Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Possible Prophylactic Effects of Sulforaphane on LPS-Induced Recognition Memory Impairment Mediated by Regulating Oxidative Stress and Neuroinflammatory Proteins in the Prefrontal Cortex Region of the Brain.

BACKGROUND: Alzheimer's disease (AD) presents a significant global health concern, characterized by neurodegeneration and cognitive decline. Neuroinflammation is a crucial factor in AD development and progression, yet effective pharmacotherapy remains elusive. Sulforaphane (SFN), derived from cruciferous vegetables and mainly from broccoli, has shown a promising effect via in vitro and in vivo studies as a potential treatment for AD. This study aims to investigate the possible prophylactic mechanisms of SFN against prefrontal cortex (PFC)-related recognition memory impairment induced by lipopolysaccharide (LPS) administration. METHODOLOGY: Thirty-six Swiss (SWR/J) mice weighing 18-25 g were divided into three groups (n = 12 per group): a control group (vehicle), an LPS group (0.75 mg/kg of LPS), and an LPS + SFN group (25 mg/kg of SFN). The total duration of the study was 3 weeks, during which mice underwent treatments for the initial 2 weeks, with daily monitoring of body weight and temperature. Behavioral assessments via novel object recognition (NOR) and temporal order recognition (TOR) tasks were conducted in the final week of the study. Inflammatory markers (IL-6 and TNF), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant (MDA) level, in addition to acetylcholine esterase (AChE) activity and active (caspase-3) and phosphorylated (AMPK) levels, were evaluated. Further, PFC neuronal degeneration, Aß content, and microglial activation were also examined using H&E, Congo red staining, and Iba1 immunohistochemistry, respectively. RESULTS: SFN pretreatment significantly improved recognition memory performance during the NOR and TOR tests. Moreover, SFN was protected from neuroinflammation and oxidative stress as well as neurodegeneration, Aß accumulation, and microglial hyperactivity. CONCLUSION: The obtained results suggested that SFN has a potential protective property to mitigate the behavioral and biochemical impairments induced by chronic LPS administration and suggested to be via an AMPK/caspase-3-dependent manner.

Investigation of the optimal dose for experimental lipopolysaccharide-induced recognition memory impairment: behavioral and histological studies.

BACKGROUND: Lipopolysaccharide (LPS) administration is one of the most commonly used methods for inducing inflammation in animal models. Several animal studies have investigated the effects of acute and chronic peripheral administration of LPS on cognitive impairment. However, no previous study has compared the effects of different doses of chronically administered LPS on recognition memory performance. AIM: Here, we aimed to investigate the optimal dose of chronically administered LPS for the induction of recognition memory impairment in mice. MATERIALS AND METHODS: LPS at different doses (0.25, 0.50 and 0.75 mg/kg) was administered to SWR/J mice daily for 7 days. On day 9, the open field, novel object recognition and novel arm discrimination behavioral tests were performed. Additionally, prefrontal cortical histological examination was conducted. RESULTS: Compared with the control group, mice injected with 0.75 mg/kg LPS notably showed no object preference (familiar vs. novel), a reduction in the discrimination index, and spatial recognition impairment. Administration of the 0.25 and 0.50 mg/kg doses of LPS showed a preference for the novel object compared with the familiar object, had no significant impact on the discrimination index, and caused spatial recognition impairment. These behavioral results are in line with the histological examination of the prefrontal cortex, which revealed that the 0.75 mg/kg dose produced the most histological damage. CONCLUSIONS: Our findings suggest that for chronic peripheral administration of LPS, 0.75 mg/kg is the optimal dose for inducing neuroinflammation-associated recognition memory deficits.

Biochanin A Improves Memory Decline and Brain Pathology in Cuprizone-Induced Mouse Model of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by the demyelination of nerves, neural degeneration, and axonal loss. Cognitive impairment, including memory decline, is a significant feature in MS affecting up to 70% of patients. Thereby, it substantially impacts patients' quality of life. Biochanin A (BCA) is an o-methylated isoflavone with a wide variety of pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective activities. Thus, this study aimed to investigate the possible protective effects of BCA on memory decline in the cuprizone (CPZ) model of MS. Thirty Swiss albino male mice (SWR/J) were randomly divided into three groups (n = 10): control (normal chow + i.p. 1:9 mixture of DMSO and PBS), CPZ (0.2% w/w of CPZ mixed into chow + i.p. 1:9 mixture of DMSO and PBS), and CPZ + BCA (0.2% w/w of CPZ mixed into chow + i.p. 40 mg/kg of BCA). At the last week of the study (week 5), a series of behavioral tasks were performed. A grip strength test was performed to assess muscle weakness while Y-maze, novel object recognition task (NORT), and novel arm discrimination task (NADT) were performed to assess memory. Additionally, histological examination of the hippocampus and the prefrontal cortex (PFC) were conducted. BCA administration caused a significant increase in the grip strength compared with the CPZ group. Additionally, BCA significantly improved the mice's spatial memory in the Y-maze and recognition memory in the NORT and the NADT compared with the CPZ group. Moreover, BCA mitigated neuronal damage in the PFC and the hippocampus after five weeks of administration. In conclusion, our data demonstrates the possible protective effect of BCA against memory deterioration in mice fed with CPZ for five weeks.