International Journal for Research in ISSN: 2349-8889 Applied Sciences and Biotechnology Volume-8, Issue-2 (March 2021) www.ijrasb.com https://doi.org/10.31033/ijrasb.8.2.27

Myristica fragrans (Jaiphal): A Significant Medicinal Herbal

Isha Kumari1, Hemlata Kaurav2 and Gitika Chaudhary3 1Research Executive, Shuddhi , Jeena Sikho Lifecare Pvt. Ltd., Zirakpur 140603, Punjab, INDIA 2Research Executive, Shuddhi Ayurveda, Jeena Sikho Lifecare Pvt. Ltd., Zirakpur 140603, Punjab, INDIA 3Research Executive, Shuddhi Ayurveda, Jeena Sikho Lifecare Pvt. Ltd., Zirakpur 140603, Punjab, INDIA

3Corresponding Author: [email protected]

ABSTRACT the direct or indirect sources where quarter of the The tradition of using herbal drugs and herbal medicines have been derived from [10,11,12]. The remedies for treating human ailments is very old. From last practice of using for the treatment of several few years, the demand of herbal remedies has been human ailments is as old as origin of mankind [13,14]. increased. fragrans Houtt, commonly known as As per the WHO reports on the use of medicinal plants, , is a very common spice, which is used around the it has observed that 80% of the total population in world. It is described in almost each medicine system such as Ayurveda, Siddha, Unani and folk system. It has wide developed countries of the world depends primarily on range of fixed oils and essential oils in it for example herbal medicines to maintain their overall health and myristicin, safrole, myristic acid, trimyristicin, eugenol, fulfill their day to day requirements [15,16,17,18]. India elimicin and meso-dihydroguaiaretic acid. Myristica is one of the countries, which are categorized under fragrans Houttis well considered medicinal plant for its world biodiversity centers. India has a very rich history extraordinary properties like aphrodisiac, of utilizing medicinal plants. It is a home to more than hepatoprotective, antimicrobial, anti-diabetic, anti-oxidant, 45000 various species of plant and this is the reason why anti-cancer etc. The review aim is to provide India is called as the Botanical garden of the world data/information related to medicinal herbal plant called [19,20]. Many traditional systems of medicine such as such as its phytomedicinal value in traditional medicine systems like Ayurveda and folk Ayurveda, Siddha, Unani Folk system and as well as system, its therapeutic uses and associated toxicity. allopathy use medicinal plants in diseases treating practices [21]. Ayurveda is the most ancient system of Keywords- Jaiphal, Rasapanchak, Myristic acid, medicine known in India which uses almost 600 Campesterol, Aphrodisiac. different medicinal herbs/plants and their parts such as leaves, roots, fruits and stem and their formulations in treating variety of diseases [22,23]. Almost 25% of the I. INTRODUCTION population in U.K. uses herbal drugs in their daily routine [24]. Since 4000 years, traditional medicines Nature is served as primary source of numerous have been in practice in Africa. As per the sources, medicines for thousands of years [1,2]. Medicinal African population still relies upon herbal drugs plants/herbs hold a great significant value than rest of the [25,26,27]. In the compendium of Materia Medica (an plants. Medicinal plants/herbs possess phytochemical ancient encyclopedia of traditional Chinese medicine), constituents that are medically important and are used there is a description of more than 1,000 plant species for developing new drugs [3,4]. Kingdom plantae is also [28]. In China plants are being in use for maintaining entitled with “the treasure house of many important health in the form of dietary therapy for many years drugs”. The use of plants for health benefits and other [29,30]. More than half of the drugs out of 104 global purposes is a very common tradition, which has been in drugs, which are used for last 37 years, have been come practice since ancient times [5]. In the old times plants from the plant sources [31]. Traditional medicines are were the only source of most of the medicinal serving as the main healthcare system among almost preparations [6]. Medicinal products/products derived 27% of the South African population [32]. Herbal from the plants are often named as herbal drugs, medicines play a vital role in the health maintenance of botanical drugs, botanicals, phytomedicines, traditional West African population [33]. 85% Swazi and Nigerian medicines, herbal medicines, traditional Chinese population depends upon traditional herbal drugs medicines (TCMs), traditional herbal medicinal [34,35]. Herbal medicines are used in almost each and products, natural health products, or plant food every corner of the world. One such valuable medicinal supplements. These herbal drugs have several plant is Myristica fragnans Houtt (figure1). It is a well- advantages over the synthetic drugs such as their easy known spice in the world, which is commonly called as availability, safety, low cost, efficiency, negligible side Jaiphal and Javitri in India. It belongs to the effects [7,8,9]. Most of the modern drugs in the present family. This medicinal plant produces two times have derived from plant sources. As per the data spices named as mace and nutmeg respectively. The seed resources, in industrialized countries tropical plants are kernel inside the fruit is termed as nutmeg whereas the 213 This work is under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

