Inflammopharmacology最新文献

Diabetic arthritis (DA) is a microvascular complication associated with diabetes mellitus (DM), necessitating the exploration of innovative therapeutic approaches. The Amazon biome, rich in bioactive compounds, offers potential treatments; notably, Bixa orellana, which contains tocotrienol and geranylgeraniol, exhibits anti-inflammatory and antioxidant properties, particularly when formulated as a nanodispersion.

Objective: This study aims to investigate the pharmacological effects of an injectable nanodispersion of Bixa orellana, termed Chronic-in®, in diabetic Wistar rats.

Method: Male Wistar rats were employed in the study, and DA was induced using an intraperitoneal injection of 100 mg/kg alloxan and an intraplantar administration of Freund's complete adjuvant. The animals were divided into five groups (n = 5): CON (normal rats treated with saline solution IM), CHR SC (DA rats treated with Chronic-in SC daily), SS (DA rats treated with saline solution IM), IND (DA rats treated with indomethacin orally), and CHR IM (DA rats treated with Chronic-in IM every 3 days). Treatment outcomes were assessed through various parameters, including changes in paw edema, Arthritic Index (AI), performance in the open field and Rotarod tests, radiographic evaluations using the Eichenholtz classification, Scanning Electron Microscopy (SEM) analysis of articular morphology, and hematological and biochemical assessments.

Results: Significant reductions in edema were observed in the CHR SC, CHR IM, and IND groups (p < 0.001) compared to the SSA group. The AI showed significant differences among the CON, CHR SC, and CHR IM groups. Enhanced exploratory behavior was noted in the open field test for the Chronic-in-treated groups, particularly with IM administration. The Rotarod test demonstrated marked differences between the Chronic-in-treated, CON and SS groups. Radiographic and SEM evaluations indicated fewer bone alterations in the CHR IM and SC groups compared to the SSA and IND groups, along with preservation of articular surfaces. Histological assessments revealed thickened synovial membranes and pannus formation in the SS and IND groups. In contrast, CHR IM and CHR SC groups exhibited minimal loss of proteoglycans akin to the CON group.

Conclusion: Treatment with Chronic-in via both IM and SC routes effectively mitigated the inflammatory manifestations of diabetic neuropathic arthritis, demonstrating lower pain intensity during ambulation and protective effects against inflammation and joint integrity as evidenced in histological analyses. These findings suggest that Chronic-in represents a promising therapeutic option for diabetic arthritis.

Background: Alzheimer's disease (AD), one of the most common neurodegenerative disorders, is characterised by hallmark abnormalities such as amyloid-β plaques and neurofibrillary tangles (NFTs). Emerging evidence suggests that faulty insulin signalling contributes to these pathological features, impairing critical cellular and metabolic processes.

Objective: This review aims to elucidate the role of insulin signalling in the central nervous system (CNS) under normal and pathological conditions and to explore therapeutic approaches targeting insulin pathways in AD and other neurodegenerative diseases.

Methods: We reviewed studies highlighting the involvement of insulin-signalling pathways in neuronal health, with a particular focus on the key components-IRS, PI3K, Akt, and GSK-3β-predominantly expressed in cortical and hippocampal regions.

Results: Insulin, an essential growth factor, regulates numerous cellular functions, including glucose metabolism, mitochondrial activity, oxidative stress response, autophagy, synaptic plasticity, and cognitive processes. Altered phosphorylation of signalling molecules in insulin pathways contributes to oxidative stress, inflammation, and the formation of AD hallmarks. Indirect modulators such as NF-κB and caspases further exacerbate neuronal damage, linking impaired insulin signalling to neurodegeneration.

Conclusion: Insulin signalling plays a crucial role in maintaining neuronal health and mitigating neurodegenerative processes. Targeting insulin pathways and associated molecules offers promising therapeutic avenues for AD and other neurodegenerative disorders.

Psoriasis, a chronic autoimmune disorder, is characterized by keratinocyte hyperproliferation and inflammatory responses. Curcumol, a bioactive terpenoid, possesses antiproliferative and anti-inflammatory properties. This study evaluates the efficacy of curcumol in treating psoriasis in both in vitro and in vivo models. In vitro, curcumol inhibits hyperproliferation and inflammatory responses in a psoriatic HaCaT keratinocyte model stimulated by M5 cytokines by inhibiting the PI3K-Akt pathway. Additionally, in vivo, curcumol ameliorates psoriasis-like skin lesions and inflammatory status in imiquimod-induced mice. Network pharmacology revealed that curcumol's beneficial effects might involve the PI3K-Akt signaling pathway. Further investigation shows that curcumol partially counteracts the activation of PI3K-Akt by recilisib in keratinocytes. These results suggest that curcumol may be a promising therapeutic option for psoriasis.

