 Gen info
- Myristica fragrans, commonly known as the nutmeg tree, is an evergreen tree indigenous to the Maluku Islands of Indonesia. It is economically significant as the primary source of two spices: nutmeg, is the seed kernel inside the fruit, and mace is the fleshy red, net-like skin covering (aril) on the kernel. (3)
- Myristica fragrans was given its binomial name by the Dutch botanist Maartyn Houttuyn in 1774. The specific epithet fragrans means "fragrant". (3)
- Annual global production of nutmeg is about 17,000 t and of mace 3000 t. Approximately 60% of nutmeg and mace in the world market is produced in Indonesia and 30% in Grenada, with small quantities from Sri Lanka. Major importers are U.S.A., Germany, Netherlands, Great Britain, and Japan. Approximate prices are US$7/kg of nutmeg, US$13.5/kg of mace. (Probably 1990s prices) (2)
 - Etymology: The name nutmeg derives from Latin, nux muscat, meaning musky nut.
- Legend: It
is said that when nutmeg sets seed, the exudes an overpowering musky smell that causes birds of paradise to fall to the ground (Krieg 1964). This could be due to the narcotic properties of nutmeg than its characteristic scent.
- Nutmeg has been used as spice and medicine in India and the Middle East as early as 700 BCE (Kalbhen 1971).
About the 12th century, nutmeg became rumored as an effective abortifacient. This use introduced the West to its narcotic properties, as a number of women became delirious after using large quantities of nutmeg to induce miscarriages (Kalbhen 1971). At the height of its value, nutmeg was considered by Europeans as an icon of wealth, graters became fashionable accoutrements, diners grating their own nutmeg at fancy restaurants. Nutmeg subsequently became a major export product of the West Indies. It is now featured on the national flag of Grenada. (12)
 Botany
• Myristica fragrans is an evergreen tree, usually 5–15 m (16–49 ft) tall, but occasionally reaching 20 m (66 ft) or even 30 m (98 ft) on Tidore. Alternately arranged leaves are dark green, 5–15 cm (2.0–5.9 in) long by 2–7 cm (0.8–2.8 in) wide with petioles about 1 cm (0.4 in) long. Species is dioecious, i.e. "male" or staminate flowers and "female" or carpellate flowers are borne on different plants, although occasional individuals produce both kinds of flower. Flowers are bell-shaped, pale yellow and somewhat waxy and fleshy. Staminate flowers are arranged in groups of one to ten, each 5–7 mm (0.2–0.3 in) long; carpellate flowers are in smaller groups, one to three, and somewhat longer, up to 10 mm (0.4 in) long. Carpellate trees produce smooth yellow ovoid or pear-shaped fruits, 6–9 cm (2.4–3.5 in) long with a diameter of 3.5–5 cm (1.4–2.0 in). Fruit has a fleshy husk. When ripe the husk splits into two halves along a ridge running the length of the fruit. Inside is a purple-brown shiny seed, 2–3 cm (0.8–1.2 in) long by about 2 cm (0.8 in) across, with a red or crimson covering (an aril). Seed is the source of nutmeg; the aril the source of mace. (3)
Distribution
- Introduced to the Philippines.
- Found throughout the Philippines except for Palawan.
- Native to Maluku.
- Cultivated for its two fruit spices: nutmeg and mace.
- Listed as vulnerable by IUCN Red List of Threatened Species.
Constituents
- Proximate nutritive analysis per 100 g of edible portion: Water 10g, protein 7g, fat (nutmeg butter) 33g, essential oil 5g, carbohydrate 30g, fiver 11g, ash 2g (Ca 0.1g, P 0.2g, Fe 4.5g). (2)
- Major chemical constituents of Myristica fragrans are alkyl benzene derivatives (myristicin, elemicin, safrole) myristic acid, alpha-pinene, terpenes, beta-pinene and trimyristin [12-13]. Nutmeg contains about 10% essential oil, chiefly composed of terpene hydrocarbons (sabinene and pinene), myrcene, phellandrene, camphene, limonene, terpinene, myrcene, p-cymene and other terpene derivatives (Jaiswal et al, 2009). (6)
 - GC-MS analysis of n-hexane seed extract identified 23 phytoconstituents with elemicin (24.44%) as the major constituent. (see study below) (10)
- Myristica fragrans essential oil (MFEO) extracted by various methods showed oil yield of 0.7-3.2, 8.1-10.3, 0.3-12.5, and 6.2 - 7.6% in leaf, mace, seed, and kernel. Primary chemical constituents of
MFEO were sabinene, eugenol, myristicin, caryophyllene, ß-myrcene, and α-pinene. (11)
- Study of fruits isolated two new phenolic compounds elucidated as (−)-1-(2,6-dihydroxyphenyl)-9-[4-hydroxy-3-(p-menth-1-en-8-oxy)-phenyl]-1-nonanone (1) and (7R,8R)-7,8-dihydro-7-(3,4-dihydroxyphenyl)-3′-methoxy-8-methyl-1′-(E-propenyl)benzofuran (2), along with (+)-Δ8′-7-acetoxy-3,4,3′,5′-tetramethoxy-8-O-4′-neolignan (3) and (7S,8S,7′R,8′S)-4,5′-dihydroxy-3,3′-dimethoxy-7,7′-epoxylignan (4). (see study below) (14)
- Study of dried ripe seeds of M. fragrans isolated six dihydro-benzofuran type neolignans, identified as licarin B (1), 3′-methoxylicarin B (2), myrisfrageal A (3), isodihydrocainatidin (4), dehydrodiisoeugenol (5), and myrisfrageal B (6). (see study below) (15)
- Nutritional info per teaspoon of serving: Calories 11.6, carbohydrates 1.1g, fat 0.8g, protein 0.1g, saturated fat 0.6 g, sodium 0.4 mg, fiber 0.5g, sugar 0.1g.
(23)
- Bioassay purification of various pericarp extracts yielded 20 compounds belonging to neolignans (0.13%), phenylpropanoids (0.28%), phenolic aldehyde (0.35%), triterpenoids (0.06%), triglycerides (0.02%), sugars (10.2%), and steroids (0.49%). (see study below) (27)
- Study of ethyl acetate fraction of M. fragrans aril yielded six compounds: malabaricone A (1), malabaricone C (2), 4-(4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzene-1,2-diol (3), nectandrin B (4), macelignan (5), and 4-(4-(benzo[d][1,3]dioxol-5-yl)-1-methoxy-2,3-dimethylbutyl)-2-methoxyphenol (6). (see study below) (29)
- Phytochemical screening of seed extracts (methanol, dichloromethane, hexane and chloroform) for essential oil yielded presence of secondary metabolites such as alkaloids, steroids, tannins, flavonoids, phenolics, and glycosides.
