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Background: Chronic inflammation is a significant driver in the development of various diseases, including cancer. Colitis-associated colorectal cancer (CA-CRC) refers to the increased risk of colorectal cancer in individuals with chronic inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. Methods: This narrative review examines the link between chronic inflammation and CA-CRC. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2000 and 2024. Studies were selected based on relevance to the role of inflammation in CA-CRC, specifically targeting molecular pathways and clinical implications. Both clinical and mechanistic studies were reviewed. Conclusion: Sustained inflammation in the colon fosters a pro-tumorigenic environment, leading to the initiation and progression of CA-CRC. Prevention strategies must focus on controlling chronic inflammation, optimizing IBD management, and implementing regular screenings. Emerging therapies targeting key inflammatory pathways and immune responses, along with microbiome modulation, hold promise for reducing CA-CRC risk. Understanding these molecular mechanisms provides a path toward personalized treatment and better outcomes for patients with IBD at risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the combination effect of apple cider vinegar (ACV) and metformin against letrozole-induced polycystic ovary syndrome (PCOS). Female Wistar rats were administered letrozole (1 mg/kg/day, p.o) for 21 days, except for the control group of animals. On the 22nd day, PCOS-induced animals were segregated into 4 groups and administered with CMC, ACV, metformin, and a combination of ACV and metformin, respectively. The treatments were continued for 15 days, and on the 36th day, all the animals were sacrificed for biochemical (blood glucose, lipid profile), hormonal (sex hormones and adiponectin), and pro-inflammatory mediator estimations in blood samples. The ovarian tissue samples were used for oxidative stress parameters and histological alterations. The PCOS control animals showed a significant alteration in the estrous cycle. The administration of letrozole resulted in the alteration of hormonal balance and elevation of body weights, glycemic state, lipid profile, pro-inflammatory mediators in serum, and oxidative stress in ovarian samples. Individual treatment groups and combination treatment groups reversed the letrozole-induced alterations in PCOS animals, and more promising results were observed with combination therapy than with individual treatment groups. Further, the therapeutic potential of the combination treatment group was also confirmed by the histological observations in the ovarian samples. The study showed that the combination of ACV and metformin significantly alleviated letrozole-induced PCOS complications in rats. This might have been achieved by mitigating the hormonal imbalance, pro-inflammatory, hyperglycemic, and hyperlipidemic states in serum, and oxidative stress in the ovary samples. [ABSTRACT FROM AUTHOR]

Ischemia/reperfusion injury (IRI) is a key determining agent in the pathophysiology of clinical organ dysfunction. It is characterized by an aseptic local inflammatory reaction due to a decrease in blood supply, hence deprivation of dependent oxygen and nutrients. In instances of liver transplantation, this injury may have irreversible implications, resulting in eventual organ rejection. The deterioration associated with IRI is affected by the hepatic health status and various factors such as alterations in metabolism, oxidative stress, and pro-inflammatory cytokines. The primary cause of inflammation is the initial immune response of pro-inflammatory cytokines, while Kupffer cells (KFCs) and neutrophil-produced chemokines also play a significant role. Upon reperfusion, the activation of inflammatory responses can elicit further cellular damage and organ dysfunction. This review discusses the interplay between chemokines, pro-inflammatory cytokines, and other inflammatory mediators that contribute to the damage to hepatocytes and liver failure in rats following IR. Furthermore, it delves into the impact of anti-inflammatory therapies in safeguarding against liver failure and hepatocellular damage in rats following IR. This review investigates the correlation between cytokine factors and liver dysfunction via examining databases, such as PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The abstract diagram illustrates the pro-inflammatory cytokines and NF-κB as primary target therapies for cytoprotecting activity versus ischemia/reperfusion injury of the liver. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (Ag-NPs) are renowned for their biological activity, while zinc oxide (ZnO) is a biocompatible metal oxide used in catalytic applications such as organic pollutant degradation and wastewater treatment. This study investigates the synthesis, characterization, and toxicological effects of silver-doped zinc oxide nanoparticles (Ag-ZnO NPs). Ag-ZnO NPs were synthesized with 3.0 mol% Ag(I) using the sol–gel method and characterized using X-ray diffraction (XRD), UV–Vis spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM–EDX). Acute toxicity was evaluated in zebrafish (Danio rerio) embryos and adults, assessing mortality rates and hematological parameters. Additionally, the impact was also evaluated on enzymatic activity levels and the expression of proinflammatory cytokine genes. The cytotoxicity of Ag-ZnO NPs was also tested on McCoy fibroblast cells using the MTT assay. Acute toxicity tests in zebrafish embryos and larvae revealed a dose-dependent increase in mortality rates with rising Ag-ZnO NP concentrations. Hematological analysis showed a significant reduction in red blood cell (RBC) count and hemoglobin (Hb) levels, likely due to RBC lysis or impaired erythropoiesis. Elevated levels of superoxide dismutase (SOD), catalase (CAT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), acid phosphatase (ACP), and alkaline phosphatase (ALP) were observed in fish tissues, particularly indicating liver damage. Upregulation of proinflammatory cytokine genes (TNF-α, COX-2, and IL-10) was most pronounced in liver tissues. The MTT assay on McCoy fibroblast cells indicated that Ag-ZnO NPs induced cytotoxicity in a dose-dependent manner, with higher concentrations causing more significant cell damage. This study highlights the complex and dose-dependent effects of Ag-ZnO NPs on zebrafish physiology and McCoy fibroblast cell viability. The findings underscore the need for careful consideration of nanoparticle concentrations in applications to mitigate potential biological and environmental risks. [ABSTRACT FROM AUTHOR]

