IngredientsSesamolin is a naturally occurring polyphenolic lignan belonging to the furofuran subclass of plant lignans. The major lignans of sesame, sesamin and sesamolin, are benzodioxol-substituted furofurans. Its full systematic (IUPAC) chemical name is 5-[4-(1,3-benzodioxol-5-yloxy)tetrahydro-1H,3H-furo[3,4-c]furan-1-yl]-1,3-benzodioxole, and it is also recorded in the chemical literature under the synonyms Sesamolin (6CI, 7CI), (+)-Sesamolin, and Sesamolin-RM. Its molecular formula is C20H18O7 and its CAS registry number is 526-07-8.
Sesamolin has the molecular formula C20H18O7. Sesamolin is in a group of lignan compounds formed from the uniting of two phenylpropanoids connected by the central carbon of their propyl side. The presence of methylene dioxyphenoxy moieties, or its metabolite form—the phenolic hydroxyl group—may be responsible for the various biological activities of sesamolin. As with all lignans, lignans are products of secondary metabolism produced by several plants to serve as molecules of defense against predators. Chemically, they are phenyl propane dimers that additionally exhibit varied biological activities.
Sesamolin has limited water-solubility that causes it to be categorized as Class II in the Biopharmaceutical Classification System, which is the class for compounds with low water solubility and high permeability. Compounds belonging to this class require physicochemical property improvement, especially in their solubility profile, to enhance pharmacological effect and viability as drug candidates. Specifically, sesamolin has water-solubility of less than 0.1 mg/mL. This limitation may become the main obstacle to researching sesamolin's pharmacological activities, yet it may also represent a research opportunity to enhance its physicochemical properties to improve therapeutic effect.
The proposed mechanism by which sesamolin stabilizes free radicals operates via hydrogen atom transfer based on Bond Dissociation Energy values. The abstraction of the allylic hydrogen atom at C-8 by a free radical generates a sesamolin radical and stabilizes the radical compound. Then the donation of a hydrogen atom at C-1 of the sesamolin radical forms a double bond leading to stabilization of the derived compound. Thus, sesamolin is able to donate two hydrogen atoms. This two-step radical-stabilizing mechanism underpins its antioxidant activity at a molecular level.
Sesame (Sesamum indicum L.), of the Pedaliaceae family, is the major source of sesamolin and other lignan compounds including sesamin, sesamol, sesaminol, sesamolinol, and glycosylated-lignans. Although other sesame lignans such as sesamin were reported to be isolated from other plant species like Piper sp., Virola sp., Magnolia sp., and Camellia sp., recent updates showed that no reports of sesamolin have been isolated from other plant families than Sesamum.
Sesamolin and sesamin have been detected in more than 40 plant species. However, due to the low amounts of sesamin in other plants and the unclear issue of identical conformations, sesame seeds remain the principal source of these two clinically important antioxidant lignans. Sesame (Sesamum indicum L.) is an ancient oilseed crop cultivated in subtropical and tropical regions of Africa, Asia, and South America as a source of edible seeds and high-quality oil.
Major lignans of sesame are sesamin and sesamolin. The total content of these two lignans in sesame seeds may exceed 1.4%. Mean levels are 2.48 mg/g (range 1.11–9.41 mg/g) and 1.72 mg/g (range 0.20–3.35 mg/g) for sesamin and sesamolin, respectively. In sesame oil specifically, the amounts of sesamin, sesamolin, and tocopherols in sesame oil have been found to be 6.02, 3.84, and 1.45 g/kg, respectively.
Lignan content varies by seed color. Among different seed colors, black-seeded accessions exhibited the highest total lignan content, while white-seeded accessions had average lower levels. Brown-seeded accessions showed relatively lower concentrations of sesamol and intermediate levels of sesamolin and sesamin compared to other colors. In broader commercial sesame products, the total lignan content of 14 sesame seed lots ranged between 405 and 1178 mg/100 g, and the total lignan content in 14 different products, including tahini, ranged between 11 and 763 mg/100 g. The content of sesamin and sesamolin in ten commercial virgin and roasted sesame oils was in the range of 444–1601 mg/100 g oil.
