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Nutmeg (myristicin) poisoning - Report on a fatal case and a series of cases recorded by a poison information centre
Abstract
In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In one of these cases, a myristicin blood level of 2 microg/ml was measured 8h after ingestion of two to three tablespoonful of nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).
... Methyleugenol Myristicin Safrole Estragole cloves 28.5 ± 0.4 mg/g [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, various baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, caprese salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews dill 28.1-76.3 mg/g [20] various curries and soups, salad dressing, sandwich fillings celery Detected † [ 21] chicken noodle soup, various stir fry dishes, various vegetarian dishes ginger Detected † [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various curries tarragon Detected † [25] 0.5-28.9% ...
... Eugenol Methyleugenol Myristicin Safrole Estragole cloves 28.5 ± 0.4 mg/g [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, variou baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, caprese salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various currie tarragon Detected † [25] 0.5-28.9% v/v [26] 17-75% v/v [26] pasta, mojito, Béarnaise sauce rosemary Detected † [27] various soups, salads, stews, and pasta sauces thyme 0.021 mg/g [14] detected † [28] seasoned roasted vegetables, various pasta sauces and soups, pizza toppings bay leaves 110-120 mg/g [29] 90-120 mg/g [29] beef stew, pate, various curries and soups [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, variou baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, caprese salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various currie tarragon Detected † [25] 0.5-28.9% ...
... Eugenol Methyleugenol Myristicin Safrole Estragole cloves 28.5 ± 0.4 mg/g [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, variou baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, caprese salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various currie tarragon Detected † [25] 0.5-28.9% v/v [26] 17-75% v/v [26] pasta, mojito, Béarnaise sauce rosemary Detected † [27] various soups, salads, stews, and pasta sauces thyme 0.021 mg/g [14] detected † [28] seasoned roasted vegetables, various pasta sauces and soups, pizza toppings bay leaves 110-120 mg/g [29] 90-120 mg/g [29] beef stew, pate, various curries and soups [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, variou baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, caprese salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various currie tarragon Detected † [25] 0.5-28.9% v/v [26] 17-75% v/v [26] pasta, mojito, Béarnaise sauce rosemary Detected † [27] various soups, salads, stews, and pasta sauces thyme 0.021 mg/g [14] detected † [28] seasoned roasted vegetables, various pasta sauces and soups, pizza toppings bay leaves 110-120 mg/g [29] 90-120 mg/g [29] beef stew, pate, various curries and soups [11] Detected † [12] Detected † [12] various curries, jams, cooking rice cinnamon 0.19-1.65 g/kg [13] Detected † [12] various curries, churros, donut, various pastries nutmeg 0.32 mg/g [14] 8 mg/g [15] 280-420 mg/kg [16] 109.8 mg/mL of extract [17] various curries, alfredo pasta, soufflés, beef stew, va baked products sweet/holy basil, basil 540 mg/kg [11] Detected † [18] Detected † [12] 710 mg/kg [11] various pesto sauces, Thai noodle and curry, capre salad star anise 98 mg/g [19] Detected † [12] 66 mg/g [19] Thai noodle, Chinese soups and stews [22] 14.0 ± 1.6 µg/g [23] 500 ± 36 mg/kg [24] various teas, sushi, congee, various soups, various cu tarragon Detected † [25] 0.5-28.9% ...
Alkenylbenzenes, including eugenol, methyleugenol, myristicin, safrole, and estragole, are potentially toxic phytochemicals, which are commonly found in foods. Occurrence data in foods depends on the quality of the analytical methodologies available. Here, we developed and compared modern reversed-phase high performance liquid chromatography (HPLC) and stacking-micellar electrokinetic chromatography (MEKC) methods for the determination of the above alkenylbenzenes in food flavouring ingredients. The analytical performance of HPLC was found better than the stacking-MEKC method. Compared to other HPLC methods found in the literature, our method was faster (total run time with conditioning of 15 min) and able to separate more alkenylbenzenes. In addition, the analytical methodology combining an optimized methanol extraction and proposed HPLC was then applied to actual food flavouring ingredients. This methodology should be applicable to actual food samples, and thus will be vital to future studies in the determination of alkenylbenzenes in food.
... Nutmeg oil has been reported to contain about 4% myristicin and about 0.6% safrole, but its composition varies depending on geographical origin (Randerath et al., 1993). One must also take into account that nutmeg is used as a low cost alternative to recreational drug and some intoxication and even fatal cases were attributed to myristicin poisoning (Demetriades et al., 2005;Hallström and Thuvander, 1997;Stein et al., 2001). The ingestion of nutmeg to "get high" can reach 5 g, corresponding to 1-2 mg myristicin/kg bw but 6-7 mg/kg bw may be the dose required to cause psychopharmacological effects in humans (Hallström and Thuvander, 1997). ...
... Death was presumably caused by a combined toxic effect with flunitrazepem. Cases of 20-80 g ingestion have been reported, the equivalent to 280-1100 mg/kg exposure (Stein et al., 2001). ...
... In a fatal case of a 55-year-old woman after ingestion of an unknown quantity of nutmeg 4 μg/mL of myristicin was detected in the postmortal serum. In another case of nutmeg intoxication caused by ingestion of approximately 280-420 mg/mL of nutmeg powder, myristicin blood level was of 2 μg/mL measured 8 h after ingestion (Stein et al., 2001). Myristicin was studied in human volunteers in the form of an alcoholic drink. ...
Alkenylbenzenes, such as estragole, myristicin and eugenol, are present is several flavourings, functional foods, plant food supplements (PFS) and in complementary and alternative medicines (CAM) including herbal medicines. The increase in consumption in functional foods observed worldwide requires a strict analysis of the scientific validity of their benefits and risk-benefit ratio associated with their intake. Some instances of acute toxicity have been reported associated with the use of herbal medicines and PFS, in particular because quality control is poor, and this poses a risk especially in internet marketed products. In particular, chronic exposure to low levels of these constituents may pose a hazard. However, given the variability in dietary habits, plant properties, plant misidentification or interaction with pharmaceutical drugs or nutrients, the assessment of risk due to the intake of alkenylbenzenes is difficult. We herein review the regulatory status of the most common alkenylbenzenes and their genotoxic activity and potential carcinogenic activity.
... M. fragrans is the most commonly used plant to isolate myristicin to exploit its effects as recreative drug. A mild cerebral stimulation in human brains is caused with 400 mg myristicin doses (6-7 mg/kg body weight), equivalent to 15 g of M. fragrans powder (Stein et al., 2001). However, myristicin doses of 1-2 mg/kg body weight, equivalent to 5 g of M. fragrans, are toxic and can lead to organ damages and impact on the cardiovascular systems (Hallström & Thuvander, 1997;Rahman et al., 2015). ...
