Euryale Seed (Euryale ferox Salisb.): A Comprehensive Reference
1. Identity and Botanical Classification
Botanical Name and Taxonomy
Euryale ferox Salisb. (prickly water lily) is the only extant species of the genus Euryale, and has been widely distributed in China, India, Korea, and Japan. It belongs to the family Nymphaeaceae, subfamily Euryalinae. The accepted binomial authority is Euryale ferox Salisb., with synonyms including Anneslea spinosa Andrews and Euryale indica Planch.
Common Names
The seed is also known as Foxnut, Lotus seeds, Gorgon nuts, and Phool Makhana. In Chinese, it is called Qianshi (芡实), also rendered as "cock's head." In Indian vernacular usage it is widely known as Makhana. Other English names recorded in the literature include Gordon Euryale, Prickly Waterlily, Fox Nut, and Gorgon Nut.
Plant Description and Habitat
E. ferox is widely distributed throughout tropical and subtropical regions of Asia and Southeast Asia. India, Japan, Korea, Bangladesh, and China are the main producing areas. Generally, it is grown in stagnant water with a depth of 0.2–2.0 m, such as ponds and lakes. It prefers warm and sunny weather and is intolerant to cold and drought. The suitable temperature ranges from 20 to 30 °C, while fertile soil with sufficient organic matter is required.
The plant bears submerged leaves that are sagittate or elliptic (4–10 cm), as well as large floating leaves that are prickly on petioles and along veins, abaxially dark purple and adaxially green, up to 1.3 (–2.7) m in diameter, subleathery, with strongly ribbed veins. The seeds of E. ferox (EFS) are widely distributed across India, Bangladesh, Myanmar, New Zealand, Russia, Thailand, and parts of East Asia.
Part Used and Common Preparations
EFS is the dried seeds of the E. ferox Salisb. plant. In addition to the seed, the whole plant of E. ferox can be used as food or medicine. As early as the report in the Compendium of Materia Medica in the Ming dynasty, China, the stems, leaves, and roots of E. ferox were applied to treat different diseases.
The seeds are commercially available in several forms: as whole dried seeds, popped (roasted/puffed) kernels (the most widely consumed snack form), seed flour, aqueous or ethanolic extracts, and as encapsulated powder supplements. In China, it is widely served as food directly in soups or rice congee. Processing can alter the chemical composition of EFS, with different methods yielding varying effects on their chemical makeup and, consequently, their efficacy.
In TCM pharmacy, the traditional preparation specified for the kernel is oral decoction. For the kernel, the oral administration form is decoction at 15–30 g, or made as pills or powders.
2. Traditional and Historical Use
Traditional Chinese Medicine (TCM)
EFS is a typical representative of "a medicine food homology species," as described in the Huangdi Nei Jing Tai Su (黄帝内经太素): "Eating it as food on an empty stomach, and taking it as medicine for patients." In China, EFS was first described in Shen Nong's Classic of the Materia Medica (Shén Nóng Bĕn Căo Jīng, 神农本草经). The seeds of E. ferox have been categorized as superior food for 2000 years in China.
As a folk medicine in China for thousands of years, EFS is primarily used to reinforce the kidney, invigorate essence, and tonify the spleen to arrest diarrhea. It is commonly employed to manage conditions such as spermatorrhea, gonorrhea, dysmenorrhea, incontinence of urine, and diarrhea of the bowels.
In the official pharmacopoeia, the Chinese Pharmacopoeia describes EFS as having the action of "fortifying the spleen and inhibiting diarrhoea, eliminating dampness and arresting leucorrhea. It is used for spermatorrhea, enuresis and frequent urination, splenoasthenic diarrhea, and leucorrhea."
As early as the report in the Compendium of Materia Medica in the Ming dynasty, China, the stems, leaves, and roots of E. ferox were applied to treat different diseases. The various plant parts are used in TCM for specific indications: the kernel is used for securing the kidney and astringing essence and nourishing the spleen for stopping diarrhea; roots are used for hernia pain, unknown pyogenic infections, and leucorrhea; leaves for hematemesis and hemafecia; the scape for thirst due to asthenic fever, and dry mouth and throat; and the kernel for emissions, stranguria with turbid urine, whitish and turbid urine, dripping urine, leukorrhea, and loose stools.
Ayurvedic Tradition (India)
In India, EFS is known as makhana and is applied in Ayurvedic medicines for treating diseases including bile disorders, persistent diarrhea, kidney disorders, rheumatic disorders, excessive leucorrhea, and hepatic dysfunctioning. In view of their great nutritional and therapeutic values, E. ferox seeds are included in the Ayurvedic pharmacopeia.