Micromeria biflora (M.B) Benth has proven anti-inflammatory efficacy, thereby, the goal of the current investigation was to assess the anti-arthritic potential of M.B ethanolic extract and fractions as well as to investigate the likely mechanism of action. The effectiveness of M.B against acute arthritic manifestations was assessed using an arthritic model prompted by formaldehyde, whereas a chronic model was developed using an adjuvant called Complete Freund's in Sprague–Dawley rats. Weekly evaluations were conducted for parameters involving paw volume, body weight, and arthritic score; at the completion of the CFA model, hematological, biochemical and oxidative stress parameters as well as the level of various mediators (PGE2, IL-1β, TNFα, IL6, MMP2, 3, 9, VEGF, NF-ĸB, IL-10, and IL-4) were evaluated. The results demonstrated the plant's ability to treat arthritis by showing a significant decrease in paw volume, arthritic score, and histological characteristics. The levels of NF-ĸB, MMP2, 3, 9, IL6, IL1β, TNFα, and VEGF were all significantly reduced after treatment with plant extract and fractions. Plant extract and its fractions substantially preserved body weight loss, oxidative stress markers and levels of IL-4 and 1L-10. PGE2 levels were also shown to be reduced in the treatment groups, supporting the M.B immunomodulatory ability. Hematological and biochemical indicators were also normalized after M.B administration. Outcomes of the study validated the anti-arthritic and immunomodulatory attributes of M.B probably through modulating oxidative stress, inflammatory, pro-inflammatory and anti-inflammatory biomarkers. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic problem of the intestine and relapsing in nature. Biochanin A is a nature‐derived isoflavonoid and has numerous bioactivities. However, its role against UC and intestinal inflammation remains obscure. We aimed to comprehensively explore the pharmacological effect of biochanin A in alleviating colitis and to evaluate the potential mechanisms. Initially, we explored the anti‐inflammatory action of biochanin A (15, 30, and 60 μM) by employing lipopolysaccharide (LPS)‐activated RAW 264.7 cells. In RAW 264.7 cells under LPS stimulation, biochanin A inhibited the elevation of reactive oxygen species (ROS) (p < 0.0001), interleukin (IL)−1β (p < 0.0001), IL‐18 (p < 0.01), and tumor necrosis factor (TNF)‐α (p < 0.01) release, nitrite production (p < 0.0001), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) proteins. Next, we studied the effectiveness of biochanin A (20 and 40 mg/kg) in mouse colitis induced with dextran sulfate sodium (DSS) by assessing colon length, disease activity index (DAI) scoring, and performing colonoscopy and histological analysis. The pro‐inflammatory cytokines were estimated using ELISA. Western blot studies were performed to assess underlying mechanisms. In mice, biochanin A treatment alleviated DAI score (p < 0.0001), restored colon length (p < 0.05) and morphology, and re‐established colon histopathology. Biochanin A affects the phosphorylation of proteins associated with NF‐κB (p65) and mitogen‐activated protein kinase (MAPK) axis and regulates colonic inflammation by reducing the expression of inflammatory cytokines and myeloperoxidase (MPO) activity. Altogether, our findings support the idea that the anticolitis potential of biochanin A is allied with anti‐inflammatory activity by inhibiting the MAPK/NF‐κB (p65) axis. Hence, biochanin A may be an alternative option to alleviate the risk of colitis. [ABSTRACT FROM AUTHOR]

According to a survey, the medicinal use of Androstachys johnsonii Prain is kept secret by traditional healers. Considering that inflammation and oxidative stress are major risk factors for the progression of various chronic diseases and disorders, we resolved to investigate the antioxidant and anti-inflammatory potentials of A. johnsonii using in vitro and cell-based assays. The antioxidant activity of A. johnsonii hydroethanolic leaf extract (AJHLE) was evaluated using the ABTS, DPPH, and FRAP assays. Its cytotoxic effect was assessed on RAW 264.7 macrophages using an MTT assay. Then, its anti-inflammatory effect was evaluated by measuring the NO production and 15-LOX inhibitory activities. Moreover, its preventive effect on ROS production and its regulatory effect on the expression of pro-inflammatory mediators such as IL-1β, IL-10, TNF-α, and COX-2 were determined using established methods. AJHLE strongly inhibited radicals such as ABTS•+, DPPH•, and Fe3+-TPTZ with IC50 values of 9.07 µg/mL, 8.53 µg/mL, and 79.09 µg/mL, respectively. Additionally, AJHLE induced a significant (p < 0.05) cytotoxic effect at 100 µg/mL, and when tested at non-cytotoxic concentrations, it inhibited NO and ROS production in LPS-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Furthermore, AJHLE showed that its anti-inflammatory action occurs via the inhibition of 15-LOX activity, the downregulation of COX-2, TNF-α, and IL-1β expression, and the upregulation of IL-10 expression. Finally, chemical investigation showed that AJHLE contains significant amounts of procyanidin, epicatechin, rutin, and syringic acid which support its antioxidant and anti-inflammatory activities. These findings suggest that A. johnsonii is a potential source of therapeutic agents against oxidative stress and inflammatory-related diseases. [ABSTRACT FROM AUTHOR]