... Half an hour after the addition of 1 mL/cage of M. fragrans seed EOs, the plasma concentration of myristicin was 3.7 μg/mL; 1 and 2 h after the addition, the levels were 5.2 and 7.1 μg/mL, respectively (Muchtaridi et al., 2010). In one girl hospitalized with atropine like symptom 6 h after ingestion of 14-21 g or 280-420 mg/kg, a myristicin blood level of 2 µg/mL was measured 8 h after ingestion, typical symptoms were seen up to 20 h after ingestion, and recover without any sequelae (Stein et al., 2001). ...
Myristicin is an allylbenzene and a major key constituent of many plant species, such as Myristica fragrans Houtt. (nutmeg), Foeniculum vulgare Mill. (fennel), and Petroselinum crispum (Mill.) Fuss (parsley). Their plant parts have been used in traditional medicine and as a flavoring seasoning for cooking but, and as biopesticides with natural compounds. Myristicin has been related with several biological effects, such as anticarcinogenic, anti-inflammatory, antimicrobial, antioxidant, antidiabetic, analgesic, and hepatoprotective. The traditional uses include the treatment of complications related to gastrointestinal tract, respiratory system, and gynecological disorders. However, several studies have been reported contraindications associated to high dose consumption of myristicin. This review summarizes the biological activities of myristicin and myristicin-rich plants, toxicological effects along with its bioavailability, and metabolism. In addition, their traditional uses and their role as ecological remedy in plants protection has been reviewed. Nutmeg is the myristicin-rich plant with more pharmacological effects reported but also with most contraindication and toxically reports.
... In the literature, it has been stated that surgical smoke contains dead and living cellular materials, blood particles, bacteria, viruses, toxic gases, vapours (benzene, toluene, carbon monoxide, etc.), and particles that damage the lung. 5 Surgical smoke threatens the health of both patients and operating room employees due to the harmful substances it contains. 5 Many international organizations, associations and institutes whose field of study is the safety of employees and patients have included surgical smoke and smoke protection in their core business activities. ...
... 5 Surgical smoke threatens the health of both patients and operating room employees due to the harmful substances it contains. 5 Many international organizations, associations and institutes whose field of study is the safety of employees and patients have included surgical smoke and smoke protection in their core business activities. The Occupational Safety and Health Administration of the US Department of Labour states that approximately 500 000 operating room employees are exposed to surgical smoke every year and emphasizes that surgical smoke should be removed from the operating room properly. ...
... The metabolic conversion of elemicin and myristicin into amphetamine-like compounds may be the cause of nutmeg seeds' psychoactivity. Elemicin and myristicin are amphetamine derivatives that metabolize to 3,4,5 trimethoxyamphetamine (TMA) and 3-methoxy-4,5-methylenediox yamphetamine (MMDA), respectively (Stein et al., 2001). Myristicin is also a poor regulator of monoamine oxidase, which may be the cause of certain cardiovascular symptoms. ...
... A 16-year-old teenager experienced tachycardia, drowsiness, dry mouth, mydriasis, warm skin, and anorexia six hours after consuming 14-21g nutmeg powder. The blood sample taken 8 hr after ingestion had a myristicin concentration of 2 g/ml and a 55-year-old woman's postmortem blood contained 4 g/ml of myristicin and 0.072 g/ml of flunitrazepam (Stein et al., 2001). ...
Spices consumptions are in direct relation with the healthy survivability of consumers throughout life as they are loaded with lists of phytoconstituents of human values. Nutmeg owes to its essential, volatile and fixed oil is in prime most interest by researchers to explore for its benefits through food utilization. Besides loaded with these phytochemical‐based benefit traits it is also rich on the mineral side preferably with potassium, magnesium and phosphorous.As for as the oil variation is concern, nutmeg essential oil composition behaves as per the geographical and varietal factors. Its beneficial aspect highlighted wherein oil of nutmeg contains Myristicin (phenylpropene organic compound) can exhibit anti‐inflammatory response and have the cytotoxic activity against human colorectal carcinoma (HCT‐116) and human breast carcinoma Michigan Cancer Foundation (MCF‐7). Associated benefits of being on antiangiogenic compounds such as myristicin in Myristica fragrans essential oil resulted in antiangiogenic activity with an IC50 of 77.64 g/ml.
... Myristica fragrans Houtt., (Myristicaceae), a plant species indigenous to Indonesia, is widely distributed in the humid tropical and coastal regions, and is known as "nutmeg", for being used in the production of the spices nutmeg and mace [1][2][3]. Historically, nutmeg was believed to be imported to Europe by Arab traders during the 12th century [4], where grated nutmeg was used as a sachet, and the Romans used it as incense. In the 1600s nutmeg became a pricy commercial spice in the Western world [5]. ...
... There was no definite relationship between DT and nutmeg EO content, as well as between DT and the concentrations of terpinen-4-ol and safrole. Since all these three models shown in Equation (1), Equation (2), and Equation (3) are nonlinear, their parameters were estimated iteratively using the NLIN Procedure of SAS [26] and the fitted models met all model adequacy requirements described in Bates and Watts [27]. ...
The intent of this study was to utilize distillation timeframes (DT) of nutmeg (Myristica fragrans) essential oil (EO) to generate fractions with differential chemical compositions and bioactivity. Ten fractions were captured at the following distillation timeframes: 0.0–0.5, 0.5–1.0, 1.0–2.5, 2.5–5.0, 5.0–10, 10–30, 30–60, 60–90, 90–120, and 120–240 min. In addition, a control EO was collected from a straight 0–240 min non-stop distillation. ANOVA and advanced regression modeling revealed that the produced EO fractions possess substantial variation in the concentration of potentially desired compounds. The concentrations (%) of α-phellandrene, 3-carene, p-cymene, limonene, α-thujene, α-pinene, camphene, sabinene, β-pinene, and myrcene decreased, while the concentrations (%) of α-terpinene, γ-terpinene, terpinolene, and myristicin increased in later DT fractions. Nutmeg EO showed some antimalarial activity against Plasmodium falciparum D6, but did not exhibit significant antifungal activity. In general, nutmeg seed oil yields increased with an increase of DT. These results may be utilized by industries using nutmeg EO.
... Safrole epoxide also can be produced by various allyl side chain oxidation routes. The second route of the safrole is occur through cleavage of methylenedioxy groups being allycatechol and propenbylcatechol (isomer from allylcatechol) [18]. Toxicological research on mice revealed that safrole possesses hepatolarsinogenic characteristics at high doses [17]. ...
This review aimed to assess the antioxidant properties of safrole, myristicin, and terpineol from Myristica fragrans Houtt. Safrole exhibited high antioxidant and cytotoxic activities against numerous cancer cell lines and also shown able to suppress tumor cell angiogenesis. Myristicin is able to increase the activity of glutathione peroxidase (GPX), glutathione reductase (GR) or glutathione-disulfide-reductase (GSR), superoxide dismutase (SOD), and catalase (CAT). Myristicin is also able to reduce the level of lipid peroxidation (LP) or lipid degradation. Terpineol or also known as alpha terpineol (α-T) revealed high antioxidant and cytostatic activities against several human cancer cell lines, especially breast adenocarcinoma (MCF-7) and myeloid leukemia (K-562).