International Journal for Research in ISSN: 2349-8889 Applied Sciences and Biotechnology Volume-8, Issue-2 (March 2021) www.ijrasb.com https://doi.org/10.31033/ijrasb.8.2.27 red lacy covering (aril) present on the kernel is called as Table 1: Vernacular Names of Myristica fragrans [51] mace. Dried kernel is the most important part of Myristica fragnans in terms of pharmacological activity English Nutmeg [36,37]. The name nutmeg has come forma Latin word Sanskrit Jati-phalam, malathi-phalam nux muscatus, which means “musky nut”. It is believed Hindi Jaiphal, malti phal that Portuguese discovered nutmeg in 1512. Arabs introduced nutmeg to Europe in the middle ages through Assamese Jayphal, kanivish, jaiphal the Venetians. It was used as a remedy to plague by Bengali Jayphala, jaepatri, jaepatri Italians whereas Indians and Egyptians used it to treat problems related to intestine and embalming. In 19th Burma Zadi-phu century, its effect on Central Nervous System was Kannada Jadikai, jaykar, jajakai observed for the very first time. Nutmeg was in the list of the expensive spices of the world in the earlier times. Kashmiri Jafal, zafal It was known as the hot-food [38].It is commonly used Malayalam Jatika, bush. as spice, which is found in almost every kitchen to add Marathi Jaiphal flavor in many dishes especially in North India where it is used as an ingredient of garam masala. Its oil is used Oriya Jaipholo in jam, chutney and juices, soft drinks, tea and also Punjabi Jaiphal mixed with milk and alcohol [39,40,41]. It is used in Sathkhai, jathikkai, jadikkay, bakery and confectionary products, pudding, meats, Tamil sausages, sauces [42]. In traditional systems of medicine jadhikai, jadhikkai, jatikkai such as Ayurveda and folk system this plant is used in Telugu Jajikaya treating variety of human ailments due to the presence of Gujarati Jaiphala, javantri different kind of phytochemical constituents in it such as alkyl benzene derivatives (myristicin, elemicin, safrole Urdu Jauzbuwa, jaiphal etc.), terpenes, alpha-pinene, beta-pinene, myristic acid Jowz buwwa, jouza atteeb, josat Arabic and triacylglycerols like trimyristin, phenolic attib compounds, flavonoids, tocopherol, ascorbic acid, Sindhi Jafar, jadika essential oils and many more [43,44]. The seeds as well as fruits both of these plant parts are used in traditional Chinese Dauh kau syuh, yuhk dauh kau practices for the treating conditions like dysentery, Dutch Nootmuskaat, muskaatnoot sexual disorders, weakness, and darkness of complexion [45]. Its essential oil is useful against sprains, muscle French Muscadier, musque pulls etc. [46]. The most common uses of Myristica Germen Achter muscatnussbaum fragnans is used as a carminative, anti-inflammatory, Hebrew Egos muskat, egoz musqat analgesic, diuretic, anti-pyretic, hypolipidemic, aphrodisiac, antiulcerogenic, anti-oxidant, hypnotic, Russian Орех muskatnyj orekh. hallucinogenic, antispasmodic, and as a stimulant agent. Meshgengouz, Mshkenkoyz, Armenian It enhances the digestion. It is used as remedy for Mekenkouz nausea, stomachache, headache, vomiting, diarrhoea associated with cholera. It is helpful in treating the Greek Moschokarido problems related to spleen, liver, and eyes. It Indonesian Pala significantly enhances the blood circulation, boosts up Italian Noce moscata the brain functioning [47,48,49,50]. Vernacular names and of M. fragrans is given in table 1&2. Portuguese Nozmoscada Romanian Nucșoară Turkish Hindistancevizi Uzbek Musqat Persian Djus hendi, jouz hendi, jozbaweh Unani Fuqlaj, moschokarido Germen Achter muscatnussbaum French Muscadier, musque Indonesian Pala