In Ayurveda, fox nuts have been valued for balancing the body's doshas and supporting sexual health, particularly in managing premature ejaculation and enhancing vigor. Their astringent nature has made them useful in remedies for diarrhea and to soothe inflammation in the digestive tract.
Kampo Medicine (Japan)
In Japan, EFS is recorded in Kampo medicine for improving metabolic arthritis, urinary incontinence, and leucorrhea.
Historical Food Use
The seeds of E. ferox have been consumed for centuries as a nutritious food and are an integral component of Ayurvedic and Traditional Chinese Medicine systems. Traditionally, they have been used to manage kidney disorders, reproductive issues, and inflammatory conditions.
3. Key Constituents and Active Compounds
Macronutritional Composition
The composition of the major macromolecules in foxnut seed is varied: carbohydrates in the range of 55–80%, protein 10–15%, and fat 0.2–0.7%. It has a high content of phosphorus, potassium, magnesium, calcium, and sodium.
EFS contains starch, protein, lipids, 20 amino acids (including six essential amino acids: leucine, isoleucine, lysine, threonine, valine, and phenylalanine, and two other essential amino acids needed especially by children, histidine and arginine), minerals (Na, Mg, Ca, Se, P, Zn, Fe, Mn, Co, and Sn), and vitamins (vitamins C and E and high amounts of beta carotene).
Phytochemical (Bioactive) Constituents
The seeds of E. ferox contain abundant phytochemicals including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids.
Specific compounds identified by chemical isolation studies include:
- Phenolic acids and flavonoids: Seven compounds were purified from a 95% ethanol extract, elucidated as protocatechuic acid, gallic acid, gallic acid ethyl ester, 5,7-dihydroxychromone, β-sitosterol, daucosterol, and 5,7-dihydroxy-6,4′-dimethoxyflavone. Additional polyphenols identified in the seed coat include gallic acid, digalloylhexoside, catechin, procyanidin B2, epicatechin, ellagic acid, and epicatechin gallate.
- Sesquineolignans (Euryalins): Studies resulted in the identification of 3 new sesquineolignans, named euryalins A–C (1–3), and 16 known compounds, all first isolated from this plant apart from 5,7,4-trihydroxy-flavanone.
- Tocopherols: Tocopherol-related compounds, including chroman-type dimers and trimers, have been isolated from the seeds and are believed to contribute to their antioxidant activity.
- Volatile and fatty acid constituents: Major metabolites identified by GC-MS include glycerol, butanoic acid, decanoic acid, myristic acid, gallic acid, palmitic acid, myo-inositol, linoleic acid, farnesol, and tricosanoic acid.
- Starch: EFS starch granules are smooth, sharp, small, and have an average diameter of 2 μm. The amylose content of North Euryale ferox seeds was found to be 23.03%.
Roasting alters the phytochemical profile: roasting significantly improved the minerals content (from 0.58 to 0.66%), protein content (from 11.40 to 14.57%), total phenolics (from 346.02 to 470.62 mg GAE/100 g), flavonoids (from 4.15 to 4.43 mg CE/g), DPPH radical scavenging activity (from 48.54 to 79.13% inhibition), and ferric reducing antioxidant capacity compared to raw seeds.
Mechanisms of Action
The evaluation of antioxidant activity occurs via three main mechanisms: directly scavenging DPPH and reactive oxygen species (ROS), activating antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and improving somatic cellular integrity.
Phenolic compounds from the EFS coat can strongly inhibit the digestion of E. ferox seed starch by inhibiting the α-amylase and α-glucosidase activities and interacting with starch by hydrogen bonds; therefore, E. ferox seeds have a promising application prospect in foods for hypoglycemia.
In the cardioprotective domain, makhana-treated hearts had increased amounts of thioredoxin-1 (Trx-1) and thioredoxin-related protein-32 (TRP32) compared to control hearts, proteins associated with cytoprotection and redox regulation.
4. Scientific Evidence by Area of Use
4.1 Antioxidant Activity
Evidence type: In vitro; some in vivo animal data. No controlled human trials.
Various in vitro and in vivo studies have indicated that E. ferox-derived extracts and phytoconstituents exhibited antioxidant and antidiabetic effects. An early study (Lee et al., 2002) published in Experimental and Molecular Medicine evaluated total extracts and fractions of Euryale ferox: total extracts showed an IC50 of 5.6 µg/ml for DPPH radical scavenging. Treatment with Euryale ferox extracts induced a dose-dependent increase in cell survival in H₂O₂-challenged V79-4 cells.
