IngredientsSedanenolide is a naturally occurring bicyclic lactone belonging to the phthalide family of plant secondary metabolites. Its primary synonym is 3-Butyl-4,5-dihydrophthalide (also rendered as 3-n-butyl-4,5-dihydrophthalide), and it is widely known in the scientific literature by the alternative name Senkyunolide A, with CAS Registry Number 63038-10-8 and molecular formula C₁₂H₁₆O₂, giving a molecular weight of approximately 192.26 g/mol. It is also listed under the synonyms (-)-Sedanenolide and (S)-Sedanenolide, reflecting its naturally predominant stereochemical configuration.
Sedanenolide must be carefully distinguished from sedanolide (CAS 6415-59-4), a closely related but distinct phthalide. Sedanolide is a tetrahydrophthalide with molecular formula C₁₂H₁₈O₂, meaning it carries two additional hydrogen atoms (i.e., a higher degree of saturation) compared to sedanenolide. Both sedanenolide (3-n-butyl-4,5-dihydrophthalide) and sedanolide are listed among the important flavor constituents of celery seed oil responsible for its characteristic aroma, where they are present at very low levels of approximately 1–3%. Because the two names are frequently treated interchangeably or conflated in secondary sources, and because the peer-reviewed pharmacological literature increasingly uses "sedanolide" as the broader research subject (encompassing closely related phthalides from the same source), this article covers both molecules while distinguishing them where data permit.
The formal IUPAC name of sedanenolide (Senkyunolide A) is (3S)-3-butyl-4,5-dihydro-1(3H)-isobenzofuranone. It is a type of phthalide — also known as an ortho-hydroxymethylbenzoic acid lactone — whose structural feature is the double ring fusion of a γ-lactone (A ring) and a benzene ring (B ring), formed by the loss of one molecule of water from a γ-hydroxycarboxylic acid. In sedanenolide specifically, one of the double bonds in the six-membered ring of the parent phthalide is reduced compared to the fully aromatic form, giving the characteristic 4,5-dihydro configuration. Phthalide compounds are generally unstable and susceptible to changes and interconversion due to factors such as light and temperature, resulting in diverse structures and biological activities among these compounds.
Sedanenolide is described physically as a colorless to yellow-brown liquid. Its antiproliferative activity has been characterized in in vitro colon cancer models, where it inhibited cell proliferation of HT-29 colon cancer cells with an IC₅₀ of 54.17 µM but showed markedly weaker activity against non-cancerous human CCD-18Co colon cells (IC₅₀ = 109.11 µM).
The related compound sedanolide (CAS 6415-59-4) has the formal name 3-butyl-3a,4,5,6-tetrahydro-1(3H)-isobenzofuranone. Its molecular formula is C₁₂H₁₈O₂ and its formula weight is 194.3. There are four stereoisomers of sedanolide.
Celery seed is derived from the dried fruits of Apium graveolens L., a biennial plant in the Apiaceae (umbellifer) family, which also includes parsley, carrot, fennel, and caraway. This species is the primary botanical source of both sedanenolide and sedanolide. The botanical sources of Senkyunolide A (sedanenolide) include the dried rhizome of Cnidium officinale (the crude drug known as senkyu in Japanese Kampo medicine) as well as Apium graveolens (celery).
Sedanolide and its close structural relatives are widely found in various Umbelliferae plants and Chinese herbs, including Ligusticum chuanxiong Hort., Cnidium monnieri (L.) Cuss., and Apium graveolens L. Phthalides more broadly are a class of bioactive natural products that are widely distributed in plants, fungi, lichens, and liverworts.
Within celery seed oil itself, the phthalide fraction is modest by weight but disproportionately important aromatically. Celery seed contains approximately 2% volatile oil, and within that oil limonene and selinene form about 60% and 20%, respectively. The character-impact compounds, however, are the phthalide lactones — 3-n-butylphthalide (CAS 6066-49-5), sedanolide (CAS 6415-59-4), and sedanenolide (CAS 63038-10-8) — present at just 1.5–11% of the oil yet responsible for the entire recognisable celery identity. Their odour threshold is extremely low.
