Inflammopharmacology最新文献

Among the chronic and progressive autoimmune disorders that primarily affect joints in the hands, wrists, and knees, rheumatoid arthritis (RA) is a highly prevalent one. A significant number of patients develop severe adverse events, display weak responses, or cannot afford long-term use of the current RA medications, requiring more efficient and safer curative alternatives. increasing evidence recommends the application of mesenchymal stem cells (MSCs)-based therapy for mitigating chronic inflammation and boosting tissue renewal in intractable disorders. Moreover, sodium hydrosulphide (NaHS) has recently been found to have anti-inflammatory effects. Therefore, this study compared the therapeutic outcomes of four approaches; bone marrow-derived mesenchymal stem cells (BM-MSCs), their conditioned media (CM), BM-MSCs pre-conditioned with NaHS, and their conditioned media in a rat model of adjuvant-induced polyarthritis. The process involved the isolation of MSCs from rat bone marrow, propagation, and characterization of the isolated cells. polyarthritis was induced in male Wistar rats via intradermal injection of type II collagen on day 0 and day 21. Affected rats were treated with naproxen, BM-MSCs, BM-MSCs-CM, NaHS, BM-MSCs preconditioned with NaHS, or BM-MSCs preconditioned with NaHS-CM. The results indicated that the administered cells homed to the bone marrow and bone trabeculae of the knee joint tissue of the afflicted rats. The proposed treatments brought about significant down-regulation of peptidyl arginine deiminase 2 (PAD2) and chemokine ligand 13 (CXCL13) genes as well as angiopoietin-1 (Ang-1) protein expression, along with substantial upregulation of the galectin-1 (GAL-1) gene and osteoprotegerin (OPG) protein expression. Compared with BM-MSCs therapy, the treatment with BM-MSCs preconditioned with NaHS and their CM exhibited superior effect, with values close to those of the controls. In addition, treatment with the CM of BM-MSCs offered a lesser effect compared to BM-MSCs therapy alone. In conclusion, NaHS has the potential to improve the therapeutic capability of BM-MSCs for RA in rats by enhancing their anti-inflammatory, immunomodulatory, and regenerative capacity.

Background: Oxidative stress, neuroinflammation, and cellular senescence interact to drive Alzheimer's disease (AD) progression. SRS11-92 is a redox-active small molecule with reported cytoprotective effects. This study sought to determine whether SRS11-92 mitigates Aβ-evoked oxidative stress and cellular senescence, and to delineate the underlying mechanism.

Methods: SH-SY5Y cells were challenged with Aβ_25-35 and pretreated with SRS11-92. Oxidative stress (ROS, MDA, SOD activity, and GSH), inflammatory mediators (TNF-α, IL-1β, and IL-6), senescence markers (SA-β-gal, p53, p16, and p21), and Nrf2/HO-1/NF-κB proteins were quantified. Pathway dependence was assessed using the selective Nrf2 inhibitor ML385. 3xTg-AD mice received SRS11-92 for 6 weeks; cognitive function was assessed by novel object recognition, cortical neuronal integrity was assessed by Nissl staining, and cellular senescence in the hippocampus was evaluated by SA-β-gal.

Results: SRS11-92 attenuated Aβ_25-35-induced cytotoxicity in a dose-dependent manner in SH-SY5Y cells, reduced ROS and MDA, and restored SOD activity and GSH. It suppressed TNF-α, IL-1β, and IL-6, decreased the percentage of SA-β-gal-positive cells, and downregulated p53, p16, and p21. Mechanistically, SRS11-92 increased total and nuclear Nrf2 and upregulated HO-1, while restricting NF-κB p65 nuclear translocation. ML385 abrogated these molecular and phenotypic benefits, confirming that SRS11-92 acts via the Nrf2 pathway in vitro. In 3xTg-AD mice, SRS11-92 improved cognitive function, partially rescued cortical Nissl-positive neurons, and reduced the hippocampal SA-β-gal-positive burden.

Conclusions: SRS11-92 exerts significant neuroprotective effects, attributable to reducing stress-induced senescence via activating Nrf2/HO-1 and constraining NF-κB signalling.

