Myristica fragrans seed extract reverses scopolamine-induced cortical injury via stimulation of HO-1 expression in male rats.

Myristica fragrans, commonly known as nutmeg, belongs to the Myristicaceae family and is used as a spice and for its medicinal properties. The purpose of this study was to assess the neuroprotective effect of M. fragrans seed methanolic extract (MFE) on scopolamine-induced oxidative damage, inflammation, and apoptosis in male rat cortical tissue. MFE or N-acetylcysteine (NAC), a standard antioxidant drug, was administered 7 days before treatment with scopolamine resulted in high levels of malondialdehyde and nitric oxide (oxidative stress biomarkers), tumor necrosis factor-alpha and interleukin-1 beta (inflammatory mediators), and Bax and caspase-3 pro-apoptotic proteins. Additionally, scopolamine significantly depleted levels of glutathione (an antioxidant marker), Bcl-2 and c-FLIP (anti-apoptotic proteins), and antioxidant enzymes activity in cortical tissue. Scopolamine also enhanced acetylcholinesterase activity. MFE treatment protected the cortex of rats from the effects of scopolamine by reversing the effects on these toxicity markers. Interestingly, the neuroprotective effect of MFE was comparable to that exerted by the reference antioxidant NAC. Thus, our findings show that MFE has antioxidant, anti-inflammatory, and anti-apoptotic effects. The beneficial effects of MFE on scopolamine were partially mediated by promoting heme oxygenase 1 (Hmox1) expression and preserving cortical tissue structure.

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2⁻related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.