(39)
- GC-MS of n-hexane extract identified 42 compounds with main constituents of sabinene (12.2%), linoleic acid (11.7%), hexadecanoic acid (10.5%), safrole (8.1%), and elemicin (7.8%). (see study below) (43)
- Study of seeds isolated three new dihydrobenzofuran neolignans, myticaganal A-C (1-3), along with five known compounds (4-8). (see study below) (44)
- Study evaluated seed extracts for mineral elements, amino acid
constituents, and fatty acids. Calcium, magnesium, and iron were the most abundant in methanol extract with concentrations of 3.21, 3.00, and 1.00 ppm, respectively. Major essential amino acids were leucine 6.24g/100g, valine 3.72g/100g, and threonine 3.50g/100g, while non-essential amino acids were glutamate 10.6g/100g, aspartate 7.60g/100g, and arginine 5.50g/100g. Major biological compounds by GC-MS were 9,12-Octadecadienoic acid methyl ester (RT: 20.768, 27.13%), Cyclododecyne (RT: 26.458, 19.33%) and octadecanoic acid (RT: 14.360, 12.24%) while the hexane extract constituents were margarinic acid (RT: 14.746, 27.04%), oleic acid (RT: 20.947, 18.96%) and 9,12-octadecadien-1-ol (RT: 26.523%, 15.10%). (59)
- Study of M. fragrans seeds isolated four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and nectandrin B. (see study below) (70)
Properties
- Studies have suggest antibacterial, analgesic, anxiogenic, sedative, sexual function enhancing, aphrodisiac, hypolipidemic, cytotoxic, antioxidative, anti-inflammatory, anti-H. pylori, antidepressant-like, memory-enhancing, anti-convulsant, anti-allergic, acetylcholinesterase inhibitory, anti-obesity, anti-Alzheimer's, hypoglycemic, antidiabetic, COX-2 inhibitory, anticariogenic, anti-mutagenic, anticancer, LDH inhibitory, anti-melanogenic, antifungal, procoagulant, antidiabetic, anti-rheumatic, pancreatic lipase inhibitory, apoptotic-inducing, hepatoprotective, burn-wound healing properties.
Physiological effects
- Inebriation: Nutmeg is considered a deliriant. In low doses nutmeg inebriation causes effects similar to combination of alcohol and marijuana. In higher doses, effects are similar to those causes by tropane alkaloids i.e. confusion, disorientation, and hallucinations, the effects coming on and dissipating in waves, with the user switching back and forth between states of consciousness and realities. (12)
- Unlike traditional psychedelics like psilocybin-containing mushrooms or LSD, nutmeg inebriation can be broken down in six stages, which depending on dosage used can last
26-32 hours.
- Stages:
Threshold stage (hours 1-4), Initial inebriation ( hours 4-8), Peak inebriation (hours 8-12), End of peak (hours 13-18), Residual inebriation (hours 19-25), Final stage-baseline (hours 26-32).
- Potency: Nutmeg potency varies. Nutmeg from the East Indies is said to be more potent than that from the West Indies. Fresh ground is reputedly more potent than pre-ground. Familiarity with potency is of utmost importance. (12)
Parts used
Seeds, essential oil, .
Edibility
- Ground nutmeg and mace are used in cooking. They are sold as spices, whole or ground.
- Grated nutmeg is used in small quantities to flavor confectionery; in Europe, for meat dishes and soups. Mace is used for savory dishes, pickles, and catsups. (3)
- Used as flavoring for baked foods, confections, puddings, meat, sausages, vegetables, and beverages. A component of curry powder, teas, and soft drinks, or mixed in milk and chocolate. (5)
- In its native range in Maluku, the pericarps are made into a sweet snack called "pala manis" or "pala gulu" by repeated soaking in sugar solution. (6)
Folkloric
- Used as folklore medicine for diarrhea, mouth sores, and insomnia. Since the Middle Ages, used as stomachic, stimulant, carminative; for intestinal catarrh and colic, to stimulate appetite, control flatulences, and as emmenagogue and abortifacient. (5)
- Used tonic for the heart and brain and for sexual and general debility. Essential oil used externally for rheumatism. (5)
- History records nutmeg's use for its sedative effect, treatment of nervous complains, and to promote sleep in Malaysia and India. Moluccans would mix nutmeg with milk and banana drink as a sleep aid for children. In Europe, women carried nutmeg in silver graters for sleep-time use. (12)
- In Thailand, the wood, nutmeg (seed) and mace (aril) are used as tonic, cardiotonic, and carminative. All three parts are used as ingredient for various remedies such as anti-pyretic, anti-inflammatory, and other remedies. (see study below) (24)
Others
- Oil: Seeds yield an essential oil.
- Fragrance: The arils, bark, flowers and leaves are used for fragrance in soaps and perfumes. (3) Fixed oil pressed from seeds used in ointments, perfumery, soaps, and candles.
