Inflammopharmacology最新文献

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.

Estrogen deficiency during menopause is linked to increased chronic pain and inflammation, partly due to gut dysbiosis and systemic release of lipopolysaccharides (LPS). These LPS molecules activate TLR-4 receptors, triggering inflammatory cascades. While 17β-estradiol is a commonly used hormone replacement therapy, poses serious side effects. Earlier studies reported that fructooligosaccharide (FOS) modulates gut microbiota and diminishes LPS release. However, its role in attenuating chronic pain through the LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway remains underexplored. We aimed that FOS may attenuate estrogen deficiency-induced chronic pain and associated inflammation via inhibiting LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway. Female Sprague Dawley rats were bilaterally ovariectomized (OVX) to stimulate postmenopausal conditions, and further treated orally with FOS (25, 50 and 100 mg/kg) for 28 days. Pain sensitivity was assessed using thermal and mechanical nociception. Oxidative stress markers and ELISA (serum LPS and NF-κB p65) were measured in the brain and colon. Inflammation was measured via analysing expression of TLR-4, TNF-α, and IL-6 genes through RT-PCR. FOS (50 and 100 mg/kg) treatment significantly attenuated pain sensitivity through improving thermal and mechanical hyperalgesia. FOS exerts a potent antioxidant via reducing oxidative stress in both the colon and brain. FOS (50 and 100 mg/kg) also attenuates inflammation via suppressing serum LPS levels, and downregulates the expression of TLR-4, NF-κB p65, TNF-α, and IL-6 in both colon and brain. FOS exhibits potent anti-inflammatory and analgesic effects by deactivating the LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway, reducing oxidative stress, and restoring the gut-brain axis, supporting its potential as a gut-targeted therapy for postmenopausal chronic pain and inflammation.

Psoriasis is a chronic inflammatory skin disease characterized primarily by hyperproliferation of keratinocytes, infiltration and activation of immune cells, including T lymphocytes and macrophages, as well as increased innervation by sensory neurons. Although several therapeutic options are available, the management of psoriasis remains unsatisfactory, with adverse effects and unmet clinical needs. In this context, channels from the Transient Receptor Potential (TRP) family, which are non-selective cation channels involved in various pathologies, have been identified as potential therapeutic targets for treating psoriasis. Growing evidence suggests the involvement of multiple TRP subtypes in the pathogenesis of psoriasis, including altered expression of vanilloid subtypes, such as TRPV1, TRPV3, TRPV4, TRPV6, the canonical TRPC6, and melastatin TRPM8 in patients. These channels are involved in processes such as keratinocyte differentiation and proliferation, immune cell activation (e.g., T cells), and sensory neuron stimulation. Although there are still few studies on the role of TRPs in the therapies currently used for psoriasis, there is evidence of the activation of TRPV1 and the TRPA1 subtypes in the adverse effects of topical pharmacotherapy and phototherapy. On the other hand, TRPV1 desensitization (usually produced by repeated treatment with the TRPV1 agonist capsaicin) can reduce the severity of psoriasis and pruritus. Thus, the pharmacological modulation of TRP channels represents a promising strategy for developing novel, efficacious, and safer therapies to treat patients with psoriasis. This review aimed to provide a comprehensive overview of the involvement of TRP channels in the pathogenesis and therapeutic approaches to psoriasis.

Inflammation is a complex biological response that varies significantly depending on the underlying disease or stress state, profoundly influencing the efficacy and safety of anti-inflammatory drugs. This review explores the multifaceted concept of drug-disease interactions in inflammatory conditions, highlighting how pathophysiological changes in autoimmune, metabolic, gastrointestinal, and infectious diseases modify pharmacokinetics and pharmacodynamics, thereby altering therapeutic responses and adverse effect profiles. We analyse a wide range of clinical studies and experimental models to elucidate the underlying mechanisms driving these interactions. The review further emphasizes personalized medicine approaches, including biomarker-guided therapies and pharmacogenomic insights, that enable tailored treatment strategies to improve patient outcomes. Strategies to optimize therapy in diverse disease states, such as drug repurposing and modulation in response to stress or comorbidities, are thoroughly examined. Additionally, emerging technologies and advanced experimental models are discussed to address current gaps and inform future research directions in conditional pharmacology. By synthesizing basic scientific knowledge with clinical practice, this comprehensive analysis aims to provide clinicians and researchers with critical insights necessary to enhance the safety and efficacy of anti-inflammatory treatments across a spectrum of inflammatory disorders.

