Bakkenolide B and Butterbur Leaf Extract: The Other Half of Petasites japonicus
The short answer
Bakkenolide B is a sesquiterpene lactone. It is the principal bakkenolide in the leaves of Japanese butterbur, Petasites japonicus, and the usual quality marker for its ethanolic leaf extracts. It is not the leaf's only active chemistry: the same leaf carries caffeic-acid esters such as fukinolic acid, a polar sesquiterpene glycoside and eremophilane esters such as S-petasin. Which of these ends up in an extract depends on the solvent, so the marker has to match the solvent.
"Butterbur leaf extract" is not one product. For many buyers it means the European hay-fever extract, made from the leaves of Petasites hybridus and standardised on petasins. The leaf research on Japanese butterbur points somewhere else entirely.
The Japanese leaf holds several distinct chemistries in the same tissue, and extraction decides which of them reach the powder. A specification that names the wrong marker is measuring a different product from the one being sold.
Bakkenolide B is the right marker for an ethanolic leaf extract of Petasites japonicus. It is not a description of everything the leaf contains.
This guide to bakkenolide B sets out how Japanese and European leaf extracts differ and how the market blurs them, which solvent carries each of the Japanese leaf's chemistries, why bakkenolide B became the quality marker and what it leaves out, how plant part and season move the number, what to watch in the HPLC method, what the research does and does not show, and how to write a leaf-extract specification.
01 Two extracts
Two Leaf Extracts Under One Name
| European Butterbur Leaf Extract | Japanese Butterbur Leaf Extract | |
|---|---|---|
| Species | Petasites hybridus | Petasites japonicus |
| Standardised on | Petasins[1] | Bakkenolide B, or total bakkenolides |
| Typical process | Sub-critical CO2 for the approved product[1] | Ethanol or water, depending on the chemistry targeted |
| Leaf chemistry | Petasins, reported at 3.3–11.4 mg/g in dried leaves[2] | Bakkenolides, caffeic-acid esters, a sesquiterpene glycoside and eremophilane esters |
| Human clinical data | Trials in seasonal allergic rhinitis on one proprietary extract | None published that we are aware of |
The two are not interchangeable. A Japanese leaf extract specified on petasins borrows a European standardisation logic that its own research literature does not support, and the rhinitis trials run on the European extract cannot be cited for a Japanese one. Two species, two chemistries and two evidence bases share a single English name.
The market blurs them further. Many Japanese butterbur leaf extracts are sold as plain ratio extracts, such as 10:1, with no marker at all. Others are quoted on petasins borrowed from the European product. One listing on a major B2B marketplace offers a "Petasites japonicus extract" quoted at 15% petasins, names P. hybridus in the same title, and gives CAS 60102-37-6 as its marker. That is the CAS number of petasitenine, the plant's carcinogenic pyrrolizidine alkaloid, not of any petasin.
02 Chemistry
Several Chemistries in One Leaf
The Japanese butterbur leaf is chemically crowded, and the anti-allergic activity reported for it has not been pinned to a single compound class.
| Chemistry | Main Compounds in the Leaf | Polarity | Solvent That Carries It | Role in the Leaf Literature |
|---|---|---|---|---|
| Bakkenolides (sesquiterpene lactones) | Bakkenolide B, bakkenolide D, petatewalide B | Lipophilic | Ethanol; bakkenolide B was isolated from the hexane fraction of a 70% ethanol extract[2] | Bakkenolide B and petatewalide B named as active anti-allergic compounds[3] |
| Eremophilane esters | S-petasin, petasin | Lipophilic | Stronger ethanol; petasin extraction rises with ethanol concentration[4] | Present, but not the focus of the leaf's anti-allergic work |
| Caffeic-acid esters and related polyphenols | Fukinolic acid, chlorogenic acids | Polar | Water and aqueous ethanol; the main component of one hot-water leaf extract[5] | Most potent mast-cell inhibitor in one activity-guided study[6] |
| Sesquiterpene glycoside sulphate | Fukinoside A | Polar | Aqueous solvents, by polarity | Named among the active anti-allergic compounds[1] |
The polyphenol side is not a footnote. In the study that screened a Japanese butterbur aerial-part extract compound by compound, the most potent inhibitor of mast-cell degranulation was fukinolic acid, a polyphenol, with an IC50 of 2.1 μg/mL.[6] A review of the genus lists fukinoside A, bakkenolide B and petatewalide B together as the active anti-allergic compounds.[1]
Solvent strength decides the mix. A Korean study on the leaves found that petasin extraction rose steadily with ethanol concentration, with an optimum near 80% ethanol. The same group recorded very low bakkenolide B in their extracts compared with the S-petasin levels of up to 680 μg/g that ethanol had given them in earlier work, and attributed the difference to the polarity of the solvents used.[4] At the other end of the range, a hot-water leaf extract studied in 2025 was standardised on fukinolic acid, which made up 26.5 mg/g of it.[5] Hot water does still carry some bakkenolide B: another Korean group optimised its hot-water extraction by temperature, time and pH.[7]
The same leaf, extracted two ways, is two different ingredients.
