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Internal mildewed nutmeg is difficult to perceive without cutting the nutmeg open and examining it carefully, which poses a significant risk to public health. At present, macroscopic identification and chromatographic analysis are applied to determine whether nutmeg is moldy or not. However, the former relies on a human panel, with the disadvantages of subjectivity and empirical dependence, whilst the latter is generally time-consuming and requires organic solvents. Therefore, it is urgent to develop a rapid and feasible approach for evaluating the quality and predicting mildew in nutmeg. In this study, the quality and odor characteristics of five groups of nutmeg samples with different degrees of mildew were analyzed by using the responses of an electronic nose combined with chemical profiling. The main physicochemical indicators, such as the levels of α-pinene, β-pinene, elemicin, and dehydro-di-isoeugenol, were determined. The results revealed that the contents of α-pinene, β-pinene, and elemicin changed significantly with the extension of storage time. Through the use of an electronic nose and HS–GC–MS technology to assess the overall odor characteristics of nutmeg samples, it was found that the production of volatile organic compounds (VOCs) such as ammonia/organic amines, carbon monoxide, ethanol, and hydrogen sulfide, as well as changes in the terpene and phenylpropene components of the nutmeg itself, may be the material basis for the changes in odor. The accuracy of the qualitative classification model for the degree of mildew in nutmeg was higher than 90% according to the electronic nose data combined with different machine learning algorithms. Quantitative models were established for predicting the contents of the chemical components, and models based on a BP neural network (BPNN), the support vector machine (SVM), and the random forest algorithm (RF) all showed good performance in predicting the concentrations of these chemical components, except for dehydro-di-isoeugenol. The BPNN performed effectively in predicting the storage time of nutmeg on the basis of the E-nose’s responses, with an RMSE and R2 of 0.268 and 0.996 for the training set, and 0.317 and 0.993 for the testing set, respectively. The results demonstrated that the responses of the electronic nose (E-nose) had a high correlation with the internal quality of nutmeg. This work proposes a quick and non-destructive evaluation method for the quality of nutmeg, which has high accuracy in discriminating between different degrees of mold in nutmeg and is conducive to early detection and warning of moldy phenomena.

The essential oil of Myristica fragrans Hutt. (nutmeg) is an important commodity used as a flavoring agent in the food, pharmaceutical, and cosmetic fields. Hydrodistillation is chiefly employed at the industrial scale for nutmeg essential oil isolation, but such a technique generates large quantities of post-distillation by-products (e.g., spent plant material and residual distillation water). Therefore, our work aimed to propose a novel strategy for the valorization of nutmeg wastes, with beneficial economic and ecological advantages. Thus, the current study assessed the phytochemical (GC-MS, LC-HRMS/MS) and biological (antioxidant, enzyme inhibitory, antimicrobial) profile of nutmeg crude materials (essential oil and total extract) and post-distillation by-products (residual water and spent material extract). Identified in these were 43 volatile compounds, with sabinene (21.71%), α-pinene (15.81%), myristicin (13.39%), and β-pinene (12.70%) as the main constituents. LC-HRMS/MS analysis of the nutmeg extracts noted fifteen metabolites (e.g., organic acids, flavonoids, phenolic acids, lignans, and diarylnonanoids). Among the investigated nutmeg samples, the spent material extract was highlighted as an important source of bioactive compounds, with a total phenolic and flavonoid content of 63.31 ± 0.72 mg GAE/g and 8.31 ± 0.06 mg RE/g, respectively. Moreover, it showed prominent radical-scavenging and metal-reducing properties and significantly inhibited butyrylcholinesterase (4.78 ± 0.03 mg GALAE/g). Further, the spent material extract displayed strong antimicrobial effects against Streptococcus pneumoniae, Micrococcus luteus, and Bacillus cereus (minimum inhibitory concentrations of 62.5 mg/L). Overall, our study brings evidence on the health-promoting (antioxidant, anti-enzymatic, antimicrobial) potential of nutmeg post-distillation by-products with future reference to their valorization in the pharmaceutical, cosmeceutical, and food industries.