Objectives: Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short‐ versus long‐term exposure to intermittent hypoxia (IH) on pro‐inflammatory mediators within vulnerable organs impacted by OSA. Study Design: Experimental animal study. Methods: A total of 8–10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short‐term) or 6 weeks (long‐term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro‐inflammatory mediators from peripheral tissues. Results: We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short‐term exposure to IH. Although there were tissue‐specific alterations in the gene expression of pro‐inflammatory mediators, with down‐regulation in the lung and up‐regulation in the heart, we also observed reduced protein levels of pro‐inflammatory mediators in the serum, lung, and heart following short‐term exposure to IH. Long‐term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart. Conclusions: We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs. Level of Evidence: NA Laryngoscope, 134:S1–S11, 2024 [ABSTRACT FROM AUTHOR]

Injury to the liver is a significant public health issue that affects people all over the world, which necessitates the creation of innovative treatments that are both effective and safe. Due to the antioxidant activity that it possesses, Ziziphus mauritiana (Z. mauritiana) has traditionally been considered to have therapeutic potential against many organ toxicity disorders. In the current work, the objective was to assess the antioxidant activities in vitro and the potential hepatoprotective effects of hydroethanolic extracts from Z. mauritiana seeds (ZMSE) against 2-nitropropane (2-NP) produced liver damage (Fibrosis) in rats. Additionally, the phytochemical contents of the extracts were to be identified. Through in vitro testing, the extract demonstrated significant antioxidant properties, as well as a high quantity of flavonoids and other phenolic compounds respectively. By activating the hepatic antioxidant defense mechanisms, modulating hepatic functions, and decreasing the production of lipid peroxidation, pro-inflammatory mediators, and collagen content, oral administration of ZMSE (especially high dose) significantly suppressed the incidence and severity of 2-NP-induced liver toxicity. However, the degree of suppression varied depending on the dose. There is a possibility that the presence of phenolic acids, flavonoids, and diterpenoids is responsible for these activities. These findings demonstrate the antioxidant and anti-inflammatory properties of ZMSE when administered in varying doses (200, 400, or 800 mg/kg body weight), demonstrate the protective and beneficial effects of the seed against 2-NP-induced hepatic toxicity in rats, and provide support for its consumption, traditional uses, and the promotion of its valorization as a nutraceutical product. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a common underlying factor in many major diseases, including heart disease, diabetes, cancer, and autoimmune disorders, and is responsible for up to 60% of all deaths worldwide. Metformin, statins, and corticosteroids, and NSAIDs (non-steroidal anti-inflammatory drugs) are often given as anti-inflammatory pharmaceuticals, however, often have even more debilitating side effects than the illness itself. The natural product-based therapy of inflammation-related diseases has no adverse effects and good beneficial results compared to substitute conventional anti-inflammatory medications. In this review article, we provide a concise overview of present pharmacological treatments, the pathophysiology of inflammation, and the signaling pathways that underlie it. In addition, we focus on the most promising natural products identified as potential anti-inflammatory therapeutic agents. Moreover, preclinical studies and clinical trials evaluating the efficacy of natural products as anti-inflammatory therapeutic agents and their pragmatic applications with promising outcomes are reviewed. In addition, the safety, side effects and technical barriers of natural products are discussed. Furthermore, we also summarized the latest technological advances in the discovery and scientific development of natural products-based medicine. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E2 (PGE2) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 μg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 μg/mL in Raw264.7 cells. BCS extract showed an IC50 of 328.77 ± 20.52 μg/mL. Notably, pre-treatment with BCS extract (30 μg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE2 and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1β and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders. [ABSTRACT FROM AUTHOR]

Air pollution exposure was known to result in body impairments by inducing inflammation and oxidation. But little is known about the associations of air pollutants with plasma fatty acid profile which may play important roles in the impairment of air pollutants based on the related mechanism, especially in pregnant women. This study aimed to explore the relationships of air pollution exposure with plasma fatty acid profile and the potential effect modification by pre-pregnancy body mass index (BMI). Based on a cohort in Wuhan, China, we measured concentrations of plasma fatty acids of 519 pregnant women enrolled from 2013 to 2016 by gas chromatography-mass spectrometry (GC-MS). Levels of exposure to air pollutants (fine particulate matter (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)) were estimated by using spatial-temporal land use regression models and calculated in three periods (average concentrations during 1 day, 1 week, and 1 month before the phlebotomizing day in the first trimester). Per interquartile range increment of the levels of air pollution exposure 1 day before phlebotomizing was related to 1.21–2.01% increment of omega-6 polyunsaturated fatty acids (n-6PUFA) and 0.63–1.74% decrement of omega-3 polyunsaturated fatty acids (n-3PUFA). Besides, relationships above were kept robust in the analysis during 1 week and 1 month before phlebotomizing. In women with normal BMI, plasma fatty acid profile was observed to be more sensitive to air pollutants. Our study demonstrated that increment of exposure to air pollutants was associated with higher plasma n-6PUFA known to be pro-inflammatory and lower plasma n-3PUFA known to be anti-inflammatory, which was more sensitive in pregnant women with normal BMI. Our findings suggested that changes in plasma fatty acid profile should cause concerns and may serve as biomarkers in the further studies. Future studies are needed to validate our findings and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a substantial burden for patients with the disease. The known medications for the disease target the mitigation of the disease's symptoms. So, drug development for the management of osteoarthritis represents an important challenge in the medical field. This work is based on the development of a new benzofuran–pyrazole–pyridine-based compound 8 with potential anti-inflammatory and anti-osteoarthritis properties. Microanalytical and spectral data confirmed the chemical structure of compound 8. The biological assays indicated that compound 8 produces multifunctional activity as an anti-osteoarthritic candidate via inhibition of pro-inflammatory mediators, including RANTES, CRP, COMP, CK, and LPO in OA rats. Histopathological and pharmacokinetic studies confirmed the safety profile of the latter molecule. Accordingly, compound 8 is considered a promising anti-osteoarthritis agent and deserves deeper investigation in future trials. [ABSTRACT FROM AUTHOR]

