Inflammopharmacology最新文献

Inflammation and oxidative stress are involved in the physiological changes associated with many chronic diseases, which has led to sustained interest in small molecules with pleiotropic properties. As part of this effort, this study reports the synthesis and evaluation of six chalcones. These six synthesized derivatives were produced using acetophenone and benzaldehyde, and structures were characterised through nuclear magnetic resonance (NMR) spectral analysis and Fourier transform infrared (FTIR) spectroscopy. The compounds were tested for their in-vitro antioxidant properties using the DPPH free radical scavenging assay and anti-inflammatory and analgesic properties using an in-vivo model in rats and carrageenan-induced paw edema, heat-induced hyperalgesia, and mechanical allodynia.Computational finding by using AutoDockVina protocol against target enzyme (COX-II) (PDB: 3LN1), where the compounds 3B, 2B, and 1A exhibited strong binding affinities of - 9.8 kcal/mol, - 9.2 kcal/mol, and - 9.2 kcal/mol, respectively.Among these compounds, compound 3B exhibited the highest antioxidant activity, demonstrating an efficacy percentage of 78.34% and an IC₅₀ value of 7.86μg/ml. The chalcone derivatives were also assessed for their effectiveness in carrageenan-induced hyperalgesia, a model used to study pain response. Compound 1A significantly increased latency periods at 30, 60, 90, and 120 min compared to compounds 2B and 3B, suggesting its potential analgesic properties. Furthermore, compound 3B significantly reduced allodynia response at 120 min, indicating its potential to alleviate mechanical sensitivity.These findings suggest that chalcone derivatives, particularly 2B and 3B, hold strong potential as lead compounds for developing novel COX-2-targeted anti-inflammatory and antioxidant therapeutics. This study offers a comprehensive preclinical framework for chalcone-based drug discovery targeting inflammation and oxidative stress. This study emphasizes structure-dependent variations in chalcones, which present potential leads and are worthy of further exploration.

The review has comprehensively examined the therapeutic potential of phytoconstituents in the treatment of arthritis with specific emphasis being given to diosgenin as a promising natural molecule. Arthritis is a significant health concern in the world, with its two most common types; Osteoarthritis and rheumatoid arthritis, becoming the causes of disability, and expensive to manage in the long run. Even though disease-modifying anti-rheumatic drugs and biologics have helped to better the patient outcomes, their side effects, high treatment cost, and inaccessibility demonstrate the necessity of safer and cheaper alternatives. The pharmacological significance of the root steroidal sapogenin, diosgenin, as a derivative of the species Dioscorea, that exhibits strong anti-inflammatory effects with clearly defined, molecular-based, mechanisms, is highlighted in this manuscript. Diosgenin suppresses cartilage destruction because of matrix metalloproteinases, the NF-kB signaling pathway as well as the major pro-inflammatory cytokines, TNF-a, IL-1b, and IL-6. It also has chondroprotective action to maintain the integrity of the extracellular matrix, increase levels of type II collagen and aggrecan, and decrease the expression of MMP-3 and MMP-13 by about 65-85% in the presence of inflammation. The challenges to clinical translation associated with formulation which are discussed in the review include the very low aqueous solubility of diosgenin (0.95 ug/mL) and oral bioavailability (< 7%). It addresses the use of the advanced delivery systems, including lipid nanoparticles, vesicular carriers and amorphous solid dispersions, which have demonstrated a 2.55-fold increase in bioavailability and also have the potential to improve therapeutic efficacy. Crucially, this review uniquely integrates these bioavailability enhancement strategies with diosgenin's underlying molecular mechanisms, illustrating how optimised delivery systems are essential to fully unlock its therapeutic potential. Despite robust preclinical evidence supporting its anti-arthritic and chondroprotective actions, clinical investigations remain scarce, with only a few small studies and none directly evaluating diosgenin for arthritis outcomes. Overall, this review emphasises the need for well-designed clinical trials to validate the therapeutic promise of diosgenin and related phytoconstituents, paving the way for safer, accessible, and multi-targeted natural interventions for arthritis management.