... 34 -36 Nutmeg (Myristica fragrans) can produce hallucinations and anticholinergic symptoms at a remarkably low dose (less than a tablespoon). 37 The agent responsible, myristicin, 37 38 has also been linked to gastrointestinal distress, difficult to control seizures, 38 39 psychosis, 40 and death, 41 with reports of nutmeg induced delirium occurring as far back as the 16th century. 42 As such, we do not recommend trying a "nutmeg challenge" either. ...
An unsystematic review, inspired by Christmas culture, examining the potential for harm from
consumption or exposure to plants associated with Christmas
... Myristica fragrans Houtt., which belongs to the Myristicaceae family, is more commonly known as nutmeg [10]. The fruit, once mature, is separated into the mace (crimson-colored), which surrounds the seed [11]. ...
This study assessed the antimicrobial, toxicity, and phytochemical profiles of Myristica fragrans extracts. Different solvent extracts were tested for antimicrobial activity against clinical and reference microbial strains, using disc and well diffusion assays and microdilution techniques. Antioxidant potential was investigated using 2,2-diphenyl-1-picryhydrazyl (DPPH) assays. Cytotoxicity assay was conducted against human umbilical vein endothelial cells (HUVECs) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Acute toxicity was assessed in laboratory Swiss albino mice at a single dose of 2,000 mg/kg body weight for 14 days. To assess the phytochemical constituents, spectrophotometric and gas chromatography-mass spectrometry (GC-MS) methods were used. The chloroform extract revealed antimicrobial potencies against the Gram-positive bacteria and C. albicans with minimum inhibitory concentrations. In the DPPH assay, the IC 50 value of the chloroform extract was determined to be 1.49 mg/mL. The phenolic and flavonoid contents were 26.64 ± 0.1 mg of gallic acid equivalents/g and 8.28 ± 0.1 mg quercetin equivalents/g, respectively. The IC 50 value was determined to be 49 µg/mL against the HUVEC line. No mortality or morbidity was observed. GC-MS analysis indicated the presence of 2-cyclopenten-1-one (44.72%) as a major compound. The current results provide scientific support for the use of M. fragrans in folk medicine.
... Previous research showed that myristicin could produce excitement and hallucinogenic effects. It may also be potentially toxic, as overdose can cause hallucinations and, in some cases, even coma (Stein et al. 2001;Sivathanu et al. 2014). Lee and Park (2011) demonstrated that myristicin has anti-inflammatory effects by inhibiting inflammatory factor expression. Lee et al. (2005) further found that myristicin induces early apoptotic events in human neuroblastoma, including cytochrome c release, caspase-3 activation and PARP lysis, leading to the death of SK-N-SH cells. ...
Context
Myristicin is a natural active compound that has inflammatory, antimicrobial and anti-proliferative properties. Yet, its effect on hepatic carcinoma has not been investigated.
Objective
To explore the role and related molecular mechanism of myristicin in hepatic carcinoma in vitro.
Materials and methods
Human hepatic carcinoma cell lines (Huh-7 and HCCLM3 cells) were treated with different concentrations of myristicin (0.5, 1 and 5 mM) for 24, 48 and 72 h. Then, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay (MTT), flow cytometer (FCM) analysis and transwell assay were performed to determine cell proliferation, apoptosis and migration/invasion, respectively. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), E-cadherin, N-cadherin and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway-related proteins were detected using Western blot assay. Gene expression was determined using quantitative real time-polymerase chain reaction (qRT-PCR).
Results
Myristicin inhibited cell proliferation and induced apoptosis in Huh-7 and HCCLM3 cells; suppressed cell migration and invasion ability, and increased E-cadherin expression and decreased N-cadherin expression, thereby inhibiting epithelial–mesenchymal transition (EMT). Finally, the findings indicated that myristicin decreased phosphorylated (p)-mTOR and p-AKT expression at the protein level.
Discussion and conclusions
Myristicin exerts an efficient therapeutic effect on hepatic carcinoma by suppressing PI3K/Akt/mTOR signalling pathway; thus, it may be used as a new potential drug for hepatic carcinoma treatment.
... The Nutmeg plant, Myristica fragrans (Houtt), is a member of the small primitive family called Myristicaceae, taxonomically placed between the Annonaceae and Lauraceae (Stein et al, 2001). At present, Myristicaceae is considered as a member of Magnotiales or its taxonomical equivalents. ...
... Intoxication symptoms after the ingestion of seeds of the nutmeg tree (Myristica fragrans, Houtt.) have been described in literature for more than 400 years. 1 Since then, numerous cases were reported after accidental, intentional, or suicidal overdosing of the seeds, leading to symptoms such as agitation, nausea, and in severe cases to seizures. 2,3 Recent publications even reported the occurrence of so-called "nutmeg challenges" on social media, that encourage the ingestion of high amounts of ground nutmeg and to subsequently record the effects on the user, indicating that these intoxications are still a contemporary problem. 4 5 Their chemical structures are shown in Figure 1. However, the detection of nutmeg ingredients and their metabolites was since limited to urine screening using GC-MS and although Neukamm et al. proposed a reporting threshold based on the detection of certain metabolites in urine, the detection of these ingredients or their metabolites in blood might facilitate an estimation of the amount that was ingested. ...
Numerous case reports of intoxications with nutmeg seeds (Myristica fragrans, Houtt.) can be found in literature often following their abuse, as psychotropic effects were described after ingestions of large doses. The successful detection of the main ingredients of the nutmeg seeds essential oil elemicin, myristicin, and safrole, as well as their metabolites in human urine by gas chromatography coupled to mass spectrometry (GC‐MS) were already described. The aim of this study was to investigate the detectability of the main ingredients of nutmeg seeds and their metabolites in human blood and urine samples using liquid chromatography coupled to linear ion trap mass spectrometry (LC‐LIT‐MSn) and liquid chromatography coupled to high‐resolution mass spectrometry (LC‐HRMS/MS) after nutmeg seed abuse. Sample material of three individuals was retrospectively investigated after a systematic screening approach indicated an intoxication with nutmeg seeds as a likely cause of symptoms. Metabolic patterns in plasma and urine using GC‐MS were comparable to those described in earlier publications. Investigations using hyphenated liquid chromatography techniques lead to the detection of myristicin and safrole, as well as further metabolites not described using GC‐MS and revealed sulfation as an additional phase II metabolic pathway. These results might help to detect or confirm future intoxications with nutmeg seeds by using LC‐MS techniques.
... It was reported that LD50 is 5.1 g/kg, and signs of abnormal behavior such as hypoactivity, unstable gait, and dizziness are seen in animals given a dose of 4 g/kg or higher [25]. Numerous cases of nutmeg abuse and poisoning were reported in recent decades [8,10,[26][27][28]. However, few studies reported the toxicity of nutmeg to the liver. ...
