Therapeutic, and pharmacological prospects of nutmeg seed: A comprehensive review for novel drug potential insights

Abstract

Background and objectives: For centuries, plant seed extracts have been widely used and valued for their benefits. They have been used in food, perfumes, aromatherapy, and traditional medicine. These natural products are renowned for their therapeutic properties and are commonly used in medicinal treatments. Their significant pharmacological profiles provide an excellent hallmark for the prevention or treatment of various diseases. In this study, we comprehensively evaluated the biological and pharmacological properties of nutmeg seeds and explored their efficacy in treating various illnesses.

Method: Published articles in databases including Google Scholar, PubMed, Elsevier, Scopus, ScienceDirect, and Wiley, were analyzed using keywords related to nutmeg seed. The searched keywords were chemical compounds, antioxidants, anti-inflammatory, antibacterial, antifungal, antiviral, antidiabetic, anticancer properties, and their protective mechanisms in cardiovascular and Alzheimer's diseases.

Results & discussion: Nutmeg seeds have been reported to have potent antimicrobial properties against a wide range of various bacteria and fungi, thus showing potential for combating microbial infections and promoting overall health. Furthermore, nutmeg extract effectively reduces oxidative stress and inflammation by improving the body's natural antioxidant defense mechanism. Nutmeg affected lipid peroxidation, reduced lipid oxidation, reduced low-density lipoprotein (LDL), and increased phospholipid and cholesterol excretion. In addition, nutmeg extract improves the modulation of cardiac metabolism, accelerates cardiac conductivity and ventricular contractility, and prevents cell apoptosis. This study elucidated the psychotropic, narcotic, antidepressant, and anxiogenic effects of nutmeg seeds and their potential as a pharmaceutical medicine. Notably, despite its sedative and toxic properties, nutmeg ingestion alone did not cause death or life-threatening effects within the dosage range of 20-80 g powder. However, chemical analysis of nutmeg extracts identified over 50 compounds, including flavonoids, alkaloids, and polyphenolic compounds, which exhibit antioxidant properties and can be used as phytomedicines. Moreover, the exceptional pharmacokinetics and bioavailability of nutmeg have been found different for different administration routes, yet, more clinical trials are still needed.

Conclusion: Understanding the chemical composition and pharmacological properties of nutmeg holds promise for novel drug discovery and therapeutic advancements. Nutmeg seed offers therapeutic and novel drug prospects that can revolutionize medicine. By delving into their pharmacological properties, we can uncover the vast potential possibilities of this natural wonder.

Keywords: Anti-inflammatory; Anticancer; Antidiabetics; Antimicrobial; Antioxidant; Bioactive compounds; Nutmeg; Oxidative stress; Psychotropics.

Unlocking the Potential: Exploring Therapeutic and Pharmacological Benefits of Nutmeg Seed

Fig. 1

Nutmeg (Myristica fragrans) tree from Balik Pulau, Pinang. (Author Source).

Fig. 2

Right image; shows a close up to a nut of Myristica fragrans fruit. Left image shows the nutmeg seed, and mace (author Source).

Fig. 3

The molecular structures of some of the main active compounds of nutmeg extract adopted from the NIST library.

Fig. 4

Anti-inflammatory mechanism of action of nutmeg. Nutmeg inhibited chemokines, nitic oxide, cytokines, and growth factors through the calcium pathway in double-stranded RNA-stimulated macrophages. It improved the joint swelling, nerve pain, and sensitivity by inhibiting COX-2 expression. Nutmeg inhibited the production of TNF-α, IL-6 and IL-1β, and NO via inhibition of inducible NO synthase (iNOS) mRNA expression. Nutmeg also inhibited some enzyme cox phospholipase A2 (PLA2), lipoxygenase (LOX), and nitric oxide synthase (NOS), which led to reduce the major mediators of inflammation such as metabolizing arachidonic acid (AA), prostaglandins (PG), leukotrienes (LT). COX-2: cyclooxygenase-2, TNF-α: Tumor Necrosis Factor Alpha, IL-1β: Interleukin-1 Beta, and IL-6: Interleukin-6, NO: nitric oxide, iNOS: inducible NO synthase, PLA2: phospholipase A2, LOX: lipoxygenase, AA: arachidonic acid, PG: prostaglandins, LT: leukotrienes.

Fig. 5

Anti-Diabetic Efficacy of nutmeg seed. Nutmeg stimulate insulin signaling and glucose reuptake by body cells, reduce blood sugar, ameliorate hyperglycemia and abnormal lipid metabolism. In addition, activated AMP- protein kinase (AMPK) enzyme in differentiated skeletal muscle cells C2C12, inhibited α-amylase and decreased serum insulin levels.

Fig. 6

Anticancer Mechanism of nutmeg seed through Apoptotic Pathways. Nutmeg inhibited melanoma cells B16-F10, oral cavity KB cell lines, and lung cancer NCI-H187 cell lines, and apoptosis via caspase-3. Induced apoptosis in Jurkat cell proliferation significantly and human leukemia cell line through Sirtuin-1 (SIRTI) mRNA downregulation pathway. Nutmeg inhibited breast cancer MCF7 cell lines and human colorectal cancer cells HCT 116 through angiogenesis pathway. Nutmeg inhibited leukemia K562 through DNA damage response pathways and the mitochondrial pathway. It also induced hepato-protectivity, through inhibiting Tumor necrosis factor-alpha (TNF- α) which is released from macrophages that lead to the suppression of apoptosis. Nutmeg induced cytotoxicity against human neuroblastoma cells SK-N-SH by apoptotic mechanism.

Fig. 7

Psychotropic mechanisms of action and narcotic effects of nutmeg seed. Nutmeg stimulates the release of serotonin that creates a feeling of relaxation or sedation. This mechanism is triggered by the nutmeg interaction with the endocannabinoid system in the brain. Nutmeg extract inhibited the and monoacylglycerol lipase (MAGL) and the endocannabinoid catabolizing enzymes fatty acid amide hydrolase, The inhibition of MAGL stimulates the anti-nociceptive, anxiolytic, and anti-emetic responses, elevate brain levels precursor of inflammatory mediators, resulting in the reduction of neuroinflammation.