generally considered safe, though some constituents have known toxicities. Although anti-inflammatory herbs are useful in the treatment of respiratory conditions, in certain situations, they may also increase the risk of lung damage. This study was designed to evaluate the effect of Butterbur on embryonic lung development using zebrafish embryos. Butterbur was extracted using four solvents of varying polarity. The n-hexane and chloroform extracts inhibited the swim bladder (lung) formation in live zebrafish larvae. The chloroform extract showed a significant level of cytotoxicity in lung cancer cell lines. Petasin, a major constituent present in butterbur extracts, showed stronger binding affinity with zebrafish Sonic Hedgehog (Shh), a critical pathway in lung morphogenesis and carcinogenesis. The novel finding of this study highlights the Butterbur’s developmental toxicity and mechanistic actions, relevant to pharmacology and toxicology research. The findings from this study have also indicated that combining two or more medicinal plants in an herbal formulation can alter their biological activities. Hence, there is a strong need to re-evaluate the safety profiles of herbal formulas, as combining medicinal plants can unveil or potentiate unforeseen toxicities.