Incidences of abuse and poisoning have been reported for nutmeg, a household spice made from grinding the seed of Myristica fragrans, owing to its hallucinogenic properties. However, there have been no reports on nutmeg hepatotoxicity in relation to dose and duration of exposure. To investigate the hepatotoxicity of different nutmeg exposure durations and doses, male mice were administered daily with normal saline, 1.0 g/kg nutmeg, or 4.0 g/kg nutmeg by intragastrical gavage for either 7 or 14 days (for a total of six treatment groups, n = 6). Body weight of each mouse was monitored daily. Histological analysis of liver tissues was performed using hematoxylin and eosin (H&E) staining to investigate the morphological changes in hepatocytes. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined using enzyme-linked immunosorbent assay (ELISA) to investigate liver function. Metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed between treatment groups for identifying differential metabolites. Mice in the nutmeg exposure groups exhibited slow growth trends, hepatocyte damage, and significantly elevated serum AST and ALT levels associated with nutmeg dose and exposure duration. Metabolomics and KEGG enrichment pathway analyses also revealed differential levels of some metabolites related to liver function upon nutmeg exposure. Therefore, the present study reasonably speculates that nutmeg exposure may cause liver damage and affect liver function depending on the dose and duration.
... The details surrounding this fatality are unclear as the report included very limited clinical information; it is unknown whether this outcome was affected by additional ingestions or underlying medical conditions. The second case involved a 55-year-old woman who died under unclear circumstances; postmortem toxicological examination revealed the presence of elevated concentrations of flunitrazepam and myristicin, and her stomach contents had an odor consistent with nutmeg [18]. ...
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.
... Later, nutmeg has been reported to have antioxidant, anti-tumor, and antibacterial effects, and more [28][29][30][31][32]. Although nutmeg has a long history of abuse [33,34], and even higher doses (20-80 g of powder) have been ingested (adult), a life-threatening situation has never been observed [35]. In recent studies, nutmeg has displayed high binding activity to the cannabinoid receptor 1 (CB1), which is associated with the obesity pathway [36]. ...
Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.
... However, few studies have addressed the toxicity of natural plants, although many questions have been raised regarding their safety. 2,3 The importance of plant species for therapeutic applications is well established but studies on certain plant-induced toxicity are scarce. However, the rationale for the utilization of medicinal plants has rested largely on long-term clinical experience with little or no scientific data on their efficacy and safety. ...
Background: Litsea glutinosa (Lauraceae) stem bark is widely used in folk medicine as a hepatoprotective, anti-diarrheal and anti-dysenteric drug but there is a lack of information about its toxicity. Objective: To evaluate cytotoxicity and acute toxicity of the stem bark ethanol extract (BEE). Materials and Methods: In vitro cytotoxicity of BEE was measured against breast adenocarcinoma, prostate, and colon carcinoma cell lines. In the acute toxicity tests, rats received oral doses of BEE as 1000, 2000, and 3000 mg/kg body weight. Mortality, signs of toxicity, body weight, food consumption, and gross findings were observed for 14 days. Blood samples were collected from anesthetized animals and used for hematological and biochemical parameters. Histopathological study was performed using liver and kidney samples. Results: The BEE does not show significant cytotoxic effect against the tested cell lines up to the range from 5 to 320 μg/ml. In acute toxicity study, also lethality was not observed up to 3000 mg/kg b.w. No significant differences were noticed in body and organ weights and histopathology examinations between the control and treated groups. Conclusion: This study authenticates stem BEE may contain bioactive compounds of potential therapeutic significance which are relatively safe from toxic effects, and evidences the medicinal use of this plant in folk medicine.
... Myristica fragrans is a familiar product in our spice cabinets, adding a special touch to cookies, cakes, and pies. However, it contains 1,8-cineole (eucalyptol) that can be dangerous when ingested in excess, causing vomiting, drowsiness, and eventually a coma [68,69]. Furthermore, Eucalyptus oil, rich in 1,8 cineole, causes vomiting and diarrhea in addition to other side effects [25,70]. ...
Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. rhamnifolioides essential oil complexed in β-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed using different physical methods. The anti-inflammatory activity was evaluated in vivo by ear edema, paw edema, cotton pellet-induced granuloma, and vascular permeability by Evans blue extravasation. The mechanism of action was validated by molecular docking of the major constituent into the cyclooxygenase-2 (COX-2 enzyme). Biology 2020, 9, 114 2 of 25 All doses of the COEFC reduced acute paw edema induced by carrageenan and dextran, as well as vascular permeability. Our results suggest the lowest effective dose of all samples inhibited the response induced by histamine or arachidonic acid as well as the granuloma formation. The complexation process showed that the pharmacological effects were maintained, however, showing similar results using much lower doses. The results demonstrated an involvement of the inhibition of pathways dependent on eicosanoids and histamine. Complexation of β-cyclodextrin/Essential oil (β-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs.
... In rat model studies, it was shown that nutmeg interactions can occur with buspirone, diazepam, and ondansetron. Simultaneous ingestion of huge quantities of nutmeg and flunitrazepam results in death (Stein et al., 2001) ...
Myristica fragrans or nutmeg is a ground spice of the family Myristicaceae. Its tree has dark leaves mainly cultivated in Grenada, Malaysia, and Kerala. It is majorly a source of two spices derived from its fruit: nutmeg (jaiphal) from its seed and mace (javitri) from the covering of seed. The important bioactive constituents present in nutmeg include macelignan, carvacrol, myristicin, β-caryophyllene, β-pinene, α-pinene, p-cymene, and eugenol. Low doses of nutmeg do not cause any side effects whereas after consuming 5g toxic overdose occurs, and central nervous system (CNS) effects were induced after consuming 1 to 2 mg/kg b.wt. of nutmeg. Various therapeutic or medicinal applications were shown by nutmeg such as antioxidant, antimicrobial, aphrodisiac, anticancer, hepatoprotective, anti-inflammatory, antidepressant, and cardioprotective activity. This review chapter focuses on ethnobotany, phytochemistry, acceptable daily intake, and different pharmacological actions of this medicinal plant.
... The scientific name of nutmeg is Myristica fragrans houtt of the family myristicaceae, it comes from the tree Myristica fragrans, which originates from the Indonesian Banda Islands, and its therapeutic applica- tions have been recorded by Arab physi- cians since the seventh century C.E, after that nutmeg appeared in Europe 1,2 . In medicine the nutmeg was prescribed for headache, fevers, mouth-sores, exces- sive heat of the body, foul breath, diarrhea, intestinal weakness, and used as analge- sic, sedative and as an anti-inflammatory 3 .The seed extracts of nutmeg possess a potent hepatoprotective activity 4 . ...