- Nutmeg butter: Fat derived from the seed is
used in perfumery, tobacco, and toothpaste. (6)
- Abortifacient: Its most infamous medical use is as an abortifacient - a popular, although ineffective
- remedy at the end of the 19th and beginning of the 20th century. (12)
- Aphrodisiac: A little known application is its traditional use as an aphrodisiac. In India, nutmeg was added to curry dishes and added to betel quids for its aphrodisiac effect (Rätsch 2005). It is still recognized for its aphrodisiac effect in Malaysia and Arab countries for this effect, and the counterpart, mace, prescribed in the Near East as an aphrodisiac (Forrest & Heacock 1972). Other experiments include the rubbing of nutmet oil on the genitals to elicit sexual excitation. More peculiar is the old German folk tradition in which the girl would swallow a nutmeg whole, and after it is passed, is powdered and mixed in the food of beloved, hoping to hopelessly enamor the man. (12) In some cultures, it is used as ingredient in love potions. (also see study below) (9)
- Inebriant / intoxicant: Nutmeg was historically used in Egypt as a substitute for hashish. In India, it has been chewed or snuffed with tobacco, or added to betel chew. In the early 20th century, it emerged in the USA prisons as an alternative to marijuana and other illicit substances. Its use in prisons became so widespread that nutmeg was ultimate removed from prison kitchens. (12)
- Others: Various nutmeg preparations are still used as analgesics, stomachics, digestives, hypnotics, aphrodisiacs, dream enhancing, and amenorrheal agents. (6)
Studies
• Antibacterial Against Oral Pathogens / Flesh, Mace, and Seed: Study evaluated ethyl acetate and ethanol extracts of flesh, mace, and seed of M. fragrans for bactericidal potential against three Gram(+) cariogenic bacteria viz., (Streptococcus mutans ATCC 25175, Streptococcus mitis ATCC 6249, and Streptococcus salivarius ATCC 13419) and three Gram-negative periodontopathic bacteria (Aggregatibacter actinomycetemcomitans ATCC 29522, Porphyromonas gingivalis ATCC 33277, and Fusobacterium nucleatum ATCC 25586). The ethyl acetate extract of flesh showed highest significant inhibitory effects against Gram(+) and Gram(-) bacteria with mean MICs ranging from 0.625 to 1.25 mg/mL, P=0.017, and highest bactericidal effects with mean MBC values range from 0.625 mg/mL to 20 mg/mL. All of the extracts showed not activity against Fusobacterium nucleatum. Results suggest potential for EA and ethanol extracts from seed, flesh, and mace as natural agents to be incorporated in oral care products. (7)
• CNS Activity / Analgesic, Sedative, and Anxiogenic: Study evaluated orally ethanolic extract (EEMF) and fractions of extract in ethyl acetate (EAMF), chloroform (CMF), and n-hexane (HMF) for CNS activities. Results showed the EEMF and EAMF exhibited significant decrease in latency of sleep and highly significant increase in duration of sleep in pentobarbitone induced sleep potentiation test. In Open field test, EEMF, EAMF and HMF showed highly significant decrease in locomotion parameters evidenced by decrease in rearing, preening, and ambulation. The EEMF, EAMF and HMF also showed highly significant increase in reaction time in Eddy's hot plate test and Tail flick test. Results suggest analgesic, anxiogenic, and sedative activity. (8)
• Male Sexual Function Enhancing Effect / Aphrodisiac: Study evaluated the aphrodisiac effect of 50% ethanolic extract of nutmeg along with adverse effects and toxicity in various animal models. Extract suspension in doses of 100, 250, and 500 mg/kg p.o. were administered to groups of male rats for 7 days. Female rats were made receptive by hormonal treatment. Sildenafil citrate was used as standard reference drug. The 500 mg/kg dose produced significant augmentation of sexual activity in male rats, with increased mounting frequency, intromission frequency, intromission latency, and significant reduction in mounting latency and post ejaculatory interval. The extract was devoid of adverse effects and acute toxicity. Results indicates the 50% ethanolic extract possess aphrodisiac activity, increasing libido and potency, which may be attributed to its nervous stimulating property. (9)
Nutmeg has been mentioned in Unani medicine for the management of male sexual disorders. Study evaluated the aphrodisiac effect of 50% ethanolic extract of nutmeg along with adverse effects and toxicity using various animal models. Dose of 500 mg/kg produced significant augmentation of sexual activity in male rats. There were no conspicuous adverse effects. The aphrodisiac activity was attributed to nervous stimulating property. (46)
• Antioxidant / Antibacterial / Elemicin / Seed: Study of n-hexane extract of seed identified 23 phytoconstituents with elemicin as the major constituent. Using lipid peroxidase, catalase, and DPPH assays, elemicin was showed to possess significant antioxidant activity. Elemicin also showed antibacterial activity with MNIC of 31.25 µg/mL against E. coli, P. aeruginosa, and S. typhi, and 62.5 µg/mL against K. pneumonia and S. aureus, and antifungal activity against Candida tropicalis and Aspergillus flavus. Results showed promising bioactive properties and potential as therapeutic agent and food preservative. (10)
• Hypolipidemic / Fruit: Study evaluated an ethanolic extract of nutmeg for effects on experimentally induced hyperlipidemia in albino rabbits. Results showed significantly lower levels of total cholesterol, LDL, and triglycerides. The extract also showed platelet anti-aggregatory ability, significantly lower total cholesterol in heart and liver. Toxicity study showed absence of adverse effect on various hematological and biochemical parameters. (13)
• Cytotoxic / Antioxidative Phenolic Compounds / Fruits: Study of fruits isolated two new phenolic compounds (1,2), along with a -neolignan (3) and an -epoxylignan (4). Compound 4, (7S,8S,7′R,8′S)-4,5′-dihydroxy-3,3′-dimethoxy-7,7′-epoxylignan, showed antioxidant activity against DPPH radicals and cytotoxicity against K-562 cells, with IC50s of 39.4 and 2.11 µM, respectively. (see constituents above) (14)
• Nitric Oxide Inhibitors / Seeds: Study of dried ripe seeds of M. fragrans isolated six dihydro-
benzofuran type neolignans, identified as licarin B (1), 3′-methoxylicarin B (2), myrisfrageal A (3), isodihydrocainatidin (4), dehydrodiisoeugenol (5), and myrisfrageal B (6). Compounds 1-6 showed inhibition of nitric oxide production in lipopolysaccharide-activated murine monocyte-macrophage RAW264.7 with IC50s of 53.6, 48.7, 76.0, 36.0, 33.6, and 45.0 µM, respectively, and compared with indomethacin and L-N6-(1-iminoethyl)-lysine with IC50s of 65.3 and 27.1 µM, respectively. Compounds 3, 5, and 6 suppressed LPS-induced iNOS mRNA expression in a dose-dependent manner in RAW264/7 cells. Compounds 3, 5, and 6 may inhibit NO overproduction via inhibition of iNOS mRNA expression. Results suggest further investigation of compounds 1-6 as anti-inflammatory and chemopreventive agents. (15)
