Inflammopharmacology最新文献

Nuclear factor kappa B (NF-kB) is a kind of transcription factor which resides in cytoplasm of each cell and on activation, it translocates to the nucleus. It is activated by a many inducible agents including endotoxins, inflammatory stimuli, carcinogens, pathogens, nicotine, and tumour promoters, etc. NF-kB is activated by canonical and non-canonical signalling pathways which has different signalling compounds and its biological functions. It controls the expression of 400 different genes including various enzymes, cytokines, viral proteins, regulatory molecules involved in the cell cycle etc. This pathway is linked with various ailments including respiratory diseases, inflammatory diseases, auto immune diseases, cancer and diabetes. NF-kB factor and signalling pathway are the mainstream of the innate and adaptive immune responses. Human subjects have been able to curb inflammation through inflammaging with the help of the phytomolecules interacting with the NF-κB pathway by adjusting the inflammation processes and alleviating aging stresses in cells. They successfully inhibit the activation of NF-κB, thereby curtailing chronic low-grade inflammation underlying both ageing and age-related disease processes. These phytocompounds discussed herewith not only down-regulate NF-κB-dependent pro-inflammatory pathways but also help build resilience at cellular levels, therefore, offering enhanced healthspan with late commencement of inflammaging pathogenesis. This review describes what stimulation and regulation of the Nuclear Factor kappa B (NF-kB) Pathway and its roles in the pathogenesis of human age related diseases. We also review the recent progress in attenuating the molecular mechanisms of the NF-kB Pathway by phytochemicals, which may open up novel therapeutic avenues.

Background: Impacts of milk proteins (MPs) on inflammation are uncertain. The current systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) evaluated the effects of whey protein (WP), casein protein (CP), or MP supplementation on serum levels of cytokines and adipokines in adults.

Methods: A comprehensive search of various online databases was conducted to find appropriate clinical trials published until September 2024. A random-effect statistical model was implemented.

Results: The meta-analysis included 53 RCTs. It was indicated that MP supplements had no substantial effects on serum values of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), adiponectin, and leptin. However, there were statistically significant decreases in serum levels of interleukin-6 (IL-6) following supplementation with MP (weighted mean difference (WMD): - 0.25 pg/mL, 95% CI - 0.48, - 0.03; P = 0.026) in the intervention group compared with the control group.

Conclusion: This study revealed that MP supplementation may not have any considerable impacts on the levels of cytokines and adipokines.

Background: Ulcerative colitis (UC) is a significant inflammatory bowel disease (IBD) that typically arises from chronic inflammation of the intestinal tract. Report suggest that anti-inflammatory drug plays a crucial role in the protection of UC. The recent study demonstrated that columbianadin has a protective effect against UC induced by dextran sulfate sodium (DSS) in rats through the modulation of HO-1/Nrf2 and TLR4-NF-κB signaling pathways.

Material and methods: In this study, Swiss Wistar rats were utilized, and UC was induced using 2% DSS. The treatment regimen included oral administration of columbianadin (5, 10 and 15 mg/kg) and sulfasalazine to the rats. The body weight, spleen index, disease activity index (DAI), colon length, food and water intake were estimated. Moreover, antioxidant, cytokines, inflammatory and apoptosis parameters were determined. mRNA expression levels were also quantitatively analyzed.

Results: Columbianadin treatment significantly (P < 0.001) boosted the body weight and suppressed the DAI. Columbianadin significantly (P < 0.001) enhanced the colon length and repressed the spleen index along with enhanced food and water intake. Columbianadin significantly (P < 0.001) suppressed the level of lactate dehydrogenase (LDH), myeloperoxidase (MPO) and altered the level of oxidative stress parameters such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), malonaldehyde (MDA), nitric oxide (NO), SA; cytokines level such as interleukin (IL)-1, 1β, 6, 10, 17, 18, TNF-α; inflammatory parameters viz., cyclooxygenase-2 (COX-2), prostaglandin (PGE₂), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-κB), transforming growth factor (TGF-β); apoptosis parameters include Bax, Bcl-2, Bcl-2/Bax ratio, caspase-1 and A-caspase-3 activity, respectively. Columbianadin significantly altered the mRNA expression of IFN-γ, IL-6, IL-1β, IL-8, TNF-α, NF-κB, TLR4, Bcl-2, caspase-9, Bax, p38, ASC, MCP-1, ZO-1, and Ocln. While this study focused on COX-2 modulation as a marker of inflammatory response, no direct measurements or inferences were made regarding leukotriene activity, which involves a separate lipoxygenase pathway.