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disorder with complex pathophysiology. Disease cycle involves immune/inflammatory cells (macrophages, CD4 + , T, and B-cells) that directly/indirectly augment NF- κB mediated inflammation/oxidative stress and vice-versa creating a vicious loop that worsens disease. Inhibition of NF-κB signalling has emerged as a target for RA alleviation thus, this study evaluates the capability of Cassia fistula leaf extracts in supressing NF-κB signalling and contribution of sennoside B in extract efficacy.

Methods: Extracts were prepared and its anti-inflammatory (IL-1β, TNF-α, IL-6, IL-17a), anti-oxidant (NO, MDA, catalase, reduced glutathione), NF-κB inhibition potential, and its effect on joint microstructure was evaluated on collagen-induced arthritis. Extracts were characterized using LC-MS and effect of sennoside B (anthraquinone glycoside detected in extracts) on NF-κB signalling was evaluated on LPS stimulated peritoneal macrophages.

Results: Ethanolic extract of C. fistula leaf significantly inhibited NF-κB signalling (transcriptional/translational level), which led to significant reduction of inflammatory mediators (IL-1β, TNF-α, IL-6, IL-17a), and restored redox imbalance (NO, MDA, catalase, and reduced glutathione). Reduced NF-κB activity supressed tissue remodelling and osteoclastogenesis markers (MMP-2, MMP-9, MMP-13, and RANKL) which resulted in joint microstructure safe-guarding, also reflected as reduced paw swelling, paw volume and disease score significantly. Sennoside B showed strong anti-inflammatory and NF-κB inhibition against LPS-stimulated peritoneal macrophages.

Conclusion: Ethanolic extract of C. fistula leaves alleviate RA by modulating NF-κB mediated inflammation and oxidative stress and disrupts the disease worsening feedback cycle. Sennoside B's capability to suppress NF-κB production/activation also plays an important role in increasing extract efficacy.

Several disrupted metabolic pathways contributed to the development of Parkinson's disease (PD). Progressive death of dopamine (DA) neurons in the substantia nigra pars compacta, abnormal aggregation of α-synuclein fibrils, and inflammation of the neural system are the hallmarks of PD. The kynurenine pathway (KP) becomes disrupted, and excitotoxic branches are activated by elevated levels of central inflammatory regulators in PD. This leads to a significant reduction in the neural protective metabolite, kynurenic acid (KYNA), and an increase in the neurotoxic metabolite, quinolinic acid (QUIN), which together promote overstimulation and heightened immune responses, both closely related to the progression and onset of PD. KP enzyme modulators, precursor-based therapies, and KYNA analogs may provide a novel way to treat PD. KP components may also serve as new prognostic indicators and therapeutic targets for PD. Finding precise biomarkers for early screening, involving preclinical and prodromal stages, is essential for improving therapeutic intervention and care at the onset of PD. The current review provides an updated analysis of KP study results related to PD. Additionally, the review highlights the need for expanded biomarker research, which could help establish new therapeutic approaches for PD.

Background: During acute ischemic stroke, a cascade of pathophysiological reactions leads to brain cell injury, primarily via disruptions in energy metabolism and increased oxidative stress. In this study, we scrutinized the neuroprotective effects of bryodulcosigenin (BRY) against acute cerebral ischemia/reperfusion (CIR) injury in rats.

Material and methods: To induce middle cerebral artery occlusion (MCAO) in rats, a nylon monofilament suture with a silicon-coated tip was inserted into the internal carotid artery. The cerebral infarct volume, brain water content, neurological deficits, brain edema, Evan Blue extravasation and blood brain barrier (BBB) leakage were estimated. The antioxidant, cytokines, inflammatory and matrix metalloproteinases (MMP) parameters were evaluated. mRNA expression and histopathological study were performed.