Background and objective: Myristica fragrans is an aromatic green tree usually growing to around 5-13 meters high, and their seeds (nutmegs) is firm broadly ovoid. The objectives of the study were to find the concentration of nutmeg oil that has maximum antibacterial action against Staphylococcus aureus and to evaluate the healing potential of this concentration on a chemically induced oral ulceration in the rabbit's cheek mucosa. Methods: Different concentrations of nutmeg oil were prepared and their antibacterial activity against Staphylococcus aureus was determined by disk diffusion method. The chemically induced oral ulcerations in rabbit's cheek mucosa were achieved by ethanol, and then these ulcerations were irrigated with 0.5ml (5%) of nutmeg oil twice daily. Biopsies were taken after four and eight days of the experiment, processed and stained by hematoxylin and eosin. Results: The concentration 100% of nutmeg oil and the dimethyl sulfoxide; which was used as diluents for preparing different concentrations of nutmeg oil, showed no inhibition zone for Staphylococcus aureus. The concentration (5%) showed maximum inhibitory zone (16.8mm) for the microorganism which was parallel to the effects of amoxicillin (positive control), both with highly significant action (P<0.05). The histopathological pictures showed a delay in the healing process of oral ulcers in rabbits treated by this concentration. Conclusion: The concentration of nutmeg oil (5%) has a good antibacterial action against Staphylococcus aureus, but it causes a delay in the healing process of oral ulcerations.
... 12 Fatal myristicin poisonings in humans are very rare, but two have been reported: one in an 8- year-old child 13 and another in a 55-year-old adult, the latter case attributed to a combination with flunitrazepam. 14 In a case reports, raw nutmeg produced anticholinergic- like symptoms, attributed to myristicin and elemicin. 15,13,16 The potential toxicity of bromate has given rise to various forms of speculations which led to its ban in Nigeria by National Agency for Food and Drug Administration Control 17 and even in some other countries by their regulatory bodies. ...
This study was aimed at investigating the toxic effects of potassium bromate on the spleen and heart of Wistar albino rat and to evaluate the protective effects of aqueous extract of African nutmeg (Myristica fragrans) against potassium bromate induced toxicity in the two organs. Twenty-four (24) male wistar albino rats weighing between 180g and 200g were divided into four groups of six animals each. Group I animals were served with rat feed and water as the control group, group II were administered daily with 30mg/kg bw potassium bromate while groups III and IV animals were administered with 0.5mL of 20% and 40% aqueous extracts of nutmeg seed in addition with 30mg/kg body weight potassium bromate respectively for two weeks. The animals were kept at optimum temperature within a 12 hours light/dark cycle while the experiment lasted. Enzyme biomarkers such as Aspartate Transaminase, Alanine Transaminase, Alkaline Phosphatase; antioxidant enzymes such as, Superoxide dismutase, Catalase; reduced Glutathione; some lipid profiles like Cholesterol, Triglyceride and malondialdehyde were measured in the spleen and heart homogenates of the animals in all the groups. Results of this study showed that potassium bromate exerted significant (P < 0.05) toxic effects on the spleen and heart homogenates while the administration of aqueous extracts of African nutmeg seed caused a marked reversal in the toxicity in a dose dependent manner. However, the results of this study showed that aqueous extract of the seed of African nutmeg is a potential antioxidant against potassium bromate toxicity in the two organs. Keywords: Toxicity, Potassium bromate, Myristica fragrans, Cardiac tissue, Antioxidant
... Nutmeg causes a wide adverse reaction to the nervous system and gastrointestinal tissues. It also causes rapid heart rate and dehydration [5]. However, in its freshlyground form, nutmeg contains myristicin, a monoamine oxidase inhibitor and psychoactive substance which can induce convulsions, palpitations, nausea, eventual dehydration, and generalized body pain [6]. ...
Myristica fragrans H. is a dieocious plant with male and female flowers on different trees. At the juvenile stage of nutmeg, their sexes is not morphologically identified until at the flowering stage. However, the female is more economical than the male plants. This challenge is making the work of nutmeg farmers difficult and also inhibiting the development of the spice and flavouring industry in Ghana. Hence, the use of molecular technique to characterize male and female nutmeg plants. SCAR markers are easy, specific, and reliable and have a high sense of reproducibility than other markers. Two different primers (F-Napf-76, R-Napf-77 and F-Napf-70, R-Napf-71) were used for the PCR amplification. It was revealed that the total genomic DNA of samples from both mature plant and seedlings of nutmeg were of good quality and was much concentrated by giving good DNA bands. Although there were no distinctions among the bands, they all lie at the same level (0.3kbp) indicating that the samples were of similar molecular weight. However, double PCR amplification was not seen in all samples when run on a 1% agarose gel but single amplifications were observed.
... It is possible that such enzyme inactivation and chelation of metals by sorbitol and nutmeg may be partially responsible for the decrease in TMA values. In addition, fatty oil of nutmeg contains 12% myristin, the glyceric ester of myristic acid, stearic acid and oleic acids [13]. These may have assisted in inhibiting the TMA values of the fish chubs during storage. ...
The objective of the study was to reduce post-harvest losses by developing a fish chub using Clarias gariepinus and to determine the effect of Monodora myristica (local nutmeg) and sorbitol on the physical quality, proximate composition and trimethyl-amine content of the product. Cooled smoked samples were packaged and stored at refrigerated and frozen storage conditions and examined for 1-12 weeks under frozen and 1-7 days under refrigerated condition at intervals. The yield for the fish chub production was about 35 %, while 65% of the starting material was lost during processing. The protein content of the samples varied between 13% and 25%. Frozen fish chubs stored at −18˚C had a shelf life of about six weeks while the refrigerated fish chub (7˚C-10˚C) sample had a shelf life of about 4 days. The combined use of local nutmeg and sorbitol increased the shelf life under both storage conditions. The production of fish chub could be a viable economic venture in places where catfish is readily available and it is likely to improve protein intake of the consumers and reduce post-harvest losses.
... Nutmeg esential oil contains pine, sabincene, camphene, myristin, elemicin, isoelemicin, eugenol, isoeugenol, methoxyeugenol, safrole, diametric phenylpropanoids, lignas and [4,5]. Those compounds have been reported causing to paralysis, poisoning, drunkenness, anger, dizziness, falling, headaches, convulsions, hallucination and death [6]. ...
Nutmeg is dried kernel of broadly ovoid seed of Myristica fragrans Houtt. It has been mentioned in ethnomedical literature as aphrodisiac, stomachic, carminative, tonic, and nervous stimulant. In order to establish the safety of nutmeg, the effect of the repeated administration of nutmeg is needed. The study was aimed to determine the toxic effect of subchronic administration of nutmeg ethanolic extract to hematological parameters in rat. A total of 28 male adult Wistar rats divided into 4 groups. Group I as control was given by 0.5% CMC-suspension, group II, III, and IV were given by 50, 100, and 200 mg/kg bw, respectively, of nutmeg ethanolic extract. The treatments were administered daily for 31 days. On day 31 bloods were taken from orbital sinus. The hematological parameter consisted of the numbers of erythrocyte and leukocyte as well as hemoglobin and total protein levels were measured. The data were statistically analyzed by one way Anova followed by LSD test. All of observed hematological parameters in rats showed that there were no significant difference between the nutmeg ethanolic extract treated groups and control group. The result indicated that the subchronic administration of 50, 100, and 200 mg/kg bw of nutmeg ethanolic extract did not cause the change of hematological parameters in rat.
Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.
