Inflammopharmacology最新文献

Volatile oils (VOs), synonymously termed essential oils (EOs), are highly hydrophobic liquids obtained from aromatic plants, containing diverse organic compounds for example terpenes and terpenoids. These oils exhibit significant neuroprotective properties, containing antioxidant, anti-inflammatory, anti-apoptotic, glutamate activation, cholinesterase inhibitory action, and anti-protein aggregatory action, making them potential therapeutic agents in managing neurodegenerative diseases (NDs). VOs regulate glutamate activation, enhance synaptic plasticity, and inhibit oxidative stress through the stimulation of antioxidant enzymes. They also reduce inflammation by inhibiting key inflammatory mediators and enzymes. Furthermore, VOs prevent neuronal apoptosis by modulating apoptosis-related proteins and caspases. Their anti-protein aggregation potential helps mitigate the accumulation of misfolded proteins, a hallmark of neurodegenerative disorders. Additionally, VOs inhibit cholinesterase enzymes, increasing acetylcholine levels, and improving neuronal communication. In addition to their neuroprotective action, it also exerts some toxic effects, such as genotoxicity, hepatotoxicity, embryotoxicity, and hypersensitivity, which are most commonly caused by the presence of monoterpenes in the volatile oils. This review examines the diverse functions of vasoactive oxidants (VOs) in neuroprotection, underscoring their therapeutic promise for various neurological conditions, with a particular emphasis on Alzheimer's disease.

Background: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.

Methods: A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4⁺ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.

Results: Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.

Conclusion: Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.

Alzheimer's Disease (AD), a progressive and age-associated neurodegenerative disorder, is primarily characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. Despite advances in targeting Aβ-mediated neuronal damage with anti-Aβ antibodies, these treatments provide only symptomatic relief and fail to address the multifactorial pathology of the disease. This necessitates the exploration of novel therapeutic approaches and a deeper understanding of molecular signaling mechanisms underlying AD. Phosphodiesterases (PDEs), particularly Phosphodiesterase 4 (PDE4), play a pivotal role in regulating cyclic adenosine monophosphate (cAMP), a key molecule involved in memory consolidation and cognitive function. PDE4 inhibitors have demonstrated potential in enhancing memory and cognition in preclinical models of AD by modulating cAMP signaling. However, their clinical translation has been limited due to challenges such as adverse effects, narrow therapeutic windows, and low specificity in mechanism of action. This review bridges the gap between preclinical discoveries and clinical applications of PDE4 inhibitors in AD. It highlights preclinical evidence supporting the neuroprotective and anti-inflammatory effects of PDE4 inhibitors while addressing challenges in their clinical development, including issues of safety, efficacy, and disease-specific targeting. By integrating findings from both preclinical and clinical studies, we provide a comprehensive understanding of the therapeutic potential of PDE4 inhibitors in AD. Furthermore, this review outlines future research directions aimed at optimizing PDE4 inhibition strategies for AD treatment, offering a roadmap to translate foundational insights into clinical realities.

Osteoarthritis, the most common arthritic condition, is an age-related progressive disease characterized by the loss of cartilage and synovial inflammation in the knees and hips. Development of pain, stiffness, and considerably restricted mobility of the joints are responsible for the production of matrix metalloproteinases and cytokines. Although several treatments are available for the management of this disease condition, they possess limitations at different levels. Recently, efforts have focused on regulating the production of the NLRP3 inflammasome, which plays a critical role in the disease's progression due to its dysregulation. Inhibition of NLRP3 inflammasome has shown the potential to modulate the production of MMP-13, caspase-1, IL-1β, etc., which has been reflected by positive responses in different preclinical and clinical studies. Aiming inhibition of this NLRP3 inflammasome, several compounds are in different stages of research owing to bring a novel agent for the treatment of osteoarthritis. This review summarizes the mechanistic pathways linking NLRP3 activation to osteoarthritis development and discusses the progress in new therapeutics aimed at effective treatment.

Objective: The aim of this study was to comprehensively investigate the clinical efficacy of intraoperative local joint injection and intramuscular injection of betamethasone in patients with severe traumatic knee osteoarthritis (KOA).

Methods: 80 patients with severe traumatic KOA undergoing total knee arthroplasty were retrospectively recruited and rolled into S1 group (intra-articular injection of ropivacaine + betamethasone and isotonic saline mixture at joint incision), S2 group (muscle local injection of betamethasone before incision closure, simultaneously intra-articular injection of ropivacaine + isotonic saline mixture at joint incision), and D group (intra-articular injection of ropivacaine + isotonic saline mixture at the joint incision). Visual analog scale (VAS) score, serum inflammatory factors (IFs), hospital for special surgery (HSS)score, Pittsburgh sleep quality index (PSQI), and adverse reaction events (AREs) were analyzed.

Results: Pain scores of patients in all three groups decreased drastically over time on postoperative days (PDs) 1, 2, and 3, with the scores in S1 and S2 groups markedly inferior to D group (P < 0.05). HSS scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were considerably superior to those in D group (P < 0.05). PSQI scores of patients in S1 and S2 groups at postoperative months 1, 3, and 6 were notably inferior to those in D group (P < 0.05).

Conclusion: Both intraoperative local joint injection and muscle injection of betamethasone are effective in patients with severe traumatic KOA.