The current study presents the most suitable method for encapsulating nutmeg essential oil with liquorice and red clover. Two widely used methods, spray-drying and freeze-drying, were employed to find the most suitable for essential oil volatile compounds’ protection. Results showed that freeze-dried capsules (LM) had a higher yield (85.34%) compared to the exact formulation of spray-dried microcapsules (SDM)—45.12%. All the antioxidant and total phenolic compounds’ results obtained with the LM sample were significantly higher compared with SDM. LM microcapsules were incorporated in two different bases with no additional sugar (gelatin and pectin) for targeted release. Pectin tablets had firmer and harder texture properties, while gelatin tablets had a more elastic texture. There was a significant impact on texture changes caused by microcapsules. Microencapsulated essential oil with extracts can be used alone or in a gel base (pectin or gelatin, depending on user preferences). It could be an effective product to protect the active volatile compounds and regulate the release of active compounds and give a pleasant taste.

Neuropathic pain is one of the most prominent chronic pain syndromes, affecting almost 10% of the United States population. While there are a variety of established pharmacologic and non-pharmacologic treatment options, including tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors, anticonvulsants, trigger point injections, and spinal cord stimulators, many patients continue to have chronic pain or suboptimal symptom control. This has led to an increased interest in alternative solutions for neuropathic pain such as nutritional supplements and essential oils. In this review, we explore the literature on the most commonly cited essential oils, including lavender, bergamot, rosemary, nutmeg, Billy goat weed, and eucalyptus. However, the literature is limited and largely comprised of preclinical animal models and a few experimental studies, some of which were poorly designed and did not clearly isolate the effects of the essential oil treatment. Additionally, no standardized method of dosing or route of administration has been established. Further randomized control studies isolating the active components of various essential oils are needed to provide conclusive evidence on the use of essential oils for neuropathic pain. In this review, we explore the basis behind some of the essential oils of interest to patients with neuropathic pain seen in rheumatology clinics.

Isoeugenol (2-methoxy-4-(1-propenyl)phenol) has been recently classified as possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer (IARC). This study conducted an analysis of isoeugenol in common herbs and spices, including basil, cinnamon, ginger, and nutmeg, using 1 H nuclear magnetic resonance (NMR) spectrometry. Additionally, over 1300 coffee samples were analysed by 1 H-NMR for isoeugenol, but it was not detected in any of the analysed samples. Various essential oils, including nutmeg, basil, clove, sweet flag, and ylang-ylang oils, were examined for isoeugenol content. Out of the twelve nutmeg oils tested, four contained isoeugenol, with concentrations ranging from 3.68 ± 0.09 g/kg to 11.2 ± 0.10 g/kg. However, isoeugenol was not detected in the essential oils of calamus, basil, ylang-ylang, and clove using NMR spectrometry. These findings warrant critical evaluation of the previous literature, given reports of high isoeugenol levels in some of these matrices. A toxicological assessment has determined that there is no risk to human health by exposure to isoeugenol via nutmeg essential oils.

Natural products have been used by humanity for many centuries to treat various illnesses and with the advancement of technology, it became possible to isolate the substances responsible for the beneficial effects of these products, as well as to understand their mechanisms. In this context, myristicin, a substance of natural origin, has shown several promising activities in a large number of in vitro and in vivo studies carried out. This molecule is found in plants such as nutmeg, parsley, carrots, peppers, and several species endemic to the Asian continent. The purpose of this review article is to discuss data published in the last 10 years at Pubmed, Lilacs and Scielo databases, reporting beneficial effects, toxicity and promising data of myristicin for its future use in medicine. From 94 articles found in the literature, 68 were included. Exclusion criteria took into account articles whose tested extracts did not have myristicin as one of the major compounds.

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. 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) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment.

