Ingredients7-Hydroxyfrullanolide (abbreviated 7HF; also written as 7-hydroxy frullanolide) is the systematic name for the compound formally designated as (3aR,5aR,9bS)-3a-hydroxy-5a,9-dimethyl-3-methylene-3,3a,4,5,5a,6,7,8-octahydronaphtho[1,2-b]furan-2(9bH)-one. It is an orally bioavailable, small-molecule sesquiterpene lactone. The compound carries CAS Registry Number 105578-87-8. Its parent scaffold is the eudesmanolide-type sesquiterpene lactone, and the unhydroxylated parent compound, frullanolide, carries the molecular formula C15H20O2 with a molecular weight of 232.3 g/mol. Frullanolide is a natural eudesmanolide-type sesquiterpene lactone (SL) with the molecular formula C15H20O2 and a molecular weight of 232.3 g/mol. 7-Hydroxyfrullanolide is the 7α-hydroxylated derivative of this scaffold, adding one hydroxyl group at the C-7 position, which is reflected in its full stereochemical name and its slightly higher molecular weight.
The compound belongs to the broader chemical class of sesquiterpene lactones (SLs), terpenoid compounds that are structurally defined by a 15-carbon skeleton and a lactone-containing ring system. Sesquiterpene lactones are a class of anti-inflammatory molecules obtained from plants belonging to the Asteraceae family.
In the literature, 7-hydroxyfrullanolide is most often referred to by the stereodescriptor 7-α-hydroxyfrullanolide (the hydroxyl group at C-7 is in the α-orientation), and both designations — "7-hydroxyfrullanolide" and "7-α-hydroxyfrullanolide" — are used interchangeably across the peer-reviewed record. The stereochemistry at the lactone fusion centers is indicated by the (3aR,5aR,9bS) configuration in the IUPAC name.
7-Hydroxyfrullanolide has been isolated from at least two distinct plant species within the Asteraceae (daisy/Compositae) family:
The new sesquiterpene compounds identified from S. indicus flowers include 11α,13-dihydro-3α-(β-glucopyranosyl),7α-hydroxyfrullanolide; 11α,13-dihydro-7α-hydroxy-13-methoxyfrullanolide; 7α-hydroxyeudesm-4-ene-6,12-β-olide; 11α,13-dihydro-7α,13-dihydroxyfrullanolide; and 11α,13-dihydro-3α,7α-dihydroxyfrullanolide, alongside known compounds caryophyllene-α-oxide and a plant sterol. 7α-Hydroxyfrullanolide, 7α-hydroxyeudesmanolide, and dihydrocholesterol were isolated from the Sphaeranthus indicus extract.
In research and commercial applications, 7HF is obtained from plant extracts through solvent-based chromatographic isolation. Fractions eluted with 20–25% ethyl acetate/hexane yielded semi-pure 7-hydroxyfrullanolide (91% purity), which was finally purified on a silica column using chloroform/hexane mixtures with fractions eluted at 25–35% chloroform/hexane combined to give pure 7-hydroxyfrullanolide (7.3 g, 99% purity).
In commercial dietary supplement applications, S. indicus extracts are standardized to defined concentrations of 7HF:
7-Hydroxyfrullanolide is a constituent of Sphaeranthus indicus, a plant with a deep and well-documented history in South Asian traditional medicine systems. Sphaeranthus indicus Linn. (Asteraceae) is widely used in the Ayurvedic system of medicine to treat vitiated conditions of epilepsy, mental illness, hemicrania, jaundice, hepatopathy, diabetes, leprosy, fever, pectoralgia, cough, gastropathy, hernia, hemorrhoids, helminthiasis, dyspepsia and skin diseases.
The plant's legacy dates back to ancient Sanskrit texts, where it is referred to as "Gorakshaganjha" in the Charaka Samhita (circa 1st–2nd century CE), and early Ayurvedic scholars lauded its balancing effects on Vata and Kapha doshas, especially in conditions characterized by chronic swelling or vitiated wind. Regional folk healers in Maharashtra and Karnataka used fresh leaf juice for topical applications in boils and abscesses, while in the Siddha tradition of South India, decoctions of the whole plant found a place in treating elephantiasis-like swellings and chronic skin eruptions.
S. indicus is traditionally used in Ayurvedic medicine for conditions such as epilepsy, mental illness, skin diseases, jaundice, joint disorders, and it also possesses rasayana (rejuvenative) properties. The plant is known across multiple Indian medical traditions: Revered in Ayurveda, Siddha, and Unani practices, this versatile herb has been used for centuries to support overall well-being and address a myriad of health concerns.
Different parts of this plant, including its leaves, stems, bark, roots, flowers, and seeds, have been used in traditional medicine to treat various ailments, attributable to the diverse range of phytochemicals present — including eudesmanolides, sesquiterpenoids, and flavone glycosides — and essential oils in the flowers and whole plant containing monoterpene hydrocarbons and oxygenated sesquiterpenes.