According to a survey, the medicinal use of Androstachys johnsonii Prain is kept secret by traditional healers. Considering that inflammation and oxidative stress are major risk factors for the progression of various chronic diseases and disorders, we resolved to investigate the antioxidant and anti-inflammatory potentials of A. johnsonii using in vitro and cell-based assays. The antioxidant activity of A. johnsonii hydroethanolic leaf extract (AJHLE) was evaluated using the ABTS, DPPH, and FRAP assays. Its cytotoxic effect was assessed on RAW 264.7 macrophages using an MTT assay. Then, its anti-inflammatory effect was evaluated by measuring the NO production and 15-LOX inhibitory activities. Moreover, its preventive effect on ROS production and its regulatory effect on the expression of pro-inflammatory mediators such as IL-1β, IL-10, TNF-α, and COX-2 were determined using established methods. AJHLE strongly inhibited radicals such as ABTS•+, DPPH•, and Fe3+-TPTZ with IC50 values of 9.07 µg/mL, 8.53 µg/mL, and 79.09 µg/mL, respectively. Additionally, AJHLE induced a significant (p < 0.05) cytotoxic effect at 100 µg/mL, and when tested at non-cytotoxic concentrations, it inhibited NO and ROS production in LPS-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Furthermore, AJHLE showed that its anti-inflammatory action occurs via the inhibition of 15-LOX activity, the downregulation of COX-2, TNF-α, and IL-1β expression, and the upregulation of IL-10 expression. Finally, chemical investigation showed that AJHLE contains significant amounts of procyanidin, epicatechin, rutin, and syringic acid which support its antioxidant and anti-inflammatory activities. These findings suggest that A. johnsonii is a potential source of therapeutic agents against oxidative stress and inflammatory-related diseases.

Sepsis is an acute condition caused by the systemic inflammatory response syndrome to an infection. There are very few drugs that could improve the severe conditions in patients with sepsis. Hence, it is important to consider different treatment options. In this survey, we studied the effect of adenosine N1-oxide (ANO) and pioglitazone on rats with cecal ligation and perforation (CLP). They were randomly divided to four groups (n = 10) including Group A: as control group receiving normal saline, Group B: the rats with CLP as surgical control group, Group C: the rats receiving ANO, and Group D: the rats receiving pioglitazone. Interleukin (IL) - 6, IL-1ß, tumor necrosis factor alpha (TNF-a), nitric-oxide (NO) in serum blood and superoxide dismutase (SOD), catalase (CAT) malondialdehyde, (MDA) and myeloperoxidase (MPO) in liver and spleen homogenates were measured. The amount of antioxidant enzymes in the spleen and liver, and finally cell viability and rats' survival were investigated. The measurement of blood serum nitric-oxide and survival of all groups of rats were also performed. The results indicated that both drugs could cause a decrease in IL-1ß, IL-6, TNF-a and NO in rat blood serum and MDA and MPO in the liver and spleen homogenates, however, a significant increase in SOD and CAT in the liver and spleen homogenates in rats that received ANO and pioglitazone was observed compared to rats with CLP group. Cell viability and rats' survival were significantly improved in rats that received ANO and pioglitazone compared to rats with CLP group. Adenosine N1-oxide showed stronger and more effective effects. [ABSTRACT FROM AUTHOR]

c-Abl is a non-receptor tyrosine kinase that promotes intracellular apoptotic signaling in prolonged epileptic seizures. PTZ and pilocarpine-induced continuous epileptic convulsions cause neuronal death and gliosis. C-Abl is linked to oxidative stress, neuronal hyperexcitability, mitochondrial malfunction, and subsequent seizures. We investigated the involvement of c-Abl in epileptogenesis by employing its selective inhibitor Imatinib (1 & 3 mg/kg; i.p.) together with conventional medication valproate (110 mg/kg; i.p.) tends to be effective in decreasing seizures threshold provoked by PTZ for 15 days and pilocarpine for 37 days. Further, Imatinib was effective in preventing epileptic seizures arbitrated oxidative stress injury. Oxidative stress has been linked to excitotoxicity that is considered to pathogenic factor in epileptic brain damage. As ELIZA and biochemical estimations showed the high level of c-Abl as an indicator of neuronal oxidative and apoptosis under chronic PTZ & pilocarpine epileptic seizures marked by decreased antioxidants and elevated levels of caspase-3 that were successfully prevented with Imatinib treatment same as valproate (standard drug). Further, the aberrant c-Abl activation is also linked with neuroinflammation that is also predisposing factor in the development of seizures. Selective inhibition of c-Abl by Imatinib also showed anti-inflammatory activity marked with suppressed levels of NF-kB and pro-inflammatory mediators (TNF-alpha, IL-1β, and IL-6) suggesting the neuroprotective effect of Imatinib same as valproate (standard drug) in epilepsy. Therefore, the current study provides preclinical evidence of Imatinib as a potential treatment for seizures, as well as an understanding of potential role of c-Ablin epilepsy. [ABSTRACT FROM AUTHOR]