Chewable gel tablets are a dosed pharmaceutical form, which can have an active substance, pharmacological effect, or value of nutrition. The texture of these tablets is soft, springy, flexible, and elastic—this is influenced by the chosen ingredients. The aim of this study was to prepare chewable gel tablets with nutmeg essential oil-loaded microcapsules and determine the volatile compounds released from this pharmaceutical form. Gel tablets were prepared by using gelatin as basis, nutmeg essential oil as active compound, and natural ingredients: thyme-sugar syrup, thyme extract, and citric acid as taste and color additives. Texture properties were measured by a texture analyzer. The release of volatile compounds from nutmeg essential oil and gel tablets were analyzed by headspace-gas chromatography with mass spectroscopy in control and artificial saliva conditions in vitro. Nutmeg essential oil microcapsules had influence on the gel tablet’s physical properties (p < 0.05, by comparing tablets without glycerol and relative sample with glycerol); glycerol protects the tablets from the formation of sugar crystals on top and keeps good physical parameters (p < 0.05). A total of 12 volatile compounds were identified in nutmeg essential oil, and the six compounds with the highest amounts were selected as controls. Gel tablets prolong the release time of volatile compounds and reduce the amount of the compounds compared to the microcapsules (p < 0.05).

The aril and seed of nutmeg, Myristica fragrans Houtt. (Myristicaceae), hold significant value in various industries globally. Our preliminary research found two morphological variations: a globose shape and an oval shape. Due to these different characteristics, the safety of consumers is of primary concern. Thus, authentication and comparative pharmacological and toxicity analyses are necessary. In this study, pharmacognostic and advanced phytochemical analyses, DNA barcoding, cytotoxicity, and the anti-nitric oxide production of commercial Thai nutmeg were examined. Via morphologic examinations and TLC fingerprinting, all the sampled aril and seed were categorized into globose and oval-shaped groups. The results of HPLC, GC-MS, and LC-MS/MS experiments revealed distinct differences between these groups. The DNA barcoding of the trn H- psb A region using the BLAST method and neighbor-joining tree analyses confirmed the globose nutmeg as M. fragrans and the oval-shaped variant as M. argentea . A comparison was then carried out between the potential toxicity and anti-inflammatory capabilities of M. fragrans and M. argentea . Cytotoxicity tests on HaCaT, 3T3-L1, Caco-2, HEK293, and RAW264.7 were performed using both methanolic extracts and volatile oil from the arils and seeds of both species. This study concludes that blending or substituting these two species maintains their therapeutic integrity without posing safety concerns.

Nutmeg is a traditional spice and medicinal plant with a variety of pharmacological activities. However, nutmeg abuse due to its hallucinogenic characteristics and poisoning cases are frequently reported. Our previous metabolomics study proved the hepatotoxicity of nutmeg and demonstrated that high-dose nutmeg can affect the synthesis and secretion of bile acids and cause oxidative stress. In order to further investigate the hepatotoxicity of nutmeg, normal saline, 1 g/kg, 4 g/kg nutmeg were administrated to male Kunming mice by intragastrical gavage for 7 days. Histopathological investigation of liver tissue, proteomics and biochemical analysis were employed to explore the mechanism of liver damage caused by nutmeg. The results showed that a high-dose (4 g/kg) of nutmeg can cause significant increased level of CYP450s and depletion of antioxidants, resulting in obvious oxidative stress damage and lipid metabolism disorders; but this change was not observed in low-dose group (1 g/kg). In addition, the increased level of malondialdehyde and decreased level of glutathione peroxidase were found after nutmeg exposure. Therefore, the present study reasonably speculates that nutmeg exposure may lead to liver injury through oxidative stress and the degree of this damage is related to the exposure dose.

Nutmeg (Myristica fragrans) essential oil has antimicrobial, antiseptic, antiparasitic, anti-inflammatory, and antioxidant properties. We have recently demonstrated that hydrodistillation of nutmeg essential oil by applying magnesium aluminometasilicate as an excipient significantly increases both the content and amount of bioactive substances in the oil and hydrolats. In this study, we aimed to compare the antioxidant, antimicrobial, and anti-inflammatory activity of hydrolats and essential oil obtained by hydrodistillation in the presence and absence of magnesium aluminometasilicate as an excipient. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method revealed that magnesium aluminometasilicate did not significantly improved antioxidant activity of both essential oil and hydrolat. Antibacterial efficiency was evaluated by monitoring growth of 15 bacterial strains treated by a range of dilutions of the essential oil and the hydrolats. Essential oil with an excipient completely inhibited the growth of E. faecalis, S. mutans (referent), and P. multocida, whereas the pure oil was only efficient against the latter strain. Finally, the anti-inflammatory properties of the substances were assessed in a fibroblast cell culture treated with viral dsRNR mimetic Poly I:C. The essential oil with an excipient protected cells against Poly I:C-induced necrosis more efficiently compared to pure essential oil. Also, both the oil and the hydrolats with aluminometasilicate were more efficient in preventing IL-6 release in the presence of Poly I:C. Our results show that the use of magnesium aluminometasilicate as an excipient might change and in some cases improve the biological activities of nutmeg essential oil and hydrolats.