• Anti-Helicobacter pylori / Anti-Inflammatory / Cytotoxic / Antioxidant / Mace: The aril (mace), known as Dok-Chan, is an ingredient in many Thai traditional medicine e.g., Ya-Hom-Thep-Bhat-Jit, Ya-Hom-Nao-Wakot, and Ya-That-Bun-Job, used for treatment of dyspepsia and other gastrointestinal maladies. Study evaluated ethanol (EA) and aqueous (AE) extracts of mace for anti-H. pyloric activities using disc diffusion method and agar dilution, anti-inflammatory activity byt LPS-induced NO inhibition in RAW264.7 cell line, cytotoxicity against gastric cancer cell line (Kato III) using sulphorhodamine B (SRB) assay, and antioxidant activities by DPPH radical scavenging and ABTS assays. Results showed the ethanolic mace extracts had anti-H. pylori, anti-inflammatory, antioxidant, and anticancer activities. (16)
• Antidepressant / Seeds: Study evaluated the effect of an n-hexane extract of M. fragrans seeds on depression in young Swiss male albino mice using forced swim test (FST) and tail suspension test (TST) with extract doses of 5, 10, and 20 mg/kg orally for 3 days. The extract significantly decreased immobility periods in both FST and TST. The 10 mg/kg dose was most potent evidenced by greatest decrease in immobility period, a dose comparable in potency to imipramine (15 mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). There was not significant effect on locomotor activity. The antidepressant effect in TST was significantly attenuated by prazosin, sulpiride, and p-chlorophenylalanine. Study suggests the antidepressant effect may be mediated by interaction with the adrenergic, dopaminergic, and serotonergic systems. (17)
• Antimicrobial Against Multi-Resistant Microorganisms / Seeds, Leaves, and Essential Oils: Study evaluated decoction (De) and methanolic extracts (ME) of seeds and leaves of M. fragrans against Staphylococcus aureus, five strains of methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and essential oil from both parts against a panel of resistant bacteria and Candida spp. The De and ME of leaves and seeds showed inhibitory effect against S. aureus and all five MRSA strains with ZOIs of 16.0 to 19.0 mm. The De and MEs did not show inhibitory activity against E. coli and P. aeruginosa. Both EOs showed activity against all MRSA with ZOI 7-12 mm. EO of leaves showed activity against K. pneumonia, Acinetobacter spp., Enterobacter cloacae and group A beta-hemolytic streptococcus with ZOIs 8-12mm. Results suggest the EO of leaves and seeds have potential for pharmaceutical applications. (18)
• Improvement of Mouse Memory / Seeds: Study evaluated the effect of n-hexane extract of M. fragrans seeds on scopolamine- and diazepam-induced impairment in learning and memory in mice. Learning and memory parameters were assessed using elevated plus maze and passive-avoidance apparatus. Extract at lowest dose of 5 mg/kg p.o. for 3 successive days significantly improved learning and memory of young and aged mice. Extract reversed scopolamine- and diazepam-induced impairment in learning and memory. Extract enhanced leaning and retention capacities. The observed memory-enhancing effect may be attributed to various plant properties viz., antioxidant, anti-inflammatory, or perhaps procholinergic activity. (19)
• Anticonvulsant / Seeds: Study evaluated the anticonvulsant, cataleptic and sedative properties of n-hexane fraction of actone insoluble part of petroleum ether extract of M. fragrans seeds. Anticonvulsant activity of MF (10, 30, 100 mg/kg i.p.) was studied against seizures induced by maximum elctroshock (MES), pentylenetetrazol (PTZ), picrotoxin, and lithium sulphate-pilocarpine nitrate (Li-Pilo). Effect on gross behavior, motor coordination, haloperidol-induced catalepsy (using Bar test) and pentobarbitone-induced sleep was studied. The MF inhibited seizures induced by MES< PTZ, and Li-Pilo, without effect on picrotoxin-induced seizures. Haloperidol-induced catalepsy was potentiated, with no significant effect on motor coordination and pentobarbitone-induced sleep. Results showed complex effects on the CNS, with anticonvulsant activity and reduced central dopaminergic activity. (20)
• Toxicity of Essential Oil / Seeds / Review: Nutmeg is reported to contain 5-15% volatile oil. It has been extensively used in aromatherapy, natural medicine, and the perfume industry. GC-MS analysis of nutmeg oil has revealed 27-38 chemical constituents at various concentrations. Numerous studies have reported biologic activities such as antioxidant, insecticidal, and anticancer activity. However, large intake of nutmeg oil can cause intoxication manifested as cardiovascular, CNS, and anticholinergic effects, along with local effects in the stomach. Symptoms are mainly attributed to effects of myristicin, saffrole, and elemicin overdose. (21)
• Protects Against DSS-Induced Colitis / Seeds: Study evaluated the protective effect of water extracts of M. fragrans seeds (MFE) against colitis induced by 5% dextran sulfate sodium (DSS) in balb/c mice. MFE in doses of 100, 300, or 1000 mg/kg was administered orally twice daily for 7 days. MFE dose dependently inhibited the colon shortening and histological damage to the colon. It did not prevent weight loss. MFE inhibited proinflammatory cytokines. Results suggest MFE ameliorates DSS-induced colitis in mice by inhibiting inflammatory cytokines. (22)
• Bioactivities of Wood, Nutmeg, and Mace / Anti-Allergic, Antioxidant, Anti-Inflammatory: Study evaluated the biological activities of 95% ethanolic extracts (EE) from M. fragrans wood, nutmeg and mace. The EE of wood exhibited potent anti-inflammatory activity by inhibitory effects on LPS induced nitric oxide production release in RAW264.7 cell lines, more than nutmeg or mace, with IC50s of 40.26, 65.42, and 75.40 µg/ml, respectively. On antioxidant activity by inhibitory effect on PMA-induced superoxide radical in DMSO-differentiated from HL-60 cells, nutmeg and mace showed high antioxidant activity while wood showed moderate activity with IC50s of 21.164m 28.897, and 71.830 µg/ml, respectively. On anti-allergic testing by inhibitory activity of ß-hexosaminidase release on RBL-2H3 cells, wood, nutmeg, and mace showed strong anti-allergic activity with IC50s of 13.29, 20.90, and 12.95 µg/ml, respectively. (24)
• Comparative Cholinesterase Inhibiting Activity / Seeds: Study evaluated the acetylcholinesterase-inhibiting activity of extracts if Glycyrrhiza glabra, Myristica fragrans seeds, and ascorbic acid in Swiss albino mice and compared their values with standard acetylcholinesterase-inhibiting drug metrifonate. G. glabra, M. fragrans, ascorbic acid, and metrifonate significantly decreased acetycholinesterase activity as compared to respective vehicle-treated control groups. (Comparative results unavailable) (25)