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Everybody eats, and what we eat – or do not – affects the brain and mind. There is significant general, applied, academic, and industry interest about nutrition and the brain, yet there is much misinformation and no single reliable guide. Diet Impacts on Brain and Mind provides a comprehensive account of this emerging multi-disciplinary science, exploring the acute and chronic impacts of human diet on the brain and mind. It has a primarily human focus and is broad in scope, covering wide-ranging topics like brain development, whole diets, specific nutrients, research methodology, and food as a drug. It is written in an accessible format and is of interest to undergraduate and graduate students studying nutritional neuroscience and related disciplines, healthcare professionals with an applied interest, industry researchers seeking topic overviews, and interested general readers.
The aim of this study was to optimize the grinding process parameters (mesh size of grinder sieve ), the peripheral velocity of the grinding wheels ), and the storage time of ground ginger rhizome and nutmeg to obtain ethanol and ethanol-water extracts with improved antioxidant properties. The optimal conditions were estimated using response surface methodology (RSM) based on a three-variable Box–Behnken design (BBD) in order to maximize the antioxidant capacity (AC) determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, and the total phenolic content (TPC) was determined by the Folin–Ciocalteu (F–C) method in spice extracts. Additionally, the phenolic acid profiles in extracts from optimized conditions were analyzed using ultra-performance liquid chromatography (UPLC). It was found that the optimal preparation conditions for antioxidant extraction were dependent on the spice source and solvent type. The best antioxidant properties in nutmeg extracts were achieved for = 1.0 mm, = 40–41 Hz and = 7 days, whereas the optimized parameters for ginger extracts were more varied (1.0–2.0 mm, 43–50 Hz and 1–9 days, respectively). The ginger extracts contained 1.5–1.8 times more phenolic acids, and vanillic, ferulic, gallic, and p-OH-benzoic acids were dominant. In contrast, the nutmeg extracts were rich in protocatechuic, vanillic, and ferulic acids.
Glycoalkaloids are abundantly found among the members of the Solanaceae family. Potatoes (Solanum tuberosum L.), tomatoes (Solanum lycopersicum L.), and eggplant (Solanum melongena L.) are the most common sources of glycoalkaloids. The most predominant glycoalkaloids present in potatoes are α-solanine and α-chaconine, and several other glycoalkaloids such as β-chaconine, γ-chaconine, β1-solanine, β2-solanine, and γ-solanine are also present in small quantities. Tomatoes contain α-tomatine and dehydrotomatine, and eggplant contains solasonine and solamargine as their main glycoalkaloids. Glycoalkaloids, especially from potatoes e.g., α-solanine and α-chaconine, are known to cause gastrointestinal problems such as gastritis, gastrointestinal disturbance, nausea, vomiting, diarrhea, fever, low blood pressure, and, in high doses, cause a fast pulse rate along with neurological and occasional death in humans and farm animals. In recent years, an increasing number of toxicological events were reported by food contaminations with glycoalkaloids. Hence, it becomes very important to identify, analyze, and characterize different types of glycoalkaloids present in food items. This book chapter comprehensively covers sources, chemistry, pharmacological, and toxicological actions of glycoalkaloids present in food items.
Nuclear magnetic resonance (NMR) spectroscopy is a robust method, which can rapidly analyze compounds or their mixtures in complex matrices without separating or purifying them. This makes the technique ideal for analysis of foods and related products. NMR continues to be an underutilized methodology in the area of food authentication and analysis, mainly due to the high cost, relatively low sensitivity, and the lack of NMR expertise among food analysts. The aim of this chapter is to explore the role of NMR methodologies in the field of food science with a special focus on analysis of food toxins. An introduction of the basic principles of NMR related to the study of foods and nutrients is given. This is followed by a detailed description of metabolomics studies. NMR with metabolomics studies together make a powerful methodology to address the challenges faced in food science. Furthermore, a comprehensive overview of their recent applications in the areas of compositional analysis, food authentication, quality control, and human nutrition is provided. In addition, use of NMR techniques in the analysis of potential food toxins is discussed. Finally, future perspective of the use NMR-based studies in the identification and characterization of food constituents and toxins is presented.
Food toxins of natural origin cover a wide diversity of macromolecules; generated by plants, algae, fungi, or degraded products of metabolism with destructive effects even at very low concentration/dose or when consumed in sufficient quantities. These toxins have diverse chemical structures and may serve definite purposes in plants or are developed as biochemical protectant against predators, insects, or microbes. Glycoalkaloids, cyanide-generating compounds, enzyme inhibitors and lectins, and mycotoxins are some important examples of natural food toxins. The toxicity of food toxins relies on the level of toxins available as well as susceptibility of a given population. These toxins may lead to acute and chronic health issues whose clinical indications may range from minor gastrointestinal distress, neurological indications, and respiratory paralysis to fatality. Analysis of food toxins requires authentication of analytical techniques for screening, quantification, and identification of contaminants. Undeniably, chromatographic analytical approaches can analyze numerous natural food toxins in a given period of time, in a sensitive and selective manner, yielding toxins concentration accurately. Even though extensively used, these approaches are costly, consume a lot of time, and deliver data following a noteworthy time lapse. Furthermore, samples (food toxins) are damaged by analytical procedures. Thus, alternative approaches/substitutes such as IR spectroscopy are actually progressively advanced to deliver simple and rapid procedures for the detection of food toxins. IR spectroscopy is a non-destructive procedure; employed to authenticate and characterize samples in high throughput. The usefulness of IR spectroscopy has directed its usage in numerous applications which comprises chemistry of soil, cereals, agricultural produce, medicine, and so forth. Since it reviews the interactions between radiation and matter, IR spectroscopy is a suitable tool for carrying out analysis of food toxins in finished foodstuffs. This chapter delivers the advancement and potential prospective of IR spectroscopy as an alternate/substitute to prevailing techniques for the assessment of food toxins.
Alkaloids are the most important class of secondary plant metabolites that have been considered as the major source of phytomedicine. These alkaloids are a group of phytochemicals that contains two fused, five-membered rings that share a bridgehead nitrogen atom, forming a tertiary alkaloid. Pyrrolizidine alkaloids are known for their hepatotoxic activities, but are also reported to cause cancer. They are abundantly found in plant families such as Apocynaceae, Asteraceae, Boraginaceae, Compositae, Fabaceae, Leguminosae, Ranunculaceae, and Scrophulariaceae. Several medicinal plants contain pyrrolizidine alkaloids such as comfrey (Symphytum officinale), coltsfoot (Tussilago farfara), and petasites (Petasites japonicus), etc. Pyrrolizidine alkaloids are also present in milk (cows and goats), honey, staple foods, herbal teas, and herbal medicines. In recent years, an increasing number of toxicological reports revealed food contaminations with pyrrolizidine alkaloids. Hence, it becomes very important to identify, analyze, and characterize different types of pyrrolizidine alkaloids present in food items. In this book chapter, sources, chemistry, pharmacological, and toxicological actions of pyrrolizidine alkaloids will be discussed.
