Inflammopharmacology最新文献

Rheumatoid arthritis is an autoimmune disorder characterized by cartilage destruction, joint inflammation, and systemic complications. Incomplete disease remission, adverse effects, and limited treatment availability underscore the need for novel therapeutic interventions. With this ultimate goal, the aim of the current study was to assess the anti-inflammatory and antiarthritic potential of chloroform and ethanol extracts of Celtis eriocarpa Decne. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of these extracts revealed the presence of diverse bioactive compounds with well-recognized anti-inflammatory and antiarthritic activities, including phytol, neophytadiene, tocopherols, hexadecenoic acid methyl ester, squalene, and 2-tert-butylphenol derivatives. In vitro assays demonstrated significant, dose-dependent inhibition of protein denaturation by these extracts, with the activity of the chloroform fraction comparable to that of the diclofenac sodium standard. In vivo studies in a formaldehyde-induced arthritis rat model revealed significantly reduced paw edema and arthritis scores and improved mobility after oral administration of Celtis eriocarpa chloroform extracts (CE). Radiographic analysis further confirmed joint preservation in a rat model treated with CE. Histopathological assessments indicated marked reductions in synovial hyperplasia, cartilage erosion, and inflammatory cell infiltration, specifically in the high-dose CE groups. Finally, hematological and biochemical evaluations revealed normalization of inflammatory markers, downregulation of the expression levels of key proinflammatory cytokines (TNF-α, IL-6, NF-κB, IL-1β, and COX-2), and upregulation of the expression levels of anti-inflammatory cytokines (IL-4 and IL-10). Collectively, these findings demonstrate that Celtis eriocarpa extracts are enriched in bioactive phytoconstituents and hold substantial potential as therapeutic candidates for the management of rheumatoid arthritis and inflammatory disorders.

Herbal remedies have been utilised in traditional medicine systems to manage chronic illnesses. The present research investigated the antioxidant, anti-inflammatory, and antiarthritic effects of Chenopodium murale L. The C. murale (CMMeE) methanolic extract, prepared from the whole plant by maceration, was analysed for phytochemicals using LC-MS. The antioxidant effects of CMMeE were assessed in an in vitro DPPH assay. The efficacy of CMMeE was assessed in in vivo carrageenan and histamine-induced acute inflammatory models, and in formaldehyde and complete Freund's adjuvant (CFA)-induced chronic arthritis models. Three different doses of CMMeE (250, 500, and 750 mg/kg) and 10 mg/kg of diclofenac sodium were administered orally to the animals. Different parameters, including reductions in paw oedema, arthritic index (AI), histopathological, biochemical, and haematological changes, were noted. ELISA and qPCR methods were used to assess the expression of antioxidant and inflammatory biomarkers in serum samples. CMMeE possesses moderate antioxidant activity (IC₅₀ = 199.7 µg/mL) when compared to gallic acid (IC₅₀ = 178.9 µg/mL) in an in vitro DPPH assay. Treatment with CMMeE alleviated paw oedematous conditions in the acute models. The CMMeE and diclofenac sodium-treated groups demonstrated a noticeable decline (p < 0.05) in joint inflammation and overall arthritic scores. Treatment with the extract and diclofenac sodium resulted in reductions in superoxide dismutase (SOD), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) levels in the serum samples. Moreover, remarkable (p < 0.05) induction of interleukin-4 and -10 and suppression of COX-2, IL-1, IL-6, NF-kβ, mPGE, and TNF-α was noticed in a dose-dependent manner in the samples of CMMeE and dilcofenac sodium treated animals. Complete blood count (CBC) data indicated no noticeable differences (p > 0.05) in RBCs and Hb levels, but a decline in platelet and WBCs levels in CMMeE-treated groups. Reduced pannus formation, bone deterioration, and synovitis were observed in tissue sections of animals treated with CMMeE and diclofenac sodium. Overall, CMMeE exhibits anti-inflammatory and antiarthritic effects, which may be due to TNF-α-directed downregulation of oxidative stress and inflammatory mediators.

The present study aimed to formulate and evaluate a curcumin-piperine (CUR-PIP) liposome-loaded hydrogel for the topical management of atopic dermatitis (AD). Liposomes were fabricated using the ethanol injection method and optimized through a 3²-factorial design, employing phospholipon 90 H and cholesterol as key formulation variables. The effects of these variables on particle size and entrapment efficiency were systematically investigated. The optimized liposomal formulation exhibited a mean particle size of 240.4 nm, a zeta potential of - 27.9 mV, and high entrapment efficiencies of 94% for CUR and 89% for PIP. Comprehensive characterization using differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction confirmed successful drug encapsulation and compatibility between the components. The liposomal hydrogel, prepared using Carbopol 980, demonstrated suitable physicochemical properties, including an appropriate pH (6.3), optimal viscosity, good spreadability, and sustained drug release over 24 h. Ex vivo skin permeation studies indicated enhanced drug retention within the skin (74.23 ± 1.12%) with minimal transdermal permeation, supporting the potential of formulation for localized therapeutic action. Antioxidant assay revealed strong free radical scavenging activity. Furthermore, in vivo evaluation in a DNCB-induced AD mouse model showed that the CUR-PIP liposomal hydrogel significantly reduced erythema, scratching behavior, ear thickness, and spleen index compared to the CUR-PIP suspension and standard dexamethasone groups. Overall, the developed CUR-PIP liposomal hydrogel demonstrated synergistic antioxidant and anti-inflammatory effects, representing a promising and effective topical therapeutic strategy for the management of AD.