The antioxidant potential of isolates was evaluated using the DPPH radical scavenging assay and mesangial cellular assay. Compounds including rel-(2α,3β)-7-O-methylcedrusin, syringylglycerol-8-O-4-(sinapyl alcohol) ether, and (+)-syringaresinol were found to be most active on the DPPH assay, and several compounds could significantly inhibit high glucose-stimulated reactive oxygen species production in mesangial cells.
The methanol, ethanol, and aqueous extracts of EFS showed DPPH scavenging effects, while the methanol extract showed anti-inflammatory activity in RAW 264.7 cell lines.
Evidence strength: Preliminary. All antioxidant studies are in vitro or in rodent models. No human interventional data have been published to date.
4.2 Antidiabetic and Hypoglycemic Activity
Evidence type: In vitro; animal models. No confirmed human clinical trials.
The E. ferox polysaccharide fraction showed hypoglycemic properties, and could therefore be used to make healthy food for diabetic people. Song et al. demonstrated that compounds isolated from E. ferox seeds could inhibit the reactive oxygen species production stimulated by high glucose levels. Their study revealed that the diverse compounds present in E. ferox seeds have high antioxidant activity and their synergistic effect is responsible for the prevention of proteinuria, an indicator of diabetic nephropathy. Hence their study suggests that E. ferox seeds will be a potential source of natural antioxidants useful for the treatment of diabetic nephropathy.
A 2015 animal study by Ahmed et al. — subsequently subject to a retraction note — used streptozotocin-induced diabetic Wistar rats: ethanolic extract of Euryale ferox was evaluated for its effect on hepatic antioxidant enzymes, glycemic control, lipid profile, and histopathology of pancreas, liver, and kidney of streptozotocin-induced diabetic Wistar rats divided into eight groups including non-diabetic control, diabetic control, and diabetic treated groups infused with different doses of Euryale ferox. It is critically important to note that this study — "Antidiabetic, antioxidant, antihyperlipidemic effect of extract of Euryale ferox salisb. with enhanced histopathology of pancreas, liver and kidney in streptozotocin induced diabetic rats" — received a retraction note (Ahmed D, Kumar V, Verma A, Shukla GS, Sharma M. BMC Complement Med Ther. 2023 Jul 1;23(1):216), and its findings should therefore be treated with caution.
EFS is consumed medicinally or for food in China. Studies revealed it to contain significant antioxidant activity, which may be associated with its medical applications as a proteinuria inhibitor of diabetic nephropathy.
Evidence strength: Preliminary and largely preclinical. The mechanistic basis (α-amylase/α-glucosidase inhibition by seed coat phenolics) is plausible from in vitro work, but no adequately powered human randomized controlled trial (RCT) has been published. One major animal study in the field has been retracted.
4.3 Cardioprotective Activity
Evidence type: In vitro; animal (isolated-heart and chronic rat) models. No human clinical trials.
Fox nut (Euryale ferox), popularly known as Makhana, has been widely used in traditional oriental medicine to cure a variety of diseases including kidney problems, chronic diarrhea, excessive leucorrhea, and hypofunction of the spleen. Based on studies revealing antioxidant activities of Euryale ferox and its glucosides composition, investigators sought to determine if Makhana could reduce myocardial ischemic reperfusion injury.
Two models were used: an acute model, where isolated rat hearts were preperfused for 15 min with Krebs–Henseleit bicarbonate buffer containing three different doses of makhana (25, 125, or 250 µg/mL) followed by 30 min of ischemia and 2 h of reperfusion; and a chronic model, where rats were given two different doses of makhana (250 and 500 mg/kg/day) for 21 days, after which isolated hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion.
At the 125 or 250 µg/mL dosage, E. ferox extract treatment significantly enhanced aortic flow and reduced the infarct size. Oral administration of 250 and 500 mg/kg/day for 21 days improved post-ischemic ventricular function and reduced myocardial infarct size. Two cardioprotective proteins, TRP32 and thioredoxin, were significantly increased. This study demonstrated the cardioprotective properties of Makhana, and the effects may be related to its upregulation of TRP32 and Trx-1 proteins and ROS scavenging activities.