S100 calcium-binding protein B, a member of the S100 protein family, plays an important role in the pathogenesis of Alzheimer's disease. Alzheimer's disease, a neurodegenerative disorder, is characterized by amyloid-beta plaques, neurofibrillary tangles, progressive dementia, and severe neuroinflammation. S100 calcium-binding protein B, predominantly secreted by astrocytes, exhibits a dual role in Alzheimer's disease, where at low (nanomolar) concentrations, it exhibits neurotrophic and neuroprotective effects and enhances synaptic plasticity, while at higher concentrations, it contributes to neuroinflammation and neuronal damage. In addition to its pathological roles in Alzheimer's disease, S100 calcium-binding protein B is also considered a potential biomarker, as increased levels correlate with cognitive decline and disease progression in cerebrospinal fluid. Targeting S100 calcium-binding protein B and/or its interaction with the receptor for advanced glycation end-products seems to be a potential target for therapeutic intervention. The development of multiple treatment approaches, such as pharmacological inhibitors, immunotherapy, and modulation of S100 calcium-binding protein B / receptor for advanced glycation end-products signalling pathways, might help to reduce neuroinflammation and amyloid-beta deposition effectively. This review aims to provide an overview of the role of S100 calcium-binding protein B in Alzheimer's disease and to explore its potential as a treatment target, well-grounded in its dual nature. Understanding S100 calcium-binding protein B's involvement in the pathogenesis of Alzheimer's disease may advance its application as a biomarker and help in the development of new treatment strategies, ultimately improving patients' quality of life.

Parkinson's disease (PD) is characterized by motor impairment, glial-mediated inflammation, redox imbalance, and α-synuclein (α-syn) aggregation. Conventional therapies relieve early PD symptoms, but they do not repair dopaminergic neurons. Berberine (BBR) and caffeine (CAF), both natural alkaloids, exhibited neuroprotective effects in many neurodegenerative disorders. Consequently, we hypothesized that the combination of BBR and CAF therapies would offer protection against PD-related impairments in the rotenone (ROT)-induced rat model when compared to the commercial drug, metformin (MTF). Our results showed that the combined administration of BBR (25 mg/kg/day) and CAF (2.5 mg/kg/day) for four weeks prevented motor deficits, weight reduction, dopamine (DA) depletion, and monoamine oxidase (MAO) activity in ROT-induced rats in comparison with monotherapy of BBR and CAF along with MTF. This combination produced a notable neuroprotective effect by reducing tumor necrosis factor (TNF)-α and interleukin-16 (IL-6) in midbrain of rats. BBR and CAF combinations markedly normalized tyrosine hydroxylase (TH) levels and decreased total α-syn and α-syn-p^ser129 aggregation and increased protein phosphatase 2A (PP2A) levels. Histological analysis indicated that damaged neurons exhibited significant amelioration with the co-administration of BBR and CAF. The molecular docking results indicated that both BBR and CAF had notable binding affinity for the protein pocket surrounding the α-syn, PP2A, and TH in comparison to MTF. They are predicted to serve as effective inhibitors of enzyme-mediated phosphorylation of α-syn-^pser129. Conclusively, combined BBR and CAF administration presents a novel strategy for neuroprotection by blocking the initial events in PD incidence, demonstrating considerable anti-oxidative and anti-inflammatory benefits relative to MTF.

Medicinal herbs continue to play an important part in modern drugs and healthcare because customers think that most of them have fewer or milder side effects than traditional modern medicines. Bioactive compounds are typically isolated from plants before being used as a source of therapeutic medicines. As a result, extracting bioactive compounds from medicinal plants is an important step in developing plant-based medications. Orientin is a flavonoid C-glycoside found in many plants, is frequently used in bioactivity studies due to its numerous beneficial properties, which include antioxidants, antiaging, anti-inflammation, vasodilation and cardioprotective, neuroprotective, antidiabetic, hepatoprotective, and adaptogenic effects. In this review, the comprehensive search for the health benefits of orientin was traced. The findings reflected that orientin could be considered one of the important natural candidates as a potential nutraceutical. This underscores its promising attributes and potential applications in health and wellness. Further research may be guaranteed to fully elucidate its benefits and mechanisms of action.