Myristica fragrans (f. Myristicaceae) seeds are better known as a spice, but their chemical compounds may have a pharmacological effect. The yield of their composition of extracts and essential oils differs due to different methodologies. The aim of this study was to evaluate an excipient material—magnesium aluminometasilicate—and to determine its influence on the qualitative composition of nutmeg extracts and essential oils. Furthermore, we wanted to compare the yield of essential oil. The extracts were prepared by maceration (M) and ultrasound bath-assisted extraction (UAE), and the essential oil—by hydrodistillation (HD). Conventional methods (UAE, HD) were modified with magnesium aluminometasilicate. The samples were analyzed by gas chromatography-mass spectrometry (GC-MS) method. From 16 to 19 chemical compounds were obtained using UAE with magnesium aluminometasilicate, while only 8 to 13 compounds were obtained using UAE without an excipient. Using our conditions and plant material, for the first time eight new chemical compounds in nutmeg essential oil were identified. Two of these compounds (γ-amorphene and cis-α-bergamotene) were obtained with the use of excipient, the other six (β-copaene, bergamotene, citronellyl decanoate, cubebol, cubenene, orthodene) by conventional hydrodistillation. Magnesium aluminometasilicate significantly increased the quantity of sabinene (from 6.53% to 61.42%) and limonene (from 0% to 5.62%) in essential oil. The yield of the essential oil from nutmeg seeds was significantly higher using magnesium aluminometasilicate; it increased from 5.25 ± 0.04% to 10.43 ± 0.09%.

The effect of the addition of ionic liquids (ILs) during the hydrodistillation of Myristica fragrans Houtt. (nutmeg) essential oil was studied. The essential oil of M. fragrans is characterized by the presence of terpenes, terpenoids, and of phenylpropanoids, such as methyl eugenol and safrole, that are regarded as genotoxic and carcinogenic. The aim of the work was to determine the best ionic liquid to improve the yield of the extraction of M. fragrans essential oil and decrease the extraction of toxic phenylpropanoids. Six ILs, namely 1,3-dimethylimidazolium chloride (1), 1,3-dimethylimidazolium dimethylphosphate (2), 1-(2-hydroxyethyl)-3-methylimidazolium chloride (3), 1-(2-hydroxyethyl)-3-methylimidazolium dimethylphosphate (4), 1-butyl-3-methylimidazolium chloride (5), and 1-butyl-3-methylimidazolium dimethylphosphate (6), were prepared by previously reported, innovative methods and then tested. An experimental design was used to optimize the extraction yield and to decrease the phenylpropanoids percentage using the synthesized ILs. The influence of the molarity of ILs was also studied. MODDE 12 software established 0.5 M 1-butyl-3-methylimidazolium chloride as the best co-solvent for the hydrodistillation of M. fragrans essential oil.

The essential oil of Myristica fragrans Hutt. (nutmeg) is an important commodity used as a flavoring agent in the food, pharmaceutical, and cosmetic fields. Hydrodistillation is chiefly employed at the industrial scale for nutmeg essential oil isolation, but such a technique generates large quantities of post-distillation by-products (e.g., spent plant material and residual distillation water). Therefore, our work aimed to propose a novel strategy for the valorization of nutmeg wastes, with beneficial economic and ecological advantages. Thus, the current study assessed the phytochemical (GC-MS, LC-HRMS/MS) and biological (antioxidant, enzyme inhibitory, antimicrobial) profile of nutmeg crude materials (essential oil and total extract) and post-distillation by-products (residual water and spent material extract). Identified in these were 43 volatile compounds, with sabinene (21.71%), α -pinene (15.81%), myristicin (13.39%), and β -pinene (12.70%) as the main constituents. LC-HRMS/MS analysis of the nutmeg extracts noted fifteen metabolites (e.g., organic acids, flavonoids, phenolic acids, lignans, and diarylnonanoids). Among the investigated nutmeg samples, the spent material extract was highlighted as an important source of bioactive compounds, with a total phenolic and flavonoid content of 63.31 ± 0.72 mg GAE/g and 8.31 ± 0.06 mg RE/g, respectively. Moreover, it showed prominent radical-scavenging and metal-reducing properties and significantly inhibited butyrylcholinesterase (4.78 ± 0.03 mg GALAE/g). Further, the spent material extract displayed strong antimicrobial effects against Streptococcus pneumoniae , Micrococcus luteus , and Bacillus cereus (minimum inhibitory concentrations of 62.5 mg/L). Overall, our study brings evidence on the health-promoting (antioxidant, anti-enzymatic, antimicrobial) potential of nutmeg post-distillation by-products with future reference to their valorization in the pharmaceutical, cosmeceutical, and food industries.