Evidence strength: Weak; limited to isolated-heart and rodent models (Das et al., 2006, Molecular and Cellular Biochemistry). Extrapolation to human cardiovascular benefit is not supported by clinical data.
4.4 Anticancer Activity
Evidence type: In vitro cell-line studies only. No human data.
Anti-cancer activity was carried out in different cell types with ethanolic extract (150 µg/kg), with promising results shown by A549 Human Caucasian Lung Carcinoma Cancer Cells. The cytotoxic effects were observed at different concentrations (50–150 µg/kg dissolved in 1% DMSO). A549 human lung cancer cells and MRC-5 human lung fibroblast cells were chosen for cell proliferation assay (LDH cytotoxicity assay and MTT colorimetric assay) and pifithrin (a p-53 inhibitor) was used as standard. The ethanolic extract (150 µg/mL) showed significant activity through 60% of control cell viability in A549 cells.
The apoptotic effects of EFS ethanol extract (ESE) in A549 lung cancer cells were also investigated, with findings suggesting pro-apoptotic mechanisms, though these are in vitro observations only.
Evidence strength: Very preliminary. All data derive from in vitro cell-line assays. There are no animal tumor models or human clinical data. In vitro anticancer results cannot be directly extrapolated to clinical efficacy.
4.5 Hepatoprotective Activity
Evidence type: Animal (rodent) models. No human trials.
Traditional systems of medicine consider makhana a tonic that nourishes the spleen, kidneys, heart, reproductive organs, and musculoskeletal systems, and various in vitro experiments have reported antioxidant, antidiabetic, anti-inflammatory, cardioprotective, hepatoprotective, anticancer, and neuroprotective effects for different fractions and extracts. Hepatoprotective effects have been reported in streptozotocin-diabetic rodent models as part of combination outcomes, but no standalone human hepatoprotective study exists.
Evidence strength: Preliminary; rodent models only.
4.6 Antifatigue Activity
Evidence type: Animal studies; one study on seed coat phenolics. No controlled human trials identified.
Anti-fatigue activities have also been reported in the pharmacological literature for E. ferox extracts, attributed principally to phenolic compounds isolated from the seed coat. These findings are from rodent forced-swim and exhaustion models and have not been validated in human subjects.
Evidence strength: Preclinical only.
4.7 Antimicrobial Activity
Evidence type: In vitro. No human clinical data.
Antibacterial activity has been reported for EFS extracts in in vitro assays. E. ferox has been evaluated as an antibacterial agent against plant pathogens and standard bacterial strains in laboratory settings; however, no human infection trial data exist.
Evidence strength: In vitro only; clinical relevance is undetermined.
4.8 Glycemic Index
Evidence type: A small study involving human subjects.
A study used roasting and seasoning to enhance consumer acceptance and compared biochemical, nutritional, and physical properties of roasted and unroasted fox nuts, including their Glycemic Index (GI) in human subjects. Results showed that roasting significantly improved minerals content, protein content, total phenolics, flavonoids, and DPPH radical scavenging activity. The study found a low GI for both roasted and raw fox nuts, supporting their potential use in diets for blood glucose management; however, this was a focused GI study, not a therapeutic trial.
Evidence strength: Limited; a single GI study in human subjects. Broader clinical implications require confirmation in larger trials.
5. Body Systems and Health Areas Associated with Euryale Seed
Based on the combination of traditional records and preclinical research, Euryale seed has been associated with the following body systems:
- Renal/Urinary System: EFS is known for its effects in tonifying the kidneys and strengthening essence. Traditionally used for spermatorrhea, enuresis, urinary incontinence, and turbid urine.
- Digestive/Gastrointestinal System: EFS is traditionally employed for invigorating the spleen and alleviating diarrhea. Also used for leucorrhea, spleen deficiency, and chronic diarrhea.
- Cardiovascular System: Cardioprotective effects have been demonstrated in isolated rat-heart ischemia-reperfusion models, attributed to upregulation of antioxidant proteins.
- Metabolic/Endocrine: Antidiabetic and antihyperlipidemic activity has been shown preclinically; the seeds' low fat content, high fiber, and enzymatic inhibitors support metabolic relevance.
- Hepatic System: Hepatoprotective properties reported in animal models.
- Reproductive System: For many years, E. ferox has been used as a remedy for various illnesses affecting the digestive, respiratory, and reproductive systems.
- Integumentary System (Melanogenesis): Antimelanogenic activity has been reported in the pharmacological literature.
- Immune/Inflammatory: Anti-inflammatory properties in RAW 264.7 macrophage cell lines have been noted.
