Fermented Mentha arvensis administration provides neuroprotection against transient global cerebral ischemia in gerbils and SH-SY5Y cells via downregulation of the MAPK signaling pathway

Abstract

Background Globally, ischemic stroke is a major health threat to humans that causes lifelong disability and death. Mentha arvensis (MA) has been used in traditional medicine to alleviate oxidative stress and inflammation-related disorders. In the present study, the neuroprotective properties of fermented MA (FMA) extract were investigated in the gerbil and SH-SY5Y cells. model of transient global cerebral ischemia. Methods Bilateral common carotid artery occlusion-induced transient global cerebral ischemia in gerbil and hydrogen peroxide (H2O2)-mediated neurotoxic effects in human neuroblastoma cells (SH-SY5Y) were investigated. FMA (400 mg/kg) was orally administered for 7 days before induction of ischemic stroke. To evaluate the neuroprotective activity of FMA, we implemented various assays such as cell viability assay (MTT), lactate dehydrogenase (LDH) assay, histopathology, immunohistochemistry (IHC), histofluorescence, and western blot. Results FMA pretreatment effectively decreased transient ischemia (TI) induced neuronal cell death as well as activation of microglia and astrocytes in the hippocampal region. The protective effects of FMA extract against H2O2-induced cytotoxicity of SH-SY5Y cells were observed by MTT and LDH assay. However, FMA pretreatment significantly increased the expression of the antioxidant marker proteins such as superoxide dismutase-1 (SOD-1) and superoxide dismutase-2 (SOD-2) in the hippocampus and SH-SY5Y cells. Furthermore, the activation of mitogen-activated protein kinase (MAPK) further activated a cascade of outcomes such as neuroinflammation and apoptosis. FMA pretreatment notably decreased TI and H2O2 induced activation of MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), and p38) proteins in hippocampus and SH-SY5Y cells respectively. Besides, pretreatment with FMA markedly reduced H2O2 mediated Bax/Bcl2 expression in SH-SY5Y cells. Conclusion Thus, these results demonstrated that neuroprotective activities of FMA might contribute to regulating the MAPK signaling pathway.

Role of Phenolic Acid Metabolism in Enhancing Bioactivity of Mentha Extract Fermented with Plant-Derived Lactobacillus plantarum SN13T

“…acidophilus showed an increase in the concentration of rosmarinic acid that could suppress MDA, NO, and corticosterone; improve body weight; decrease daily food intake and duodenum histology; and increase serotonin and β-endorphin levels in immobilization-induced stressed rats [ 12 ]. In another study, such fermented M. arvensis extract administration also provided neuroprotection against transient global cerebral ischemia in gerbils and SH-SH5Y cells by downregulating MAPK signaling [ 13 ]. In addition, M. piperita fermented with Bacillus subtilis suppressed PMA-induced ROS, ERK, and MUC5AC mRNA protein expression in lung epithelial cells [ 14 ].…”

Role of Phenolic Acid Metabolism in Enhancing Bioactivity of Mentha Extract Fermented with Plant- Derived Lactobacillus plantarum SN13T

“…Such fermented extracts could suppress MDA, NO, and corticosterone; improve body weight; decrease daily food intake and duodenum histology; and increase serotonin and βendorphin levels in immobilization-induced stressed rats [24]. In another study, such fermented M. arvensis extract administration also provided neuroprotection against transient global cerebral ischemia in gerbils and SH-SH5Y cells by downregulating MAPK signaling [25]. In addition, M. piperita fermented with Bacillus subtilis suppressed PMA-induced ROS, ERK, and MUC5AC mRNA protein expression in lung epithelial cells [26].…”

Olanzapine Ameliorates Ischemic Stroke-like Pathology in Gerbils and H2O2-Induced Neurotoxicity in SH-SY5Y Cells via Inhibiting the MAPK Signaling Pathway

“…Transient cerebral ischemia in gerbils is brought on by blocking both common carotid arteries for 5 min [ 46 , 47 , 48 ]. In our previous study, severe neuronal cell damage was identified 5 days after induction of ischemic insult [ 36 , 49 ]. We also found neuronal cell death and activation of microglial cells and astrocytes in the most vulnerable part of the brain (hippocampus) after 5 days of TI.…”

“…We implemented a technique to induce TI in gerbils that was described previously [ 35 , 36 ]. In brief, inhalation anesthesia was implemented with a combination of nitrous oxide, oxygen, and isoflurane (68%, 32%, and 2.5%, respectively).…”