The phthalide content of the leaf oil and the stalk oil of Apium graveolens are 39.8% and 29.95% respectively; the phthalides identified in the leaf oil are isomeric compounds of senkyunolide I and senkyunolides J & N, while the major phthalide constituents of the stalk oil include 3-n-butylphthalide, sedanolide, neocnidilide, and sedanenolide/senkyunolide A.
Among 12 compounds identified as potent odorants of celery, 3-n-butylphthalide, sedanenolide, and trans- and cis-sedanolides were assessed to be most contributive to the overall odor of celery. MacLeod and Ames similarly reported that limonene and sedanenolide were the major aroma components of celery, based on detailed analyses using GC, GC-mass spectrometry, and GC-olfactometry.
Celery is used in various forms such as fresh herb, stalk, seeds, oil, and oleoresin for flavoring of foods and for medicinal purposes. Sedanenolide and sedanolide are present across all of these forms, but are most concentrated in the essential (volatile) oil extracted from the seeds. Celery seed contains approximately 2% volatile oil that finds application for flavoring of foods and also in the perfumery industry. In research settings, isolated sedanenolide and sedanolide are produced by column chromatography and purified by gas chromatography from seed oil. Phytochemical studies of Apium graveolens extract have resulted in the isolation of both 3-n-butylphthalide and sedanenolide using column chromatography; both compounds have been purified by gas chromatography, and their structures established on the basis of extensive spectral data analysis (UV, FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrum).
Apium graveolens (Apiaceae) has a long history of use in the Ayurveda and Unani systems of medicine. In Ayurveda, the plant is known as Ajamoda or Ugragandhika. Celery was known to the Chinese since at least the fifth century BCE, and even before that, it was widely in use in India especially for its healing properties. In Ayurveda, the roots and seeds of celery were more commonly used than leaves in medicinal preparations. In India, celery is used in Ayurvedic medicine to relieve flu, colds, poor digestion, water retention, disorders of the spleen and liver, and different types of arthritis.
Apium graveolens has been used in the Unani system of medicine as an anti-inflammatory, uricosuric, and diuretic agent, and to treat rheumatism, besides other ailments. Celery seed oil, a significant source of sedanolide and related phthalides, has been specifically used as an herbal remedy to treat inflammatory-associated conditions such as gout and rheumatism.
Phthalides are important bioactive constituents in Si-Wu-Tang and Fo-Shou-San, two commonly used Traditional Chinese Medicine (TCM) combined prescriptions, mainly derived from Radix Angelica and Rhizoma Chuanxiong. The crude drug senkyu, derived from Cnidium officinale rhizome, has been employed for centuries in Japanese Kampo medicine and is formally recognized as a significant botanical source of sedanenolide (Senkyunolide A). This herb complex has traditionally been used in East Asian medicine for conditions including blood stagnation, menstrual irregularities, and cardiovascular complaints — though these indications are attributed to the multi-ingredient formulae and are not isolate-specific.
Egyptians placed wild celery in King Tutankhamen's tomb, and Romans were among the first to cultivate celery for medicinal use. Celery, a native herb of Europe, has a long history of use in Ayurveda and the Unani medicinal system as a therapeutic agent. The characteristic aroma compounds — including sedanenolide — were present in all of these preparations, though the constituent was not identified or isolated until the modern era of analytical chemistry.
Phthalides are a class of bioactive natural products widely distributed in plants, fungi, lichens, and liverworts; they have attracted much attention owing to their complicated chemical structures and various pharmacological activities including antimicrobial, anti-inflammatory, antitumor, and antidiabetic activities. Within celery and related Apiaceae plants, the most pharmacologically studied phthalides alongside sedanenolide include:
The Nigerian celery plant has been characterized as a good source of phthalides, which are known for their nutraceutical properties such as antioxidant, antitumor, anti-platelet aggregation, hypotensive, hypoglycemic, and hypolipidemic properties. Phthalides, especially sedanenolide, are considered to possess many health benefits, and celery extracts are reported to possess nutraceutical properties including antioxidant, hypolipidemic, hypoglycemic, and anti-platelet aggregation effects.