A new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a Diamonsil™ ODS C18 column with methanol–water containing 0.1% formic acid (81:19, v/v) as a mobile phase. Detection of DDIE was performed on a positive electrospray ionization source using a triple quadrupole mass spectrometer. DDIE and daidzein were monitored at m/z 327.2→188.0 and m/z 255.0→199.2, respectively, in multiple reaction monitoring mode. This method enabled quantification of DDIE in various brain areas, including, cortex, hippocampus, striatum, hypothalamus, cerebellum and brainstem, with high specificity, precision, accuracy, and recovery. The data herein demonstrate that our new LC-MS/MS method is highly sensitive and suitable for monitoring cerebral nuclei distribution of DDIE.

The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10−8–10−6 cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10−6–10−5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10−8–10−7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.

Neuropathic pain is one of the most prominent chronic pain syndromes, affecting almost 10% of the United States population. While there are a variety of established pharmacologic and non-pharmacologic treatment options, including tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors, anticonvulsants, trigger point injections, and spinal cord stimulators, many patients continue to have chronic pain or suboptimal symptom control. This has led to an increased interest in alternative solutions for neuropathic pain such as nutritional supplements and essential oils. In this review, we explore the literature on the most commonly cited essential oils, including lavender, bergamot, rosemary, nutmeg, Billy goat weed, and eucalyptus. However, the literature is limited and largely comprised of preclinical animal models and a few experimental studies, some of which were poorly designed and did not clearly isolate the effects of the essential oil treatment. Additionally, no standardized method of dosing or route of administration has been established. Further randomized control studies isolating the active components of various essential oils are needed to provide conclusive evidence on the use of essential oils for neuropathic pain. In this review, we explore the basis behind some of the essential oils of interest to patients with neuropathic pain seen in rheumatology clinics.

Nutmeg ( Myristica fragrans ) essential oil has antimicrobial, antiseptic, antiparasitic, anti-inflammatory, and antioxidant properties. We have recently demonstrated that hydrodistillation of nutmeg essential oil by applying magnesium aluminometasilicate as an excipient significantly increases both the content and amount of bioactive substances in the oil and hydrolats. In this study, we aimed to compare the antioxidant, antimicrobial, and anti-inflammatory activity of hydrolats and essential oil obtained by hydrodistillation in the presence and absence of magnesium aluminometasilicate as an excipient. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method revealed that magnesium aluminometasilicate did not significantly improved antioxidant activity of both essential oil and hydrolat. Antibacterial efficiency was evaluated by monitoring growth of 15 bacterial strains treated by a range of dilutions of the essential oil and the hydrolats. Essential oil with an excipient completely inhibited the growth of E. faecalis , S. mutans (referent), and P. multocida , whereas the pure oil was only efficient against the latter strain. Finally, the anti-inflammatory properties of the substances were assessed in a fibroblast cell culture treated with viral dsRNR mimetic Poly I:C. The essential oil with an excipient protected cells against Poly I:C-induced necrosis more efficiently compared to pure essential oil. Also, both the oil and the hydrolats with aluminometasilicate were more efficient in preventing IL-6 release in the presence of Poly I:C. Our results show that the use of magnesium aluminometasilicate as an excipient might change and in some cases improve the biological activities of nutmeg essential oil and hydrolats., Competing Interests: The authors declare no conflict of interest.