This is the fact most leaf-extract specifications skip. A strongly ethanolic extract concentrates bakkenolides and eremophilane esters. A water or weakly alcoholic extract concentrates caffeic-acid esters and polar glycosides, with bakkenolides as a minor fraction. A marker chosen without reference to the solvent will be a real number that describes the smaller part of the product.
03 Marker
Why Bakkenolide B Is the Marker
| Bakkenolide B at a Glance | |
|---|---|
| CAS number | 18455-98-6 |
| Formula and molecular weight | C22H30O6, 390[2] |
| Class | Bakkenolide-type sesquiterpene lactone: a cis-hydrindane skeleton with a spiro-fused β-methylene-γ-butyrolactone[1] |
| Side chains | One acetate and one angelate ester[2] |
| Polarity | Lipophilic; isolated from the hexane fraction of an ethanol extract[2] |
| Best HPLC-UV response | 210–215 nm[2] |
| Where it concentrates | Leaf rather than petiole or rhizome; younger leaves; earlier in the season[2] |
The case for bakkenolide B rests on a validated method as well as on pharmacology. The study that isolated it from mast-cell-active leaf material described it as a major component of the leaves.[3] A later Korean group developed a validated HPLC method for it, described it as the major sesquiterpene lactone in P. japonicus and proposed it as the basis for quality evaluation, finding it at higher levels in the leaf than in the petiole or rhizome.[2]
The wording matters. Bakkenolide B is the major lactone. A bakkenolide B specification tells a buyer the strength of the lactone fraction of an ethanolic leaf extract, and that the material behaves like leaf rather than root. It says nothing about fukinolic acid, fukinoside A or the other polar actives.
That limit shows up in the data. In the Korean study that optimised hot-water extraction of the leaves for bakkenolide B, the extracts' ability to inhibit mast-cell degranulation correlated poorly with their bakkenolide B content.[7] A marker is a measure of consistency and identity. It is not a measure of total activity, and the two should not be confused on a label or in a sales conversation.
A marker is a measure of consistency and identity. It is not a measure of total activity.
Bakkenolides also occur in other Petasites species, so bakkenolide B supports identity without proving it. The identity question is covered in Petasites japonicus vs Petasites hybridus: Japanese and European butterbur compared.
04 Content
How Much the Leaf Contains, and Where
The natural level. The open literature gives no direct figure for bakkenolide B in the dried leaf. What it does give is an isolation yield: the Korean group recovered 173.8 mg of purified bakkenolide B from 1 kg of fresh leaves, a figure that can only understate what was there.[2] Whatever the exact natural level, leaf grades specified at 7.5–15% total bakkenolides are concentrates. A buyer is entitled to ask how the figure is reached and what share of it is bakkenolide B itself.
Plant part: why "total bakkenolides" needs a name. Total bakkenolides is a looser specification than it sounds, because different bakkenolides concentrate in different organs. In a Korean analysis of methanol extracts, bakkenolide D reached 107 mg per gram of extract from the root, against 0.4–4.4 mg/g in extracts of the other parts.[8] Bakkenolide B runs the other way, highest in the leaf.[2] A leaf extract specified only on total bakkenolides could reach part of its figure on root-derived bakkenolide D if underground material entered the process. Naming bakkenolide B as the principal constituent, stating the plant part and separating leaves from underground parts at harvest close that gap.
Season: earlier harvest, higher content. In the same Korean work, leaf, petiole and rhizome were sampled monthly from March to August. Bakkenolide B fell in all three as collection moved later into the season, and was concentrated in the younger, metabolically active leaves.[2] Harvest timing is part of the specification the plant hands to the extractor, and late-summer leaves are a weaker starting material for a bakkenolide extract than spring leaves.