The second botanical source of 7HF, Grangea maderaspatana, also has an established ethnopharmacological record. This plant is widely found in many tropical countries and has often been used in various traditional medicine applications, including promotion of menstruation, antispasmodic activity, and relief from stomach ache, coughs, and ear ache; in Thai ethnopharmacology, this species is referred to as a "bitter tonic" and is often used for treating flatulence and diarrhea. It has been used for thousands of years in traditional Ayurvedic Indian medicine to treat a number of diseases, with studied properties including oestrogenicity, antifertility, analgesic, anti-inflammatory, antiarthritic, cytotoxic, antioxidant, hepatoprotective, diuretic, and antibacterial effects; the leaves have stomachic, sedative, carminative, emmenagogue, and antiflatulent properties.
Historically, S. indicus was administered in multiple traditional forms. Ayurvedic texts describe aqueous decoctions (kwatha) of the whole plant or its flowers as the most common oral preparation. Whether taken as a powder, decoction, or blended preparation, the plant continues to play a vital role in natural wellness traditions. It should be noted clearly that, while 7HF is the primary bioactive marker compound isolated from these traditional medicines, the traditional use pertained to the whole-plant preparations — not the isolated compound itself, which has only been characterised and investigated scientifically in the modern era.
The allergenic and bioactive properties of sesquiterpene lactones, including frullanolide-type compounds, are linked with the presence of the α-methylene-γ-butyrolactone group in their structure — the same structural element that underlies both their pharmacological activity and their potential for contact sensitization.
Studies on 7HF have shown it to exert strong biological effects, including anti-bacterial, anti-inflammatory, and anticancer effects.
The most extensively characterized mechanism of 7HF is its inhibition of the NF-κB signaling pathway, a master regulator of pro-inflammatory gene transcription.
7HF has been documented to engage multiple oncology-relevant molecular pathways:
7-HF increased the mRNA expression of the cardioprotective gene Nrf2 and reduced the mRNA expression of iNOS, and also improved cardiac function by decreasing cardiac workload through negative chronotropic and negative inotropic effects, as well as reducing peripheral vascular resistance via inhibition of voltage-dependent calcium channels and release of calcium from intracellular calcium stores.
This is the area with the largest body of published peer-reviewed research on 7HF. The evidence spans ex vivo human cell studies, animal models, and limited primary data from human cells derived from clinical populations.
7-Hydroxyfrullanolide (7HF) is a sesquiterpene lactone that was found to be efficacious in multiple animal models of inflammation by suppression of pro-inflammatory cytokines. A key early published study (European Journal of Pharmacology, 2010) investigated anti-inflammatory potential across a multi-tiered experimental framework:
A subsequent mechanistic study (European Journal of Pharmacology, 2011) elucidated the molecular pathway using microarray gene expression analysis: 7-Hydroxyfrullanolide suppressed LPS-induced NF-κB-related transcripts in human PBMCs and in freshly collected synovial cells from rheumatoid arthritis patients, by inhibiting the nuclear translocation of NF-κB through inhibition of IKK phosphorylation in THP-1 cells.
A later study (ScienceDirect, 2021) added mechanistic detail through calcium channel biology: Intraperitoneal administration of 7HF lowers serum inflammatory cytokines IFNγ and IL-6, and reduces the effects of DSS-induced colitis with respect to colon length and colon damage.
Strength of evidence: The anti-inflammatory evidence for 7HF is robust at the mechanistic and preclinical level. Use of freshly isolated synovial cells from human rheumatoid arthritis patients adds translational relevance beyond typical animal-only studies. However, no published randomised controlled trials in human subjects using isolated 7HF as an intervention for inflammatory conditions have been identified in the peer-reviewed literature. Evidence remains preclinical and ex vivo, and should be characterised accordingly as promising but not yet clinically validated for any specific human inflammatory disease.
Anticancer research on 7HF spans several cancer types and has been conducted by multiple independent research groups.
A 2019 study published in Carcinogenesis (Oxford Academic), conducted at the CSIR-Central Drug Research Institute, Lucknow, India:
Two independent research groups at Prince of Songkla University (Thailand) published consecutive papers (Molecules, 2022; PeerJ, 2022) on 7HF in TNBC cell lines:
Strength of evidence: All cancer studies are preclinical — conducted in vitro in cell lines and/or in rodent syngeneic models. No human clinical oncology studies involving 7HF have been identified. While results are mechanistically coherent and scientifically promising, they should not be interpreted as evidence of clinical efficacy in human cancer patients.
A 2023 study published in Biomedicines (MDPI) examined 7HF in an animal model of myocardial infarction:
Strength of evidence: This is an animal study (rodent model) with a limited sample size (n = 5). No human cardiovascular clinical trials involving 7HF have been reported. Results are preliminary and mechanistically exploratory.