The present study explores the metabolic profiling and molecular wound-healing mechanisms of Echinacea purpurea (L.) Moench (EP) flowers aqueous (AE) and ethanol (EE) extracts in an excision wound-healing model. Metabolic profiling of the extracts was investigated using UHPLC-ESI-TOF-MS and molecular networking. Antioxidant activity was carried out using the DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and FRAP (ferric reducing antioxidant power). Carboxy methylcellulose gels of 5 and 10% of both aqueous (AE) and ethanol (EE) extracts were prepared. The wounds were explored macroscopically, histologically, and immunohistochemically. The UHPLC-ESI-TOF-MS method enabled the identification of 3 organic acids, 14 phenolic acids, 3 phenylethanoid glycosides, and 11 flavonoids from EP extracts. EE had significant antioxidant activity compared to AE. The EP treated wounds healed faster. The EE succeeded in improving healing properties and controlling the inflammatory response by reducing IL-6 and increasing IL-10 expression and enhancing angiogenesis and remodeling via increased NF-κB, TGF-β, VEGF, CD31 expression and α-SMA and collagen deposition. It is worth mentioning that the EE groups also showed improvement in the histopathological examination in a dose-dependent manner. The effectiveness of EE in wound-healing may be attributed to its higher content of polyphenols which also made the antioxidant potential of the EE and its capacity to donate electrons higher than that of AE. This study scientifically enables the understanding of the molecular mechanisms Echinacea purpurea extract in wound healing via modulating skin inflammatory response and indicates the potential usefulness of EP ethanol extract for wound healing.

The main objective of the present study was to combine the ethanol extracts of Ziziphus mauritiana and Ziziphus spina-christi (ZMZS) and fractioned with different solvents of increasing polarity for evaluation of antioxidant, anti-inflammatory and analgesic potentials. The ethanolic extracts of leaves were prepared using Soxhlet apparatus, mixed in ratio (1:1 w/w) and then fractionated into n-hexane, ethyl acetate and n-butanol. In vitro antioxidant activity of all fractions was assessed using total phenolic contents (TPC), total flavonoid contents (TFC), 2,2-dipehnyl, 1-picryl hydrazyl (DPPH) free radical scavenging ability, reducing power and bleachability of β-carotene in Linoleic acid system assays. Ethyl acetate fraction (EAF) showed the highest antioxidant activity in terms of the highest TPC (212.15 mg/g) and TFC (39.54 mg/g), better DPPH radical scavenging (IC_50, 4.82 µg/ml), reducing power and β-carotene bleachability. The reverse-phase high-performance liquid chromatography (Rp-HPLC) was performed for the characterization of polyphenols in Ziziphus mauritiana and Ziziphus spina-christi extracts individually and ethyl acetate fraction of ZMZS. Results showed that EAF was enriched with phenolic acids, notable coumarin, gallic acid, salicylic acid and chlorogenic acid, whereas quercetin and kaempferol were the most abundant flavonoids. In vivo anti-inflammatory activity of most potent ethyl acetate fraction was performed using a carrageenan-induced model and analgesic activity using hot plate method in male Sprague Dawley rats. Further, the suppression of inflammatory biomarkers and the oxidative stress parameters were evaluated. Results indicate that EAF possesses significant anti-inflammatory and anti-analgesic properties at 500 mg/kg BW as evidenced by their ability to reduce paw edema, percentage inhibition and prolonged latency time and proinflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP). The EAF also normalized the oxidative stress levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GP_X), reduced glutathione (GSH) and catalase (CAT) when compared to the standard drug indomethacin. The present study concluded that ethyl acetate fraction (EAF) of combined ZMZS extract has remarkable antioxidant as well as anti-inflammatory and analgesic potentials possibly due to interactions of total phenolic and total flavonoid contents.

Background: Recent advancements in the treatment of paediatric dermatological conditions have emerged with the introduction of biologics and small molecule inhibitors (SMIs). These therapies target specific inflammatory pathways, which may enhance treatment outcomes for diseases like atopic dermatitis, psoriasis, and alopecia areata.

Objectives: This systematic review seeks to assess the effectiveness and safety of biologics and SMIs for dermatologic conditions in children and adolescents, with an emphasis on randomised clinical trials.

Methods: We performed an extensive literature search across PubMed, Scopus, and Web of Science, following PRISMA guidelines. Studies included in the review were those that analysed systemic treatments using biologics and SMIs in subjects under 18 years of age. We extracted data on participant demographics, treatment regimens, effectiveness outcomes, adverse effects, and follow-up details. The risk of bias in the studies was determined using the Cochrane Risk of Bias Tool (RoB2).

Results: From an initial pool of 1,454 studies, 49 articles fitting the inclusion criteria were identified, encompassing 6372 cases. The review found that biologics such as Dupilumab, along with investigational JAK inhibitors like Abrocitinib and Upadacitinib, exhibited considerable efficacy in treating various conditions, particularly atopic dermatitis and psoriasis. Dupilumab specifically demonstrated significant improvements in both disease severity and quality of life. While most reported adverse events were mild to moderate, some serious adverse events were noted with certain treatments.

Conclusions: Biologics and SMIs show great promise as therapeutic options in paediatric dermatology, offering better efficacy compared to traditional treatments. Despite these encouraging findings, additional research is needed to verify their long-term safety, especially in relation to growth and development in younger patients. Future investigations should aim to include a broader range of patient demographics and dermatological conditions beyond those currently studied.