This study investigates the anti-inflammatory effects and molecular targets of the chemical components in Cichorium glandulosum. Active compounds were isolated and purified from the ethyl acetate extract of Cichorium glandulosum, and their anti-inflammatory effects were evaluated using both in vitro and in vivo models. The results demonstrated that sesquiterpene lactones in Cichorium glandulosum possess significant anti-inflammatory properties. Molecular docking and biofilm interference analysis revealed that these compounds, particularly compound 4 (Lactucin) and compound 7 (Lactucopicrin), exhibit high affinity for IL-1β, interacting through hydrogen bonds and van der Waals forces, thus inhibiting inflammation. In vitro experiments showed that Lactucin and Lactucopicrin notably reduced the release of NO, IL-6, TNF-α, and IL-1β in LPS-stimulated RAW264.7 cells, highlighting their potent anti-inflammatory activity. Animal studies further confirmed the anti-inflammatory effects of these compounds in an acute inflammation model, with Lactucopicrin demonstrating superior anti-inflammatory efficacy compared to the positive control, indomethacin. Structure-activity relationship studies identified the α-methylene-γ-lactone group in sesquiterpene lactones as the key pharmacophore responsible for their anti-inflammatory activity. In conclusion, sesquiterpene lactones in Cichorium glandulosum inhibit inflammation by targeting IL-1β, demonstrating significant anti-inflammatory potential and providing new theoretical insights into the pharmacological research of active components in Cichorium glandulosum.

The prevalence of arthritis continues to increase, which has driven research on new therapeutic approaches. However, existing treatments often have limitations. Angiogenesis and pathological changes in the synovium are the key contributors to the early development of arthritis. Rebastinib, a tie-2 receptor inhibitor, blocks the activation of tie2-expressing macrophages, which are involved in angiogenesis. Although previous studies have highlighted the importance of angiogenesis in early arthritis, few have focused on targeting the tie-2 receptor to slow disease progression. In this study, we evaluated the effects of rebastinib encapsulated in pH-dependent liposomes in a rabbit model of surgically induced arthritis. Additionally, we investigated the efficacy of a pH-dependent liposomal formulation, developed using microfluidic technology for sustained drug release. The results demonstrated that rebastinib-loaded pH-dependent liposomes were stable and provided controlled release and rebastinib effectively inhibited the progression of early stage arthritis in this model. Statistical analyses were performed using SPSS software (IBM Corp., Armonk, NY, USA), and significance was assessed using one-way ANOVA. In conclusion, rebastinib encapsulated in pH-dependent liposomes holds promise as a potential therapeutic strategy for the treatment of early arthritis, offering both stability and efficacy in disease suppression.

Protein Kinase C (PKC), a zinc-dependent signaling enzyme pivotal for neuronal survival and synaptic plasticity, has emerged as a central player in the pathogenesis of Alzheimer's disease (AD). Dysregulated PKC activity contributes to amyloid-β accumulation, tau-driven neurofibrillary tangles, and chronic neuroinflammation, mediated through key molecular cascades such as NF-κB, GSK-3β, and MAPK. Notably, conditions such as osteoporosis and rheumatoid arthritis further illustrate how chronic cytokine release can link systemic inflammation to PKC dysregulation and subsequent neurodegeneration. Although mechanistic insights into these pathways have expanded, AD remains a therapeutic enigma with no disease-modifying interventions available. Interestingly, traditional Indian medical texts like the Charaka-Samhita documented herbal and metallic remedies, including gold-based formulations such as Swarna Prashana, reputed for enhancing cognition. Translating this ancient wisdom into modern medicine, aurothioglucose, an FDA-approved agent for rheumatoid arthritis, has demonstrated potent anti-inflammatory properties through PKC modulation. Emerging preclinical evidence now positions aurothioglucose as a promising neuroprotective candidate, capable of mitigating oxidative stress, dampening neuroinflammation, and preserving synaptic integrity via PKC-linked pathways. This review underscores the evolving role of aurothioglucose in AD, highlighting its potential to bridge traditional knowledge with contemporary therapeutics, while emphasizing the pressing need for translational studies to confirm its disease-modifying efficacy, as supported by evidences from current state of art.