One of the earliest and best-characterized mechanisms attributed to both sedanolide and sedanenolide is the induction of the detoxifying enzyme glutathione S-transferase (GST). Sedanolide is a natural phthalide first isolated from seed oil of the Umbelliferae family, and it induces the expression of glutathione S-transferase and reduces chemical-induced carcinogenesis in mice.
Bioassay-directed fractionation of celery seed oil from Apium graveolens led to the isolation of five natural products, including d-limonene and sedanolide, among others. Of these, 3-n-butyl phthalide and sedanolide exhibited high activities to induce the detoxifying enzyme GST in the target tissues of female A/J mice. At a dosage of 20 mg/dose every two days for a total of 3 doses, they increased GST activity 4.5–5.9 and 3.2–5.2 times over controls in the mouse liver and small intestinal mucosa, respectively.
A study investigating sedanolide's function in suppressing hydrogen peroxide (H₂O₂)-induced oxidative damage in the human hepatoblastoma cell line HepG2 found that sedanolide activated the antioxidant response element (ARE)-dependent transcription mediated by the nuclear translocation of NRF2. Pathway enrichment analysis of RNA sequencing data revealed that sedanolide upregulated the transcription of antioxidant enzymes involved in the NRF2 pathway and glutathione metabolism. Additional studies have confirmed that sedanolide activates the NRF2 pathway to protect mice from acetaminophen-induced liver injury and is also associated with modulation of bacteria such as Lactobacillus.
Sedanolide exhibits moderate anti-inflammatory effects through the inhibition of cyclooxygenases 1 and 2 (COX-1 and COX-2), which play crucial roles in the inflammatory process. Sedanolide inhibits cyclooxygenases-1 and -2 at 250 pg/ml and blocks topoisomerase-I and -II activity at 100 µg/ml. COX inhibition underlies the anti-inflammatory and analgesic effects long attributed to celery seed preparations in traditional medicine, while topoisomerase inhibition is a recognized mechanism relevant to antiproliferative and potential anticancer activity.
In studies using the hepatocellular carcinoma cell line J5, sedanolide suppressed cell viability by inducing autophagy. PI3K-I, mTOR, and Akt protein levels decreased, whereas PI3K-III, LC3-II, and Beclin-1 protein levels increased following sedanolide treatment. Additionally, sedanolide treatment upregulated nuclear p53 and damage-regulated autophagy modulator (DRAM) and downregulated cytosolic p53 and TIGAR expression. The cytosolic phosphorylation of IκB and nuclear p65, and the DNA-binding activity of NF-κB, also increased. These results suggest that sedanolide induces cell autophagy by regulating PI3K, p53, and NF-κB autophagy-associated signaling pathways.
Sedanolide has been shown to alleviate dextran sulfate sodium (DSS)-induced colitis by diminishing inflammation and strengthening the intestinal barrier, reshaping the gut microbiota (particularly by decreasing BSH-expressing bacteria, resulting in an increased ratio of conjugated to unconjugated bile acids), and inhibiting the intestinal FXR pathway, thereby increasing expression of SMPD3. SMPD3-modulated accumulation of the key ceramide (d18:1/16:0) is proposed to mediate the protective effects of sedanolide.
Senkyunolide A (sedanenolide) protects against cell injury induced by corticosterone in PC12 cells (a neuronal cell model) in a time-dependent manner when used at concentrations ranging from 0.125 to 0.5 mg/ml, and reduces corticosterone-induced apoptosis at a concentration of 0.5 mg/ml. It also reverses increases in protein levels of phosphatase 2A (PP2A) and alpha-synuclein, and reverses decreases in the phosphorylated forms of PP2A and alpha-synuclein.
