Inflammopharmacology最新文献

Duguetia furfuracea, popularly known as "araticum-seco," is traditionally used in folk medicine for the treatment of pain and inflammatory disorders. This study aimed to analyze the chemical composition and investigate the anti-inflammatory and antinociceptive activities of the alkaloid fraction obtained from the leaves of D. furfuracea (DfFAlk). The chemical composition of DfFAlk was characterized using ultra-fast liquid chromatography (UFLC) coupled with mass spectrometry (UFLC/ESI). In vivo anti-inflammatory activity was assessed using the carrageenan-induced paw oedema model. The effects of DfFAlk on polymorphonuclear leukocyte recruitment and tumor necrosis factor alpha (TNF-α) levels were also evaluated in mouse footpads. In addition, the antinociceptive effect was investigated using the abdominal writhing test, formalin test, and thermal hyperalgesia models, and motor and balance performance were assessed using the rota-rod test. Thirty-four alkaloids were annotated belonging to the aporphine, tetrahydroprotoberberine, benzyltetrahydroisoquinoline, tetrahydroisoquinoline, (bis)benzyltetrahydroisoquinoline, and proaporphine classes. Oral treatment with DfFAlk (100 and 300 mg/kg) significantly inhibited paw oedema, from 2 to 6 h post inflammatory stimulus. The alkaloid fraction (300 mg/kg) attenuated the tissue inflammatory infiltrate 4 and 6 h after carrageenan injection, and decreased TNF-α production, 4 h post carrageenan. The fraction (300 mg/kg) also significantly attenuated the acetic acid-induced writhing response and the formalin-induced licking in both phases. Furthermore, in the hot-plate model, the DfFAlk (300 mg/kg) increased the latency to response from 1 to 3 h after oral treatment. Additionally, DfFAlk-treated mice did not show any alteration of motor and balance performances. The data indicate that DfFAlk has anti-inflammatory and antinociceptive activities.

Background: This meta-analysis evaluated the efficacy and safety of topical Tapinarof compared to placebo in patients with mild to moderate Atopic Dermatitis (AD).

Methods: We searched PubMed, Embase, and Cochrane databases until March 2025. A total of 41 studies of Tapinarof (0.5%, 1%) versus placebo on mild to moderate AD patients, assessing IGA, EASI, PP-NRS, and safety outcomes, were identified; out of which, six RCTs met the inclusion criteria (14.6%). Two independent reviewers extracted data following PRISMA guidelines, and study quality was assessed using the Cochrane Risk of Bias 2 tool. Random-effects models were used to pool the outcomes. Primary outcome was IGA success (score 0/1 or ≥ 2-point improvement); secondary outcomes included EASI75, PP-NRS reduction, and AEs, measured as odds ratios (ORs) with 95% CIs.

Results: Data from the six included RCTs (n = 1545) showed that Tapinarof significantly improved IGA success rate (OR = 5.07, 95% CI: 2.81-9.13, p < 0.001) and EASI75 (OR = 3.76, 95% CI: 1.94-7.27, p < 0.001) compared to placebo. AEs were higher with Tapinarof (OR = 2.22, 95% CI: 1.73-2.84, p < 0.001), mild to moderate severity (e.g., folliculitis). Heterogeneity was moderate (I²=61.4% for IGA); sensitivity analysis confirmed robustness.

Conclusions: Topical Tapinarof (0.5%, 1%) is effective and well-tolerated for mild to moderate atopic dermatitis, but higher adverse event rates require monitoring.

Microglial cells play a pivotal role in the different CNS related conditions as they have the power to destruct as well protect the Central Nervous System. Depending on the environment they are in, they respond to different stimuli and carry out a function. Majority of the cases, the microglial cells are activated which cause inflammation to a very large extent and for a prolonged period of time which causes the various signs and symptoms of the neurodegenerative disorders. Cannabinoid Type-2 (CB2) receptor crosstalk is a key modulator of microglial plasticity, influencing both pro-inflammatory and anti-inflammatory states in the brain. Activation of CB2 receptors in microglia can suppress neurotoxic inflammation, promote anti-inflammatory phenotypes, and facilitate microglial migration and environmental surveillance. By shifting microglial polarization away from pro-inflammatory states, CB2 stimulation helps control neuroinflammation and supports tissue repair in neurodegenerative and neuroinflammatory conditions. This intricate crosstalk highlights CB2 as a promising therapeutic target for managing central nervous system dysfunctions mediated by microglial activity. The present review discusses CB2 receptor crosstalk and its role in microglial plasticity and neuroinflammation.