Myristicin [5-allyl-1-methoxy-2,3-(methylenedioxy)benzene] is the major constituent of the seasoning nutmeg oil and powder. Sometimes myristicin is misused via its ingestion at high doses to cause hallucination. In these high doses, myristicin could cause severe adverse health effects, including convulsion, delirium, and palpitation. Hence there is a strong need for a sensitive method for its analysis, such as fluorescence determination. Myristicin has a very weak fluorescence and also lacks derivatizable groups like the carboxylic, hydroxyl, or amino group in its structure, which makes its fluorescence derivatization challenging. In this research, we developed a fluorescence labeling method for myristicin based on the Mizoroki-Heck coupling reaction of its terminal alkene with a fluorescent aryl iodide derivative, 4-(4,5-diphenyl-1H-imidazol-2-yl)iodobenzene (DIB-I). Then, we developed an HPLC fluorescence detection method for the determination of myristicin utilizing this labeling reaction. The developed method showed a good linear response for myristicin (r = 0.995) in the range of 0.01-10 µmol/L with excellent sensitivity down to the detection limit of 2.9 nmol/L (9.6 fmol/injection). Finally, the developed method could be successfully applied to determine myristicin content in nutmeg powder, oil samples, and human plasma with simple extraction methods and good recoveries ranging from 89.3 to 106%.
Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
The study examined the nutmeg plant components spectrophotometrically using FT-IR and UV-Visible devices and knowing its components using FT-IR device. The solubility were measured using different solvent (e.g.: benzene, diethyl ether, water, hexane, ether, acetone & chloroform). The study also examined the effect of the nutmeg components on the biological processes of the human body for its various constituents. g.: oils and others. It was also observed that an increase in absorbance of solvents after the addition of the nutmeg to the solvents and according to the following sequence (Di ethyl ether> Hexane > Benzene> Chloroform> Water>Acetone> Ethanol).
Psychoactive natural products play an integral role in the modern world. The tremendous structural complexity displayed by such molecules confers diverse biological activities of significant medicinal value and sociocultural impact. Accordingly, in the last two centuries, immense effort has been devoted towards establishing how plants, animals, and fungi synthesize complex natural products from simple metabolic precursors. The recent explosion of genomics data and molecular biology tools has enabled the identification of genes encoding proteins that catalyze individual biosynthetic steps. Once fully elucidated, the "biosynthetic pathways" are often comparable to organic syntheses in elegance and yield. Additionally, the discovery of biosynthetic enzymes provides powerful catalysts which may be repurposed for synthetic biology applications, or implemented with chemoenzymatic synthetic approaches. In this review, we discuss the progress that has been made toward biosynthetic pathway elucidation amongst four classes of psychoactive natural products: hallucinogens, stimulants, cannabinoids, and opioids. Compounds of diverse biosynthetic origin - terpene, amino acid, polyketide - are identified, and notable mechanisms of key scaffold transforming steps are highlighted. We also provide a description of subsequent applications of the biosynthetic machinery, with an emphasis placed on the synthetic biology and metabolic engineering strategies enabling heterologous production.
The study examined the nutmeg plant components spectrophotometrically using FT-IR and UV-Visible devices and knowing its components using FT-IR device. The solubility were measured using different solvent (e.g.: benzene, diethyl ether, water, hexane, ether, acetone & chloroform). The study also examined the effect of the nutmeg components on the biological processes of the human body for its various constituents. g.: oils and others. It was also observed that an increase in absorbance of solvents after the addition of the nutmeg to the solvents and according to the following sequence (Di ethyl ether> Hexane > Benzene> Chloroform> Water>Acetone> Ethanol).
Introduction
Les rhabdomyolyses d’origine infectieuses sont rares. Elles ne représenteraient que 5 % des causes de rhabdomyolyse non traumatique. L’élévation des enzymes musculaires semble très rare au cours de l’infection tuberculeuse et sa physiopathologie reste mal élucidée. A notre connaissance, c’est la première fois qu’une rhabdomyolyse est décrite dans le cadre d’une tuberculose ganglionnaire, mais également dans le cadre d’une tuberculose causée par Mycobacterium bovis.
Présentation du cas
Un jeune homme de 21 ans, sans antécédents particuliers, se présente aux urgences, pour douleurs musculaires de la nuque, des bras et des cuisses évoluant depuis une semaine, avec une fièvre et parfois des frissons intenses. L’examen trouvait un patient fébrile à 40°C, en sueurs, avec des constantes hémodynamiques normales en dehors d’une tachycardie. Une aréflexie généralisée a été constatée ainsi qu’une une faiblesse musculaire minime des quadriceps, et une sensibilité abdominale modérée. Le reste de l’examen était sans particularités.
A la biologie, on notait un important syndrome inflammatoire biologique avec une insuffisance rénale aigue avec une rhabdomyolyse importante (CPK = 26 000 UI/l). La protéinurie était à 2.61g/24h et l’ECBU d’entrée était stérile. La radiographie pulmonaire et l’échocardiographie trans-thoracique étaient normales. Devant ce tableau associé à une hypertriglycéridémie à 2,75g/l et une ferritinémie élevée à 1300ng/ml, un myélogramme a été réalisé ne retrouvant pas d’images d’hémophagocytose.
La TDM TAP retrouvera des adénopathies mésentériques multiples, avec infiltration du mésentère et un discret épanchement péritonéal dans le cul de sac de douglas. La tomographie par émission de positons (TEP) au 18fluoro-désoxyglucose (FDG) a montré de multiples adénopathies sous diaphragmatiques d’activité métabolique très élevée. En parallèle, le T spot TB était positif.
Une cœlioscopie diagnostique, réalisée pour biopsie de ces adénopathies profondes, a permis de retrouver des adénites nécrotiques avec présence d’un Mycobactérium bovis à la culture, dont l’identification a été confirmée par PCR spécifique. L’examen anatomopathologique a également confirmé le diagnostic de tuberculose ganglionnaire profonde. Il n’y avait pas d’atteinte pulmonaire. L’EMG retrouvait un tracé myogène au niveau des muscles quadriceps et l’IRM des cuisses retrouve un hyper signal musculaire prédominant sur les muscles droit fémoraux.
L’évolution est partiellement favorable, avec une simple hyperhydratation. Une quadrithérapie antituberculeuse a ensuite été instaurée avec une nette amélioration sur le plan clinique. Après l’identification du Mycobactérium bovis, le pyrazinamide a pu être supprimé. Deux mois après l’introduction du traitement, celui-ci a pu être simplifié pour une bithérapie à base de rifampicine et isoniazide.
Conclusions
Une rhabdomyolyse a rarement été décrite au cours de la tuberculose. Pour autant, un clinicien confronté à une rhabdomyolyse fébrile peut être amené à évoquer ce diagnostic, si une cause plus fréquente n’est pas été retrouvée.
Nutmeg is one of the most used spice all over the world and has been for many centuries. When ingested in large quantities, it has been reported to have toxic effects and described in literature for long time. Fatal case was described at the beginning of the 20th Century and a more recent in 2001.