Important caveat: The overwhelming majority of published research on sedanenolide/sedanolide is preclinical — conducted in cell culture (in vitro) systems or animal models (in vivo in rodents). No peer-reviewed human clinical trials specifically targeting isolated sedanenolide as the sole intervention have been identified in the literature to date. All human-level evidence derives from studies using whole celery seed extract or oil, or from cell lines of human origin tested in laboratory conditions. The evidence strength for each area is characterized accordingly.
Evidence level: Animal (in vivo) and cell-based (in vitro). No human clinical trials on the isolate.
In a benzo[α]pyrene-induced forestomach cancer model in mice, sedanolide reduced tumor incidence by 57% and tumor multiplicity by 83% by increasing glutathione S-transferase (GST) activity. This is the most frequently cited in vivo anticarcinogenic finding for this compound class. The mechanism — enzymatic induction of phase II detoxification — is a well-recognized chemopreventive strategy.
In cell-based experiments, Senkyunolide A (sedanenolide) inhibited cell proliferation of HT-29 colon cancer cells with an IC₅₀ of 54.17 µM, while showing markedly weaker activity (IC₅₀ = 109.11 µM) against non-cancerous human CCD-18Co colon cells, suggesting a degree of selective antiproliferative activity. However, these are isolated cell experiments and cannot be extrapolated to clinical outcomes.
In hepatocellular carcinoma J5 cells, sedanolide induces autophagy through modulation of PI3K/Akt/mTOR signaling, elevating PI3K-III, LC3-II, and Beclin-1 expression, and activating p53 and NF-κB pathways. This cellular mechanism is consistent with a tumor-suppressive role in liver cancer cell lines, but again represents in vitro evidence only.
Evidence level: Cell-based and animal model studies. No human clinical trials.
A study in human HepG2 hepatoblastoma cells found that sedanolide activated antioxidant response element (ARE)-dependent transcription via nuclear translocation of NRF2, and upregulated the transcription of antioxidant enzymes involved in the NRF2 pathway and glutathione metabolism. Additional research reported that sedanolide protects against liver injury by modulating the antioxidative Nrf2 pathway, with the authors noting that this may indicate usefulness for treating multiple organs and the whole body.
An earlier in vitro study (Woods et al., 2001) tested the protective properties of sedanolide against hydrogen peroxide (H₂O₂)- and tert-butyl hydroperoxide (tBOOH)-induced toxicity in HepG2 and CaCo-2 cells. Viability of HepG2 and CaCo-2 cells was unaffected by a 24-hour exposure to sedanolide at concentrations of 7–500 µM; however, when cells were cultured in sedanolide-free medium for a further two cell cycles (72 hours), a decrease in cell viability was observed for HepG2 cells previously exposed to 500 µM of the compound. Sedanolide was found to be relatively nontoxic to cells in culture; however, the protection it afforded against H₂O₂- and tBOOH-induced toxicity was not statistically significant. This is an important limitation: protective antioxidant effects in cell-based systems were modest and did not reach statistical significance in this study.
Evidence level: Enzyme inhibition assays (in vitro) and animal model studies.
Sedanolide inhibits cyclooxygenases-1 and -2 at 250 pg/ml and blocks topoisomerase-I and -II activity at 100 µg/ml in biochemical assay systems. These findings from Momin and Nair (2002, published in Phytomedicine) represent direct enzyme inhibition data but do not constitute clinical evidence of anti-inflammatory efficacy in humans.
Evidence level: Rodent model studies.
For evaluation of the impact of different concentrations of sedanolide on DSS-induced colitis, mice were treated with 5 or 20 mg/kg sedanolide. During the experiment, DSS decreased the weight of the mice and increased the disease activity index (DAI) score; however, 20 mg/kg sedanolide (SE20) significantly increased body weight and decreased the DAI score, and also increased colon length shortened by DSS in DSS-treated mice.
Overall, the research revealed protective effects of sedanolide against DSS-induced colitis in mice, suggesting that sedanolide may be a potential clinical treatment for colitis. The authors note this as a hypothesis to be tested in human trials, which have not yet been published. Protective effects of the downstream mediator ceramide (d18:1/16:0) against inflammation and gut barrier disruption were further demonstrated in vitro using the human cell line Caco-2.