The use of nanoparticles in medicine is sometimes hampered by their potential to activate immune cells, eliciting inflammation or allergy. We investigated whether magnetic nanoparticles (MNPs) or biomimetic magnetic nanoparticles (BMNPs) affect relevant activities of human monocytes. We found that the nanoparticles neither elicited the production of pro-inflammatory mediators IL-6 and TNFα by resting monocytes (when BMNP dose < 300 μg/mL) nor enhanced their secretion induced by R848, a molecule engaging virus-recognizing receptors, or bacterial lipopolysaccharide (LPS). MNPs and BMNPs neither induced the generation of reactive oxygen species (ROS), nor affected the ROS production elicited by the NADPH oxidase activator phorbol myristate acetate (PMA) or the fungal derivative β-glucan. BMNPs, but not MNPs, caused an up-regulation of the maturation markers CD80, CD83, and CD86 in immature monocyte-derived dendritic cells (DCs), whereas both nanoparticles did not affect the LPS-induced expression of these markers. Moreover, the nanoparticles were greedily ingested by monocytes and DCs without altering their viability. Therefore, these nanoparticles are candidates for medical applications because they do not activate pro-inflammatory activities of monocytes. Furthermore, their ability to stimulate DC maturation could be used for the design of vaccines. Moreover, harmlessly engulfed nanoparticles could be vehicles to carry molecules inside the immune cells to regulate the immune response. [ABSTRACT FROM AUTHOR]

Objective: To study the therapeutic effects of Shenyuan Gan (参远苷, SYG) on the inflammatory response in BV2 microglial cells induced by lipopolysaccharide (LPS). Methods: The cytotoxicity of SYG to BV2 microglial cells was evaluated using a Cell Counting Kit-8 (CCK-8) assay, and the effect of SYG concentrations on LPS-induced BV2 microglial cells was studied. The morphological changes were observed using an optical microscope. The nitric oxide (NO) concentration in cell culture supernatant was determined using Griess reagent. The expression of cytokines and inflammatory mediators were also measured by an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to determine the levels of inducible NO synthase (iNOS), nuclear factor-kappa B (NF-κB) p65, alpha inhibitor of NF-κB (IκB-α), phosphorylation-IκB-α (p-IκB-α), NOD-like receptor 3 (NLRP3), and caspase-1 expression. Moreover, the expression of iNOS, NLRP3, and ionized calcium binding adapter molecule 1 (Iba1) was also observed using immunofluorescent staining. Results: SYG had a low cytotoxic effect on BV2 microglial cells and could significantly decr-ease LPS-induced morphological changes of BV2 microglial cells (P

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E2 (PGE2) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 μg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 μg/mL in Raw264.7 cells. BCS extract showed an IC50 of 328.77 ± 20.52 μg/mL. Notably, pre-treatment with BCS extract (30 μg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE2 and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1β and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders.

Osteoarthritis is a substantial burden for patients with the disease. The known medications for the disease target the mitigation of the disease’s symptoms. So, drug development for the management of osteoarthritis represents an important challenge in the medical field. This work is based on the development of a new benzofuran–pyrazole–pyridine-based compound 8 with potential anti-inflammatory and anti-osteoarthritis properties. Microanalytical and spectral data confirmed the chemical structure of compound 8. The biological assays indicated that compound 8 produces multifunctional activity as an anti-osteoarthritic candidate via inhibition of pro-inflammatory mediators, including RANTES, CRP, COMP, CK, and LPO in OA rats. Histopathological and pharmacokinetic studies confirmed the safety profile of the latter molecule. Accordingly, compound 8 is considered a promising anti-osteoarthritis agent and deserves deeper investigation in future trials.

Protocatechuic acid (PCA), a phenolic compound found in teas, fruits, and vegetables, is widely recognized with its antioxidant and anti-inflammatory activities. Here, we verified the protective role of PCA on carrageenan (CGN)-induced paw edema in mice. Forty-five male Swiss albino mice were assigned into five groups: control group, CGN-injected group (1% w/v), PCA (25 mg/kg) + CGN group. PCA (50 mg/kg) + CGN group and diclofenac sodium (20 mg/kg) + CGN group. PCA and diclofenac sodium were administered orally for 5 consecutive days prior to the CGN injection. PCA pretreatment notably decreased the volume of the developed edema and alleviated the histopathological alterations induced by carrageenan. Additionally, PCA administration enhanced the cellular antioxidant capacity as demonstrated by the increased levels of catalase, superoxide dismutase, and reduced glutathione, in addition to the decreased malondialdehyde level in the edematous tissue. Interestingly, PCA administration was able significantly to suppress the developed inflammatory response upon carrageenan injection as indicated by the decreased levels and expression of pro-inflammatory cytokines and mediators including tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-II, prostaglandin E2, monocyte chemoattractant protein-1, myeloperoxidase and nuclear factor kappa B. These results collectively confirm the protective effect of PCA against carrageenan-induced paw edema owing to its antioxidant and anti-inflammatory characteristics. [ABSTRACT FROM AUTHOR]