Biosynthesis of furofuran lignans begins with the dimerization of coniferyl alcohol, followed by the formation of dioxoles, oxidation, and glycosylation. Most genes of the lignan pathway in sesame have been identified, but the inheritance of lignan content is poorly understood.
Sesamolin undergoes significant chemical transformation when sesame seeds are roasted or processed. The most important transformation is the production of sesamol from sesamolin. The term sesamol was coined by Hans Kreis in 1903 for the yet-unidentified phenolic product of sesame responsible for color tests used to identify sesame oil. Roasting of sesame seeds degrades the lignan sesamolin to sesamol, which increases the oxidative stability of sesame oil synergistically with tocopherols. Infrared roasting is particularly efficient: IR roasting of sesame seeds at 200°C for 30 minutes increased the efficiency of conversion of sesamolin to sesamol from 51% to 82%, compared to conventional heating. Additionally, upon refining of sesame oil, acid-catalyzed transformation of sesamin to episesamin and of sesamolin to epimeric sesaminols takes place, making the profile of refined sesame oils different from that of virgin oils.
Numerous minor lignans present in seeds in low concentrations and/or generated by chemical transformations during seed and oil processing have been described. Among them, sesamol, episesamin, and samin were studied extensively. Sesamol is a degradation product that is present in traces in unroasted seeds but occurs at high concentrations in roasted seeds and processed sesame oil.
Sesamolin is consumed primarily as a constituent of whole sesame seeds and cold-pressed (virgin) sesame oil, where it is most abundant as an intact molecule. It is not a stand-alone commercially marketed dietary supplement in the way that sesamin isolates have been, given that the research base for isolated sesamolin is comparatively limited. Sesame lignans—sesamin, sesamolin, and sesamol—are unique bioactive compounds responsible for the nutritional function of sesame oils. In the research setting, sesamolin is available as a purified reference standard (≥98% purity), dissolved in solvents such as DMSO for in vitro work. The isolated lignan mixture can be subjected to semi-preparative HPLC and TLC to result in successful separation of sesamolin in an independent fraction, with purity confirmed by TLC and LC–MS, and structural detail confirmed by NMR.
The history of sesamolin as a bioactive compound cannot be separated from the history of Sesamum indicum itself. Sesame is one of the world's oldest cultivated oilseed crops, with a history stretching back over 5,000 years. Celebrated for its nutty flavor, high oil content, and adaptability, sesame has played an essential role in cuisines, traditional medicine, and trade networks across Asia, Africa, the Middle East, and beyond. Archaeological evidence suggests sesame was domesticated in the Indian subcontinent between 3500–3000 BC. By 2000 BC, sesame oil was a valuable commodity traded between Mesopotamia and the Indus Valley. Ancient Egyptian medical texts, including the Ebers Papyrus (~1550 BC), listed sesame oil for medicinal use.
Ever since the Bronze Age, the sesame plant has been closely linked with the traditions of Southwest Asian culture. Sesame seeds are also the oldest condiment known to man, dating back to as early as 1600 BC. Records show that the Egyptians prescribed sesame as medicine about 1500 BC and used the oil as ceremonial purification.
Sesame oil is used for massage and health treatments of the body in the ancient Indian Ayurvedic system, with types of massage called Abhyanga and Sirodhara. With respect to Ayurveda, sesame oil is viewed as the most viscous of the plant oils and is believed to pacify health problems associated with Vata aggravation. According to Ayurveda, the sesame seed is sweet, pungent, astringent, and bitter, with a heating effect. It is one of Ayurveda's most popular oils for self-massage due to its nourishing, calming, and warming result. It has been used as a demulcent in dysentery and urinary diseases in combination with other medicines.