As of the most recent reviews, six pharmacological activities have been mapped in the literature: antidiabetic, cardioprotective, antioxidant/anti-aging, hepatoprotective, anti-fatigue, and antimicrobial/anticancer. Three unresolved research priorities identified are: human RCTs, extract standardization, and socioeconomic value-chain analysis.
6. Dosage Forms and Reported Dosages
Traditional Dosage (TCM Pharmacopoeia)
In traditional pharmacopoeia records: roots are administered orally by decoction at 30–60 g, or cooked, and may also be applied externally as a smashed preparation; leaves are taken orally at 9–15 g by decoction, or burnt, powdered, and dissolved for administration; the anthocaulus (flower stalk) is administered at 15–30 g by decoction; and the kernel is administered orally at 15–30 g by decoction, or made into pills or powders.
Dosages Used in Preclinical Studies
- Cardioprotective (acute, isolated heart model): Three doses of makhana (25, 125, or 250 µg/mL) were used in an acute ischemia-reperfusion model.
- Cardioprotective (chronic oral, rats): E. ferox (250 and 500 mg/kg/day) oral administration for 21 days improved post-ischemic ventricular function and reduced myocardial infarct size.
- Antidiabetic (animal): Doses in the range of 60 mg/kg orally were used in some rodent studies evaluating glycemic parameters.
- Anticancer (in vitro): Ethanolic extract at 150 µg/kg was used for anticancer assays, with cytotoxic effects observed at different concentrations from 50–150 µg/kg dissolved in 1% DMSO.
Note on Human Dosage
No established therapeutic dosage for Euryale seed extract in humans has been validated in peer-reviewed clinical trials to date. The traditional culinary consumption range (food-level intake) is distinct from extract-based dosing used in preclinical experiments. Any supplement label dosages reflect manufacturer decisions rather than clinically derived dose-response data.
7. Safety Considerations
Traditional Contraindications
Classical TCM texts specify caution or contraindication in certain conditions. Traditional sources state: "Use with caution in cases of food detention; not for use in those with adverse urine." The implication is that Euryale seed, given its astringent and binding properties in TCM theory, may be inappropriate where there is constipation, difficult urination, or active stagnation.
Food Safety and Long-Term Use
The seeds of E. ferox have been categorized as superior food for 2000 years in China, and their long history of broad dietary use without documented toxicity in traditional sources supports a generally favorable safety profile as a food ingredient. Its excellent qualities and remarkable efficacy have been highlighted in clinical applications, which are mainly used for the treatment of cancer, hypertension, diabetes, pelvic inflammatory disease, thyroid, and prostatic disorders, but formal clinical toxicity evaluations remain scarce in the peer-reviewed literature.
Potential Concerns: Retracted Research
A notable safety-adjacent concern is the retraction of the study "Antidiabetic, antioxidant, antihyperlipidemic effect of extract of Euryale ferox salisb. with enhanced histopathology of pancreas, liver and kidney in streptozotocin induced diabetic rats" by Ahmed D et al., retracted in BMC Complement Med Ther. 2023 Jul 1;23(1):216. The retraction underscores the importance of relying on replicated, high-quality studies when assessing both efficacy and safety claims.
Heavy Metal Accumulation
Like many plant-based foods, Euryale ferox seeds can accumulate heavy metals from soil or water sources. Prolonged consumption of contaminated seeds may pose health risks associated with heavy metal toxicity. Choosing reputable sources and ensuring proper cultivation practices can mitigate this concern.
Potential Drug Interactions
Euryale ferox may interact with certain medications, particularly those metabolized by the liver or affecting blood clotting. The antihypoglycemic properties demonstrated preclinically raise the theoretical possibility of additive effects with antidiabetic medications; however, this has not been formally evaluated in human pharmacokinetic or interaction studies.
Pregnancy and Lactation
Limited information is available regarding the safety of Euryale ferox consumption during pregnancy and lactation. Due to potential risks including allergenicity and unknown effects on fetal development, pregnant and breastfeeding women should exercise caution.
Overall Evidence Gaps
Although the main constituents and bioactivities of EFS have been extensively investigated, detailed summaries are few. Furthermore, the pharmacological mechanisms of active components remain to be reviewed. The field is characterized by a predominance of in vitro and animal studies, with no completed large-scale human RCTs having been published on any therapeutic endpoint as of the literature reviewed. Three unresolved research priorities are: human RCTs, extract standardization, and socioeconomic value-chain analysis.
References
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