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Table 2: Taxonomy of Myristica fragrans III. GEOGRAPHICAL DISTRIBUTION

Taxonomic Rank Taxon OF MYRISTICA FRAGRANS

Kingdom Plantae Myristica fragrans is a native medicinal herb of Subkingdom Viridiplantae Moluccas and Banda Islands in the South Pacific. It is Infrakingdom Streptophyta grown in tropical areas, mainly in , in Division Tracheophyta the West Indies and Sri Lanka. In India it is found primarily in South India particularly in certain pockets of Subdivision Spermatophytina Kerala, Tamil Nadu and . Indonesia and Class Magnoliopsida Granada are the major producers of Myristica Superorder Magnolianae fragrans with the production rate 75% and 20% Order respectively. In Indonesia nutmeg primarily comes from North Sulawesi [53,54,55]. Family Myristicaceae

Genus Myristica IV. PHYTOCHEMICAL Species fragrans CONSTITUENTS OF MYRISTICA Common name Nutmeg FRAGRANS

II. MORPHOLOGY OF MYRISTICA Myristica fragrans is known for presence of FRAGRANS different phytochemical constituents in it such as fixed oils, volatile oils, starch, cellulose, pentosans, resin, and Myristica fragrans is a unisexual, aromatic, mineral elements and many more [56,57,58]. evergreen plant, which reaches up to the height of 5– Fixed oils 13m and sometimes may reach up to 20 m. Bark is Lipids are the main fixed oils, which are present greyish to black in color. A sticky pink or red sap in Myristica fragrans for eg. myristic, petroselinic, and exudes out when bark get injured. Slender twigs are palmitic acids. Myristic acid constituent 74.9% of the present towards the upper side of diameter 1-2mm. total lipid content of nutmeg. Trimyristin is the major Simple alternate leaves are present which are fixed oil of this plant. Nutmeg butter chartaceous in nature. 1cm long is present. (expressed/extracted fixed oil) is composed of saturated Elliptical to lanceolate blade is present with acute base fats (90%) with 10% unsaturated fats. Other compound and margins are present all over the surface. Upper of fixed oils are Monoterpene hydrocarbons, oxygenated surface of the leaf is shiny which is of dark green in monoterpenes, sesquiterpenes, alkenes, aromatic ethers, color whereas the lower surface of leaf is pale green in aromatic monoterpenes, organic acids [59,60,61,62,63]. color. Axillary inflorescences are present in, in Essential oils umbellate cymes. There is presence of 1-10 flowers in As per the reports of experimental study male cymes whereas in female cymes 1-3 flowers are conducted by Kapoor et al., by using clevenger and present. Flowers are usually pale yellow in color having soxhlet apparatus, it was revealed that there is vast fragrance in them and sparse glabrescent is present with variety of essential oils present in this medicinal plant minute tomentum and there is presence of 3- lobed such as α-Thujene, α-Pinene, camphene, sabinene, β- perianth. On a slender pedicel of thickness less than 1 Pinene, myrcene, α-Phellandrene, 3-Carene, α- mm, 5-7 mm long male flowers are present which have Terpinene, p-Cymene, limonene, β-Phellandrene, γ- 8-12 . Whereas female flowers are slightly Terpinene, cis-Sabinene hydrate, terpinolene, trans- longer than the male flowers. There is presence of 1- Sabinene hydrate, cis-p-Menth-2-en-1-ol, trans-p-Menth- celled ovary in the female flowers, which is superior and 2-en-1-ol, Terpinen-4-ol, p-Cymen-8-ol, α-Terpineol, sessile having single basal ovule in it. 5-8 cm long cis-Piperitol, trans-Piperitol, citronellol, bornylacetate, subglobose yellowish fleshy fruit is present with a long safrole, α-Cubebene, terpenyl acetate, citronellyl acetate, medial groove which is usually berry or drupe-like in α-Copaene, geranyl acetate, methyl eugenol, β- shape. Fruit splits out into two halves on ripening with Caryophyllene, trans-α-Bergamotene, α-Humulene, the presence of one seed. The seeds of M. fragrans are myristicin, elemicin, docosane [64]. Marzuki et al., 2–3 cm long with broad ovoid structure. A laciniate red extracted myristicin, elemicin, safrole, (Iso) eugenol by aril is present around the shiny dark brown seed. Seeds using hydro-distillation method [65]. Sabinene, are usually hard and stony which are wrinkled in a myristicin, elemicin, α-pinene, β-pinene, limonene, longitudinal direction. On getting dried aril starts terpinen-4-ol and myristic acid were reported by Morsy becoming horny and brittle and turns into yellowish- et al., by using 1:4 of material and absolute ethanol ratio brown colour. There is a presence of small embryo and at room temperature [66]. Myristicin, elemicin, safrole, ruminate endosperm in the kernel where essential oils eugenol and eugenol derivatives are categorized under are stored [52]. phenylpropanoids.