• Anxiogenic / Seeds: Study evaluated a n-hexane extract of M. fragrans seeds, acetone-insoluble part of the n-hexane extract (AIMF) and trimyristin (TM) for anxiogenic activity. The AIMF, MF, and TM administered intraperitoneally exhibited anxiogenic activity in elevated plus-maze (EPM) paradigm. In the EPM test, all three decreased the time spent by mice in open arm and entries in open arm. In open-field test, AIMF and TM reduced the number of rearing and locomotion. Inhibition of anxiolytic activity of ondansetron (5-HT3 receptor antagonist), buspirone (5-HT1A receptor agonist), and diazepam (acting on γ-aminobutyric acid: GABAA receptor) suggests a nonspecific anxiogenic activity of TM and a link between 45-HT and GABA systems in the anxiogenic activity of TM. (26)
• Anti-Inflammatory / Antioxidant / Pericarp: Study evaluated M. fragrans pericarp for bioactive components using invitro and anti-inflammatory assay. Hexane, ethyl acetate and methanolic extracts inhibited lipid peroxidation (LPO) by 82.5, 70.1, and 73.2% and cyclooxygenase enzymes COX-1 by 44, 44, and 42% and COX-2 by 47, 41, and 36%, respectively, at 100 µg/mL. Pure isolates 1-5 inhibited LPO by 70-99% and 3-12 inhibited COX-1 and -1 enzymes by 37-49%. (27)
• Anti-Cholinesterase Activity / Seeds: Study evaluated M. fragrans ethyl acetate fraction of methanol extract of seeds and isolated compounds. Spectropica analysis isolated and identified 13 compounds. Compound 8, {[(7S)-8′-(4′-hydroxy-3′-methoxyphenyl)-7-hydroxypropyl]benzene-2,4-diol}, showed most effective activity with IC50 of 35.1 µM, followed by compound 2, [(8R,8′S)-7′-(3′,4′-methylenedioxy-phenyl)-8,8′-dimethyl-7-(3,4-dihydroxyphenyl)-butane], and 11 (malabaricone C) with IC50s of 42.1 and 44.0 µ≤M, respectively. Results suggest potential for treatment of Alzheimer's disease. (28)
• Anti-Cholinesterase Activity / Aril: Study evaluated the ethyl acetate fraction of M. fragrans for invitro anticholinesterase activity as well as neuroprotective activity against H2O2-induced cell death in PC12 neuronal cells and ability to chelate bio-metals (Zn, Fe, and Cu). The fraction was inactive against acetylcholinesterase (AChE), but inhibited butyrylcholinesterase (BChE) with IC50 of 68.16 µg/mL, compared with donepezil as reference drug (IC50 1.97 µg/mL). It showed good % neuroprotective (86.28% at 100 µg/mL) against H2O2-induced neurotoxicity and moderate metal chelating ability. Phytochemical study isolated 6 compounds, of which compound 2, malabaricone C, showed best activity toward both AChE and BChE with IC50s of 25.02 and 22.36 µM, respectively, compared with donezepil (0.07 and 4.73 µM). (see constituents above) (29)
• Effect on Food Intake and Body Weight: Study evaluated effect of M. fragrans extract on food intake and body weight in normal and obese wistar albino rats. Extract in doses of 200 and 400 mg/kg were used. After 35 days of treatment (between 36-70 days), there was significant reduction in FI (food intake) capacity and BW (body weight) in groups II and IV in a dose dependent manner (p<0.01). Results suggest potential clinical value in the treatment of obesity due to inhibitory effect on FI capacity by inhibiting hunger sensory mechanism and BW by inhibiting pancreatic lipase enzyme. (30)
• Hypoglycemic / Antidiabetic / Seeds: Study evaluated the hypoglycemic and antidiabetic activity of petroleum ether extract of seeds of M. fragrans in normoglycemic and alloxan-induced diabetic rats. Results showed oral pretreatment with PEMF at dose of 200 mg/kg induced a significant (p<0.05) decrease in blood glucose level and OGTT. After 2 weeks of daily PEMF, diabetic treated rats showed improvement in body weight, organ weight, lipid profiles and hemoglobin content compared to diabetic control rats. (31)
• Antimicrobial / Antioxidant / Cyclooxygenase 2 Inhibitory / Seeds: Study evaluated acetone and methanol extracts of nutmeg seeds for antimicrobial, antioxidant, and anti-inflammatory activities. Antimicrobial testing by agar well diffusion against Gram(-) E. coli and Klebsiella spp., Gram(+) S. aureus and S. epidermis, and Candida albicans showed acetone extract inhibition with ZOI range between 11-15 mm. No inhibition was seen with the methanol extract. The acetone extract showed high concentration of phenolic compounds (0.6217 mg/ml) and DPPH assay indicated high amount of antioxidant compounds. Acetone extract showed inhibition of COX-2 activity better than anti-inflammatory drug aspirin. Results suggest the acetone extract of nutmeg as a source of antimicrobial, antioxidant, and anti-inflammatory agent. (32)
• Role in Morphine Dependence: Study evaluated the role of ethanolic extract of M. fragrans (EEMF) in morphine dependence in Wistar albino rats. Regimens used were: (a) EEMF 200 mg/kg along with morphine twice daily for 4 ad 7 days in moderately and severed induced morphine dependence, and (b) EEMF 400 mg/kg p.o. single dose 10 hours after the last dose of morphine in both moderately and severely induced dependence in rats. Oral administration of EEMF showed a significant reduction in mean scores of morphine withdrawal symptoms in both study groups. Reduction was significantly more in regimen "a" than "b". Results suggest a potential as substitute therapy in morphine de-addiction. (33)
• Macelignan / Anticariogenic Against Streptococcus mutans: Study isolated an anticariogenic compound from methanol extract of S. mutans and identified as macelignan. The minimum inhibitory concentration (MIC) of macelignan against S. mutans was 3.9 µg/ml, which was much lower than anticariogenic agents such as 15.6 µg/ml of sanguinarine, 250 µg/ml of eucalyptol, 500 µg/ml of menthol and thymol, and 1000 µg/ml of methyl salicylate. Macelignan showed preferential activity against other oral microorganisms such as Streptococcus sobrinus, S. salivarius, S. sanguis, Lactobacillus acidophilus, and L. casei in MIC range of 2-31.3 µg/ml. In a bactericidal test, macelignan at 20 µg/ml completely inactivated S. mutans in 5 mins. Results suggest potential as natural antibacterial agent in functional foods or oral care products. (34)
• Analgesic / Alkaloids / Toxicity Study / Seeds: Study evaluated the analgesic effect of alkaloids in a mouse model of acetic acid-induced visceral pain. Alkaloids were extracted from ground nutmeg seed kernels with 10% acetic acid in 95% ethyl alcohol. Alkaloids extract at dose of 1 g/kg significantly reduced the number of writhing responses in female, but not male mice; 0.5 g/kg had not effect in either sex. LD50 was 5.1 g/kg. Signs of abnormal behavior, including hypoactivity, unstable gait, and dizziness were seen at dose of 4 g/kg or higher. Abnormal behavior lasted for several hours after administration of alkaloids. Results showed analgesic activity and very slight toxicity. (35)
• Antimutagenic / Anticancer / Leaves: Study evaluated the potential anticancer efficacy of M. fragrans methanol leaf extract. In S. typhimurium (TA100), the mutagenicty ratio at 200, 500, and 1,000 µg/well was ≥2/ Cell division in A. cepa root tips and mouse bone marrow was significantly (p≤0.05) inhibited at 2,000 and 4,000 mg/kg. Inhibition of benzo[a]pyrene- and cyclophosphamide-induced mutagenicity was above 40%. Results showed strong antimutagenic activity of the MeOH leaf extract, which may be due to the antioxidant activity, and suggests a potential as anticancer agent. (36)