05 Measurement
Measuring Bakkenolide B
A weak chromophore. Bakkenolide B absorbs weakly in the ultraviolet. In the validated Korean method, the response was strongest at 210–215 nm and weaker at 235, 254 and 265 nm.[2] Detection that low in the UV brings a cost: almost every organic compound in a plant extract absorbs there too. Whether the bakkenolide B peak is cleanly separated from its neighbours matters more here than for most markers, and a result is only as good as the method's demonstrated specificity.
Different wavelengths for different bakkenolides. Published bakkenolide methods do not all detect at the same wavelength. The bakkenolide D study used 290 nm,[8] and a method for four bakkenolides in a related species switched between 265 and 235 nm.[2] That is a direct consequence of the compounds' different UV behaviour, and it raises the same problem covered for the petasins in Total Petasins explained: petasin, isopetasin and how to specify butterbur extract. A total bakkenolides figure calculated entirely against a bakkenolide B calibration at one wavelength will misstate any bakkenolide that responds differently. A total built from several compounds needs a response factor for each.
Reference standards. Bakkenolide B is available as a research-grade reference compound, and published methods have used material isolated in-house at 97–98% purity.[2] A laboratory has no reason to report bakkenolides without a bakkenolide B standard.
06 Evidence
What the Research Shows, and What It Doesn't
Preclinical activity. The best-known bakkenolide B study found that it inhibited antigen-induced degranulation in mast cells, suppressed induction of iNOS and COX-2 in mouse macrophages, and showed activity in an ovalbumin-induced asthma model.[3] The polyphenol side has its own evidence: an aqueous-ethanol extract of the aerial parts suppressed passive cutaneous anaphylaxis in rats at a single oral dose of 1,000 mg/kg, and inhibited leukotriene synthesis and TNF-α release in mast cells.[6] All of this is laboratory and animal work.
Human data. We are not aware of any published controlled human trial on a P. japonicus leaf extract.
Food use and safety. The leaf itself is food: in Korea it is eaten as a wild leafy vegetable.[2] Single-dose, repeated-dose and genotoxicity studies on the leaves have been published, with a no-observed-adverse-effect level of 5,000 mg/kg/day in a two-week rat study and no mutagenicity.[1] That is short-term data, not a chronic study.
Alkaloids. Leaf extracts need the same pyrrolizidine alkaloid testing as root extracts. How alkaloid levels differ between the plant's parts, and what a PA result has to state, is set out in Pyrrolizidine alkaloids in butterbur: why the standard EU panel misses Petasites japonicus.
07 Specification
Writing a Leaf-Extract Specification
A leaf-extract specification that can be compared across suppliers states six things.
The marker, by name. Write "bakkenolide B" as the principal constituent. If the figure is a total, list the bakkenolides included, the compound the total is calculated as, and the bakkenolide B content on its own.
The plant part and the harvest window. State "leaf" rather than "aerial parts" if petioles and flower stalks are excluded, and give the harvest months.
The solvent and its strength. An ethanol percentage tells a buyer which of the leaf's chemistries the extract carries before any assay is read. In the published leaf work, bakkenolide B was isolated from a 70% ethanol extract, petasin extraction peaked near 80% ethanol, and a fukinolic-acid-rich extract was made with hot water.
The detection wavelength and specificity. For a marker read at 210–215 nm, the method's resolution from neighbouring peaks is part of the result.
A second marker where the positioning needs it. A product built on the polyphenol literature should specify fukinolic acid alongside bakkenolide B, because the bakkenolide figure says nothing about it.
The basis. State dry basis or as-is, with the loss-on-drying method, for the reasons set out for the root line.
PhytoVale's leaf line is ethanol-extracted and standardised on Total Bakkenolides at 7.5%, 10% and 15% by HPLC, with bakkenolide B as the principal constituent. It is made from leaves separated from underground parts at harvest, between March and June, on the company's own Petasites japonicus base in Henan. Grades and specifications are on the Petasites japonicus extract product page. Samples are free, MOQ is 1 kg, and quotations are returned within 24 hours.
08 Questions
Bakkenolide B: Frequently Asked Questions
Is bakkenolide B stable in storage?
No published stability study on bakkenolide B in extracts turned up in our review. The molecule carries two ester side chains, an acetate and an angelate, and esters are generally vulnerable to hydrolysis under alkaline or hot, wet conditions. Until data exist, ask the supplier for re-test results on aged lots rather than assuming stability.