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Ligans fragrans. Other sterols which are present in this The presence of ligans like 8-O-4′ neolignans, medicinal plant are campesterol, desmosterol, and for example, ′ erythroΔ8 -4,7-dihydroxy-3,3′,5′- lanosterol [69,70]. trimethoxy-8-O-4′neolignan and Δ8′-4-hydroxy-3,3′,5′- Others trimethoxy-8-O-4′-neolignan, have been reported It contains minerals like potassium, phosphorus, [67,68]. and magnesium, calcium, iron. M. fragrans contains fair Sterols amount of vitamins like riboflavin, thiamine, niacin. It As per the report of study conducted by Khatib also contains fibers, carbohydrates and starch, flavonoid et al., sitosterol is the predominant sterol found in M. like epicatechin, phenyl propanoid ethers [71, 72].

Figure 2: Chemical Structures of some of Phytochemical Constituent of Myristica fragrans

V. TRADITIONAL AND MODERN Properties and uses of Myristica fragrans [79,80] VIEW OF MYRISTICA FRAGRANS Sansthanik karm-wahaya: Its topical applications include its use an anti-inflammatory and analgesic agent. a. Ayurvedic View It is beneficial for skin disorders, acts as an air freshener. Myristica fragrans Houtt is commonly known It is used in treating cold and headache. It is used against as “Jatiphala” in Ayurveda. It is a valuable medicinal join inflammation in lepa form. It is useful in removing plant. It is used in many Ayurvedic practices for the the foul smell of wound. treatment of numerous diseases. It significantly works on Abhyantar- nadi sansthan: It is an analgesic and vitiated vatta (air and space components of the body) and antiepileptic agent. It is used in treating insomnia, kapha (earth and water components of the body) [73]. epilepsy and pain. Myristica fragrans Houtt is a single herbal remedy Paachan sansthan: It is used as an appetizer and anti- which is used to treat “Vyanga” (melasma). Its use helminthic agent. It enhances digestion and increases the against vyanga has also been considered by Acharya liver metabolism. It is used in the treatment of diarrhoea, Bhavamishra [74]. In Ayurveda it is used a stomachic, dysentery, irritable bowel syndrome, constipation, lose astringent, heart tonic, carminative, stimulant, motion, cholera. It reduces thirst. aphrodisiac, appetizer, blood purifier, anti-thirst, Rakatwah sansthan: It is helpful in treating cardiac intestinal trouble [75,76]. Rasapanchak of M. fragrans is problems. shown in table 3. Swasan sansthan: It is used as an anti-mucolytic agent. It is helpful against cold, cough, asthma nd hickups. Table 3: Rasapanchak of Myristica fragrans as per Prajannan sansthan: It is an aphrodisiac. It is helpful in Ayurveda [77,78] inducing menstruation and ovulation. It is used in Sanskrit/English Sanskrit/English treating erectile dysfunctioning, amenorrhea, Veerya/Potency Ushna/Hot dysmenorrhea. Vipak/Metabolic Kattu/Pungent Twacha: It is useful against various skin related property disorders. Guna/Physical Laghu/Light , Taapkram: It is used as an anti-pyretic. Property Teekshan/Sharp Satmikaran: It is used in treating malnutrition caused by Rasa/Taste Tikat/Bitter ,Kattu/Pungent diarrhoea and lose motion. 216 This work is under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Formulations: Due to its extra-ordinary therapeutic [101]. In Chanpur and Andabaaz villages in Bagerhat properties M. fragrans is used in many herbal district, Bangladesh, kavirajes use seed and fruit of M. formulations [81]. fragrans against paralysis, malaria, rheumatoid arthritis, Jatiphaladi churna: It is the most commonly used leprosy and colic. They are also used as aphrodisiac Ayurvedic polyherbal formulation in which M. agents [102]. Nigerian people use seed powder or fragrans is one of the main ingredients. It is used in decoction of the seeds against diarrhea, rheumatism and treatment of diarrhoea, dysmenorrhea and cough, also use it as carminative, rubefacient. The seed powder anorexia, nasal congestion, dyspnea, rhinitis. The is used in cooking to enhance the flavor and odor of the description of Jatiphaladi choorna lepa is mentioned in food [103]. In India it is used a sedative to treat various Bhavapraksha [82,83]. disorders related to nervous system [104]. In district Dashamularishta: It is a polyherbal formulation which Coimbatore, Tamil Nadu people use fruits of M. is used by females after the childbirth to normalize fragrans to heal mouth wounds and stomach wounds thephysiological processes. It is also helpful to get relief [105]. The tribal people of Kurumba, Tamil Nadu, use from fatigue and helpful in removing the dead cells from fruits in pickle form to cure problems related to