Great butterbur

A proven hepatocarcinogen, not a theoretical hazard. ACI rats given a 0.05 percent solution in drinking water all died or were killed moribund within 72 days with hepatic necrosis, haemorrhage and marked bile duct proliferation. At 0.01 percent, 8 of 10 rats surviving beyond 160 days developed liver tumours: haemangioendothelial sarcomas in 5 and liver cell adenomas in 5, two animals with both. No control animal developed a tumour. Like other 1,2-unsaturated pyrrolizidine alkaloids it is bioactivated in the liver to pyrrolic esters that alkylate DNA and sinusoidal endothelium, the mechanism of hepatic sinusoidal obstruction syndrome.

The acetylated congener of petasitenine. It belongs to the same 1,2-unsaturated class that carries the hepatotoxic and genotoxic liability of the group, and is hydrolysed toward petasitenine.

Notable for being shared with coltsfoot, Tussilago farfara, the source of the pharmacopoeial drug Kuan Dong Hua for which this plant's flower buds have historically been substituted. A patient given the wrong one of these two drugs is not protected by the substitution: both carry senkirkine, and this plant carries petasitenine as well.

Its description in 2019 makes the point that the alkaloid inventory of this plant is still being added to. Any statement about the total pyrrolizidine burden of a sample is limited by which alkaloids the assay was set up to look for, and new members of the series are still being found.

The principal non-alkaloid active of the genus. In 3T3-F442A preadipocytes it suppressed differentiation with an IC50 of 0.95 micromolar and reduced PPAR-gamma, C/EBP-alpha and aP2 expression. The activity is structurally specific: isopetasin and petasol, its close analogues, did not reproduce it, which the authors attribute to the C11-C12 double bond and the angeloyl ester. Petasin is also the compound to which the antispasmodic and leukotriene-inhibiting effects of butterbur extracts are attributed.

Included partly as a negative result: in the anti-adipogenic screen it was inactive where petasin was potent. The petasin to isopetasin ratio is used as a chemotype and quality marker across Petasites, and a product's activity cannot be inferred from total sesquiterpene content alone.

Inhibited adipogenesis in 3T3-L1 preadipocytes, reduced glucose uptake and triglyceride accumulation, and downregulated PPAR-gamma and its target genes dose-dependently. Its late discovery in this species is a good illustration of how much of the butterbur literature was generated in Petasites hybridus and only later checked in Petasites japonicus.

Concentration-dependently inhibited antigen-induced degranulation of RBL-2H3 mast cells measured by beta-hexosaminidase release, suppressed induction of inducible nitric oxide synthase and cyclooxygenase 2 in mouse peritoneal macrophages, and in an ovalbumin asthma model strongly reduced eosinophil, macrophage and lymphocyte accumulation in bronchoalveolar lavage fluid. This is the best-supported anti-allergic constituent of the leaf, in mice.

Petasitesin A significantly inhibited both prostaglandin E2 and nitric oxide production in RAW264.7 macrophages and suppressed inducible nitric oxide synthase and cyclooxygenase 2 expression. Because they were isolated from a hot water extract they are constituents that a decoction actually delivers, which is not true of every compound reported from this plant.

Inhibited prostaglandin E2 and nitric oxide production in RAW264.7 macrophages with potency comparable to petasitesin A. Its name reflects its first description in Cimicifuga; it is a good example of a phenolic marker shared across unrelated Asteraceae and Ranunculaceae drugs and therefore of no use for identity confirmation.

Ordinary dietary flavonols, responsible for a large part of the antioxidant capacity measured in this plant in vitro. They are not distinctive to the species and they are not what makes it either useful or dangerous.

The source text usually cited for the Chinese drug. Gives the actions as resolving toxin and dispelling stasis, for tonsillitis, abscesses and toxic sores, and venomous snakebite. The drug is defined as the rhizome and whole herb, harvested in summer and autumn. There is no entry for this plant in the Han, Tang, Song or Ming materia medica under its own name: as a Chinese drug it is a twentieth-century regional record, not a classical one.

Gives the actions as reducing swelling and stopping pain, resolving toxin and dispelling stasis, for traumatic injury and venomous snakebite. Records the local practice of pounding the fresh root and applying it around a snakebite wound. Nature and flavour are given as bitter and acrid, cool, at 9 to 15 g in decoction.

Establishes that the mainstream botanical source of Kuan Dong Hua through the dynasties was Tussilago farfara, while recording that the flower buds of Petasites japonicus were also used as Kuan Dong Hua in some periods. This is the documentary basis for treating the two as a substitution pair rather than as separate drugs that never meet.

The petioles and the young flower stalks, fuki and fuki-no-tou, are a normal seasonal vegetable, and the roots and stems have been used for migraine, tension headache and spasm in Japan and Korea. The traditional preparation always involves boiling and prolonged soaking with the water discarded, which is nominally for bitterness but has been shown to reduce the pyrrolizidine alkaloid content of the petioles and young spikes. A long record of food use is therefore not evidence that the untreated plant is safe.