Evidence level: Cell-based studies (neuronal cell line).
Senkyunolide A (sedanenolide) protects against cell injury induced by corticosterone in PC12 cells in a time-dependent manner, reducing corticosterone-induced apoptosis at a concentration of 0.5 mg/ml. It also reverses increases in protein levels of phosphatase 2A (PP2A) and alpha-synuclein and reverses decreases in the phosphorylated forms of PP2A and alpha-synuclein. Dysregulation of alpha-synuclein is implicated in Parkinson's disease pathology, and PP2A regulation has broader implications in neurodegenerative disease models; however, these observations derive exclusively from a cell line model and cannot be extrapolated to human clinical benefit.
Evidence level: Bioassay studies (Momin & Nair, 2001, J. Agric. Food Chem.).
Sedanolide was found to have mosquitocidal, nematicidal, and antifungal activities. It shows no cytotoxicity against normal mammalian cells in these assays. These findings are of relevance to agricultural and food preservation applications, but have not been developed into clinical applications for human infectious disease.
Reviews of the sedanolide/phthalide class report many physiological functions including antioxidant, anti-inflammatory, and antimicrobial activity, with a therapeutic mechanism involving multiple targets, multiple pathways, and bidirectional regulation. When consumed as part of celery and related plants, phthalides have been reported to have effects including improved reproductive capacity, hepatoprotection, treatment of gout, anticancer activity, antioxidant properties, anti-inflammatory effects, hypotensive action, hypolipidemic effects, and treatment of neurodegenerative diseases. These reports encompass the entire phthalide class found in celery and related plants; attributing any specific benefit exclusively to isolated sedanenolide, as distinct from other co-occurring phthalides, would require isolate-specific clinical evidence that is not currently available in the published literature.
The following dosages appear specifically in primary research sources. These are research-context figures only, not recommended human intake levels.
Sedanolide is mosquitocidal, nematicidal, and antifungal but shows no cytotoxicity against normal mammalian cells at the concentrations tested in the referenced bioassay studies. Sedanolide is relatively nontoxic to cells in culture at concentrations up to and including 500 µM over short exposure periods.
A meaningful safety caveat emerges at high concentrations: a significant increase (p < 0.05) in DNA strand breaks, as measured by the comet assay, was observed in HepG2 cells (but not CaCo-2 cells) following a 24-hour incubation with 500 µM sedanolide. Although generally nontoxic, high concentrations were shown to cause DNA strand breaks in HepG2 cells. This finding is from an in vitro experiment at a concentration likely not achievable under normal dietary or supplemental exposure, but it represents a genotoxicity signal that warrants awareness in research contexts.
Phthalide compounds are unstable and susceptible to changes and interconversion due to factors such as light and temperature, resulting in diverse structures and biological activities of these compounds. This chemical instability is relevant to product quality and standardization: preparations containing phthalides such as sedanenolide may change in composition over time or under adverse storage conditions.
In numerous animal experiments, no toxicity has been observed with sedanolide-class phthalides at doses used in the published research, though the dataset remains limited to preclinical models.
Celery (Apium graveolens) is a recognized major food allergen listed in EU food labeling law and the WHO/IUIS allergen nomenclature. Individuals with celery allergy may react to preparations derived from celery seed oil containing phthalides; however, the allergenic components of celery are primarily proteins (e.g., Bet v 1 homologues, profilins), not the phthalide fraction. The clinical relevance of phthalide components to celery allergy has not been established in the peer-reviewed literature reviewed here.
It must be stated clearly that no human clinical trials on isolated sedanenolide or sedanolide as a dietary supplement or pharmacological agent have been identified in the peer-reviewed literature searched. Sedanolide has received widespread attention due to its unique biological activity and potential medicinal value, but the translation of preclinical findings to verified human outcomes has not yet occurred. With the development of modern science and technology, research on sedanolide continues to deepen, and its application prospects in the fields of medicine, agriculture, and industry are becoming increasingly broad.
Health conditions that Sedanenolide may help support.
Body systems that Sedanenolide may help support.
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