Objective: Neuroinflammation is a key contributor to many neurodegenerative diseases. Cuprizone, a copper-chelating agent, is widely used in research to induce neurotoxicity and demyelination, mimicking the pathology of multiple sclerosis. This study investigates the protective and therapeutic effects of curcumin and piperine nanoformulations prepared in Zanthoxylum rhetsa seed oil against cuprizone-induced neurotoxicity in mice.Methods: Seventy-five Swiss albino mice were divided into five groups: control, cuprizone-treated, blank formulation-treated, curcumin-treated, and curcumin with piperine-treated groups. Behavioral assessments, along with biochemical and histological analyses of the hippocampus, were conducted to evaluate learning and memory, antioxidant enzyme activity, neuroinflammatory markers, and cellular integrity.Results: Cuprizone exposure significantly impaired cognitive function and induced oxidative stress, as evidenced by decreased levels of key antioxidant enzymes like catalase, superoxide dismutase, glutathione and glutathione peroxidases. Additionally, increased levels of neuroinflammatory markers such as GFAP, MCP-1, MIP-1, and CCL-5 were observed. Treatment with curcumin and piperine nanoformulations mitigated these effects by restoring antioxidant defenses and modulating inflammatory responses. The curcumin-piperine combination exhibited superior neuroprotection compared to curcumin alone, enhancing memory performance and reducing neuroinflammation more effectively. The results highlight the potential of curcumin and piperine nanoformulations in alleviating neurotoxicity and cognitive impairments associated with neurodegenerative disorders.Conclusion: These findings suggest that curcumin-based nanoformulations could serve as promising therapeutic agents for treating neuroinflammatory diseases, warranting further studies to explore their precise mechanisms and optimize their clinical applications.

Ibudilast (IBD) is a new drug that has been released as treatment for multiple sclerosis (MS). Retinoic acid (RA), a metabolite of vitamin A, is known for its pro-regenerative and anti-inflammatory properties, therefore, it has been suggested as a supplementary treatment for MS. The objective of this study is to investigate the therapeutic effects of RA and IBD against cuprizone (CPZ) induced mouse models. Seventy-two Swiss Albino male Mice (SWR/J) were divided into two main groups control (n = 18); normal chow and CPZ (n = 54); 0.25% of CPZ mixed into chow at demyelination stage (first 5 weeks). The following 4 weeks included two stages of remyelination: early remyelination (2 weeks after CPZ discontinuation) and late remyelination (week 9). In the early stage of remyelination, the CPZ group was divided into four subgroups beside daily treatment intraperitoneal injections CPZ (+ve control- no treatment), RA (20 mg/kg), IBD (10 mg/kg), and RA + IBD, with (n = 12/group), while the control group had 12 mice. At the end of each stage 6 mice/ group were sacrificed. Mice response to different treatments was assessed using several locomotor and cognitive behavior tests including open field test, rotarod test, grip strength test, novel object recognition test (NORT) and Y-maze test. The expression levels of several genes MS associated genes Tumer Necrosis Factor- Alpha (TNF- α), Cyclooxygenase-2 (COX-2), Nerve Growth Factor (NGF), Signal transducer and activator of transcription 3 (STAT-3) and Nuclear factor kappa-light-chain-enhancer of activated b-cell (NFKB-P105) in the brain of mice were measured using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. The results demonstrated that RA supplementation helped in alleviating the symptoms of MS induced mice with or without using IBD treatment. This was indicated as an improvement in locomotor activity, motor coordination and muscular strength as well as improving the cognition and memory functions. The mRNA expression pattern of various MS associated genes indicated that the treatments effectively mitigated the detrimental effects of CPZ in mouse brain. The findings of this study indicate that RA supplements could be effectively unitized as adjuvant therapy alongside with IBD for MS treatment.

Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits and cognitive decline. Cuprizone (CPZ)-induced demyelination is a well-established model for studying multiple sclerosis-like neurotoxicity. This study investigated the neuroprotective and immunomodulatory effects of self-nanoemulsifying drug delivery systems (SNEDDSs) incorporating curcumin, piperine, and Zanthoxylum rhetsa seed oil. Methods: Male mice were divided into five groups: control, CPZ-only, and CPZ co-treated with three nanoformulations BFZ (blank SNEDDS), CFZ (curcumin-SNEDDS), and PFZ (curcumin–piperine SNEDDS). CPZ was administered for 5 weeks, followed by a 2-week recovery or treatment phase. Key neuroinflammatory markers like CD4, CD8, cholinergic (acetylcholinesterase, AChE), myelin integrity (MBP), BDNF, CREB, TNFα, Il-1β were assessed at weeks 5 and 7 using ELISA. Alterations in antioxidant enzymes, brain histology, and behavioral outcomes were also investigated. Results: At week 5, CPZ significantly increased CD4 and CD8 expression and reduced AChE and MBP levels, indicating neuroinflammation, cholinergic impairment, and demyelination. Nanoformulation treatments (both prophylactic and therapeutic) markedly reduced CD4 and CD8 levels, with PFZ showing the most pronounced effect. AChE activity was significantly restored in all treatment groups, with PFZ and CFZ exceeding baseline levels, suggesting enhanced cholinergic function. MBP levels were highest in PFZ-treated mice, surpassing control values and indicating strong remyelination potential. These improvements persisted and further advanced at week 7, especially in PFZ and CFZ groups. Conclusions: Curcumin-based SNEDDS, particularly PFZ, significantly mitigated CPZ-induced neuroinflammation, promoted remyelination, and restored cholinergic activity in the frontal cortex. These findings highlight the therapeutic potential of bioenhanced curcumin nanoformulations for treating demyelinating and neuroinflammatory disorders.

Background/Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal loss. Despite available therapies, there is currently no effective cure for MS. Ibudilast (IBD), a phosphodiesterase inhibitor, and 6-shogaol (SH), a bioactive compound from ginger, have independently shown therapeutic potential in MS models. This study aimed to evaluate the therapeutic efficacy of combining SH and IBD in modulating neuroinflammation and improving functional recovery in a cuprizone (CPZ) mouse model of MS. Methods: Male SWR/J mice were exposed to 0.3% CPZ for 5 weeks to induce demyelination, followed by 4 weeks of spontaneous remyelination after CPZ withdrawal. During remyelination, the CPZ group was subdivided into four groups: no therapy, SH (25 mg/kg), IBD (10 mg/kg), and SH + IBD. Behavioral tests were used to assess locomotion, muscle strength, coordination, and memory. Gene expression of proinflammatory and anti-inflammatory cytokines was analyzed in brain tissue. Results: The combined treatment significantly improved locomotor activity, muscle strength, and memory during remyelination phases while suppressing proinflammatory gene expression and enhancing anti-inflammatory pathways in the brain. Conclusions: SH and IBD combination therapy provides enhanced anti-inflammatory and functional benefits compared with monotherapies, supporting its potential as a promising multi-target therapeutic strategy for improving functional recovery and modulating neuroinflammation during the spontaneous remyelination phase following CPZ withdrawal.

This study aimed to compare total polyphenol content and antioxidant activity of different forms of Al-Kbous black tea: teabag (TB), loose tea (LT), and opened teabag (OTB). Total polyphenol content was assessed by the Folin–Ciocalteu method, and DPPH and FRAP assays were used to determine antioxidant activity. The results revealed that TB and OTB have significantly more polyphenol than LT at the 5- and 15-minute brewing times. In addition, the data indicated that TB and OTB exhibit signif