• Suppression of Tumor Growth and Metabolism via Inhibition of Lactic Dehydrogenase A: Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation. Study demonstrated water extracts from seeds of M. fragrans (MF) inhibit invitro enzymatic activity of LDH. MF
effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Lactate production and LDH activity were decreased in MF-treated cells. Intracellular ATP levels were also decreased and uptake of glucose reduced. MF effectively reduced growth of allotransplanted Lewis lung carcinoma cells. Results suggest MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. Study suggest potential for a novel drug against cancer through LDH activity inhibition. (37)
• Antimicrobial on Endodontic Pathogens / Essential Oil: Study evaluated the antimicrobial effect of essential oil of M. fragrans on common endodontic pathogens of primary tooth. EO of nutmeg was extracted by hydrodistillation method. The EO was effective against all tested common endodontic microorganisms i.e., Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, Candida albicans, Lactobacillus casei, Actinomyces viscosus, Prevotella intermedia, and Porphyromonas gingivalis. Results suggest an effective medicament for treatment of endodontic infections. (38)
• Antioxidant / Anti-Food-Borne Bacterial Activity / Leaves and Fruits: Study evaluated leaves and different fruit parts (pericarp, aril, seed-kernel and shell) for total phenolic content, antioxidant, and anti food-borne bacterial activities. The 80% methanolic extracts of aril, seed-kernel and shell shared highest total phenolic content, The shell extract showing highest primary antioxidant activity, by having highest FRAP activity with EC50 9.7 µg/mL, ß-carotene bleaching activity EC50 21.5 µg/mL, and DPPH scavenging activity EC50 160.9 µg/mL. The pericarp showed highest secondary antioxidant activity as metal chelator (EC50 75.6 µg/mL). Only the aril and seed-kernel extracts showed inhibition of food-born bacteria with lowest MIC of 50 µg/mL against S. aureus and B. cereus. Results suggest potential for the aril and seed-kernel extracts as natural food preservative and source of natural antioxidant for food and pharmaceutical industries. (40)
• Hepatorenal Toxicity / Seeds: Study evaluated the effects of oral administration of high doses of methanol (ME) and n-hexane (NHE) extracts of M. fragrans seed for one to two weeks on histology and serum markers of kidney and liver in white male Wistar rats. Both extracts revealed presence of terpenoids, flavonoids, alkaloids, phenols, steroids, and tannins. There was no obvious sign of toxicity nor mortality in acute toxicity testing up to 5000 mg/kbw. However, there were significant (p<0.05) elevations in urea, total bilirubin and creatinine concentrations, alkaline phosphatase, AST, ALT, and LDH activities in rats fed extracts for 7 or 14 days. The n-hexane extracts at 1000 mg/kg elicited some histological changes consistent with hepatotoxicity. Results suggest long-term administration of high doses of extracts elicits hepato-renal toxicities. (41)
• Anti-COVID-19 Potential: Molecular docking, molecular dynamics, and solvent screening for extraction of specified compounds and prediction of drug properties were methods used to evaluate compounds from M. fragrans. Molecular docking revealed malabaricones B and C and licarins A, B and C bound to SARS-CoV-2/ACE2 and SARS-CoV-2 Mpro with low binding energies compared to that of standard ligand. Results showed the M. fragrans compounds have potential as effective medicines to combat the COVID-19 pandemic. (42)
• Anti-Melanogenic Against Aspergillus fumigatus: Aspergillus fumigatus is an opportunistic fungal pathogen associated with a wide array of diseases. It produces 1,8-dihydroxy naphthalene (DHN) melanin that imparts a greenish gray color to conidia and is an important virulence factor. Study evaluated the anti-melanogenic effect of M. fragrans extracts on Aspergillus fumigatus. The hexane extract inhibited melanin production (76.09%), reduced ergosterol content (83.63%), and hydrophobicity of the cell (72.2%) at the MEC of 0.078 mg/mL. Results concludes M. fragrans extract has potential antifungal properties, and a combination with available antifungals may be helpful for large number of patients suffering with A. fumigatus infections. (see constituents above) (43)
• Cytotoxic Neolignans / Anticancer / Seeds: Study of seeds isolated three new dihydrobenzofuran neolignans, myticaganal A-C (1-3), along with five known compounds (4-8). The compounds were tested for invitro cytotoxic activities against three human cancer cell lines (KZB, oral cavity; MCF-7 breast cancer; and NCI-H187, small cell lung cancer). Neolignan 3 showed significant cytotoxicity against KB and NCI-H187 cells lines with IC50s of 5.9 and 6.3 µM, respectively. (44)
• Antibacterial / Antibiotic Modifying Activity: Study evaluated the in vitro antibacterial activity and antibiotic modifying activities of crude seed kernel methanol extract (MFS)(, fractions (MFSa-e) as well as 3',4',7-trihydroxyflavone from MF against a panel of multi-drug resistant (MDR) gram-negative bacteria. The crude extract showed antibacterial activity with MIC range of 32 to 1024 µg/mL on the majority of 29 Gram(-) bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of tested bacterial strains, as well as 3',4',7-trihydroxyflavone (12/12) with MIC range from 32-1024 µg/mL and 4 to 128 µg/mL, respectively. The compound 3',4',7-trihydroxyflavone potentiated the activity of antibiotics in the majority of bacterial strains. Results suggest nutmeg and its major antibacterial component, 3',4',7-trihydroxyflavone, has potential for treatment of bacterial infections including MDR phenotypes. (45)
• Potential for Cryptosporidum parvum Infection: Cryptosporidiosis is a major waterborne disease affecting humans and ruminants worldwide, causing diarrhea and neonatal mortality in buffalo calves, and watery diarrhea and mortality in children and immunodeficient patients. Study evaluated the efficacy of Mf methanolic extract for treatment of C. parvum infection in comparison with NZX (nitazoxanide), an FDA-approved drug) in immunosuppressed and immunocompetent Swiss albino mice. Results showed significantly decreased oocyst shedding in stool samples, with 79.7, 81.2, and 85.5% reduction in immunocompetent mice treated with NZX, M. fragrans, and their combination. Serum IgG level was lowest in mice treated with a mixture of Mf and NZX. Regarding cytokine levels, all groups treated with Mf had low levels of IFN-γ and IL-4 on day 21 post-infection. Results suggest efficacy of treatment of cryptosporidiosis with Mf extract. Mf reduced C. parvum oocyst shedding and serum IgG, IFN-γ, and IL-4 in immunocompetent and immunosuppressed mice. (47)
