Butterbur (Petasites hybridus) and Menstrual cramps: evidence and sources

For hundreds of years butterbur (Petasites hybridus) has been used against many diseases. Modern indications are the prophylaxis of migraine, tension headache, spasms of the urogenital tract, gastro-intestinal tract and bile duct and hopefully hay fever and asthma in the near future. The petasines, the main components of butterbur, inhibit the synthesis of leucotrienes and decrease the intracellular concentration of calcium which explains the anti-inflammatory and spasmolytic properties of extracts of butterbur. Thanks to extraction with supercritical CO(2) the concentrations of the potentially hepatotoxic and carcinogenic pyrrolizidine alkaloids lie below the detection limits. Until now four cases of a reversible cholestatic hepatitis have been probably associated with long-term administration of butterbur (incidence of 1:175.000). It is unknown which components of butterbur are responsible for the long-term hepatotoxicity. Further side effects involve the gastrointestinal tract and are usually mild.

Ethnopharmacological relevance Petasites (butterbur, Asteraceae) species have been used since Ancient times in the traditional medicine of Asian and European countries to treat central nervous system (migraine), respiratory (asthma, allergic rhinitis, bronchitis, spastic cough), cardiovascular (hypertension), gastrointestinal (ulcers) and genitourinary (dysmenorrhea) disorders. Aim of the review This study summarized and discussed the traditional uses, phytochemical, pharmacological and toxicological aspects of Petasites genus. Materials and methods A systematic search of Petasites in online databases (Scopus, PubMed, ScienceDirect, Google Scholar) was performed, with the aim to find the phytochemical, toxicological and bioactivity studies. The Global Biodiversity Information Facility, Plants of the World Online, World Flora Online and The Plant List databases were used to describe the taxonomy and geographical distribution. Results The detailed phytochemistry of the potentially active compounds of Petasites genus (e.g. sesquiterpenes, pyrrolizidine alkaloids, polyphenols and essential oils components) was presented. The bioactivity studies (cell-free, cell-based, animal, and clinical) including the traditional uses of Petasites (e.g. anti-spasmolytic, hypotensive, anti-asthmatic activities) were addressed and followed by discussion of the main pharmacokinetical and toxicological issues related to the administration of butterbur-based formulations. Conclusions This review provides a complete overview of the Petasites geographical distribution, traditional use, phytochemistry, bioactivity, and toxicity. More than 200 different sesquiterpenes (eremophilanes, furanoeremophilanes, bakkenolides), 50 phenolic compounds (phenolic acids, flavonoids, lignans) and volatile compounds (monoterpenes, sesquiterpenes) have been reported within the genus. Considering the phytochemical complexity and the polypharmacological potential, there is a growing research interest to extend the current therapeutical applications of Petasites preparations (anti-migraine, anti-allergic) to other human ailments, such as central nervous system, cardiovascular, malignant or microbial diseases. This research pathway is extremely important, especially in the recent context of the pandemic situation, when there is an imperious need for novel drug candidates.

Petasides hybridus (butterbur) is a perennial shrub, found throughout Europe as well as parts of Asia and North America, that has been used medicinally for centuries. During the Middle Ages butterbur was used to treat plague and fever; in the 17th century its use was noted in treating cough, asthma, and skin wounds. The plant can grow to a height of three feet and is usually found in wet, marshy ground, in damp forests, and adjacent to rivers or streams. Its downy leaves can attain a diameter of three feet, making it the largest of all indigenous floras, and their unique characteristics are responsible for the plant's botanical and common names. The genus name, Petasites, is derived from the Greek word petasos, which is the felt hat worn by shepherds. The common name of butterbur is attributed to the large leaves being used to wrap butter during warm weather. Other common names include pestwurz (German), blatterdock, bog rhubarb, and butter-dock. Currently, the primary therapeutic uses for butterbur are for prophylactic treatment of migraines, and as an anti-spasmodic agent for chronic cough or asthma. It has also been used successfully in preventing gastric ulcers, and in treating patients with irritable bladder and urinary tract spasms.