Helicteres isora L. is widely used in traditional medicine for the treatment of gastrointestinal disorders, diabetes, and inflammatory conditions, yet its anti-arthritic potential has not been systematically explored. Given the limitations of conventional rheumatoid arthritis (RA) therapies, evaluation of this plant may provide scientific validation for its ethnomedicinal use against inflammatory diseases. The present study aimed to investigate the anti-arthritic efficacy and underlying mechanisms of ethanolic extract of Helicteres isora L. (EEHI) in a Complete Freund Adjuvant (CFA) induced arthritis model in rats and to relate these findings to its traditional application in inflammation management. EEHI was prepared and phytochemically profiled using GCMS. Anti-arthritic activity was assessed through in vitro protein denaturation assay and in vivo in CFA induced arthritic rats administered EEHI at 100, 200, and 400 mg/kg for 28 days. Clinical parameters (paw diameter, arthritic score, body weight, and organ weights), hematological and biochemical markers (RF, CRP), oxidative stress indices (SOD, CAT, GSH, MDA), pro-inflammatory gene expression (NF-κB, TNF-α, IL-6, COX-2), and histopathological changes were evaluated. Diclofenac sodium served as the standard drug. EEHI treatment resulted in significant, dose dependent improvements across all evaluated parameters. The 400 mg/kg dose markedly reduced paw swelling and arthritic scores, improved hematological indices, and restored antioxidant enzyme levels. Serum CRP and RF were significantly decreased. Gene expression analysis confirmed downregulation of NF-κB, TNF-α, IL-6, and COX-2, while histopathology showed substantial protection of joint architecture. GCMS identified several bioactive compounds, including dodecanoic acid, 11-octadecenoic acid, and 8, 11-octadecadienoic acid, which may contribute to the observed pharmacological effects. The findings provide scientific evidence supporting the ethnomedicinal use of Helicteres isora L. in inflammatory conditions. EEHI demonstrated potent anti-arthritic, antioxidant, and anti-inflammatory activities through modulation of cytokines and oxidative stress. This work validates traditional knowledge and highlights Helicteres isora L. as a promising natural therapeutic candidate for rheumatoid arthritis, warranting further pharmacological and clinical studies.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that primarily effect synovial joints, leading to primarily cartilage and bone damage. The present study aimed to develop Escin loaded biodegradable nanoparticles (ESNPs) through the ionic gelation method using chitosan as biodegradable polymer, followed by comprehensive characterization of the nanoparticles. Additionally, the in-vivo anti-arthritic efficacy of the nanoparticles was assessed by Complete Freund's Adjuvant (CFA). ESNPs has 213 nm size, + 0.4 mV charge, and a polydispersity index of 0.42 with loading capacity of 81%, and entrapment efficiency of 87%. XRD revealed a semi-crystalline structure of ESNPs, whereas scanning electron microscopy suggested a spherical, uneven shape. For anti-arthritic potential, 0.15 ml CFA was injected in left hind paw in all rats aside from normal rats at day 1. From the eighth to twenty-eighth day, ESNPs (2.5, 5, and 10 mg/kg) and Escin (ES 10) were given orally, whereas blank nanoparticles were given to normal and disease controls. The standard reference medication utilized was methotrexate (1 mg/kg). In treated rats, paw edema was notably reduced and body weight was restored by ESNPs at 10 mg/kg. At all dosage levels, ESNPs demonstrated strong analgesic effects in arthritic rats. When compared to ES 10 and disease control, ESNPs significantly adjusted the impaired blood parameters, oxidative stress markers, and neurotransmitters levels as evident from the histological analysis of the treated rats' ankle joint. Treatment with ESNPs at 10 mg/kg, significantly altered the expression of IL-4, IL-6, cyclooxygenase-2, nuclear factor kappa-β and TNF-α. The results indicated that, in comparison to ES 10 and methotrexate, ESNPs, primarily at 10 mg/kg, demonstrated strong anti-arthritic activity.

Background: Psoriasis is a chronic, immune-mediated disease with an overabundance of cytokines and aberrant keratinocyte proliferation.

Objective: To assess the therapeutic activity of topical application of 10% sulfasalazine in an imiquimod-induced murine model and to compare its therapeutic activity with that of clobetasol.

Methodology: Thirty-two male mice were randomly assigned into four groups, with each group consisting of eight individuals: normal control group, IMQ + vehicle group, IMQ + clobetasol group, and IMQ + 10% sulfasalazine group. IMQ was administered for 7 days, and then daily topical application was conducted for 14 days. Lesion severity was determined by PASI scores, and histological scores and concentrations of TNF-α and IL-6.

Results: Both sulfasalazine and clobetasol led to significant reduction in PASI scores, compared to IMQ + vehicle (p < 0.05). The regimen of sulfasalazine improved epidermal structure, acanthosis, and inflammation, as well as.

Conclusion: Topical sulfasalazine was found to possess significant anti-inflammatory activity, both clinical and histological, against IMQ-induced inflammation resembling psoriasis.

