Computational Evaluation of Pharmacokinetics, Potential Bioactive Compounds Targets of Glutathione S-transferases against Deleterious Effects of MSG: The Health Benefits of Turmeric (Curcuma longa L.)

This study sought to investigate the health benefits and bioactive compounds profile of Turmeric and its modulatory activity against the deleterious effects of Monosodium Glutamate (MSG) on Glutathione S-transferases (GSTs). MSG is a widely used flavor enhancer that contributes an umami taste to food. While MSG naturally occurs in some foods, its synthetic version has raised concerns due to potential toxic effects when consumed in excess. Chronic exposure may lead to tissue inflammation and cellular damage. In contrast, GSTs are essential detoxification enzymes that conjugate glutathione to various electrophilic compounds, mitigating cellular damage from both endogenous and exogenous toxicants. Amid rising concerns over synthetic additives, natural alternatives like spices have attracted attention for their therapeutic benefits. Turmeric (Curcuma longa L.) is a culinary spice that has been used for thousands of decades for the prevention, management and treatment of various diseases. The proximate analysis, mineral compositions, and the phytochemical constituents of Turmeric were investigated using standard analytical methods. The identification and quantification of the embedded bioactive compounds were carried out using HPLC-UV spectroscopy. Computational studies including molecular docking, induced-fit docking, MM/GBSA calculations, and ADMET profiling, were employed to evaluate the interaction between Turmeric bioactive compounds and GSTs. The results of the proximate and mineral analyses showed macromolecules such as carbohydrate, protein, crude fat, and Mg, Ca, Fe, P, K, Na, amongst others. However, the predominant identified compounds include, hydroxybezoic acid (31.10 mg/100g); protocatechuic acid (5.56 mg/100g); gallic acid (8.96 mg/100g); caffeic acid (8.92 mg/100g), ferulic acid (5.29 mg/100g), quercetin (155.16 mg/100 g), kaempferol (61.56 mg/100 g), zingerone (21.83 mg/100g), turmerone (12.45 mg/100 g), coumaric acid (11.23 mg/100 g), stigmasterol (10.61mg/100 g), beta-sitosterol (6.83 mg/100), luteolin (4.761 mg/100 g), beta-caryophyllene (8.56 mg/100g), beta-phyllandrene (2.917 mg/100g), 3-carene (4.64 mg/100 g), sabinene (4.631 mg/100 g) and vanillin (5.81 mg/100 g). Nevertheless, the bioactive compounds of Turmeric which displayed higher binding energies include, curcumin (7.58 Kcal/mol.), quercetin (-7.14 Kcal/mol), kaempferol (-7.02 Kcal/mol), rhamnetin (-7.02 Kcal/mol) and luteolin (-5.96 Kcal/mol). The results of induced fit docking core isolated compounds against human GSTs revealed luteolin (-472.23 Kcal/mol), rhamnetin (-469.47 Kcal/mol), curcumin (-469.34), quercetin (-468.34 Kcal/mol) and kaempferol (-466, 39 Kcal/mol). The ΔG free binding values for isolated compounds gave (-64.02 Kcal/mol, -48.56 Kcal/mol, -47.74 Kcal/mol, -44.85 Kcal/mol, and -43.64 Kcal/mol) for curcumin, rhamnetin, quercetin, kaempferol and luteolin respectively. The findings suggest that Turmeric is embedded with a lot of macromolecules, minerals, phytochemicals, flavonoid, polyphenol amongst many others. These natural compounds might modulate GST activity, offering potential protective effects and could significantly impact human health.