• Cytotoxicity Against Seven Human Cancer Cell Lines / Seed: Study evaluated the in-vitro anticancer effects of ethanolic extract of seed of Mf against seven human cancer cell lines i.e., colon cell (Colon502713, Colo205), liver (Hep-2), lung (A-549), ovary (OVCAR-5), and prostate (PC-5) using SRB assay to test for cytotoxicity. Results showed promising anticancer activity. The ethanolic extract showed highest anticancer activity against OVCAR-5. (48)
• Inhibition of Hepatic Drug-Metabolizing Enzyme Activity / Seed: A nutmeg seed hexane extract significantly inhibited hepatic drug-metabolizing enzyme activity. SiO2 column fractionation and vacuum liquid chromatography assay isolated three active principles: myristicin (1), licarin-B (2) and dehydro-
diisoeugenol (3). Compounds 2 and 3 with single treatment of 200 mg/kg ip showed significant prolongation of hexobarbital-induced sleeping time and significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds 1 and 2 provoked a sleep episode at subhypnotic dose suggesting CNS-depressant properties. (49)
• Antidiabetic/ Antihyperlipidemic / Fruits: Study evaluated the effect of hydroalcoholic extract of fruits of M. fragrans on chlorpromazine-induced glucose and triglyceride elevations in male Swiss albino mice. After 7 days of oral administration, extract doses of 150 and 450 mg/kg ameliorated the metabolic abnormalities caused by chlorpromazine evidenced by significant reduction of glucose and triglyceride levels (41 and 53% of glucose and triglyceride at 450 mg dose, p<0.01). In rats fed a high cholesterol diet, Mf extract significantly reduced elevated TG and cholesterol, along with a reduction in hepatic TG secretion after tyloxapol administration. Results suggest Mf ameliorates hyperglycemia and abnormal lipid metabolism in animal models. (50)
• Procoagulant / Antidiabetic: Study evaluated the effect of M. fragrans on blood clotting by blood coagulation time and the fibrinolytic system. None of the isolated compounds showed fibrinolytic activity, but could inhibit the fibrinolytic activity of urokinase. Compound 2 showed highest inhibitory activity (IC50 1.747 mg/ml) followed by compound 4 (IC50 1.818 mg/mL) and compound 1 (IC50 2.407 mg/ml), which were higher than Danshen drug tablets (IC50 6.577 mg/mL) used in China. Compounds 1 and 2 also showed strong α-glucosidase inhibitory activity in a dose dependent manner with IC50s of 21.76 and 21.31 µg/mL, respectively. Results suggest promising candidates as procoagulant and antidiabetic agents. (51)
• Anti-Obesity / AMPK Activators: AMP-activated protein kinase (AMPK) is a potential therapeutic target for treatment of metabolic syndrome including type 2 diabetes and obesity. Study found the total extract of Mf activated the AMPK enzyme in differentiated C2C12 cells. Study isolated active constituents, seven 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, tetrahydrofuroguaiacin B (1), saucernetindiol (2), verrucosin (3), nectandrin B (4), nectandrin A (5), fragransin C1 (6), and galbacin (7). Compounds 1, 4, and 5 at 5µM produced strong AMPK stimulation in differentiated C2C12 cells. The protective effect of a tetrahydrofuran mixture (THF) on weight gain in a diet-induced animal model was also examined. Results showed nutmeg and its active constituents have potential for development as agents to treat obesity and possible T2-diabetes and other metabolic disorders. (52)
• Effect on Hematological Indices / Seeds: Study evaluated the effects of ethanolic extract of Mf on some hematological indices in an albino rat model. Rats received 50% ethanolic seed extract orally at doses of 100, 250, and 500 mg/kg. Results showed significant decreases (p<0.05) in RBC count, PCV (packed cell volume), HbC (hemoglobic concentration) and platelet count at high doses. There was significant increase (p<0.05) in total WBC count. Results suggest possible deleterious effects on hematopoiesis at high doses. (53)
• Antiangiogenic / Antioxidant / Essential Oil: Study evaluated the anti-angiogenic and antioxidant properties of M. fragrans (nutmeg) and Morinda citrifolia (menkudu) essential oils. Results showed nutmeg oil has nigher antioxidant activity than mengkudu oil. Nutmeg oil effectively inhibited oxidation of linoleic acid (88.68%) compared to mengduku oil (69.44%). Nutmeg oil showed reducing power with EC50 of 181.4 µg/mL. Nutmeg oil showed significant antiangiogenic activity with IC50 of 77.64 µg/mL compared to mengduku oil with IC50 of 109.30 µg/mL. Results suggest potential for nutmeg essential oil as antiangiogenic drug. (54)
• Anti-Rheumatic / Essential Oil: Rheumatoid arthritis (RA) is an inflammation associated autoimmune disorder, with current therapeutic regimens associated with severe side effects. Study evaluated Mf mace and seed for management of inflammation and RA. ATR-FTIR showed occurrence of aromatic amine, phenolic, and carboxylic acid groups mostly found in terpenoids. Molecular docking study showed interaction of Myristicin with 4F5S. A significant antioxidant activity was seen with DPPH, H2O2, and FRAP assays. EO also showed protective effect during heat induced hemolysis (66%), BSA denaturation assay (61%), and higher levels of proteinase inhibition (70%). Acute anti-inflammatory model in rat showed significant decrease in inflammation with the EO. Study suggest Mf EO possess significant (p<0.005) anti-inflammatory potential and a key role in the management of RA. (55)
• Effect on Chewable Gel Tablets on Texture and Shelf-Life: Chewable get tablets are not sweet and can impart an active substance, pharmacological effect, and nutritional value. Study prepared gelatin-based chewable tablets with M. fragrans as preservative and evaluated its effect on shelf-life variability depending on storage conditions and evaluate texture changes. Chewable tablets were prepared using silicone form. Mold was found to likely grow on packaged squeezable bags, with 60% of all formulations having a mold after 14 days, p<0.05. Most stable tablets (over 180 days) were in sealed boxes and contained nutmeg essential oil or its solution, or ethanolic nutmeg extract. Gel tablets firmness increase 4 times when stored in opened plastic boxes, and springiness decreased 1.65 times after 28 days. Nutmeg hydrolat had highest influence on texture variation (p<0.05). (56)
• Antioxidant / Anti-α-Glucosidase Activity / Seeds: Study of various solvent extracts of Mf seeds exhibited relatively strong antioxidant activities by DPPH. ABTS, superoxide, and hydroxyl radical scavenging tests. Methanol extract also exhibited significant anti-α-glucosidase activity. Among isolated compounds by HPLC analysis, dehydrodiisoeugenol, malabaricone B and malabaricone C were main antioxidant components in seeds of Mf. Malabaricone C exhibited stronger antioxidant capacities than others with lower IC50 values in DPPH and ABTS radical scavenging assays, and also showed significant inhibition of α-glucosidase. (57)