Ayurveda acharyas describe tila (sesame) as first in the rank of oils of vegetable origin, due to its wide medicinal role compared to other oils from plants such as coconut, castor, mustard, or flax. Ayurveda describes three varieties of sesame based on seed color: raktha (red), krishna (black), and shweta (white). Krishna tila—black sesame seeds—are considered to have excellent medicinal properties and are preferred for Ayurvedic treatments and preparations.
While white sesame seeds were widespread in many cultures, it was the black variety that gained particular reverence in East Asia, especially in traditional Chinese medicine (TCM). According to Traditional Chinese Medicine, black sesame seeds can help tonify the blood, build the spirit, and improve kidney and liver health. They are also used to help naturally treat issues like constipation, dizziness, weakness, and backaches.
Sesame seeds have a variety of medicinal properties and are used for their tonic, nutritive, and diuretic properties in the treatment of asthma, dry cough, ulcers, inflammation, urinary diseases, vertigo, lung diseases, and migraines. In addition to their culinary and medicinal uses, sesame seeds have been deeply intertwined with symbolic traditions and spiritual beliefs. In Hindu culture, sesame (known as til) is considered sacred and often offered during pujas and festivals. In Buddhist traditions, black sesame symbolizes purification and transcendence. In Daoist rituals, the seeds were used in alchemy to promote internal balance and eternal life.
Important note: The traditional medicinal uses documented above refer to whole sesame seeds, sesame oil, and sesame preparations as consumed across cultures. These preparations would have contained sesamolin as a constituent along with other lignans, tocopherols, unsaturated fatty acids, and other phytochemicals. No traditional medical system isolated or identified sesamolin as a discrete compound; the isolation and structural characterization of sesamolin as an individual molecule is a product of modern analytical chemistry.
Two classes of lignans, the oil-soluble and glycosylated water-soluble lignans, which include a total of 17 compounds, have been isolated from sesame seeds. Among sesame lignans, sesamin and sesamolin are the primary compounds that have gained the attention of pharmacologists and clinicians due to their health-promoting properties against lifestyle-related diseases. Sesame oil contains lignans such as sesamin and sesamolin and several antioxidant compounds such as sesamol and sesaminol, along with other methylenedioxyphenol derivatives.
Unlike the other sesame lignan compounds (i.e., sesamin and sesamol), the study of the pharmacological activity of sesamolin has not been explored widely. This reflects a research gap rather than an absence of activity: sesamolin, one of the major sesame lignan compounds, has been reported to possess antioxidant, neuroprotective, and anticancer activities. Notwithstanding, the report related to exploration of the pharmacological activities of sesamolin is limited.
At the molecular level, sesamolin's antioxidant activity is explained by its ability to donate hydrogen atoms to free radicals. The proposed mechanism of sesamolin stabilizes the free radical via hydrogen atom transfer based on Bond Dissociation Energy value. The abstraction of the allylic hydrogen atom at C-8 to a free radical generates a sesamolin radical and stabilizes the radical compound. Sesamolin's methylenedioxyphenoxy structural moieties are structurally related to those responsible for the antioxidant properties of the wider sesame lignan family. Sesame oil exerts antioxidative activity and possesses health-promoting properties, which are attributed to tocopherols, tocotrienols, and lignans.
Sesame lignans (sesamin and sesamolin) act as potent modulators of lipid metabolism through the activation of peroxisome proliferator-activated receptor alpha (PPARα), leading to enhanced fatty acid oxidation and reduced lipogenesis, which explains the observed improvements in lipid profiles. Specifically, sesame lignans (sesamin and sesamolin) act as potent modulators of lipid metabolism through the activation of peroxisome proliferator-activated receptor alpha.
Sesamolin's anti-inflammatory effects are thought to be mediated through modulation of several inflammatory signaling pathways common to the sesame lignan class. In the presence of sesame oil aqueous extract, transcription and translocation of NF-ÎşB was suppressed. It has been shown that sesamin and sesamolin have antihypertensive effects, increase the antioxidant activity of vitamin E in the lipid peroxidation system, lower cholesterol, raise the oxidizing enzymes of fatty acids in the liver, and protect neurons against hypoxia and brain damage.