Sulphasalazine (SSZ) has been used to treat a range of inflammatory conditions since the 1940s. It functions as a pro-drug that, upon azoreduction by selected gastrointestinal bacteria (including the bacterial triggers of some inflammatory diseases), releases an antioxidant protective molecule, 5-aminosalicylate (5-AS), and the antibacterial molecule sulfapyridine (SP). SSZ, 5-AS and SP were evaluated for growth inhibitory activity against some bacterial triggers of rheumatoid arthritis (Proteus spp.), ankylosing spondylitis (Klebsiella pnumoniae), multiple sclerosis (Acinetobacter baylyi and Pseudomonas aeruginosa) and rheumatic fever (Streptococcus pyogenes). These bacteria have previously been reported to have azoreductase activity and therefore they may locally convert the SSZ pro-drug into 5-AS and SP. The potency of all compounds, as well as a combination of 5-AS and SP, were evaluated under aerobic conditions by MIC, ƩFIC and isobologram analysis. Noteworthy antibacterial activity was calculated for SSZ, with MIC values as low as 625 µg/mL against P. mirabilis and K. pneumoniae. The azoreduction product SP had substantially more potent antibacterial activity (MICs 78-625 µg/mL). It was particularly potent against the Proteus spp. triggers of rheumatoid arthritis. Whilst 5-AS also inhibited bacterial growth, it was substantially less potent than SP. However, 5-AS potentiated the activity of SP when tested in combination. Indeed, synergy was noted for the combination against P. vulgaris, whilst additive effects were recorded against P. mirabilis and K. pneumoniae. Taken together, these results highlight the pro-drug properties of SZ against the bacterial triggers of selected inflammatory diseases. Future studies into the pharmacological properties of SSZ, as well as the 5-AS and SP combination are warranted. In particular, these compounds should be evaluated against additional strains of these bacteria (including antibiotic-resistant strains), as well as against bacterial triggers of further inflammatory diseases.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures, generally associated with an imbalance of neurotransmitters, neuroinflammation, and oxidative stress. Formononetin, a naturally occurring isoflavone found in several medicinal plants, has been previously explored for its anti-inflammatory and antioxidant effects in preclinical studies. These properties suggest a possible role of formononetin in modifying the pathological pathways underlying epilepsy. Pentylenetetrazol (PTZ)-induced kindling is one of the most reliable animal screening models for exploring the anti-epileptic potential of investigational natural compounds, such as formononetin, enabling its examination in reducing seizure susceptibility and severity in the mouse model. This study evaluates the anticonvulsant efficacy of formononetin by modulating neuroinflammation in a pentylenetetrazol-induced kindling mouse model. Male and female mice were divided into five groups: naïve, Negative control (PTZ-kindled), positive control (sodium valproate 200 mg/Kg), and PTZ + formononetin (10 mg/kg, 20 mg/kg, and 40 mg/kg). PTZ was administered at a dose of 40 mg/kg every alternate day, followed by assessment of seizure severity score using the Racine scale. Neuroinflammatory biomarkers (IL-1β, NF-κB) and neurotransmitter levels (GABA, Glutamate) were measured. Histopathology was performed to identify the morphological changes in the brains of mice following treatment. Formononetin exhibited dose-dependent anticonvulsant and neuroprotective effects in the PTZ-kindling mouse model, reducing seizure severity, improving motor coordination, and easing anxiety-like symptoms. It restored the glutamate-GABA balance, suppressed NF-κB and IL-1β expression, and preserved neuronal integrity, underscoring its potential as a multi-target therapeutic agent for epilepsy through modulation of neurotransmission and neuroinflammation.

Medicinal plants have been traditionally used to treat wounds. The aim of this study was to investigate the antioxidant activity, wound healing effect and chemical content of the aerial parts of Chaiturus marrubiastrum (L.) Ehrh. ex Rchb. Pressure wound model in rats was used to evaluate the wound healing effect of the extracts. The antioxidant activity of the extract was evaluated using total antioxidant capacity, reducing power, metal chelation, DPPH and ABTS scavenging tests. The chemical profile of the extract was evaluated by LC-MS/MS analysis. The extract had 83.50 ± 0.11% and 70.73 ± 1.30% inhibition in DPPH and ABTS scavenging tests, respectively. The metal chelation capacity of the extract increased with increasing concentration. The reducing power of the extract (at 2 mg/mL) was similar to that of quercetin (3.521 ± 0.07, 3.831 ± 0.03, respectively). The most abundant substance in the extract was rosmarinic acid (165.611 mg/g extract). In vivo experiments, wound healing occurred faster in the group treated with C. marrubiastrum extracts in pressure wounds created on rats compared to the control groups. Histopathological analyses showed that connective tissue development and vascularization increased and inflammation decreased in this group. In addition, immunohistochemical analyses have shown that C. marrubiastrum extract reduces TNF-α, VEGF and caspase-3 levels, thus inhibiting inflammation and apoptosis. These findings suggest that the wound healing-accelerating effects of C. marrubiastrum are based on strong antioxidant and anti-inflammatory properties. It is concluded that future studies should optimize this extract for clinical use and evaluate its efficacy in humans.