The effect of nutmeg essential oil constituents on Novikoff hepatoma cell viability and communication through Cx43 gap junctions

Nutmeg (Myristica fragrans Houtt.) essential oil: A review on its composition, biological, and pharmacological activities

“…The yield of minor EO constituents of South India grown nutmeg mace are α‐phellandrene (1.9%), γ‐asarone (1.4%), p‐cymene (1.1%), α‐thujene (1.0%), methyleugenol (0.6%), caryophyllene (0.5%), α‐terpineol (0.4%), eugenol (0.4%), copaene (0.4%), β‐linalool (0.3%), germacrene‐D (0.3%), β‐terpineol (0.2%), and γ‐elemene (0.2%), while kernel oil had 3‐carene (1.8%), terpinen‐4‐ol (1.7%), copaene (1.7%), α‐thujene (1.5%), isoterpinolene (1.3%), γ–terpinene (1.2%), β‐terpineol (0.8%), γ‐asarone (0.8%), α‐phellandrene (0.8%), γ‐elemene (0.7%), myristicin (0.7%), p‐cymene (0.7%), 4‐carene (0.7%), caryophyllene (0.5%), p‐menth‐8‐en‐1‐ol (0.5%), safrole (0.5%), α‐terpinyl acetate (0.4%), β‐phellandrene (0.3%), camphene (0.3%), and α‐cubebene (0.3%) (Ashokkumar et al, 2022). Furthermore, the minor constituents of nutmeg seed essential oil are terpinen‐4‐ol (2.4%), copaene (2.4%), γ‐asarone (2.3%), β‐phellandrene (2.2%), myristicin (1.9%), α‐thujene (1.3%), 3‐carene (1.2%), β‐terpineol (1.1%), γ‐terpinene (1.0%), isoterpinolene (0.9%), p‐menth‐8‐en‐1‐ol (0.9%), γ‐elemene (0.8%), safrole (0.7%), methyleugenol (0.7%), 4‐carene (0.7%), p‐cymene (0.7%), α‐bergamotene (0.6%), α‐phellandrene (0.5%), camphene (0.4%), and α‐terpinyl acetate (0.4%) (Ashokkumar et al, 2022; Mickus et al, 2021; Waman, 2020). The variation in the minor components of MFEO might be due to the EO of four plant parts of nutmeg used.…”

“…The variation in EO depends upon the source and extraction method (Table 1). MFEO was extracted by various methods including, hydrodistillation (Ashokkumar et al, 2022;Carolina & Maman, 2016;Ibrahim et al, 2020;Mickus et al, 2021;Muchtaridi et al, 2010;Nikolic et al, 2021;Waman, 2020), steam distillation (Al-Jumaily & Al-Amiry, 2012;Carolina & Maman, 2016;Purseglove et al, 1981), microwave-assisted hydrodistillation (Sagarika et al, 2018), and CO 2 supercritical fluid extraction (Hanif et al, 2010). Ashokkumar et al (2022) found that the Western Ghats, southern India, grown nutmeg leaf EO yield (3.2%) was greater than that found in Bogor, West Java, Indonesia, grown nutmeg leaf (0.7%; Carolina & Maman, 2016).…”

“…Interestingly, the other nutmeg seed essential oil from Andaman & Nicobar Islands, India, extracted by hydrodistillation method, contained higher myristicin, sabinene, α-thujene, α-pinene, 4-terpineol, limonene, (Waman, 2020). In a recent study, the Western Ghats (South India) grown nutmeg seed (with rind/shell) oil was predominantly composed of sabinene (27.7%) (Ashokkumar et al, 2022) and it was found to have a two-fold lower concentration of sabinene (52.8%) in Grenada grown nutmeg seed EO (Mickus et al, 2021). The molecular structures of major EO constituents isolated from various parts of M. fragrans were drawn by ChemDraw software as shown in Figure 2.…”

“…β-terpineol (0.8%), γ-asarone (0.8%), α-phellandrene (0.8%), γ-elemene (0.7%), myristicin (0.7%), p-cymene (0.7%), 4-carene (0.7%), caryophyllene (0.5%), p-menth-8-en-1-ol (0.5%), safrole (0.5%), α-terpinyl acetate (0.4%), β-phellandrene (0.3%), camphene (0.3%), and α-cubebene (0.3%) (Ashokkumar et al, 2022). Furthermore, the minor constituents of nutmeg seed essential oil are terpinen-4-ol (2.4%), copaene (2.4%), γ-asarone (2.3%), β-phellandrene (2.2%), myristicin (1.9%), α-thujene (1.3%), 3-carene (1.2%), β-terpineol (1.1%), γ-terpinene (1.0%), isoterpinolene (0.9%), p-menth-8-en-1-ol (0.9%), γ-elemene (0.8%), safrole (0.7%), methyleugenol (0.7%), 4-carene (0.7%), p-cymene (0.7%), α-bergamotene (0.6%), α-phellandrene (0.5%), camphene (0.4%), and α-terpinyl acetate (0.4%) (Ashokkumar et al, 2022;Mickus et al, 2021;Waman, 2020). The variation in the minor components of MFEO might be due to the EO of four plant parts of nutmeg used.…”

Evaluation of Cx43 gap junction inhibitors using Quantitative Structure-Activity Relationship model

“…On the other hand, modulation of GJ function is onerous due to the shortage of specific and Cx type-selective GJ inhibitors. Most GJ inhibitors are non-specific compounds, such as antimalarial drugs, polyamines, glycyrrhetinic acid, volatile anaesthetics, arachidonic acid, cyclodextrins, anti-cancer drugs cisplatin and oxaliplatin, fatty acid amides, terpenes [4][5][6], and other drugs. In addition, most of these compounds have been shown to inhibit not only intercellular communication through GJs but also affect the membranous Na + , K + , and Ca 2+ channels that are crucial for the generation and spread of action potential [7][8][9].…”