Cytokine and oxylipin profiles in rat brain homogenates were characterized as an inflammatory response 6 h after a single intracerebroventricular injection of LPS (19.3 µg LPS/ventricle), serving as a model of the inflammatory process in trauma, stroke, and similar stroke-like conditions that cause acute reactions. The potential use of 4-methylumbelliferone (4-MU), an inhibitor of hyaluronic acid (HA) synthesis, clinically approved for the treatment of bile spasm, as an anti-inflammatory drug in the early stages of the brain's response to a damaging stimulus was evaluated. i.c.v. injection of LPS induced proinflammatory genes expression (TNFα, IL-6 and IL-1β) and oxylipins synthesis. Simultaneous addition of 4-MU with LPS reduced LPS-induced TNFα, IL-1β, IL-6 release and reduced the increase in COX-derived metabolites-PGF, PGE, 6-keto-PGF, TXB, 12-HHT, and 15-HETE. LPS stimulated only the expression of HAS2, while the addition of 4-MU reduced the expression of LPS-stimulated HAS2, and induced the expression of HYAL1, but not HYAL2. Our results reveal significant changes in cytokines and oxylipins synthesis in the model of acute inflammation, and suggest that 4-MU can be viewed as a promising therapeutic agent in the early stages of neuroinflammation.

Ulcerative colitis (UC) is the main representative of inflammatory bowel diseases (IBD) are chronic conditions characterized by intestinal inflammation, caused by the overproduction of pro-oxidant species and an immune response that damages the gut mucosa.

Acorus calamus L. is a traditional remedy for inflammatory, neurological, and gastrointestinal disorders. Herein, we explored the anti-inflammatory, antioxidative, and anti-arthritic activities of A. calamus rhizome's extracts using an adjuvant-induced rheumatoid arthritis (AIA) rat model. The maceration method was used to prepare methanol (MEAC) and n-hexane (HEAC) extracts of A. calamus rhizomes, and high-performance liquid chromatography (HPLC) analysis was performed for the quantification of polyphenols. In vivo, 100 µL of Complete Freund's adjuvant (CFA) was injected into the right hind paw to develop AIA in rats. Fifty-four female Wistar rats were divided into nine groups (n = 6) and orally treated with meloxicam (MEL; 3 mg/kg) and three doses (125, 250, and 500 mg/kg/day) of MEAC and HEAC for 28 days. Then, physical, hematological, biochemical, radiological, histopathological, and gene expression analyses were performed. Results indicated that each extract exhibited dose-dependent mitigation of arthritis in AIA rats compared to the standard drug. MEAC and HEAC decreased paw swelling and arthritic scores in a dose-dependent manner, restored body and immune organ weights, normalized hematological indicators (RBCs, Hb, WBCs, and platelets), and significantly reduced serum inflammatory (RF, CRP, TNF-α, and PGE2) and oxidative stress (SOD, CAT, and MDA) markers. Additionally, radiological and histological examinations of MEAC and HEAC administered AIA rats revealed fewer degenerative changes. In particular, both plant extracts (500 mg/kg) persuasively downregulated the expression levels of TNF-α, IL-1β, IL-6, and IL-17 A, upregulated IL-4 and IL-10, and modulated OPG, RANKL, and OPG/RANKL ratio in paw tissues. Moreover, MEAC demonstrated promising pharmacological activity in AIA rats compared to HEAC. Our findings suggest that A. calamus exerts anti-arthritic activity by inhibiting inflammation, potentiating antioxidant defense mechanisms, and subsequently modulating the OPG/RANKL pathway. Thus, A. calamus rhizomes may be a potential natural alternative for the treatment of inflammatory and autoimmune diseases.

Pulmonary diseases are still a serious threat to human health today, particularly in light of the recent rise of novel viruses such as SARS, influenza A, and COVID-19, which have made the situation even more dire by worsening the disease's effects on global public health. Isorhamnetin (ISO), as the active component of many medicinal plants and preparations, exhibits good antiviral, anti-inflammatory, antioxidant, and anti-tumor effects. ISO has been proven to have both preventive and treatment efficacy against pulmonary diseases. This review summarizes the effects of ISO in different pulmonary diseases, including COVID-19, pneumonia, acute lung injury/acute respiratory distress syndrome, lung cancer, asthma, pulmonary arterial hypertension, and pulmonary fibrosis, highlighting its specific molecular mechanisms against various pulmonary diseases, which is helpful for providing new perspectives on the preclinical trial and clinical application of ISO.