Conclusion: Columbianadin exhibited the protective effect against DSS-induced UC via alteration of HO-1/Nrf2 and TLR4-NF-κB signaling pathway.

Clove oil obtained from Syzygium aromaticum (L.) is traditionally employed to treat inflammation associated with rheumatism, gastric disorders, and as an analgesic. Chemo-herbal combinations are known to have potent anti-inflammatory and analgesic effects, while mitigating the drug related side effects. The purpose of this study was to evaluate anti-inflammatory, analgesic and antipyretic effects of a combination of flurbiprofen and clove oil in a micro-emulsion (FCM) form using various in vivo models. Micro-emulsion of flurbiprofen and clove oil (FCM) was prepared following reported protocols and three different dose combinations (25, 12.5 and 6.25 mg/kg) were evaluated in carrageenan and histamine-induced acute inflammation, CFA-induced arthritis, yeast-induced pyrexia, and acetic acid-induced writhing models. qPCR studies were conducted to explore the possible mechanism of action. GC-MS of clove oil was performed to explore its chemical composition. FCM 25 mg/kg treated group exhibited significantly better (p < 0.05) effects compared to clove oil (CM) and flurbiprofen (FBR) (25 mg/kg) treated groups in both acute and chronic models. Histopathological study of joints showed a reduction in infiltration of inflammatory cells, bone erosion, and tissue oedema in FCM (25 mg/kg) treated group as compared to other treatment groups. Significant up-regulation in mRNA expression of anti-inflammatory (IL-4, IL-10) and down-regulation of pro-inflammatory genes (NF-κB, IL-6, TNF-α, IL-1β and COX-2) was observed in all the FCM-treated groups but, 25 mg/kg-treated group showed comparatively better results. Gross macroscopic examination of stomach sections also showed relatively less deleterious effects of test treatments (CM and FCM) as compared with FBR treated group. Serum levels of liver enzymes (alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), blood urea nitrogen (BUN) and creatinine were also found to be normal as compared to FBR and tween-water (TW) treated groups. GC-MS of clove oil revealed that it was rich in eugenol contents.  This study reveals that a combination of flurbiprofen and clove oil in a micro-emulsion form could be a promising approach to enhance therapeutic actions and to mitigate synthetic drugs related side effects in clinical settings. It might implicate a synergistic action on the modulation of inflammatory genes expression. Further research is warranted to explore the full potential of this combination in treating various inflammatory conditions.

Rheumatoid Arthritis (RA) is an autoimmune, chronic, systemic inflammatory disease that causes redness, swelling, stiffness, and joint pain. It is a long-lasting disease that can have a widespread impact on the body, often affecting the hands, feet, and wrists. The immune cells, such as dendritic cells, T cells, B cells, macrophages, and neutrophils, play a significant role in bone degradation and inflammation. Several cytokines, including TNF-α and IL-17A, play a significant role in causing bone erosion, cartilage deterioration, and joint inflammation. Progesterone and estrogen have a crucial impact on the pathophysiology of RA, influencing the immune system. Research has demonstrated that hormone replacement therapy (HRT) can effectively reduce inflammation, improve disease activity, enhance joint health, alleviate pain, and promote bone strength. Treatments such as tamoxifen and raloxifene, known as selective estrogen receptor modulators (SERMs), are effective against chronic inflammatory illnesses like RA. The treatment with Gonadotropin-releasing hormone (GnRH) has an impact on the hypothalamic-pituitary-gonadal axis, which in turn affects the activity of RA illness. These alternative treatments hold promise in enhancing well-being and alleviating joint pain for individuals with RA.

The currently approved drugs for Alzheimer's disease (AD) are only for symptomatic treatment in the early stages of the disease but they could not halt the neurodegeneration, additionally, the safety profile of the recently developed immunotherapy is a big issue. This review aims to explain the importance of the drugs repurposing technique and strategy to develop therapy for AD. We illustrated the biological alterations in the pathophysiology of AD including the amyloid pathology, the Tau pathology, oxidative stress, mitochondrial dysfunction, neuroinflammation, glutamate-mediated excitotoxicity, insulin signaling impairment, wingless-related integration site/β-catenin signaling, and autophagy. Additionally, we demonstrated the different repurposed drugs in the experimental models of AD including the anti-inflammatory, anti-hypertensive, anti-diabetic, antiepileptic, antidepressant and anticancer drugs. Further, we showed the pipeline and FDA approved drugs for AD. The repurposed drugs have a promising therapeutic activity against AD, confirming the value of the drugs repurposing technique to elucidate curative therapy for AD.

Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed. ENPs were synthesized using the ion gelation method and their characterization was done. The formulated ENPs had a particle size of 205.1 nm, a polydispersity index of 0.574, zeta potential of 3.6 ± 0.1 mV, and entrapment efficiency of 68%, SEM analysis showed round spherical and irregularity from the outer surface, XRD revealed amorphous nature. Drug release from the carrier by erosion method. For anti-arthritic potential, 0.1 ml Complete Freund's Adjuvant was injected in the left hind paw of all Wistar rats except normal rats on day 1 and treatment with ENPS at 5, 10, 20, ESC and methotrexate (standard drug) was started at 8th day orally and continued for 21 days. Treatment with methotrexate, ESC, and ENPs revealed a significant reduction of paw edema and pain, restoration of body and immune organ weight, Treatment with ENPs 20 mg/kg remarkably (p < 0.0001) restored serotonin and noradrenaline level, oxidation status, hematological and biochemical parameters with significant down-regulation (p < 0.0001) of IL-6, COX-2, TNF-alpha, NF-κβ whereas, up-regulation of IL-4 and IL-10 in comparison to disease control group as obvious from histological examination of sciatic nerve, liver, and ankle joint. The LD₅₀ of ENPs was more than 2000 mg/kg in the acute toxicity study. The ENPs exhibited anti-inflammatory and anti-arthritic activities especially ENPs at 20 mg/kg.

Juice and decoction of leaves of Suaeda fruticosa, a halophytic medicinal plant of Cholistan desert, is traditionally used to treat rheumatism. The current study was carried out to probe into in vivo anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of the whole plant of S. fruticosa (Et-SF) and its bioactive molecules. GC-MS screening of Et-SF revealed presence of various bioactive compounds including phytol, thymol, n-hexadecanoic acid, farnesol, and 1-heptacosanol. DPPH in vitro radical scavenging assay demonstrated moderate antioxidant potential of Et-SF. Safety evaluation of Et-SF confirmed no lethal effects in female albino rats up to the single oral dose of 5000 mg/kg. In  all in vivo models, Et-SF was administered in three doses (125, 250, and 500 mg/kg) and a single dose of flurbiprofen (FP) (10 mg/kg). Et-SF significantly (p < 0.05) attenuated acute inflammation in carrageenan, histamine, and serotonin-induced rat paw oedema models in a time-dependent manner. Et-SF alleviated oedema, restored haematological parameters, and reduced severe pannus formation, inflammatory cell infiltration, and fibrous tissue proliferation in the paws of CFA-induced arthritic rats. Moreover, treatment with thymol, farnesol and n-hexadecanoic acid alone and in combination also attenuated the arthritic progression in the arthritic rats indicating involvement of these compounds towards anti-arthritic potential of Et-SF. Et-SF and FP significantly (p < 0.05) down-regulated IL-1β, TNF-α, IL-6, NF-κB, and COX-2 mRNA expression, and up-regulated IL-4 and IL-10 mRNA expression in arthritic rats. Hot plate and acetic acid-induced writhing models results indicated the analgesic attributes of Et-SF in mice models. This study suggests that S. fruticosa ethanol extract may regulate the expression of inflammatory markers involved in nociceptive, inflammatory, and arthritic disorders. Its phytochemicals could target multiple phases of these conditions at cellular and subcellular levels. Further research is needed to confirm this hypothesis.

Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA's interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors.

Introduction: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a cataclysmic pandemic. Several SARS-CoV-2 mutations have been found and reported since the COVID-19 pandemic began. After the Alpha, Beta, Gamma, and Delta variants, the Omicron (B.1.1.529) is the most recently emerged variant of concern (VOC), which has evolved as a result of a high number of mutations, particularly in the spike protein, raising concerns about its ability to evade pre-existing immunity acquired through vaccination or natural infection.

Methods: This is a review based on studies published from November 2021 to September 2024.

Result and discussions: The current article discusses the advent of the SARS-CoV-2 Omicron variant, its key characteristics and significant global health concerns, as well as measures for dealing with it in the context of the continuing COVID-19 pandemic. Various mutations in Omicron have been discussed that contribute to increased transmissibility and immune evasion from vaccine-induced or natural immunity acquired after infection. To understand the similarities and differences between different VOCs and Omicron, we conducted a comparative investigation.

Conclusion: Strengthening research, improving genomic surveillance and tracking, developing highly effective vaccines and immunotherapies, designing appropriate strategies, action plans, and future preparedness plans must all be prioritized and implemented quickly at global levels to mitigate the high global health concerns associated with the emergence of this new Omicron variant well before it causes large-scale COVID-19 outbreaks.