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.

Background: Presbycusis is a neurodegenerative disease associated with chronic inflammation. Metformin is an anti-inflammatory agent used to treat diabetes. However, its efficacy in delaying presbycusis has not been established.

Aim: The study aimed to investigate the protective effects of metformin against presbycusis and elucidate its mechanistic role in modulating the SIRT1/PINK1/GPX4 signaling pathway in vitro and in vivo.

Materials and methods: The target genes of presbycusis were identified using bioinformatics. The HEI-OC1 cells were subsequently induced with D-galactose (D-gal) and co-treated with metformin in vitro. Their viability, mitochondrial function, and molecular markers were subsequently monitored. Meanwhile, C57BL/6J mice were injected with metformin, and their auditory brainstem response (ABR) thresholds were assessed by ABR test. Animal histopathological examination, immunofluorescence staining, and western blotting were used to assess the protective effects of metformin against presbycusis in mice.

Results: Metformin increased the viability of senescent auditory cells, enhanced mitochondrial function by reducing reactive oxygen species production, and inhibited ferroptosis in vitro. It also improved the auditory function of C57BL/6J mice, reduced their cochlear concentrations of Fe²⁺ and malondialdehyde, and prolonged their hair cell survival in vivo. Metformin upregulated SIRT1, PINK1, and GPX4 in vitro and in vivo.

Conclusion: Metformin activates the SIRT1/PINK1/GPX4 signaling pathway, and it may be effective for treating presbycusis.

Urochloa distachya (Poaceae) is a creeping annual or short-lived perennial plant found all over India. The species is used as a feed grass for ruminants. Since most Poaceae species are small annual herbs, the entire plant are used to cure a variety of diseases. Consideringthe potential of secondary metabolites in Poaceae forage grasses, this study aimed to investigate the hepatoprotective activity of U. distachya using paracetamol and Carbon tetrachloride (CCl₄)-induced hepatotoxicity in albino Wistar rats. The phenolic and flavonoid contents of the Ethanol extract of Urochloa distachya (EUD) were analyzed using the HPLC method. GC-MS and LC-MS techniques were used for the detection of phytochemicals. In vitro, antioxidant activity was assessed using the DPPH, ABTS, H₂O₂, and TAC methods. In vivo, hepatoprotective activity was evaluated by administering EUD at a dose of 100, 200, and 400 mg/kg body weight using paracetamol and CCl₄-induced models. Molecular docking studies were carried out to predict the interaction of the identified compound with the target protein TGF-β1. HPLC analysis identified nine phenolic acids (Gallic acid, Protocatechuic acid, Chlorogenic acid, Vanillic acid, Caffeic acid, Syringic acid, p-Coumaric acid, Ferulic acid, and Sinapic acid), and four flavonoids (Rutin, Quercetin, Naringenin, and Kaempferol). GC-MS revealed 19 compounds, with 1-hydroxypropane (50.36%) as the major constituent. LC-MS analysis identified Betaine and (3beta,9xi)-3-(beta-D Glucopyranosyloxy)-14-hydroxycard 20(22)-enolide as a key compounds. EUD showed significant in vitro antioxidant activity, with percentage inhibition of DPPH (63.06 ± 0.72%), ABTS (53.65 ± 1.22%), H₂O₂ (41.45 ± 0.54%), and TAC (57.04 ± 0.30%). Treatment with EUD at 100, 200, and 400 mg/kg body weight reduced ALT, AST, bilirubin, and MDA levels while increasing TP, SOD, CAT, and GSH levels. Docking scores ranged from - 3.4 to - 10.2, indicating strong binding affinity of the phytoconstituents. U. distachya possesses significant hepatoprotective activity by restoring liver function markers and enhancing antioxidant enzyme levels in hepatotoxicity models. The presence of phenolic and flavonoid compounds with strong molecular interactions suggests the promising hepatoprotective activity of U. distachya.

Introduction: 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.

Objective: To evaluate the anti-inflammatory and protective effect of Citral, a monoterpene, on in vitro and in vivo models of UC.