PKC-NF-κB-NLRP3 inflammasome axis and its non-coding RNA (ncRNA) regulatory network triggers robust innate immune activation and neuroinflammation, culminating in neuronal apoptosis and death during Global cerebral ischemia (GCI). The present mechanistic overview illustrates how condensed and hydrolysable tannins, along with related polyphenols, modulate such regulatory network to confer neuroprotection. Ischemia-associated danger signals activate Toll-like receptor-2 (TLR2) through di/tri-acylated lipopolysaccharides, engaging MyD88 and TRAF6 to stimulate protein kinase C (PKC). PKC activation promotes nuclear factor-κB (NF-κB) signaling, leading to interleukin-1β (IL-1β) production and priming of the NLRP3 inflammasome. Subsequent caspase-1 activation drives neuroinflammation and neuronal apoptosis, ultimately resulting in neuronal death. Compounds such as tannic acid, punicalagin, corilagin, pedunculagin, chebulagic acid, chebulinic acid, castalagin, and epigallocatechin gallate (EGCG) suppress NF-κB/IL-1β signaling, while tellimagrandin II, procyanidin C1/B2, paeoniflorin gallate, rosmarinic acid, and savinin directly inhibit NLRP3 activation. Additional phytochemicals, including baicalin and carnosic acid, attenuate upstream PKC signaling. Crucially, these effects are fine-tuned by ncRNAs: miR-146a and miR-155/lncRNA TUG1 regulate NF-κB activity, miR-124 and miR-223 constrain PKC and NLRP3 signaling, and lncRNA NEAT1 modulates caspase-1 activation. Collectively, the integrated suppression of PKC/NF-κB/NLRP3-ncRNA neuroinflammatory signaling by tannins limits inflammasome activation, reduces neuronal apoptosis, and mitigates ischemia-induced neuronal loss. This framework underscores tannins as promising multi-target neuroprotective agents for GCI.

Long COVID is defined by the World Health Organisation (WHO) as a condition arising within 3 months of an acute COVID infection with symptoms lasting for a minimum of 2 weeks. However, this syndrome is poorly understood and has been recorded to include many systemic manifestations, including neurological, respiratory, cardiovascular, gastrointestinal, dermatological, psychosocial, and metabolic systems. Constitutional symptoms also include fatigue, insomnia, body weight changes, poor attention span, hair loss, sexual dysfunction, myalgia, and joint pain, with fatigue being the most common. Given the various proposed mechanisms published in the literature, the postulated mechanisms and pathways are discussed in this paper to contribute to the understanding of defining this syndrome. In this review article, the authors first explored how endothelial damage from COVID infection can lead to a hypercoagulable state. In addition, the effects of an insufficient initial immune response can lead to viral persistence alongside a potentially prolonged hyperactive immune response that includes a cytokine storm and mast cell activation syndrome. Furthermore, the viral persistence can be exacerbated by antibody-dependent enhancement or complicated by molecular mimicry. Current pharmacological therapies are explored and evaluated to investigate their efficacy in addressing this complex and chronic presentation. This review article has been written after an extensive literature review to increase the understanding and awareness regarding Long COVID, as a sincere effort to direct further research for an effective diagnosis and management.

Sepsis is a heterogeneous clinical syndrome characterized by dysregulated host response to infection. The pathophysiology of sepsis is very complex and it is now considered that sepsis has a variety of subtypes. During sepsis, apart from immune dysfunction, simultaneous activation of the complement and coagulation systems occur. These alterations damage the endothelium, cause microcirculatory dysfunction and decreased perfusion to tissues resulting in hypoxic damage causing vicious cycle in sepsis.Sodium-glucose cotransporter inhibitors (SGLTi) are a class of medications initially developed as glucose-lowering agents that have since been proven to have profound effects for kidney and heart protection in broad populations with or without diabetes. Especially SGLT2i, but also the combination of SGLT1/2i, have cardiovascular and renal benefits, independent of their glucose lowering effects. Interestingly, recent experimental studies have shown that SGLT2i have favorable effects during sepsis by modulation of immune system, improving tissue perfusion and hemodynamics. Clinical studies have shown that SGLT2i decreased sepsis severity and hospitalizations during sepsis. Apart from above mentioned effects, SGLT2i potentially modify gut microbiota, energetics and mitochondrial function which are involved in the pathogenesis of sepsis. In this review, we have summarized the experimental and clinical studies regarding the use of SGLT2i in sepsis and described potential mechanisms underlying these beneficial effects.