Inflammopharmacology最新文献

The relation between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and severity of COVID-19 has been the subject to debate since the outbreak of the pandemic. Despite speculations about the possible harmful or protective effects, the position currently most supported by the scientific community is that there is no association between use of NSAIDs and COVID-19 outcomes. With the aim of contributing to increase the body of evidence on this issue, we conducted a case-control study using real-world data to investigate the association between prior use of NSAIDs, by active ingredient and type (traditional NSAIDs and selective COX-2 inhibitors), and important COVID-19-related outcomes, including susceptibility, PCR + patient progression, and hospitalisation. Our findings suggest that, in general, the use of traditional NSAIDs is not associated with any adverse COVID-19 outcome. However, we observed a possible association between diclofenac and a higher risk of PCR + patient progression. Our results also suggest that selective COX-2 inhibitors might be related with a reduction in the risk of PCR + patient progression. These results suggest that, with the possible exception of diclofenac, the use of NSAIDs should not be advised against for relief of symptoms in patients with COVID-19. In addition, they support the importance of continue to investigate the treatment potential of selective COX-2 inhibitors in the management of COVID-19, something that could have significant implications for the treatment of this disease and other viral infections.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) staining revealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction.

Background: The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro, in vivo assays and in silico approaches.

Methods: In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE_2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA).

Results: β-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat's paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE₂, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100 mg/kg) increased gastric PGE_2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues.

Conclusions: The anti-inflammatory, anti-oxidant, and gastro-protective effects of β-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE_2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.

Background: Long COVID (LC) is a frequent complication of COVID infection. It usually results in cognitive impairment, myalgia, headache and fatigue. No effective treatment has been found yet. We aimed to explore the effect of glucocorticoid (GC) treatment during COVID-19 infection on the later development of LC.

Methods: We examined electronic health records from Clalit Health Services for documentation of COVID-19, GC treatment, and LC frequency. Background diagnoses, demographic data, hospitalization rates, and the use of anti-COVID drugs were recorded.

Results: 1,322,599 cases of COVID-19 infection met the inclusion criteria; 13,530 patients (1.02%) received GC treatment. 149,272 patients, 11.29% of COVID-19 patients were diagnosed with LC. Age and female gender were prognostic risk factors for LC (OR 1.06 for age, OR 1.4 for female gender; p value < 0.0001). Background psychiatric diagnoses, migraine, backache and irritable bowel syndrome were predisposing conditions for LC (OR 2.7, p value < .0001). Higher BMI was associated with a greater probability of LC (OR of 1.25 for obese population). COVID patients who received GC were diagnosed with LC more frequently: 2294 cases (16.95%) compared to 146,978 cases (11.23%) in the non-GC group; (adjusted OR of 1.28 ± 0.07, 95% CI, p < 0.0001).

Conclusions: GC treatment during COVID-19 is correlated with the development of LC. In vivo and animal models may be used to explore the mechanism of this correlation. Future directions include prospective studies as well.

Background: The clinical presentations of Parkinson's disease (PD), a chronic neurodegenerative condition, include bradykinesia, hypokinesia, stiffness, resting tremor, and postural instability. Recently, neuroinflammation is involved in pathogenesis of PD. Application of nonsteroidal anti-inflammatory drugs captured attention to treat these neuroinflammation.

Aim: To investigate the possible effectiveness of celecoxib in patients with PD treated with conventional treatment.

Methods: Sixty outpatients who fulfilled the inclusion requirements for PD were enrolled in this randomized, prospective, and controlled study. The patients were allocated into two groups at random (n = 30); the control group received standard PD treatment, consisting of levodopa/carbidopa, and the celecoxib group received standard PD treatment plus celecoxib. A neurologist evaluated each patient at the beginning of the treatment and after 6 months. Assessment of Unified Parkinson's disease rating scale (UPDRS) for each patient. Before and after treatment, α -synuclein (α-Syn), tumor necrosis factor alpha (TNF-α), Toll like receptors-4 (TLR-4), nuclear factor erythroid 2-related factor 2 (Nrf-2) and brain-derived neurotropic factor (BDNF) were assessed. Paired and unpaired t tests were used to assess statistical significance within and between groups respectively.

Results: The celecoxib group exhibited a significant and statistical reduction in the level of measured parameters by unpaired t test as followed: TLR-4 (p = 0.004), TNF-α (p = 0.042), and α-Syn (p = 0.004) apart from a significant increase in BDNF (p = 0.0005) and Nrf-2 (p = 0.004), in comparison with the control group. Also, UPDRS was significantly decreased in celecoxib group (p < 0.05).

Conclusion: Celecoxib could be a promising adjuvant therapy in managing patients with PD.

Trial registration number: NCT05962957.