Curcuma comosa Roxb., a Thai medicinal plant, has long been used to relieve postmenopausal symptoms and is known to exhibit anti-inflammatory properties. Isocoronarin D, a labdane diterpene and the main bioactive compound in the aerial parts of C. comosa, has previously been reported to induce foetal haemoglobin synthesis. However, its anti-inflammatory activity, predicted molecular targets, pharmacokinetic characteristics, and toxicity remain insufficiently characterised. Therefore, this study integrates in silico predictions of its molecular targets, pharmacokinetic behaviour and toxicity with in vitro validation of its anti-inflammatory effects and underlying mechanisms to address these knowledge gaps. Initially, network pharmacology analysis identified protein kinase Cδ (PKCδ), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2) as inflammation-related targets computationally associated with isocoronarin D. These predicted targets were subsequently validated in vitro, where isocoronarin D significantly reduced the production of inflammatory mediators, including inducible nitric oxide synthase (iNOS), COX-2, tumour necrosis factor-α, interleukin (IL)-1β, and IL-6, in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Moreover, isocoronarin D inhibited the phosphorylation of PKCδ, PI3K, and Akt, indicating suppression of key inflammatory signalling pathways. The observed inhibition of these inflammatory proteins, together with the predicted interactions revealed by molecular docking, supports a mechanistically relevant role for these proteins as inflammatory targets of isocoronarin D. In addition, in silico SwissADME, pkCSM, and GUSAR analyses suggested drug-like characteristics, favourable pharmacokinetic properties, and a non-toxic safety profile. Collectively, these findings indicate that isocoronarin D exerts multi-target anti-inflammatory activity and warrants further in vivo investigation to better elucidate its therapeutic relevance in inflammation-related diseases.

Ulcerative colitis (UC) represents a chronic, relapsing inflammatory condition primarily affecting the colonic and rectal mucosa, presenting substantial challenges to healthcare systems globally. Conventional therapeutic approaches, including aminosalicylates, corticosteroids, immunosuppressants, and biological agents, face significant limitations including premature drug release, systemic toxicities, narrow therapeutic windows, and inadequate colonic accumulation. Hydrogel-based drug delivery systems have emerged as promising platforms for addressing these multifaceted challenges through their unique physicochemical properties, biocompatibility, and versatile functionalization capabilities. This comprehensive review examines the current landscape and future potential of hydrogel-enabled drug delivery for ulcerative colitis therapy, encompassing material design strategies, stimuli-responsive mechanisms, targeting approaches, and therapeutic cargo delivery. Natural polymer-based hydrogels, including polysaccharides and proteins, offer exceptional biocompatibility and intrinsic therapeutic properties, while synthetic and hybrid systems enable precise control over release kinetics and mechanical properties. Stimuli-responsive mechanisms, including pH, enzyme, and redox sensitivity, facilitate site-specific drug release in response to pathophysiological conditions unique to the inflamed colon. Advanced targeting strategies encompass mucoadhesive systems, cell-specific delivery, and inflammation-site accumulation mechanisms. The therapeutic cargo has expanded from traditional small molecules to encompass biologics, living therapeutics, and engineered nanomedicines. Novel formulation technologies, including injectable systems, microencapsulation approaches, and hybrid delivery platforms, demonstrate superior therapeutic efficacy in preclinical models compared to conventional formulations. Clinical translation faces challenges related to scalability, regulatory considerations, and personalized medicine implementation. Future perspectives point toward smart hydrogels with artificial intelligence integration, combination therapies, gut-brain axis targeting, and biomarker-guided precision medicine approaches. The convergence of materials science, biotechnology, and digital health technologies positions hydrogel-based therapeutics at the forefront of inflammatory bowel disease management, promising to transform treatment paradigms and improve outcomes for millions of patients worldwide.