The antihypertensive effects attributed to sesame lignans align with their ability to inhibit angiotensin-converting enzyme (ACE) and enhance endothelial nitric oxide synthase (eNOS) activity, promoting vasodilation and blood pressure regulation.
Studies have shown that sesamolin can decrease PPARγ2 and C/EBPα expression through MAPK signaling, leading to decreased adipogenesis in 3T3-L1 cells. Data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Evidence also indicates that Nrf2 was required for sesamolin to regulate adipogenic gene expression in MEF and adipocytes.
A notable and relatively recently characterized mechanism involves brain cholesterol metabolism. The inhibitory effects of sesame lignans on CYP46A1 activity were investigated. Inhibition kinetics analyses revealed that sesamin and sesamolin produce mixed partial competitive inhibition of CYP46A1, while sesamol produces non-competitive inhibition. Molecular simulations revealed that the sesame lignans have excellent orientations within the active cavity of CYP46A1. Importantly, the sesame lignans had high permeability coefficients and low efflux ratios. Collectively, sesame lignans exhibit significant inhibitory effects on CYP46A1 activity, highlighting their potential therapeutic role in treating excitatory neurotoxicity.
Sesamolin can inhibit the JAK2/STAT3 pathway in colon cancer cells. Sesamolin triggered the phosphorylation of the p38, ERK1/2, and JNK pathways in NK cells to enhance cytolytic activity.
An established and historically documented non-dietary biological function of sesamolin is its role as an insecticide synergist. The toxicity of some insecticides, notably pyrethrin (from chrysanthemums) and synthetic pyrethrins (pyrethroids), can be increased many times by the addition of compounds which themselves are not insecticides. These synergists include sesamin, sesamolin, piperonyl butoxide, MGK-264 (bicycloheptenedicarboximide), and sesamex. This synergistic activity is mechanistically related to sesamolin's methylenedioxyphenyl structure, which allows it to interact with cytochrome P450 enzyme systems in insects, inhibiting the metabolic detoxification of pyrethrin compounds. Lignans enhance the efficiency of insecticides and possess antifeedant activity, but their biological function in plants remains hypothetical.
Important preface: Unlike the other sesame lignan compounds (i.e., sesamin and sesamol), the study of the pharmacological activity of sesamolin has not been explored widely. The large majority of evidence for sesamolin's biological activities derives from in vitro (cell culture) and in vivo (animal) studies. There are currently no published randomized controlled clinical trials (RCTs) that have isolated sesamolin as a single intervention in human subjects. Human clinical evidence exists for sesame seed and sesame oil preparations as whole foods, and for sesamin as an isolated supplement, but not for sesamolin as an isolated compound. Each section below clearly notes the type and strength of evidence.
Evidence level: In vitro and in vivo (preclinical); no human trials with isolated sesamolin.
Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anticancer, and neuroprotective properties and potential benefits in the liver, cardiovascular diseases, and metabolic syndrome. The antioxidant activity of sesamolin is biologically plausible given its methylenedioxyphenoxy structure and its ability to donate two hydrogen atoms to stabilize free radicals. Lignans in sesame oil have been extensively studied with respect to their antioxidant, anti-inflammatory, antihypertensive, anticancer, and antihyperlipidemic effects.
In cell-based and lipid peroxidation systems, sesamin and sesamolin have been shown to increase the antioxidant activity of vitamin E in the lipid peroxidation system. This synergism with tocopherols is considered one of sesamolin's most pharmacologically significant properties and may partly explain the exceptional oxidative stability of sesame oil compared to other vegetable oils. Overall, antioxidant evidence for sesamolin as an isolated compound is preliminary and based on mechanistic and preclinical work only.
Evidence level: Preclinical (in vitro and animal); human clinical data available for sesame products but not for isolated sesamolin.
Comparative effects of sesame lignans (sesamin, sesamolin, and sesamol) on oxidative stress and lipid metabolism have been studied in steatosis HepG2 cells. It has been shown that sesamin and sesamolin lower cholesterol and raise the oxidizing enzymes of fatty acids in the liver. Animal studies found that sesame can decrease lipid peroxidation and affect the enzymes which control the balance of oxidative status in the body.