Methodology: Male C57BL/6J mice were used for DSS 3%-induced UC for 5 days in drinking water. Concomitantly, daily oral citral (25, 100, and 300 mg/kg, p.o.) or vehicle was administered. Colonic segments were collected to evaluate neutrophil infiltration, lipid peroxidation, and the expression of antioxidant markers. NCM-356 and RAW-294 cells were stimulated with LPS (10 and 100 ng/mL, respectively). Cell viability, nitrite levels, scratch wound healing assay, and gene expression of inflammatory and growth factors were assessed.

Results: Acute treatment with citral (100 and 300 mg/kg) exhibited an anti-colitis effect by reducing the disease activity index (DAI) score compared to that in the DSS-vehicle group. This response was mediated by a significant reduction in myeloperoxidase activity and thiobarbituric acid reactive species levels, associated with an increase in superoxide dismutase activity, indicating anti-inflammatory and antioxidant activities (p < 0.05). The monoterpene reversed LPS-induced intestinal epithelial disturbance in the scratch wound healing process under different conditions and possibly reduced inos expression.

Conclusion: Citral treatment prevents the development of UC via anti-inflammatory, antioxidant, and healing effects.

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.

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by persistent joint inflammation, cartilage degradation, and systemic complications. Phytochemicals such as curcumin, resveratrol, phenolic acids, flavonoids, lignans, and organosulfur compounds have demonstrated significant disease-modifying potential through modulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and key signaling pathways (NF-κB, MAPK, PI3K/AKT/mTOR). Curcumin, for example, regulates immune homeostasis by restoring the Th17/Treg balance and inhibiting NF-κB and mTOR signaling, while resveratrol suppresses angiogenesis via VEGF inhibition and induces apoptosis in fibroblast-like synoviocytes. Despite their pharmacological promise, poor aqueous solubility, rapid metabolism, and low systemic bioavailability limit clinical translation. Advances in nanoformulation technologies-including polymeric nanoparticles, liposomes, micelles, solid lipid nanoparticles, and stimuli-responsive carriers-have markedly improved phytochemical stability, pharmacokinetics, targeted delivery, and therapeutic efficacy. Analytical characterization methods such as dynamic light scattering, zeta potential analysis, FTIR, HPLC, and TEM facilitate precise formulation optimization and evaluation of biological interactions. Preclinical studies reveal that nano-curcumin can achieve efficacy comparable to methotrexate, while resveratrol-loaded gold nanoparticles enhance anti-inflammatory effects and joint-specific accumulation. This review integrates mechanistic insights, formulation strategies, and analytical approaches, highlighting the opportunities and regulatory considerations for translating nano-phytochemicals into clinically viable RA therapies.

Pulmonary fibrosis is a serious threat to global health, especially in after math of covid-19 infection, eventually results in fibrotic remodeling and organ damage. This SARS-CoV 2 induced fibrosis initiates cascade of proinflammatory responses such as cytokine release. EMT (Epithelial-mesenchymal transition) is a central event in post COVID 19 pulmonary fibrosis which is characterized by the accumulation of stimulated fibroblast and myoblast, finally epithelial morphology changed to mesenchymal traits. This transformation is marked by the loss of intercellular adhesion and polarity. A study of SARS-CoV 2 pathogenesis and EMT can provide insights to pulmonary fibrosis. Hence identification of biomarkers of EMT activation helps early diagnosis and determination of therapeutic approaches against pathogenesis. This review focusing on the mechanism of post-covid 19 pulmonary fibrosis through EMT with a special importance to TGF-β/Smad, NF-κB pathways and oxidative stress. Previous studies marked the EMT induced fibronectin, collagen deposition that can potentially disrupt lung structure and its function. SARS CoV 2 infection can trigger Hyper activation of profibrotic pathways like TGF-β/Smad, NF-κB pathways that maintain EMT via downregulation of E-Cadherin and upregulation of vimentin, fibronectin and α-SMA. SARS-CoV spike-protein binds to AEC-2 cells initiates cytokine storm followed by amplified NF-κB pathway, and oxidative stress. Elevated activation of this pathway increases Snail, Slug, Twist expression that leads to EMT. Moreover, increased ROS production creates fibrotic environment in lung. This review examined the mechanism behind the pulmonary fibrosis by analyzing interplay between the SARS-CoV 2 infection and EMT, providing effective therapeutic strategies to prevent EMT.