Earlier studies reported that long-term treatment with thymoquinone (TQ) at a high dose (20 mg/kg) exerts a cardioprotective effect against isoproterenol (ISO)-triggered myocardial infarction (MI) in rats. In the present study, we tested the hypothesis that TQ, as a potent molecule, can exhibit cardioprotective effects at the lower dose for a short-term regimen. The rats were administered with TQ (5 mg/kg, intraperitoneal) at the 4 h interval for 2 days. ISO (100 mg/kg/day, subcutaneous) was given for 2 days to produce MI. ISO challenge results in deformation in ECG wave front, elevated left ventricular (LV) end-diastolic pressure, and reduced LVdP/dtmax and LVdP/dtmin. The levels of the cardiac biomarker in serum, such as creatine kinase MB, alanine aminotransferase, and aspartate aminotransferase, were increased. In the myocardium, a rise in malonaldehyde and decreased superoxide dismutase, glutathione, and catalase contents were observed. Furthermore, increased levels of tumor necrotic factor-α, interleukin-6, and interleukin-1β were observed in the myocardium. TQ pretreatment significantly normalized alterations in hemodynamic parameters, strengthened the antioxidant defense system, and decreased the contents of pro-inflammatory cytokines and hepatic enzymes as compared to the ISO group. Based on the results, TQ appears to be cardioprotective at low doses, and effective even administered for a shorter duration. [ABSTRACT FROM AUTHOR]

Polygonum odoratum var. Pakphai has been used in traditional Thai medicine for the treatment of flatulence and constipation and to relieve the inflammation caused by insect bites. Quercetin (Q), which is abundant in plant-based foods, has been found to exert anti-inflammatory properties. This study evaluated the anti-inflammatory activity of P. odoratum ethanolic extract in RAW264.7 macrophage cells. Leaves were extracted with 50% ethanol, phenolics and flavonoids were then analyzed using UHPLC-QTOF-MS and HPLC-DAD. RAW264.7 cells were induced with lipopolysaccharides (LPSs). They were then treated with the extract and prostaglandin E2 (PGE2), and interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-α) concentrations were determined. Levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6 and TNF-α mRNAs were analyzed using qRT-PCR. Chemical analysis demonstrated that the extract was abundant with Q while also containing catechin, gallic acid, epicatechin gallate and coumarin. The extract increased the viability of RAW264.7 cells and dose-dependently decreased nitric oxide production, PGE2, IL-6 and TNF-α levels in the medium from the LPS-induced RAW264.7 cell culture. Consistently, COX-2, iNOS, IL-6 and TNF-α mRNA levels were decreased in a concentration-dependent manner (p < 0.05). Thus, the quercetin-rich ethanolic extract derived from P. odoratum var Pakphai leaves can exert anti-inflammatory activity in LPS-induced RAW264.7 cells through a reduction of the pro-inflammatory mediator response. [ABSTRACT FROM AUTHOR]

Current treatment options for triple-negative breast cancer (TNBC) are limited to toxic drug combinations of low efficacy. We recently identified an aryl-substituted fatty acid analogue, termed CTU, that effectively killed TNBC cells in vitro and in mouse xenograft models in vivo without producing toxicity. However, there was a residual cell population that survived treatment. The present study evaluated the mechanisms that underlie survival and renewal in CTU-treated MDA-MB-231 TNBC cells. RNA-seq profiling identified several pro-inflammatory signaling pathways that were activated in treated cells. Increased expression of cyclooxygenase-2 and the cytokines IL-6, IL-8 and GM-CSF was confirmed by real-time RT-PCR, ELISA and Western blot analysis. Increased self-renewal was confirmed using the non-adherent, in vitro colony-forming mammosphere assay. Neutralizing antibodies to IL-6, IL-8 and GM-CSF, as well as cyclooxygenase-2 inhibition suppressed the self-renewal of MDA-MB-231 cells post-CTU treatment. IPA network analysis identified major NF-κB and XBP1 gene networks that were activated by CTU; chemical inhibitors of these pathways and esiRNA knock-down decreased the production of pro-inflammatory mediators. NF-κB and XBP1 signaling was in turn activated by the endoplasmic reticulum (ER)-stress sensor inositol-requiring enzyme 1 (IRE1), which mediates the unfolded protein response. Co-treatment with an inhibitor of IRE1 kinase and RNase activities, decreased phospho-NF-κB and XBP1s expression and the production of pro-inflammatory mediators. Further, IRE1 inhibition also enhanced apoptotic cell death and prevented the activation of self-renewal by CTU. Taken together, the present findings indicate that the IRE1 ER-stress pathway is activated by the anti-cancer lipid analogue CTU, which then activates secondary self-renewal in TNBC cells. [ABSTRACT FROM AUTHOR]

The present study investigated the potential nephro‐ and pneumoprotective effect of silibinin (Si) after hepatic ischemia–reperfusion (I/R) injury, by measuring pro‐inflammatory factors. Sixty‐three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45‐min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45‐min hepatic ischemia followed by intravenous administration of lyophilised SLB‐HP‐β‐CD before reperfusion. Control and silibinin groups were further subdivided into time‐point groups, according to the duration of reperfusion. TNF‐α, IL‐6 and MCP‐1 expressions were determined immunohistochemically and by qrT‐PCR at each time‐point. Kidney TNF‐α expression was significantly lower at 180 and 240 min, while lung TNF‐α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time‐points showed very strong evidence of difference at 240 min, with the levels of IL‐6 shifting towards lower values in the Si group. Finally, we found a high MCP‐1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro‐inflammatory mediators in the kidney and lung, whereas silibinin shows a time‐dependent nephro‐ and pneumoprotective effect. [ABSTRACT FROM AUTHOR]