The most advanced human clinical research involving 7HF has been conducted on standardized combination botanical extracts where it is the reference marker compound of the S. indicus component, combined with Mangifera indica bark extract (a source of mangiferin).
A randomized, double-blind, placebo-controlled 56-day clinical trial of the proprietary blend LI12542F6 (RipFACTOR®/MyoTOR®) was published in a peer-reviewed food and nutrition journal:
Strength of evidence: This is the most clinically advanced area of research involving 7HF-standardized preparations. Two randomized double-blind placebo-controlled trials have been conducted, representing a meaningful step above purely preclinical data. However, an important limitation must be clearly stated: the clinical trials tested the combined formulation (both S. indicus and M. indica extracts together), not isolated 7HF. Attribution of observed effects specifically to 7HF versus mangiferin or other phytochemicals in the blend cannot be made from these trials alone. Additionally, industry involvement in trial design and sponsorship should be noted as a potential source of bias.
A study published on PubMed (2009, PMID: 19774607) investigated microbial biotransformation products of 7α-hydroxyfrullanolide and evaluated the resulting metabolites for antibacterial activity: Compounds 2–4 were found to be new metabolites; compounds 1–9 were evaluated for antibacterial activity and found to exhibit a wide range of bioactivities. Additionally, methanolic and ethanolic crude extracts and purified flavonoid and sesquiterpenoid extracts of G. maderaspatana exhibit antioxidant, anti-microbial, and analgesic activities.
Strength of evidence: Antimicrobial data for 7HF specifically is limited and preliminary, primarily derived from in vitro testing and biotransformation product evaluation. No human clinical data on antimicrobial efficacy are available.
The following dosages are stated as reported in the sources and apply to research settings, not as recommendations.
7-Hydroxyfrullanolide, as a sesquiterpene lactone from the Asteraceae family, shares a structural characteristic — the α-methylene-γ-lactone moiety — that is well-established in the dermatology and allergy literature as a contact allergen.
Sesquiterpene lactones with an α-methylene group on the γ-lactone ring were identified as the main contact allergens in the Asteraceae (Compositae) family; skin exposure to SLs through contact with plants or topical application of products containing Compositae extracts may cause sensitization resulting in allergic contact dermatitis.
The allergenic properties observed in sesquiterpene lactones are linked with the presence of the α-methylene-γ-butyrolactone structural group. Plants from the Asteraceae family used in folk medicine as anti-inflammatories can cause allergic contact dermatitis because of their content of sesquiterpene lactones, which have been reported as the anti-inflammatory principles in these species.
Sesquiterpene lactones are a large, diverse group of chemicals found in several plant families that cause allergic contact dermatitis; the biological, botanical, allergenic, and structural significance of sesquiterpene lactones is associated with characteristic cutaneous reactions.
The parent compound frullanolide (from liverwort Frullania spp.) is historically documented as an allergen in occupational and environmental settings; 7-hydroxyfrullanolide, derived from Asteraceae plants, carries a structurally related risk profile by class.
The α-methylene-γ-butyrolactone group is necessary for cross-reaction among sesquiterpene lactones, but to be active it must first be substituted; the unsubstituted moiety itself does not elicit cross-reactions in sensitized patients. Individuals with known sensitivity to Asteraceae plants, chrysanthemums, artichokes, or other Compositae allergens may be at increased risk of cross-reactive responses to 7HF-containing preparations.
In the context of the anticancer studies, a selective index was reported: 7HF exhibited less cytotoxicity to normal cells (IC50 = 12.99 ± 7.42 µg/mL, selective index >3) and was highly selective toward cancer cells — indicating strong anti-breast cancer activity with weak cytotoxicity to normal cells at the concentrations tested in vitro. This selectivity finding, however, derives from cell-line experiments and has not been evaluated in a formal human toxicology or clinical safety study.
The drug-like properties of 7HF were predicted using the Swiss-ADME webtool, suggesting computational drug-likeness. 7HF has been described as orally bioavailable. Formal pharmacokinetic studies in humans have not been published in the peer-reviewed sources reviewed here.
No formal published clinical toxicology, maximum tolerated dose determination, or established acceptable daily intake (ADI) data specific to isolated 7-hydroxyfrullanolide as an ingredient were identified in the peer-reviewed literature or from regulatory bodies (NIH ODS, EMA, EFSA, WHO, or pharmacopoeial monographs). The safety data available are limited to the combination botanical formulations used in clinical trials, where adverse events, if any, were not prominently reported in the abstract-level data available.
Many of the plant's traditional effects still need further scientific validation through additional research and clinical trials.
As of the present literature review, 7-hydroxyfrullanolide occupies an active but early-stage position in drug discovery and nutraceutical research. It has not been approved as a drug by any regulatory authority. Significant knowledge gaps remain:
Health conditions that 7-hydroxyfrullanolide may help support.
Body systems that 7-hydroxyfrullanolide may help support.
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