digestion the body and stimulates the regeneration of cells. It is while the seeds are used along with the breast milk to used as a sedative and tonic. M. frgrans is used in provide immunity to the infants [106]. Traditional general class of herbs in this herbal fomulation [84]. healers of Karimnagar district, Telangana, use M. b. Folk View fragrans leaves and fruits to treat nervous disorders Myristica fragrans is an important and most [107]. In Deogarh district, Odisha, people use M. commonly used medicinal plant around the world. It is fragransfruits in many home remedies [108]. The used in many folk cultures for its numerous therapeutic decoction of fruit is administered orally against properties and food enhancing properties. It is used as a dysentery in Chikmagalur district of Karnataka [109]. medicinal drug as well as cooking spice in many cuisines People use boiled seeds of M. fragrans along with with around the world. For instance, in Maluku Province of P. nigrum, P. longum and O. tenuiflorum to treat malaria Indonesia and Central and East Java M. fragrans is used in Karnataka [110]. In Paliyan tribes of Sirumalai Hills for the treatment of diarrhea, mouth sores, and insomnia of Southern India, people use seeds along with milk to [85]. Maluku people use M. fragrans oil to keep their enhance their digestion [111]. In Rangamanti district, body temperature warm [86].The fruits of M. this medicinal plant is used against fever [112]. Some fragrans are used as anti-parasitic in Enugu State of tribes of Gujrat use M. fragrans fruit against hemorrhoid Nigeria [87]. In Kaduna State, Nigeria, this medicinal [113]. In Rjasthan, the fruit of this plant is used in plant is used as a spice [88]. In South Aceh, Indonesia cooking as a spice and to enhance the flavor [114]. The M. fragrans fruit is used in cooking as a spice. [89] In Gaddi tribes of Kangra district of use China, people use nutmeg as a spice in hotpots [90]. jaiphal along with ajwain seeds and choti elaichi to treat Chinese people use seed powder in the treatment of diarrhoea among infants [115]. In , Jaiphal is used dysentery [91]. In Tanane Province of Southwest in treating dysmenorrhea [116]. Jaiphal is a very Morocco, people use seed powder in the treatment of common home remedy for cough and cold [117]. problems related to respiratory system, digestive system, c. Modern View: skeleton, genital [92]. People in Republic of the Union In the modern times the herbal drugs are of Myanmar, use seeds of M. fragrans for treating piles preferred more due to their several advantages over and leucorrhea [93]. In Bhutan the seeds are used as modern synthetic drugs made up of inorganic sources. anticephalagic and adaptogen. They are used to treat Herbal drugs have negligible adverse impacts on the vertigo, dysphoria, insomnia, giddiness, headache and living systems also these are less expensive than heart related problems [94]. In Aceh, people use this synthetic drugs. But due to increasing market demand of plant as a remedy for headache [95]. Batak people of these herbal drugs their quality is getting degraded due North Sumatra, Indonesia use the fruits of M. to factors like adulteration and contamination fragrans plant as steam-bathing material. They also use [118,119,120]. Unintentional adulteration of herbal this plant in the treatment of rheumatism, syphilis and drugs is induced by misidentification of species or tooth ache [96]. Fruits and seeds of M. fragrans are used sometimes by misidentification of plant parts. It is most in the preparation of oke sou which is an herbal drink probably happened due to the conflict in similarities of used in Lako Akediri Village of North Moluccas vernacular names as well as scientific names of various Indonesia [97]. The Karonese people from North medicinal plants. And this practice is directly or Sumatra, Indonesia use M. fragrans seeds against indirectly associated with the degradation of herbal cancer, virility, child immunity [98]. Seeds are used for drugs [121]. For instance, M. malabrica (false nutmeg)is the treatment of neurological disorders in the Region of a most common adulterant which is used in true mace Middle Oum Rbia (Morocco) [99]. In Brazil, people use herbal drugs [122]. Intentional adulteration is the seeds in tea for soothing effect [100]. People in primary reason behind degradation of herbal drugs Bangladesh, use fruit powder of M. fragrans as a remedy which is induced derive maximum profit. It is done by for burning, general weakness, headache and insomnia using either orthodox drugs or by the substitution of 217 This work is under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