Reactive oxygen species (ROS) and nitrogen-derived oxidants, such as nitric oxide (NO), are produced by immune cells through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and nitric oxide synthases (NOS), respectively. These pro-oxidants disrupt physiological homeostasis, contributing to hyperalgesia, the excessive release of inflammatory markers and oxidative stress during ulcerative colitis (UC). Consequently, diphenyleneiodonium chloride (DPI), an inhibitor of NOXs and NOS, could be effective in alleviating visceral pain and UC. This study examines the antioxidant and analgesic properties of DPI, as well as its ability to modulate oxidative stress and pro-inflammatory responses in UC. The antioxidant properties of DPI and its ability to bind free iron were determined using ABTS and DPPH tests, as well as a ferrous iron chelating capacity assay. DPI's analgesic activity was investigated using a 0.6% acetic acid (AA) mouse model of hyperalgesia, and its preventive effects against UC were determined using a 3% AA rat model of UC. Our results demonstrate that DPI limits free radicals, chelates ferrous iron and reduces writhing number (Wn) by p < 0.001, confirming its analgesic activity. Furthermore, intraperitoneal administration of DPI (100 ng/kg) protected rats from UC by repairing large-scale colonic damage, lowering oxidative stress by decreasing NO levels and restoring antioxidant enzymatic activities in colonic tissue. DPI also lowers plasmatic C-reactive protein (C-RP), NO content, lactate dehydrogenase (LDH) and γ-glutamyl transferase (γ-GT) activity during colitis. Therefore, targeting NOXs and NOS with DPI could be a promising strategy for treating inflammatory diseases such as colitis.

Polymorphonuclear neutrophils (PMNs) contribute to the pathogenesis of arthritis by releasing excessive reactive oxygen species (ROS) and proteolytic enzymes, leading to joint damage. Targeting PMNs activation represents a promising therapeutic approach. This study aimed to evaluate the immunomodulatory and anti-arthritic effects of clove essential oil (CEO) and its main constituent, eugenol, through in vitro, in vivo, and in silico approaches. CEO chemical composition was determined by GC-MS. In vitro assays assessed PMNs degranulation (lysozyme release) and oxidative burst (NBT reduction), along with antioxidant, anti-hemolytic, and antiplatelet activities. Arthritis was induced in mice by CFA injection, and therapeutic efficacy was evaluated by paw edema, histopathology, and body weight monitoring. Molecular docking was conducted to predict interactions with inflammatory targets (COX-1, COX-2, TNF-α). GC-MS revealed 77.67% eugenol in CEO. Both CEO and eugenol significantly inhibited PMN degranulation (52.81% and 57.54%) and oxidative burst (41.85% and 75.41%; p < 0.001). CEO and eugenol also displayed strong antioxidant and anti-hemolytic activities, and reduced collagen-induced platelet aggregation. In vivo, treatment markedly reduced paw edema and histopathological damage without hepatic toxicity. Docking analysis suggested potential inhibitory interactions with COX-2 and TNF-α. CEO and eugenol exert potent anti-inflammatory and immunomodulatory effects by modulating PMNs activity, preventing oxidative stress, and alleviating arthritis symptoms. These findings highlight their therapeutic potential as natural candidates for managing arthritis and related inflammatory conditions.

Amyloid-beta (Aβ) plaques and the intracellular buildup of hyperphosphorylated tau protein are hallmarks of Alzheimer's disease (AD), a progressive neurodegenerative disease that causes synaptic dysfunction and neuronal death. Glycogen synthase kinase 3 beta (GSK3β), protein kinase B (AKT), and phosphatidylinositol 3-kinase all have aberrant signaling pathways that contribute to the pathophysiology of AD. The PI3K/AKT neuroprotective pathway is seriously inhibited in AD, which leads to brain insulin resistance (BIR) and neurodegeneration. However, AD leads to hyperactivation of GSK3β, which in turn produces tau hyperphosphorylation, Aβ accumulation, and cognitive impairment. BIR and PI3K/AKT/GSK3β signaling in AD have a complicated interaction that is covered in this article. The pathway has both neuroprotective and pathogenic functions. The therapeutic use of GSK3β inhibitors and PI3K/AKT activators to decrease AD pathogenesis is also discussed. Changing these pathways can improve cognitive function, reduce tau and Aβ pathology, and restore insulin signaling, according to preclinical and clinical research. Finding highly specialized treatments with minimal side effects remains a challenge. More research is required to thoroughly assess the safety and efficacy of medications that target specific pathways and to clarify the molecular mechanisms underlying PI3K/AKT/GSK3β dysregulation in AD in order to create novel and effective treatment alternatives.

