Inflammopharmacology最新文献

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.

Astaxanthin, a xanthophyll carotenoid derived primarily from Hematococcus lacustris, has been proposed as a potent bioactive compound demonstrating wide therapeutic applicability. In addition to its distinct molecular structure, astaxanthin has exceptional antioxidant property, surpassing that of other carotenoids and conventional antioxidants, while also exerting robust anti-inflammatory effects. The present review focuses on the current evidence of the complex multifaceted therapeutic actions of astaxanthin, including cardiovascular protection, neuroprotection, hepatoprotection, renal support, dermatological health, immune modulation, and emerging roles in metabolic disorders, reproductive health, and cancer prevention. Mechanistic insights highlight its potential to control key molecular mechanisms, including the NF-κB, Nrf2, MAPK, and TGF-β/Smad pathways, alongside the enhancement of endogenous antioxidant defenses. Preclinical and clinical findings have demonstrated benefits in conditions such as atherosclerosis, myocardial ischemia, nonalcoholic fatty liver disease, hypertension, Alzheimer's disease, Parkinson's disease, and inflammatory skin diseases. By integrating evidence drawn from molecular, experimental, and clinical studies, this review underscores astaxanthin's potential as a complementary therapeutic agent and functional nutraceutical. The breadth of its bioactivity positions astaxanthin as a promising natural compound for targeted disease prevention and health promotion.

Objective: Trans-Chalcone (TC) is an anti-inflammatory flavonoid that reduces hyperalgesia by targeting nuclear factor κB and inflammasome in gout arthritis model. However, a direct modulation of nociceptors by TC has never been investigated, which was the aim of the present study.

Methods: Experimental models of overt pain-like behaviors were applied as the stimuli-induced behavior depends, at least in part, on nociceptive neuron activation by the stimuli themselves making them suitable to investigate if a drug candidate can inhibit nociceptive neuron activation. The selected models involve transient receptor potential (TRP) vanilloid 1 (V1)⁺ and TRP ankyrin 1 (A1)⁺ nociceptive neuron activation.

Results: TC (10 mg/kg, per oral, 30 min pretreatment) inhibited abdominal contortions induced by acetic acid (58.8%) and phenyl-p-benzoquinone (PBQ-54.6%), and paw flinching (44 and 48%) and licking (38 and 46%) triggered by formalin and complete Freund's adjuvant (CFA-46 and 43%), indicating TC inhibits varied overt pain-like behaviors. Considering TRPV1 and TRPA1 channels are activated in those models, TC activity was also tested in experimental conditions in which capsaicin (a TRPV1 agonist)- and allyl isothiocyanate (AITC, a TRPA1 agonist)-triggered nociceptive behavior. TC inhibited capsaicin (44 and 37.5%) and AITC (35.1 and 52%) paw flinching and licking behavior. TC (3 μM) also reduced the calcium influx caused by capsaicin (30%) and AITC (37.6%) stimulation of primary dorsal root ganglia neurons. Additionally, TC inhibited CFA-induced hyperalgesia, paw inflammation without toxic effects.

Conclusions: TC reduces overt pain-like behavior, at least in part, by inhibiting nociceptive neuron TRPV1 and TRPA1 channels activation.

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.

The progressive neurodegenerative disease known as Alzheimer's disease (AD) is characterized by widespread neuronal death, memory loss, and cognitive decline. The NLRP3 inflammasome has emerged as a key modulator of neuroinflammation, which is increasingly implicated in the pathophysiology of AD. In response to endogenous and pathogenic danger signals, the innate immune system's multiprotein complex known as the NLRP3 inflammasome is activated. Pyroptosis and neuroinflammatory cascades are eventually triggered by its activation, which causes caspase-1 to be cleaved and pro-inflammatory cytokines like interleukin-1β and interleukin-18 to be released. NLRP3 activation is strongly stimulated by tau aggregation and β-amyloid plaques in AD, which accelerates neuronal damage and prolongs chronic inflammation. The control and activation of inflammasomes are involved in both canonical and non-canonical pathways as well as mitochondrial dysfunction. Significantly, animal models indicate that NLRP3's therapeutic potential is highlighted by the reduction of amyloid burden and amelioration of cognitive decline that results from its inhibition or genetic deletion. Small-molecule inhibitors and natural substances that can alter NLRP3 activity have been discovered recently, providing intriguing approaches to AD treatment. Despite tremendous advancements, issues with medication selectivity and blood-brain barrier penetration still need to be resolved before these discoveries can be used in clinical settings. Comprehending the complex relationship between NLRP3 activation and Alzheimer's pathology may open the door to new, focused treatments meant to slow or stop the progression of the illness.

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.

Drimiopsis maculata is a member of Asparagaceae family, has been used to treat inflammatory and pain conditions since long. The intention of performing this study was to determine anti-inflammatory properties in polyarthritis in D. maculata methanol extract (DMME). The extract was phytochemically characterized using proximate analysis, HPLC and GCMS profiling. DMME 200, 400, and 600 mg/kg were used to evaluate in vivo efficacy in formaldehyde-induced polyarthritis rat model. Diameter of paw, body weight, arthritic score, hematological indices, and biochemical markers were among the parameters that were assessed. Levels of HSP-70, PGE-2, NO, iNOS, IL-6, TNF-α, SOD, CAT, and MDA were quantified using ELISA. Inflammatory gene expression was determined by qRT-PCR. Organ Histological and radiological examinations were also carried out. Phytochemical evaluation confirmed the presence of various secondary metabolites, with HPLC and GCMS detecting diverse bioactive compounds. In vivo, treatment with DMME showed a dose-dependent decrease in paw inflammation and polyarthritis severity. Improvements were noted in hematological and biochemical characteristics, along with histological indication of decreased inflammation, bone degradation, and pannus formation. Analysis of gene expression revealed that anti-inflammatory genes were up-regulated whereas pro-inflammatory mediators were down-regulated. The outcomes of this research study show that DMME holds strong anti-inflammatory potential and provide scientific ground supporting its conventional use in the management of inflammation in polyarthritis.