International Journal for Research in ISSN: 2349-8889 Applied Sciences and Biotechnology Volume-8, Issue-2 (March 2021) www.ijrasb.com https://doi.org/10.31033/ijrasb.8.2.27 inferior products or by adding foreign particles which Antithrombotic are most commonly called as contaminants such as sand, As per the data report of an in-vitro study metals, soil etc. [123,124,125]. Mercury, arsenic, and carried out by Janssens et al., it was revealed that lead, cadmium, copper and thallium, pesticides, eugenol and iso-eugenol were associated with inhibition microbes and mycotoxins are the most commonly used of platelet aggregation, this attributes to its contaminants in the herbal drugs antithrombotic activity [142]. [126,127,128,129,130,131,132]. Powders, capsules, Hepatoprotective extracts are the commonly available forms of herbal Zhao et al., conducted an experimental study to drugs in the market. Usually adulterants are added in the check the effects of AEN (alcohol extract of nutmeg, the herbal drugs either before the processing phase or during seed of Myristica fragrans on obesity and inflammation the processing phase. Proper quality analysis and which are associated with Nonalcoholic fatty liver standardization protocols are need to be applied during disease (NAFLD). They use mice models for the study. these phases so that the health risk can be avoided Models were fed with high-fat-diet. It was revealed from [133,134,135].Standardization ensures the quantity and quality of the herbal drugs [136]. The most preferred the study, alcohol extract of nutmeg significantly technique in today’s time is standard DNA barcode reduced the body weight and levels of inflammation, which significantly works on identification of species cholesterol and lipid accumulation, blood glucose which [137]. supports its use as an hepatoprotective agent [143]. Dkhil et al., also studied hepatoprotective activity of VI. THERAPEUTIC USES OF Myristica fragrans. The study was carried out on rat models. Models were administered with paracetamol MYRISTICA FRAGRANS (acetaminophen; N-acetyl-p-amino-phenol (APAP) for the artificial induction of hepatotoxicity. Myristica Myristica fragrans Houtt. (nutmeg) is fragrans Kernel extract showed some significant effect associated with wide range of biological properties against APAP induced toxication [144]. which are useful in treating several diseases. Someof its Anti-cancer therapeutic properties are discussed below. Prakash et al, studied the anti-cancerous Aphrodisiac behavior of Myristica fragrans in an in-vitro study on Ahmed et al., conducted a study on male rat human cell lines Colon cell (Colon502713,Colo205), models to evaluate the activity of Myristica Liver (Hep-2), Lung (A-549), Ovary OVCAR-5 and fragrans Houtt. (nutmeg) on sexual behavior. It was Prostrate (PC-5) and central nervous system. Ethanolic observed that 50% ethanolic extract of the plant extract of seed of Myristica fragrans (Houtt) was found exhibited aphrodisiac activity [138]. to be effective against these cell lines. Ethanolic extract Effect on memory exhibited highest anti-cancerous activity against Parle et al., conducted a study on mouse models OVCAR-5. The results of this study demonstrated that for evaluating the effect of Myristica fragrans seeds on Myristica fragrans is a potent anti-cancer agent [145]. the learning capacity and memory of the models used. Anti-oxidant The memory impairment was induced by scopolamine Dorman et al., conducted an in-vitro study to and diazepam. It was found that n-hexane extract check the anti-oxidant potential of many medicinal herbs significantly worked on learning capacity and memory against synthetic anti-oxidants like BHA (butylated [139]. hydroxyanisole), BHT (butylated hydroxytoluene), alpha Anti-stress tocopherol and pyrogellol. It was found from the study Anti-stress activity was examined by Dhingra et that essential oil extracted from nutmeg is an effective al., on mice models. Stress was induced in the models by anti-oxidant agent [146]. using two methods that are the forced swim test (FST) Anti-microbial and the tail suspension test (TST) method. It was Orabi et al., conducted an experimental study in observed that M. fragrans extract significantly reduced 1991 to check the anti-microbial potential of mace of M. the immobility periods of mice in both the FST and the fragrans against Staphylococcus aureus and Candida TST methods [140]. albicans. It was revealed that resorcinols malabaricon B Anti-diarrhoeal [1] and malabaricon C [2] both showed significant anti- A study was conducted by Gupta et al., on ileal loops of rabbit and guinea pig. E. coli heat labile (LT) microbial potential against Staphylococcus aureus and and heat stable (ST) enterotoxins were used in this Candida albicans [147]. As per the results of study experimental study. The result revealed that hexane- conducted by Hattori et al., dehydro-di-isoeugenol and soluble fraction was associated with inhibition of 5-methoxydehydrodiisogenol were found to be effective secretory responses which were induced by E. coli heat against Streptococcus mutans. They significantly helped labile (LT) and heat stable (ST) enterotoxins [141]. in the inhibition of Streptococcus mutans growth [148]. 218 This work is under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Hypolipidemic effect Anti-diabetic In-vivo study conducted on rabbit models by As per the study report of Han et al.,macelignan Ram et al., suggested that the oral administration extracted from M. fragrans is associated with anti- of ethanolic extract of nutmeg at the dosage of 500 diabetic potential. It activates the peroxisome mg/kg at the regular interval of 60 days in artificially proliferator receptor (PPAR, á/ã) which helps in induced hypolipidemic rabbits significantly lowered the improving the insulin sensitivity and lipid metabolic lipoprotein lipids levels which supports its use as an disorders [151]. hypolipidemic agent [149]. Sharma et al., carried out an Anti-convulsant in-vivo study on hypercholestrolemic rabbit models Wahab et al., studied anti-convulsant potential which revealed that administration of seed extract of M. of M. fragran in well-established animal seizure models. fragrans exhibited properties like reduction in serum It was observed that nutmeg oil exhibits anti-convulsant cholesterol and LDL cholesterol by 69.1 and 76.3%. It properties. During the study nutmeg oil showed anti- also lowered down the ratio of cholesterol/phospholipid convulsant activity against tonic seizures induced by by 31.2% and it significantly elevated the ratio of pentylenetetrazole which supports its use as an decreased HDL [150]. anticonvulsant agent [152].