Inflammatory bowel disease is a chronic inflammatory disorder accompanied by occasional flare-ups, abdominal pain, and rectal bleeding. Persicaria bistorta Samp. is a medicinal plant repeatedly mentioned in traditional Persian medicine for the treatment of bleeding and tissue damage in different organs, including the intestines. The current study aimed to evaluate the effect of bistort root in an animal model of colitis. Freeze-dried aqueous extract of the plant (PB) was prepared and analyzed using liquid chromatography-mass spectrometry and high-performance liquid chromatography. The anti-inflammatory effect of oral PB (300, 500, and 700 mg/kg) was evaluated in acetic acid-induced colitis in Wistar rats compared with negative control and positive control (dexamethasone). The role of nitric oxide (NO), opioid receptors, Toll-like receptors (TLR-4), interleukin (IL)-1β, IL-6, TNF-α, NF-κB, myeloperoxidase, and intestinal tissue damage using immunohistochemistry staining for cyclooxygenase-2 (COX-2) were also assessed. A total of 29 compounds were identified in the extract. The gallic acid content of the extract was 4.973 ± 1.102 mg/g. PB significantly ameliorated the gross morphological damage from 4.66 ± 0.577 in negative control to 1.33 ± 0.56 in PB 700 (p < 0.001). Also, PB 700 lowered the levels of TNF-α (p < 0.01), TLR-4 (p < 0.001), NF-κB (p < 0.0001), IL-1β (p < 0.0001), and IL-6 (p < 0.0001) compared to the negative control. Additionally, while blocking NO and opioid pathways, the therapeutic effect of the extract was not significant, compared to the negative control, suggesting that PB 700 has exerted its therapeutic effect via these two pathways. However, further mechanistic and clinical studies are recommended to confirm PB as a natural treatment for colitis.

Alzheimer's disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ_(25-35) in glial (BV-2 and SW-1783) and neuron (SH-SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA-Trpv1-Nrf2 pathway.

Background: There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.

Methods: By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic, colocalization, and assessment of horizontal pleiotropy, were further conducted to validate the discovered genes. In addition, replication analyses were performed in AD GWAS from the FinnGen consortium. Finally, we further identified existing drugs that target or interact with the druggable genes and reviewed the studies about the associations between these drugs and AD.

Results: SMR analysis revealed 342 genes associated with AD across 14 immune cell types. Further sensitivity analyses identified nine genes, CTSH, FCER1G, FNBP4, HLA-E, JAZF1, KNOP1, PLEKHA1, RP11-960L18.1, and ZNF638 that had significant associations with AD across nine specific immune cell types. JAZF1, KNOP1 and PLEKHA1 were replicated in an independent analysis using the GWAS data. The review on gene-related drugs also supported these findings.

Conclusions: Our research suggests that the expression of the genes JAZF1, KNOP1, and PLEKHA1 in specific immune cell types is related to the risk of AD.

Gaultheria trichophylla Royle is a traditional treatment for inflammatory conditions including arthritis. The objective was to evaluate the anti-arthritic activity of the extracts and salicylate-rich fractions through adjuvant-induced arthritis, histopathological analysis, radiological imaging, hematological, biochemical parameters along with using bioinformatic tools. In vivo anti-arthritic efficacy of the extract and SRF (at 100, 200, 300, and 150 mg/kg doses) was assessed using healthy albino rats. Molecular docking of identified compounds along with network pharmacology analysis helped to determine the route of action of drug. Both the extract and SRF showed dose-dependent anti-arthritic activity by decreasing the joint diameter, increase in pain threshold and body weight compared with negative control group. Along with SRF (150 mg/kg), EEGT (300 and 200 mg/kg) shows significant (P < 0.01) anti-arthritic activity by lowering levels of WBC, platelets, serum C-reactive protein (CRP), and rheumatoid factor (RF) and raising levels of RBC and Hb. The modified biochemical measures (AST, ALT, ALP, and total protein level) further supported the anti-arthritic action. Histopathology and radiology study showed that EEGT (300 and 200 mg/kg), SRF (150 mg/kg) and diclofenac (10 mg/kg) inhibited joint destruction. GCMS analysis showed the presence of methyl salicylate, sitosterol, calcifediol, and ergosta-5,22-dien-3-ol, acetate as important bioactive constituents. Moreover, as the significant node in the pharmacology network and docking against TNF-α, a classical therapeutic target in RA showed potential of G. trichophylla in treatment of RA. The results showed that G. trichophylla have effectively reduced the inflammation of the joints.

The increased production of reactive oxygen species (ROS) by human neutrophils can lead to oxidative imbalances and several diseases, such as inflammatory bowel disease (IBD). Opuntia ficus-indica (O. ficus-indica) is rich in bioactive substances with anti-inflammatory properties. This study aimed to identify the bioactive compounds present in aqueous cladodes extract (ACE) of O. ficus-indica using high-performance liquid chromatography (HPLC) and to test its effects on human neutrophil inflammatory functions and on ulcerative colitis (UC) induced by acetic acid (Aa) in rats. ROS production and degranulation by neutrophils were assessed by luminol-amplified chemiluminescence, enzymatic techniques, and western blotting. In vivo, the experiment involved seven groups of rats: a negative control group (NaCl), the acetic acid group (Aa), and groups treated with oral sulfasalazine (150 mg/kg) or various doses of ACE for 7 days. Colonic lesions were induced by an intra-rectal Aa injection, and inflammation was assessed. HPLC analysis identified gallic acid, catechin, caffeic acid, and ferulic acid as major compounds in ACE. In vitro, ACE inhibited neutrophil ROS production, including superoxide anion produced by NADPH oxidase, and significantly reduced myeloperoxidase activity and neutrophil degranulation. In vivo, ACE protected rats from Aa-induced histopathological damage of the colonic mucosa, significantly increased catalase, superoxide dismutase and reduced glutathione levels, and significantly suppressed the increases of plasma cytokines (TNF-α and IL-1β) observed in the Aa group. In conclusion, O. ficus-indica ACE has significant anti-inflammatory properties by restoring oxidative balance, indicating that it could be a potential source of therapeutic agents for inflammatory diseases, particularly UC.