Wounds and burn injuries are major global health challenges, often exacerbated by methicillin-resistant Staphylococcus aureus (MRSA) infections. This study investigated the wound-healing efficacy of Rubus ulmifolius (RU) leaf extract, which contains bioactive compounds including rutin, vanillic acid, syringic acid, gallic acid, and protocatechuic acid. Network pharmacology analysis identified interactions between these compounds and key inflammatory and antibacterial targets, notably TNF-α and IL-1β, suggesting a role in modulating MRSA-associated inflammation.

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.

The gut-brain axis plays a vital role in migraine pathophysiology. Studies highlight reciprocal interactions between the central nervous system and the gastrointestinal tract. Previous research suggests that factors such as gut microbiota profiles, inflammatory mediators, neuropeptides, serotonin pathways, stress hormones, and nutritional substances influence this interaction. The pathophysiology of migraine has been linked to changes in the gut-brain axis, which affects migraine severity and frequency. Additionally, dietary approaches, including the ketogenic diet, vitamin D supplementation, omega-3 intake, probiotics, and weight loss plans, have shown promising effects in reducing migraine symptoms by positively impacting the gut microbiota and the gut-brain axis. Understanding these connections could lead to novel therapeutic strategies for effectively managing migraines. It is worth noting that research highlights several innovative treatments for migraine, such as Zelirex and Cevimide, implantable devices like Cefaly and Revilion, and new effective routes of administration for Sumatriptan. Finally, patients' perspectives and concerns were thoroughly discussed, with a focus on future directions in the migraine-gut axis research.

Urarthritis is an inflammatory disorder triggered by monosodium urate (MSU) crystal deposition, and its pathogenesis involves interaction between oxidative stress (OS) and inflammation. Diacerein, an agent endowed with anti-inflammatory and antioxidant properties, has not yet been fully characterized in acute urarthritis. This study was designed to evaluate the therapeutic efficacy of diacerein in acute urarthritis and to elucidate its regulatory effects on the Nrf-2/HO-1 and NF-κB pathways.

Diabetic foot ulcers (DFUs), a debilitating manifestation of diabetes mellitus, involve persistent inflammation, oxidative stress, and impaired wound healing, largely driven by NF-κB overactivation. Amlexanox (ALX), a synthetic anti-inflammatory and antioxidant agent, was evaluated for its therapeutic potential in DFUs.

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.

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.

Throughout the world-wide COVID-19 pandemic, there has arisen a significant and a sustained public-health issue, whereby a significant proportion of individuals report persistent symptoms, well beyond the acute period of infection. The non-united array of chronic, multisystemic events, such as fatigue, cognitive deficit, respiratory dysfunction, cardiovascular abnormalities, and neuropsychiatric disorders characterize this sequela, which is referred to as LCS. LCS is much more than the starting viral insult, as it causes long-term complications that impact various organ systems. The current review questions the pathophysiological mechanisms of LCS, including scrutinizing the importance of the dysregulation of immunity, the persistence of viral reservoirs, endothelial dysfunction, autonomic imbalance, and mitochondrial injury. We highlight the heterogeneity of the syndrome and the associated diagnostic and treatment difficulties. In addition, we stress the urgency of powerful biomarkers that will be used to diagnose LCS as early as possible and monitor it over time. Present treatment strategies, including pharmacologic therapy (immunomodulators, anticoagulants, antiviral medications, etc.) and non-pharmacologic treatment (rehabilitative programs, etc.) are discussed against the backdrop of recent clinical findings. This review incorporates the recent literature and presents a review of potential treatment options that alleviate symptoms and improve the quality of life of LCS patients. Finally, this integrated synthesis can be used by both clinicians and researchers to gain practical information on the diagnosis, treatment, and future treatment directions of LCS.