At the cellular level, sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation, with the specific dose range tested being 20 to 80 µM.
Human clinical evidence for cardiovascular benefits is available for sesame preparations as a whole food rather than for isolated sesamolin. A GRADE-assessed systematic review and meta-analysis of sesame products and their bioactive compounds in humans found improvements in lipid profiles and blood pressure, attributing the mechanisms in part to sesamin and sesamolin, but this evidence does not establish sesamolin as a specific independent cardiovascular agent in clinical practice. The evidence for isolated sesamolin's cardiovascular effects in humans remains extrapolated from preclinical data.
Evidence level: Preclinical; mechanistically plausible in humans as part of sesame preparations.
It has been shown that sesamin and sesamolin have antihypertensive effects. The antihypertensive effects align with sesame lignans' ability to inhibit angiotensin-converting enzyme (ACE) and enhance endothelial nitric oxide synthase (eNOS) activity, promoting vasodilation and blood pressure regulation. Sesame oil also shows preventive effects for the development of atherosclerosis and hypertension. Human clinical data from RCTs of sesame oil supplementation show blood pressure reductions, but these outcomes are attributed to the whole oil matrix and not specifically to isolated sesamolin.
Evidence level: In vitro and limited in vivo (animal); no human data for isolated sesamolin.
Sesamolin possessed neuroprotective activity against hypoxia-induced reactive oxygen species (ROS) and oxidative stress in neuron cells by reducing the ROS and inhibiting apoptosis. The mechanistic basis for neuroprotective effects includes CYP46A1 inhibition: inhibition kinetics analyses revealed that sesamin and sesamolin produce mixed partial competitive inhibition of CYP46A1. Inhibition of CYP46A1 activity serves as a therapeutic target for excitatory neurotoxicity.
Sesamin and sesamolin have been shown to protect neurons against hypoxia and brain damage. Additionally, it was demonstrated that sesamolin inhibits β-secretase, presenting an important role for prevention of dementia by daily consumption. This β-secretase inhibition, if substantiated in further studies, would have implications for Alzheimer's disease research, as β-secretase (BACE1) is a key enzyme in the amyloidogenic processing of amyloid precursor protein. However, this finding is preclinical and no human trials exist for sesamolin in dementia. All neuroprotective evidence is currently at the in vitro and animal stage.
Evidence level: In vitro; no clinical trial evidence for isolated sesamolin in humans.
The major compounds of sesame—sesamin and sesamolin—have shown many pharmacological activities, such as antiproliferative, antihypertensive, anti-inflammatory, and anticarcinogenic effects. The anticancer activities of sesamolin that have been specifically demonstrated in vitro include:
All anticancer data for isolated sesamolin are derived from cell culture (in vitro) experiments. No animal models or human clinical trials have been conducted specifically for sesamolin as an isolated anticancer agent as of the most recent literature review. Evidence is preliminary and descriptive.
Evidence level: In vitro; no human clinical trial data for isolated sesamolin.
In an in vitro study evaluating regulatory effects of 20 to 80 µM sesamin and sesamolin on adipogenesis using 3T3-L1 cells as a model cell line, the researchers hypothesized that the lignans would inhibit adipogenic differentiation through regulation of peroxisome proliferator-activated receptor γ (PPARγ). Data indicated that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Specifically, sesamolin can decrease PPARγ2 and C/EBPα expression through MAPK signaling, leading to decreased adipogenesis in 3T3-L1 cells.
Evidence level: Preclinical (cell and animal); limited extrapolation to humans from sesame product trials.
A review of recent findings examined the mechanism by which sesame and its active compounds sesamin and sesamolin regulate atherosclerosis. Sesame can decrease lipid peroxidation and affect the enzymes which control the balance of oxidative status in the body. Sesame oil aqueous extract significantly reduced inflammatory markers in both macrophages and endothelial cells in a concentration-dependent manner, was also effective in inhibiting LPS-induced TNF-α and IL-6 levels in vivo at different concentrations, and suppressed transcription and translocation of NF-κB.