• Pancreatic Lipase Inhibition / Anti-Obesity: Study evaluated the antioxidant and lipase inhibitory potential of various extracts of Mf invitro. The ethanolic extract showed strongest pancreatic lipase inhibitory activity at 100 µg/mL (66.24%), with closest potential to standard drug, Orlistat (81.57%).Extract also showed potent antioxidant activity, with 88% inhibition by DPPH free radical scavenging assay, compared to standard ascorbic acid at 90%. (58)
• Apoptosis in Human Leukemia Cell Line: Study evaluated the effect of methanolic extract of Mf on Jurkat leukemia T cell line using MTT assay and on apoptosis using annexin V staining. At 50 and 100 µg/mL, the ME significantly inhibited Jurkat cell proliferation and induced apoptosis. Downregulation of SIRTI mRNA expression in Jurkat cells was observed even at 10 µg/mL. (60)
• Cytotoxic and Apoptotic on Human Oral Epidermal Carcinoma KB Cell Line: Study evaluated the cytotoxicity and apoptotic induction potential of Mf mace extract by MTT assay on human oral epidermal carcinoma KB cell lines. The mace extract exhibited cytotoxicity and anticancer effect against KB cell lines and suppressed the growth of cancer cells. The apoptotic potential was accompanied by reduced gene expression of Bcl-2 compared to untreated KB cells. Mace showed cytotoxic activity and induced apoptosis via modulation of target genes Bcl-2 in the KB cell lines, suggesting potential of mace for oral cancer chemoprevention. (61)
• Inhibition of Bacterial Efflux Pumps Against MRSA / Seeds: Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) were applied as efflux pump inhibitors (EPIs), thereby enhancing antimicrobial activity of drugs there were used in. Major substances in the CE and EO, which function as EPIs, in descending order of % peak area include elemicin, myristicin, methoxyeugenol, and asarone. Synergy between cirpofloxacin and CE or CO revealed the most significant viability of MRSA, depending on norA and mepA. Study suggests CE and CO from nutmeg can act as EPIs in combination with substances that act as efflux system, thereby ensuring MRSA strain susceptibility to antibiotic treatment. (62)
• Hepatoprotective / MAP Herbal Blend: Study evaluated the potential use of MAP, a standardized blend of three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating chemical induced acute liver toxicities i.e. acetaminophen (APAP) and carbon tetrachloride (CCL4)-induced acute liver toxicity models in mice. MAP at doses of 150-400 mg/kg showed statistically significant and dose-correlated inhibitions of ALT in APAP and CCL4 models, along with reductions in AST, bile acid, and total bilirubin. Mice treated with oral doses of MAP at 300 mg/kg showed statistically significant reduction in hepatocyte necrosis. Results suggest MAP has potential as effective detoxifying agent for protection against liver damage. (63)
• Myristicin / Hepatoprotective / Lipopolysaccharide/D-Galactosamine Toxicity: Study evaluated the hepatoprotective activity of 21 spices fed to rats with liver damage caused by LPS-plus D-galactosamine (D-GaIN). Assessed by aminotransferase activity, nutmeg showed the most potent hepatoprotective activity. Bioassay-guided isolated for active compound in nutmeg yielded myristicin, one of the major EO of nutmeg. Myristicin was found to possess remarkable hepatoprotective activity, markedly suppressing LPS/D-GaIN-induced enhancement of serum TNF-α and hepatic DNA fragmentation. The hepatoprotective activity of myristicin may be partly due to inhibition of TNF-α release from macrophages. (64)
• Inhibition of Locomotor Activity / Seed Essential Oil: Study evaluated the inhibitory effect of nutmeg seed essential oil on locomotor activity of mice in a wheel cage. Results showed inhalation of seed EO at dose of 0.5 mL/cage decreased locomotion by 68.62%, and inhalation of 0.1 and 0.3 mL/cage inhibited locomotion by 62.81 and 65.33%, respectively. The most concentrated compound in the plasma was myristicin. Study suggests the volatile compounds of nutmeg EO may correlate with the locomotor-inhibiting properties of oil when administered by inhalation. (65)
• Copper Nanoparticles / Antibacterial Kaempferol: Study reports on the biogenical synthesis of copper nanoparticle using Mf seeds. Seed extracts of Mf exhibited strongest antibacterial properties. Results suggest potential for use of antibacterial CuNPs phyto-formulated from nutmeg extracts for treatment of microbial diseases. (66)
• Herbal Decoction for Spasmodic Dysmenorrhea / Randomized Comparative Study: Single-blind, prospective, parallel study compared the efficacy and safety of herbal decoction of M. fragrans arils and Cassia fistula pods with mefenamic acid in spasmodic dysmenorrhea for two consecutive menstrual cycles. The herbal decoction (C. fistula pod's pericarp 21 g, M. fragrans arils 3 g, gand siyah (jaggery) 30g) was administered orally in the morning for 3 days before expected start of menstruation. Control group received mefenamic acid 500 mg orally twice daily. During the second menstrual cycle, improvement in HRQoL health survey scores and reduction in pain duration were significantly higher in the treatment group than control. No side effects were reported. Results suggest the herbal decoction was effective in relieving pain in spasmodic dysmenorrhea. (67)
• Anti-Diabetic Silver Nanoparticles / Seeds: Study reports on the synthesis of silver nanoparticles from hydroethanolic extract of M. fragrans seeds. The NPs showed significant efficiency against inhibition of α-amylase and α-glucosidase enzymes and also retarded the glucose transport across the membrane, analyzed by glucose diffusion and glucose uptake assays. Acarbose was used as standard. Results suggest therapeutic potential for the treatment of diabetes mellitus. (68)
• Wound Healing / Cream Formulation / Essential Oil: Study evaluated the phytochemical constituents of nutmeg essential oil and the wound healing effect of nutmeg cream on Wistar rats with second-degree burns. Treatment groups consisted of: B (burn-treated base cream), B+B (burn-treated 3% nutmeg cream), B+SSD (burn-treated silver sulfadiazine:BSS), and B+N+SSD (burn-treated 3% nutmeg cream and SSD in 1:1 ratio). Results showed the B+SSD group exhibited the highest percentage of burn wound healing (56.80%), which was significantly different from base cream (p<0.05). Percentage wound healing in rats given 3% nutmeg creams was 41.88%, suggesting nutmeg creams could promote burn wound healing in rats with second-degree burns. (69)
• Cytotoxic / Anti-Tumor Lignans / Seeds: Study of M. fragrans seeds isolated four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and nectandrin B, and evaluated for the cytotoxic activity against 8 cancer cell lines. Of these, DHGA exhibited potent cytotoxicity against H358 with IC50 of 10.1 µM. DHGA also showed antitumor activity in allogenic tumor-bearing mice model. (70)
Availability
- Wild-crafted.
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