Table 4: Reported therapeutic uses of Myristica Fragrans

Sr. Extract Method Property References No. 1. Ethanolic extract In-vivo study on rat models Aphrodisiac 138 2. n-hexane extract In-vivo study on mice models Effect on memory 139 3. Hexane soluble fraction In-vitro study Anti-diarrhoeal 141 4. eugenol and iso-eugenol In-vitro study Antithrombotic 142 5. Alcoholic extract In-vivo study on mice models Hepatoprotective 143 6. Ethanolic extract In-vitro study Anti-cancer 145 7. Essential oil In-vitro study Anti-oxidant 146 a. Malabaricon B [1] and a. In-vitro study malabaricon C [2] 8. b. Dehydro-di-isoeugenol Anti-microbial 147,148 and 5- b. In-vitro study methoxydehydrodiisogenol 9. Ethanolic extract In-vivo study on mice models Hypolipidemic effect 149 10. Macelignan Clinical study Anti-diabetic 151 11. Nutmeg oil In-vivo study Anti-convulsant 152

Toxicity study anti-stress, anti-diabetic etc. Apart from its therapeutic A case study on the toxicity of M. fragrans uses, it is well known spice used in almost all type of reported by Green et al., revealed that myristicin cooking. In Ayurveda it is used to treat insomnia, pain, extracted from the volatile oil of plant has toxicity epilepsy, vomiting, stress, IBS, cardiac disorders, associated with it. It was observed that nutmeg at higher erectile dysfunctioning etc. This medicinal plant with dose i.e. above 4 gm exhibits depressive actions on multiple therapeutic uses can be a promising and reliable Central Nervous System [153]. source of new drugs in future.

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