Results: Bryodulcosigenin significantly suppressed the neurological deficits, cerebral infarct volume, brain edema, brain water content, BBB leakage and Evan Blue extravasation. It also suppressed brain injury markers like K⁺-Cl^- cotransporter 1 (KCC1), S100 calcium-binding protein B (S-100β), neuron specific enolase (NSE), occludin and clusterin. Moreover, bryodulcosigenin altered antioxidant levels via enhancing the level of glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), while reducing malonaldehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OhdG). It altered the pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-1β, IL-4, IL-6, IL-10, as well as inflammatory mediators such as inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), vascular endothelium growth factor (VEGF), prostaglandin (PGE₂), nuclear factor kappa B (NF-κB) and MMP (MMP-2, MMP-3 and MMP-9) level in the serum and brain tissue. Additionally, bryodulcosigenin modulated the mRNA expression of Toll-Like Receptor 4 (TLR4), syndecan-1, cerebrospinal fluid (CSF), aquaporin-1 (AQP1), organic cation transporter 3 (OCT3), reduced expression 1 (REX1) and improved the histopathological condition.

Conclusion: Bryodulcosigenin exerted anti-inflammatory and neuroprotective effects against CIR injury via alteration of TLR4/NF-κB signaling pathways.

Epilepsy is a neurological disease that significantly reduces the quality of life in diagnosed individuals. Given the imbalanced release of synaptic energy in the brain, seizures are the main hallmarks of epilepsy disorder. Conventional treatments often fall short in managing symptoms and preventing seizure recurrence. Curcumin has shown potential in seizure management due to its anti-inflammatory, antioxidant, anti-apoptosis, and neuroprotective properties. To gather latest evidence on effects of curcumin in treatment and prevention of seizures, focusing on its mechanisms of action and therapeutic potentials. Clinical, in vivo, and in vitro original studies have been gathered up to August 2024 from valid motor engines including PubMed, Google Scholar, Cochrane Library, and ScienceDirect. Curcumin significantly decreases pro-inflammatory cytokines (IL-6, IL-1β, MCP, TNF-α), while simultaneously increasing anti-inflammatory cytokines (IL-10). It suppresses expression of inflammatory genes and signaling pathways such as COX-2 and NLRP3. Its antioxidant effects are evidenced by the elevation of SOD, CAT, GPx, and GSH, along with reduction of oxidative stress markers (NO, MDA, iNOS, MLK, RIP-1, GFAP). Diminished caspase-3 levels and increased CA1 neuron survival ensure its anti-apoptotic properties. Additionally, curcumin regulates pivotal pathophysiological pathways including AP-1, JNK, c-fos, and c-jun. These actions collectively lead to a reduction in seizure severity, duration, and frequency, with increased seizure latency. Curcumin demonstrated significant therapeutic properties in the management of seizures through its anti-inflammatory, antioxidant, and anti-apoptotic effects. However, its clinical application is limited by bioavailability issues, necessitating further research to optimize delivery methods and confirm efficacy and safety through extensive clinical trials.

Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by macrophage activation and pro-inflammatory signaling, particularly via TNF-α and NF-κB pathways. Current therapies, including methotrexate and biologic agents, provide clinical benefits but are limited by systemic toxicity, high costs, and treatment resistance. Here, we report the development of sodium alginate (SA)-encapsulated nanoparticles incorporating Colchicum micranthum (CM) and Colchicum chalcedonicum (CC) extracts as a novel therapeutic approach for RA. Phytochemical profiling revealed distinct polyphenolic signatures in CM and CC, with CC exhibiting superior flavonoid content and antioxidant activity. Nanoparticles fabricated via ultrasonic homogenization displayed uniform nanoscale morphology (55-130 nm), enhanced thermal stability, and strong polymer-phenolic interactions, as confirmed by FTIR, DSC, TGA, and FEGSEM analyses. In THP-1 macrophages, free extracts exhibited dose- and time-dependent cytotoxicity, whereas encapsulated forms (SA/CM, SA/CC) improved cell viability and minimized toxicity. Upon LPS stimulation, SA/CC significantly suppressed TNF-α and NF-κB expression while restoring metabolic activity, outperforming both free extracts and SA/CM. These findings demonstrate that alginate encapsulation not only enhances the safety and bioactivity of Colchicum-derived compounds but also enables targeted modulation of inflammatory pathways central to RA pathogenesis. By combining the anti-inflammatory properties of plant-derived bioactives with the precision of nanodelivery, SA/CC nanoparticles represent a promising, cost-effective alternative to conventional DMARDs and biologics, warranting further preclinical and clinical evaluation.