What is fukinolic acid?
It is a caffeic-acid ester first described from Petasites japonicus, from which it takes its name (fuki), and it also occurs in black cohosh. It is the polyphenol most associated with the Japanese leaf's anti-allergic activity in laboratory studies. It is polar, so it concentrates in water and aqueous-ethanol extracts rather than strong ethanol ones.
Is a bakkenolide B reference standard available?
Yes. It is sold as a research-grade compound under CAS 18455-98-6. Any laboratory reporting bakkenolides should be able to name its standard and the standard's purity.
Can butterbur leaf extract be used in drinks and water-based products?
It depends on how the extract was made. A strong ethanolic extract rich in bakkenolides and eremophilane esters is lipophilic and disperses poorly in water. A water or aqueous-ethanol extract rich in polyphenols suits beverages better. Choose the extract type for the format before choosing the grade.
Is Japanese butterbur leaf a novel food in the EU?
Check before launch. A food with at least 25 years of customary use in a third country can use the EU's simplified traditional-food route, but the Novel Food Catalogue sometimes treats different extract forms of the same plant differently. For lion's mane, for example, only the aqueous extract is explicitly listed as not novel. The status of the leaf as eaten does not automatically carry over to an ethanolic extract.
Can leaf and root extracts be combined in one formula?
Yes. Specify each on its own marker, Total Petasins for the root and bakkenolide B for the leaf, account for pyrrolizidine alkaloids separately for each, and calculate the finished product's PA load from both inclusion rates.
09 Evidence base
References
[1] Kulinowski, Ł., Luca, S. V., Minceva, M., Skalicka-Woźniak, K. (2022). A review on the ethnobotany, phytochemistry, pharmacology and toxicology of butterbur species (Petasites L.). Journal of Ethnopharmacology, 293, 115263. DOI: 10.1016/j.jep.2022.115263
[2] Isolation, quality evaluation, and seasonal changes of bakkenolide B in Petasites japonicus by HPLC. Journal of Life Science, 2014, 24(3), 252–259. View source
[3] Lee, K. P., Kang, S., Park, S. J., Choi, Y. W., Lee, Y. G., Im, D. S. (2013). Anti-allergic and anti-inflammatory effects of bakkenolide B isolated from Petasites japonicus leaves. Journal of Ethnopharmacology, 148, 890–894. DOI: 10.1016/j.jep.2013.05.037
[4] Optimization of a process for extraction of petasin from Petasites japonicus leaves by response surface methodology. View source
[5] Anti-photoaging effects of a standardized hot water extract of Petasites japonicus leaves in ultraviolet B-exposed hairless mice. Pharmaceuticals, 2025, 18, 1490. View source
[6] Shimoda, H., Tanaka, J., Yamada, E., Morikawa, T., Kasajima, N., Yoshikawa, M. (2006). Anti type I allergic property of Japanese butterbur extract and its mast cell degranulation inhibitory ingredients. Journal of Agricultural and Food Chemistry, 54, 2915–2920. DOI: 10.1021/jf052994o
[7] Optimization of extraction conditions for bakkenolide B from the leaves of Petasites japonicus by using response surface methodology. Korean study, cited in [4].
[8] Quilantang, N. G., Lee, K. H., Lee, D. G., Lee, J. S., Cho, E. J., Kim, H. Y., Lee, S. (2017). Quantitative determination of bakkenolide D in Petasites japonicus and Farfugium japonicum by HPLC/UV. Natural Product Sciences, 23(4), 270. DOI: 10.20307/nps.2017.23.4.270
Reviewed by
Prof. Bingji MaScientific Advisor at PhytoVale. Professor and medicinal plant science expert. Research focus covers Chinese medicinal materials, phytochemistry, natural products and medicinal plant quality.
Written by
FloraContent Editor at PhytoVale. Product content and editorial specialist, focused on botanical ingredient specifications, sourcing information and B2B technical content.
This article is intended for ingredient sourcing, formulation and technical information only. It is not medical advice and makes no health claim for any PhytoVale product. Pharmacological findings are cited as compound-level, preclinical research context. The solvent figure in section 02 is a schematic summary of published extraction studies, not a measured distribution. Composition varies with plant part, harvest time, solvent and method, so specifications should always be agreed on the method as well as the number.
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