Maejo 341 Sweet potato (MSP) is a new purple sweet potato variety cultivated in Northern Thailand, but its health benefits are unknown. This study aimed to investigate its antioxidant, anti-inflammatory, and anti-osteoporotic activities, as well as its anthocyanin content. The peel and flesh of MSP were extracted with ethanol and water. Compared with the flesh extracts, the peel extracts presented greater antioxidant capacity and were rich in phenolics, flavonoids, and anthocyanins, namely, cyanidin-3-O-glucoside, peonidin-3-O-glucoside, pelargonidin-3-O-glucoside, cyanidin, and peonidin. The peel extracts suppressed lipopolysaccharide-induced inflammation by inhibiting the secretion of proinflammatory cytokines and enzymes, including TNF-α, IL-1β, IL-6, COX-2, and iNOS, as well as reducing nitric oxide and matrix metalloproteinase-9 secretion. The extracts inhibited the RANKL-induced NF-κB and MAPK pathways and downregulated osteoclastogenic marker expression. Under LPS and RANKL treatment, the peel extracts notably reduced reactive oxygen species production while increasing antioxidant gene expression. Furthermore, they increased osteoblast viability and slightly raise alkaline phosphatase activity. These findings suggest that MSP peel could be used as a functional food to alleviate oxidative stress and inflammation-related osteoporosis.

Objective: This study aimed to assess the potential antifibrotic impact of zinc sulfate in chronic Hepatitis C Virus (HCV) patients receiving direct-acting antiviral therapy.

Methods: This randomized controlled study included 50 chronic HCV-infected patients with fibrosis stage (F1 & F2). Participants were randomly assigned to two groups: Group 1 (Control group, n = 25) received standard direct-acting antiviral therapy for 3 months, while Group 2 (Zinc group, n = 25) received 50 mg/day of zinc sulfate in addition to the standard direct-acting antiviral therapy for the same duration. Baseline and 3-month post-intervention assessments included evaluating serum levels of hyaluronic acid, transforming growth factor beta-1, and fibronectin. Furthermore, indices of liver fibrosis, such as the Fibrosis Index based on the 4 factors (FIB-4) and the Aspartate Transaminase-to-Platelet-Ratio Index (APRI), were calculated during these assessments.

Results: At baseline, the two studied groups had no statistical difference in demographic and laboratory data. After treatment, serum zinc levels significantly increased in the zinc-treated group compared to the control group. Additionally, serum fibronectin and hyaluronic acid levels were significantly reduced in group 2 (zinc group) compared to group 1 (control group). Moreover, zinc group showed lower APRI scores than the control group after a 3-month follow-up period, but there was non-significant difference in FIB-4 scores between the two groups after treatment. Furthermore, total bilirubin levels were reduced after zinc therapy for 3 months.

Conclusions: Administering zinc sulfate could potentially serve as a safe and efficient therapeutic strategy for the management of hepatic fibrosis in individuals with chronic hepatitis C virus.

Trial registration: ClinicalTrials.gov identifier: NCT05465434, On 19/7/2022.

Background: Chronic inflammation has been linked to many psychiatric disorders, and therefore, pertinent anti-inflammatory therapies have been empirically evaluated for management. An enduring example of long-term safety, attainability, and versatility has been pentoxifylline (PTX). PTX is a phosphodiesterase inhibitor that modulates inflammatory mediators and affects most blood components and the blood vessels.

Methods: Major databases were systematically searched to identify randomized controlled trials (RCTs) on PTX in psychiatric and neuropsychiatric disorders until September 25, 2024.

Results: 21 RCTs were included. Five studies evaluated clinical depression: four on major depressive disorder (MDD) and one on bipolar patients experiencing treatment-resistant depression. PTX significantly reduced depressive symptoms in MDD in the four double-blind, randomized, placebo-controlled trials, with the three studies combining PTX and SSRIs showing statistically significant improvements in response rates. Ten RCTs on cognitive impairment reported beneficial effects, particularly in vascular dementia. Meta-analyses support its efficacy in reducing depressive symptoms, cognitive decline, asthenia, and inflammatory markers.

Conclusion: Exploring the effects of PTX on psychiatric and neuropsychiatric conditions has provided considerable support for its utility across various disorders, most notably in moderate to severe major depressive disorder (as adjunctive therapy with SSRIs) and cognitive impairment in vascular dementia (as monotherapy). Relevantly, the potential of PTX across a wide range of conditions might prove beneficial in cases of co-occurrence.

Alzheimer's disease (AD) is a type of neurodegenerative disease that describes cognitive decline and memory loss resulting in disability in movement, memory, speech etc. Which first affects the hippocampal and entorhinal cortex regions of brain. Pathogenesis of AD depends on Amyloid-β, hyper-phosphorylation of tau protein, mitochondrial dysfunction, cholinergic hypothesis and oxidative stress. In comparison with males, females are more prone to AD due to reduced estrogen level. Some of the FDA-approved drugs and their conventional formulations available in the market are discussed in this review. Nose-to-brain delivery system provides the target specific drug delivery via olfactory and trigeminal nerve (active and passive drug targeting strategies) and bypassing the Blood Brain Barrier. Mucoadhesive agents and permeation enhancers are mostly utilized to enhance the retention time and bioavailability of the drugs. Liposomes, niosomes, cubosomes, solid lipid nanoparticles, nanoemulsions, micelles, and many more nanocarriers for nose-to-brain delivery of drugs are also described thoroughly in this review. It also covers the clinical trials and patents for nose-to-brain delivery. In this article, we investigate the nose-to-brain pathways for AD treatment strategies.