Method : Our study was based on calls compiled by the Marseille Poison Control Center (CAP) between June 2008 and June 2018. The Marseille’s center covering the entire French Mediterranean coast. Ingested nutmeg was given in grams when available and we classified effects on patients.
Results : Over the period understudy we observed 22 cases of human exposure. Eleven (50%) cases were intentionally exposed and eleven (50%) unintentionally. The majority of exposures intentionally were men (72%) and they were young (72% under 20 years old). Clinical effects were gastrointestinal in 56%, Neuropsychiatric disorders in 54% and tachycardia in 36%. No death and no combined drug intoxication reported in our case series. Treatment required was symptomatic, and some cases needed hospital admission.
Conclusion : Nutmeg is commonly used in cooking and is also known for its medicinal virtues and its toxicity with high doses. Intoxication – voluntary or not – is rare, but this spice is considered to be a low-cost drug, especially for its recreational psychotic effects.
Myristicin is widely distributed in spices and medicinal plants. The aim of this study was to explore the role of metabolic activation of myristicin in its potential toxicity through metabolomic approach. The myristicin-N-acetylcysteine adduct was identified by comparing the metabolic maps of myristicin and 1'-hydroxymyristicin. Supplement of N-acetylcysteine could protect against the cytotoxicity of myristicin and 1'-hydroxymyristicin in primary mouse hepatocytes. When the depletion of intracellular N-acetylcysteine was pretreated with diethyl maleate in hepatocytes, the cytotoxicity induced by myristicin and 1'-hydroxymyristicin was deteriorated. It suggested that N-acetylcysteine adduct resulting from myristicin bioactivation was closely associated with myristicin toxicity. Screening of human recombinant cytochrome P450s (CYPs) and treatment with CYPs inhibitors revealed that CYP1A1 was mainly involved in the formation of 1'-hydroxymyristicin. Collectively, this study provided a global view of myristicin metabolism and identified N-acetylcysteine adduct resulting from myristicin bioactivation, which could be utilized for understanding the mechanism of myristicin toxicity.
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Proximate composition, vitamin contents and mineral contents of four commonly used spices in the southeastern part of Nigeria were investigated. The spices are Myristica fragrans, Rosmarinus officinalis, Monodora myristica and Piper guineense.. Proximate analysis showed moisture contents of 10.83% in Rosmarinus officinalis, 12.78% in Monodora myristica and 12.35% in piper guineense .crude fibre contents ranged from 8.79% in (Piper guineense) to 14.26% in Rosmarinus officinalis. Crude fat ranged from 3.48% in Rosmarinus officinalis to 13.34% in Myristica fragrans. Crude protein ranged from 5.86% in Piper guineense to 14.30 in Rosmarinus officinalis; while carbohydrate content ranged from 41.57% in Myristica fragrans to 57.32% in Piper guineense. Ash content ranged from 6.33% (Piper guineense) to 11.78% in Rosmarinus officinalis. All samples had high contents of dry matter. The analysis for the vitamin contents of the spices showed the presence of vitamin A, B 1 , B 2 , B 3 and vitamin C. All four samples had high concentrations of vitamin C. The B complex vitamins for the four samples were of low concentration. The vitamin A levels ranged from (7.08 µg/g) in Piper guineense to 14.87 µg/g in Rosmarinus officinalis. The test for mineral content of the four samples showed that the spices contain calcium, magnesium, potassium, sodium, phosphorus and iron. The calcium concentration of the four spices are quite high. Also the spices contain high concentrations of phosphorus. Piper guineense contains the lowest potassium level of (98.52 mg/100g) when compared with Myristica fragrans, Monodora myristica and Rosmarinus officinalis which posses (334.78 mg/100g, 316.64 mg/100g and 343.82 mg/100g) respectively. Magnesium content ranged from 35.54 mg/100g in Piper guineense to 85.66 mg/100g in Rosmarinus officinalis. The iron (Fe) concentrations appeared to be the lowest compared with other minerals in all the spices.
p> Objective: To evaluatethe role of Myristica fragrans Houtt . for its analgesic, sedative and anxiogenic activity.
Method: Charles Foster rats were administered orally the ethanolic extract (EEMF) and fractions of extract in ethyl acetate (EAMF), chloroform (CMF), and n-hexane (HMF). They were screened for sedative activity using Pentobarbitone sleep potentiation test, analgesic activity using Eddy’s hot plate and Tail flick test; and anxiogenic or anxiolytic activity using Open field test.
Result: In pentobarbitone induced sleep potentiation test, the ethanolic extract (EEMF) and ethyl acetate fraction (EAMF) showed significant decrease in latency of sleep and highly significant increase in duration of sleep. In Open field test, EEMF, EAMF and HMF showed highly significant decrease in locomotion parameters as shown by decrease in rearing, preening and ambulation. In Eddy’s hot plate test and Tail flick test, highly significant increase in reaction time was seen in EEMF, EAMF, HMF groups.
Conclusion: The observed results suggest that Myristica fragrans has analgesic, anxiogenic and sedative activity.
Bangladesh Journal of Medical Science Vol.17(1) 2018 p.98-106</p
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Selected References
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Panayotopoulos DJ, Chisholm DD. Hallucinogenic effect of nutmeg. Br Med J. 1970 Mar 21;1(5698):754–754. [PMC free article] [PubMed]
Nutmeg is a common household spice sometimes abused for its hallucinogenic properties. This abuse is well reported in the medical literature over the last century. Ingestion of less than one tablespoon can produce symptoms similar to those of an anticholinergic toxic episode. Common presenting complaints are hallucinations, palpitations, and feelings of impending doom. We report a case of intentional nutmeg intoxication in a 23-year-old college student. As laboratory tests are usually normal, this diagnosis should be considered in patients presenting with an acute psychotic break accompanied by symptoms resembling an anticholinergic toxic episode. Treatment is primarily supportive once other life-threatening conditions have been ruled out.
The abuse of nutmeg for narcotic purposes has led to renewed chemical and pharmacological interest in this drug. Several allylbenzene derivatives whose biological transformation products have structures resembling mescaline and amphetamine have been identified as psychotropic constituents. It is suggested that the intensity of the hallucinogenic action of these compounds is due to the possibility of simulation of LSD-like structural elements.
Nutmeg and its active component, myristicin, show evidence of central monoamine oxidase (MAO) inhibition by their ability to lower the convulsive dose of intravenous tryptamine in mice and to increase rat brain 5-hydroxytryptamine concentrations. They also show some ability to antagonize reserpine-induced ptosis of the eyelids. Myristicin is chemically unique as a nitrogen-free MAO inhibitor. Although its potency in this respect is not comparable to some of the more potent inhibitors such as tranylcypromine and iproniazid, it seems quite adequate when compared to its low toxicity. Other volatile components of nutmeg such as borneol, geraniol and safrole, do not show tryptamine potentiation, although some appear to cause C.N.S. stimulation in high doses. Further study is recommended for more direct evidence of nutmeg and myristicin as enzyme inhibitors and for their utility as anti-depressant drugs.
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