Based on the preclinical evidence reviewed, sesamolin has been studied in association with the following body systems and health areas:
Because there are no published clinical trials administering isolated sesamolin to human subjects, there is no established human dosage for sesamolin as a standalone compound. The following dosages and dosage forms appear in the scientific literature:
No standardized supplemental dose for isolated sesamolin has been established in any regulatory framework or official monograph. Dosages used in clinical trials examining whole sesame or sesamin—a related but structurally distinct compound—are not directly applicable to sesamolin.
Sesamolin is consumed as part of sesame seeds and sesame oil by large human populations worldwide and has an extensive history of dietary use. Sesamolin has limited water-solubility that causes it to be categorized as Class II in the Biopharmaceutical Classification System, a class for low water solubility and high permeability compounds. The compound belonging to this class needs physicochemical properties improvement, especially the solubility profile, to improve its pharmacological effect and to be developed as a drug candidate. The low water-solubility affects its bioavailability and systemic exposure after oral consumption.
No study has reported the structure-activity relationship of sesamolin regarding which functional group constitutes the pharmacophores for its biological activity. Specific toxicological data for isolated sesamolin are limited in the published literature.
Sesame is recognized as a major food allergen in multiple regulatory jurisdictions, including the United States (where it was added to the list of major allergens under FASTER Act, 2021, effective January 2023). Sesame allergy primarily relates to seed proteins rather than to lipid-soluble lignans such as sesamolin; however, individuals with confirmed sesame allergy should avoid all sesame-derived products, including sesame oil preparations that may contain trace proteins.
The lignans such as sesamin, episesamin, sesaminol, and sesamolin are major constituents of sesame oil and all have a chemically methylenedioxyphenyl group. Although it was shown that piperonyl butoxide and safrole interact with some P450 isozymes both in insects and mammalian species due to having a methylenedioxyphenyl group, there is no data available in the literature on the interaction between sesame oil or its lignans and drugs. However, based on structural analogy, sesame oil could interact with P450 isozymes and affect drug metabolism or disposition in humans.
This is not a trivial concern: the inhibitory effects of sesame lignans on CYP46A1 activity have been investigated, with inhibition kinetics analyses revealing that sesamin and sesamolin produce mixed partial competitive inhibition of CYP46A1, while sesamol produces non-competitive inhibition. CYP46A1 is a brain-specific enzyme; the broader clinical significance of this inhibition for drug interactions is not yet established. Sesamin also inhibits enzymes involved in CYP450 and 20-hydroxyeicosatetraenoic acid production. The methylenedioxyphenyl (MDP) group that sesamolin shares with known CYP inhibitors such as piperonyl butoxide warrants attention in research contexts, though confirmatory human pharmacokinetic data for sesamolin-drug interactions are absent.
The toxicity of some insecticides, notably pyrethrin and synthetic pyrethroids, can be increased by the addition of synergists including sesamin and sesamolin. Piperonyl butoxide is perhaps the most widely used synthetic pyrethrin synergist. This property is relevant to occupational or formulated-product exposure rather than to dietary consumption of sesame, where sesamolin concentrations achieved are unlikely to produce meaningful insecticide-synergist effects in humans.
Sesamolin has limited water-solubility that causes it to be categorized as Class II in the Biopharmaceutical Classification System. This issue may become the main obstacle to researching sesamolin's pharmacological activities, yet it may also become a research opportunity to enhance the physicochemical properties of sesamolin in order to improve its therapeutic effect. The absence of human clinical trials means that effective doses, pharmacokinetics, bioavailability, and long-term safety in humans have not been characterized for isolated sesamolin. All health claims extrapolated from sesame product research must be interpreted with caution regarding sesamolin's specific contribution, as sesame preparations contain numerous other bioactive constituents.
Health conditions that Sesamolin may help support.
Body systems that Sesamolin may help support.
Go back