Nutmegs and wild nutmegs: An update on ethnomedicines, phytochemicals, pharmacology, and toxicity of the Myristicaceae species.

Prized medicinal spice true nutmeg is obtained from Myristica fragrans Houtt. Rest species of the family Myristicaceae are known as wild nutmegs. Nutmegs and wild nutmegs are a rich reservoir of bioactive molecules and used in traditional medicines of Europe, Asia, Africa, America against madness, convulsion, cancer, skin infection, malaria, diarrhea, rheumatism, asthma, cough, cold, as stimulant, tonics, and psychotomimetic agents. Nutmegs are cultivated around the tropics for high-value commercial spice, used in global cuisine. A thorough literature survey of peer-reviewed publications, scientific online databases, authentic webpages, and regulatory guidelines found major phytochemicals namely, terpenes, fatty acids, phenylpropanoids, alkanes, lignans, flavonoids, coumarins, and indole alkaloids. Scientific names, synonyms were verified with www.theplantlist.org. Pharmacological evaluation of extracts and isolated biomarkers showed cholinesterase inhibitory, anxiolytic, neuroprotective, anti-inflammatory, immunomodulatory, antinociceptive, anticancer, antimicrobial, antiprotozoal, antidiabetic, antidiarrhoeal activities, and toxicity through in-vitro, in-vivo studies. Human clinical trials were very few. Most of the pharmacological studies were not conducted as per current guidelines of natural products to ensure repeatability, safety, and translational use in human therapeutics. Rigorous pharmacological evaluation and randomized double-blind clinical trials are recommended to analyze the efficacy and therapeutic potential of nutmeg and wild nutmegs in anxiety, Alzheimer's disease, autism, schizophrenia, stroke, cancer, and others.

A Proteomics Study on the Mechanism of Nutmeg-Induced Hepatotoxicity.

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.

Stoned on spices: a mini-review of three commonly abused household spices.

INTRODUCTION: Although spices are widely used as food products and are generally regarded as safe, intentional abuse of household spices may occur and is likely underreported in the medical literature. Spices are inexpensive and widely available for purchase by individuals of all ages and may be perceived as being safer than traditional drugs of abuse. DISCUSSION: Nutmeg, cinnamon, and vanilla are commonly abused spices. The major component of nutmeg is myristicin; myristicin has activity at serotonergic receptors and may result in psychomimetic symptoms after exposure. Cinnamon oils contain local irritants which may cause dermatitis or ulcerations after topical application. Ground cinnamon contains cellulose fibers; these are biopersistent and bioresistant, and inhalational exposure to cinnamon powder can result in chronic pulmonary inflammation and fibrosis. Pure vanilla extract contains a minimum of 35% ethanol according to the United States Food and Drug Administration standards, and abuse of vanilla extract may occur among individuals seeking ethanol intoxication. CONCLUSIONS: Overall, misuse or abuse of these spices frequently results in mild to moderate symptoms that do not require medical intervention, although more serious intoxications may require hospitalization. Clinicians should be aware of the potential dangers of household spice abuse and understand management strategies for these exposures.

Phytochemical and pharmacological properties of Myristica fragrans Houtt.: an updated review.

Myristica fragrans Houtt. (Myristicaceae), an aromatic evergreen tree, is well known as a commercial source of mace (aril) and nutmeg (seed), which have long been widely used as spices in the culinary field. In addition, various parts of M. fragrans have been used in folk medicine for treating several diseases. Since its extensive uses in the culinary sector and folk medicine, M. fragrans has long attracted a great deal of attention from pharmacologists and chemists. Numerous studies have indicated that M. fragrans contains diverse phytochemicals such as lignans, neolignans, diphenylalkanes, phenylpropanoids, and terpenoids, which exhibit many of pharmacological activities. Among them, macelignan (1), meso-dihydroguaiaretic acid (2), myristicin (111), and malabaricone C (Mal C, 104) are the most active compounds. The aim of this review is to comprehensively summarize the phytochemical and pharmacological properties of M. fragrans that have reported to date.

A Design of Experiment Approach for Ionic Liquid-Based Extraction of Toxic Components-Minimized Essential Oil from Myristica fragrans Houtt. Fruits †.

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.

Nutmeg poisonings: a retrospective review of 10 years experience from the Illinois Poison Center, 2001-2011.

Nutmeg is a commonly consumed spice. The toxic effects of nutmeg have been purported to be due mainly to myristicin oil. Prior poison center series of nutmeg exposures show very few unintentional exposures of nutmeg to children younger than 13. Case series from these centers did not record drug exposures combined with nutmeg. This study is a review of Illinois Poison Center (IPC) data regarding nutmeg exposures from January of 2001 to December 2011. The goal of this study was to compare the Illinois data to the literature as well as look for current trends in nutmeg poisonings. The data were extracted using the code for hallucinogenic plants in the IPC database, and poisonings unrelated to nutmeg exposure were eliminated. Medical outcomes were noted as recorded. Thirty-two cases of nutmeg ingestion were reported. Of the 17 (53.1 %) unintentional exposures, 10 subjects (58.8 %) were under the age of 13. Four of the exposures in children under the age of 13 were ocular exposures. Fifteen exposures (46.9 %) were intentional exposures. Of these intentional exposures, five (33.3 %) were recorded to have combined drug intoxication. All of these were between the ages of 15 and 20. One patient with polypharmaceutical exposure required ventilatory support in the hospital. Our study shows an unexpected percentage of unintentional exposures in juveniles under the age of 13, out of the total exposures to nutmeg. Mixing of nutmeg with other drugs was seen and required more intervention in adolescents. More education about these two factors, i.e., nutmeg exposures as intentional polypharmacy in adolescents and unintentional exposures in young children, is advised.

An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg).

BACKGROUND: Myristica fragrans Houtt. (nutmeg) has been mentioned in Unani medicine to be of value in the management of male sexual disorders. The present study was undertaken to evaluate the aphrodisiac effect of 50% ethanolic extract of nutmeg along with its likely adverse effects and acute toxicity using various animal models. METHODS: The suspension of the extract was administered (100, 250 and 500 mg/kg, p.o.) to different groups of male rats daily for seven days. The female rats involved in mating were made receptive by hormonal treatment. The general mating behaviour, libido and potency were studied and compared with the standard reference drug sildenafil citrate. Likely adverse effects and acute toxicity of the extract were also evaluated. RESULTS: Oral administration of the extract at the dose of 500 mg/kg, produced significant augmentation of sexual activity in male rats. It significantly increased the Mounting Frequency, Intromission Frequency, Intromission Latency and caused significant reduction in the Mounting Latency and Post Ejaculatory Interval. It also significantly increased Mounting Frequency with penile anaesthetization as well as Erections, Quick Flips, Long Flips and the aggregate of penile reflexes with penile stimulation. The extract was also observed to be devoid of any adverse effects and acute toxicity. CONCLUSION: The resultant significant and sustained increase in the sexual activity of normal male rats without any conspicuous adverse effects indicates that the 50% ethanolic extract of nutmeg possesses aphrodisiac activity, increasing both libido and potency, which might be attributed to its nervous stimulating property. The present study thus provides a scientific rationale for the traditional use of nutmeg in the management of male sexual disorders.