Background: Blepharis maderaspatensis is an ethnomedicinal plant used by the Mavilan and Koraga tribes of Kerala state, India for the treatment of liver diseases. Thus, the present study aims to evaluate the liver protective activity of defatted ethanolic extract of B. maderaspatensis on lipopolysaccharide-induced acute liver inflammation and oxidative stress in Wistar rat model. Methods: Preliminary phytochemical evaluation and high-performance thin-layer chromatography fingerprint validation were performed. The total phenolic and flavonoid contents were measured using the Folin-Ciocalteu method and the aluminium chloride method, respectively. The acute oral toxicity study was conducted in Swiss albino mice in accordance with OECD 423 guideline. Effect of defatted ethanolic extract of the whole plant of B. maderaspatensis (BmE) on liver inflammation was evaluated in LPS-induced Wistar rat model. The rats were treated with BmE (100, 250 and 500 mg/kg body weight) once daily for 7 days prior to the LPS (single dose i.p., 10 mg/kg b.w.) challenge. Liver tissue biochemicals (ALT, AST and ALP), and antioxidant status (SOD, CAT, GSH, MDA, NO and MPO) in euthanised experimental rats were carried out using commercial kits/standard procedures. Haematology (RBC, WBC, Hb and PLT; 4 and 24 h), and histopathology analysis were also performed. Serum IL-1β, IL-6, TNF-α and PGE2 production were determined by ELISA. The expressions of COX-2, iNOS, IL-1β, IL-6, TNF-α and NF-κB were analysed by qRT-PCR. Phosphorylation of IκB-α was measured by Western blotting. LC-MS analysis of BmE was also performed. Results: The LD50 value of BmE was found to be >5000 mg/kg b.w. BmE500 showed significant protection from LPS-induced liver injury as evidenced by reduced serum enzyme levels (AST, ALT and ALP; p≤ 0.001) and markedly improved the liver antioxidant status (MDA, GSH, SOD and CAT; p≤ 0.001), when compared to the LPS alone treated group. Haematology (24 h, RBC, WBC, Hb and PLT; p≤ 0.001) and histopathology also supported the above results. BmE500 pre-treatment significantly suppressed the LPS-induced expression of iNOS (p≤ 0.001) and COX-2 (p≤ 0.001), and the subsequent release of NO (p≤ 0.001) and PGE2 (p≤ 0.001). Moreover, BmE500 inhibited the gene expression of pro-inflammatory cytokines, including IL-1β (p≤ 0.001), IL-6 (p≤ 0.001), and TNF-α (p≤ 0.01), which is supported by ELISA results. In addition, BmE500 markedly attenuated the activation of transcription factor NF-κB (p≤ 0.001) as well as phosphorylation of IκBα, as evidenced from the qRT-PCR and Western blot analysis, respectively. The silymarin (100 mg/kg b.w.) drug standard also showed significant improvement in all parameters analysed. Conclusion: Results of the present investigation suggest that BmE has a significant protective effect on LPS-induced acute liver inflammation via attenuating inflammatory reactions, evidenced by the inhibition of NF-κB signalling cascade, and also through its antioxidant effects. Thus, the pharmacological data generated provide experimental evidence that clearly justifies the use of B. maderaspatensis as a liver protective agent in tribal medicine.

Santolina insularis is a Sardinian endemism that is widely used in traditional medicine. The essential oil was obtained with a yield of 2.7% and is mainly characterized by β-phellandrene (22.6%), myrcene (11.4%) and artemisia ketone (7.6%). The oil significantly reduced NO production without affecting macrophages viability. In addition, it substantially inhibited the expression of two key pro-inflammatory enzymes, iNOS and COX-2 (71% and 25% at 0.54 mg/mL). Furthermore, the oil had a promising antifungal activity being Cryptococcus neoformans (MIC = 0.13 mg/mL) and the majority of dermatophytes (MIC = 0.13 mg/mL) the most susceptible fungi. Moreover, it significantly decreased the yeast-to-hypha transition (80% inhibition at 0.13 mg/mL) on C. albicans long before showing inhibitory effects. Overall, these results show that S. insularis could be applied in the treatment of fungal infections and associated inflammatory response. [ABSTRACT FROM AUTHOR]

Context Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis. Objective The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms. Materials and methods The rats were immunized by intradermal injection of complete Freund’s adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses. Results The LD50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1β), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p

The use of nanoparticles in medicine is sometimes hampered by their potential to activate immune cells, eliciting inflammation or allergy. We investigated whether magnetic nanoparticles (MNPs) or biomimetic magnetic nanoparticles (BMNPs) affect relevant activities of human monocytes. We found that the nanoparticles neither elicited the production of pro-inflammatory mediators IL-6 and TNFα by resting monocytes (when BMNP dose < 300 μg/mL) nor enhanced their secretion induced by R848, a molecule engaging virus-recognizing receptors, or bacterial lipopolysaccharide (LPS). MNPs and BMNPs neither induced the generation of reactive oxygen species (ROS), nor affected the ROS production elicited by the NADPH oxidase activator phorbol myristate acetate (PMA) or the fungal derivative β-glucan. BMNPs, but not MNPs, caused an up-regulation of the maturation markers CD80, CD83, and CD86 in immature monocyte-derived dendritic cells (DCs), whereas both nanoparticles did not affect the LPS-induced expression of these markers. Moreover, the nanoparticles were greedily ingested by monocytes and DCs without altering their viability. Therefore, these nanoparticles are candidates for medical applications because they do not activate pro-inflammatory activities of monocytes. Furthermore, their ability to stimulate DC maturation could be used for the design of vaccines. Moreover, harmlessly engulfed nanoparticles could be vehicles to carry molecules inside the immune cells to regulate the immune response.

The purpose of our study was to evaluate the effectiveness of sodium deoxyribonucleate (Derinat, solution for intramuscular injection) in combination with standard therapy in the treatment of COPD Group C patients in outpatient settings. Materials and Methods: The study included 80 patients (43 men and 37 women) with COPD (Group C), mean age of 51.7±1.4 years. Blood sampling for the study was carried out 3 times—before the start of therapy, and on days 5 and 15. Using monoclonal antibodies, we determined the number of lyphocytes carrying markers CD3+, CD+, CD8+, and CD72+. The quality of life (QL) indicators were evaluated using the St. George’s Respiratory Questionnaire (SGRQ). For at least 15 days, patients received standard COPD therapy. All patients were divided into 2 groups: Group 1 included 41 patients who received Derinat 75 mg intramuscularly once daily for 5 days; then - 5 injections with an interval of 48 hours against the background of standard therapy. Group 2 included 39 patients who continued to receive standard COPD therapy. Results: The inclusion of Derinat in the complex therapy of COPD contributed to the normalization of the T-cell to B-cell ratio, an increase in the number of T suppressors. Assessing the clinical effects of combination therapy with the inclusion of the studied drug, a marked decrease in shortness of breath, cough, and the amount of sputum excreted can be noted in comparison with standard therapy. The improvement of the immunological status and clinical indicators against the background of complex therapy was accompanied by an increase in QL.

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by limited treatment options and a poor prognosis. Its aggressiveness is attributed not only to the uncontrolled proliferation and invasion of tumor cells but also to the complex interplay between these cells and the surrounding microenvironment. Within the tumor microenvironment, an intricate network of immune cells, stromal cells, and various signaling molecules creates a pro-inflammatory milieu that supports tumor growth and progression. Docosahexaenoic acid (DHA), an essential ω3 polyunsaturated fatty acid for brain function, is associated with anti-inflammatory and anticarcinogenic properties. Therefore, in this work, DHA liposomes were synthesized using a microfluidic platform to target and reduce the inflammatory environment of GBM. The liposomes were rapidly taken up by macrophages in a time-dependent manner without causing cytotoxicity. Moreover, DHA liposomes successfully downregulated the expression of inflammatory-associated genes ( IL-6 ; IL-1β ; TNFα ; NF-κB , and STAT-1 ) and the secretion of key cytokines (IL-6 and TNFα) in stimulated macrophages and GBM cells. Conversely, no significant differences were observed in the expression of IL-10 , an anti-inflammatory gene expressed in alternatively activated macrophages. Additionally, DHA liposomes were found to be more efficient in regulating the inflammatory profile of these cells compared with a free formulation of DHA. The nanomedicine platform established in this work opens new opportunities for developing liposomes incorporating DHA to target GBM and its inflammatory milieu.

Conventional anti-inflammatory drugs are associated with serious adverse effects which bring about an ever-increasing demand to supersede them with natural and safe anti-inflammatory agents. Hence, the prime objective of this study was to evaluate the anti- inflammatory potential of an underutilized culinary spice "Amomum subulatum". To assess anti-inflammatory activity of MEAS, acute and chronic inflammation studies were carried out in carrageenan and formalin induced mice paw edema models respectively. Paw volume was measured by vernier caliper. Status of antioxidant enzymes and oxidative stress markers were determined in paw tissue homogenates following standard protocols. Histopathology and immunohistochemistry analysis of paw tissue samples were also performed. Levels of proinflammatory cytokines in serum were quantified by ELISA. Effect of MEAS on vascular permeability was evaluated by evans blue dye extravasation assay. Involvement of heme oxygenase (HO)-1 pathway in anti-inflammatory action of MEAS was investigated by pretreating mice with zinc protoporphyrin (ZnPP) IX, a specific inhibitor of HO-1. MEAS administration significantly reduced paw edema, as evidenced by paw volume measurement and histopathology analysis. Additionally, pretreatment with MEAS markedly reduced vascular permeability, serum proinflammatory cytokine levels, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Further, the anti-inflammatory mechanism of MEAS showed the involvement of HO-1 pathway when HO-1 was inhibited by ZnPPIX. Our results manifested strong anti-inflammatory activity of MEAS, suggesting its potential use as a therapeutic alternative for treating inflammatory disorders. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Inflammation process in human body can lead to many serious inflammation-related diseases. Hence, there are urge to find better solution for the treatment of the inflammation processes. Solution can be found in application of poly(methacrylic acid) hydrogels which have potential for targeted delivery and controlled release of drugs. These pH-sensitive hydrogels can swell at the pH values between 5 and 8, and release drug in the process. So, taking into account that pH value at the inflammation site is around 6, these hydrogels are materials of choice. It is very important that the system for controlled release be prepared through mild and non-toxic conditions in order to preserve bioactivity of the drug and keep good impact on environment. Enzymes are good candidates for ecofriendly preparation of hydrogels, because these green substances can initiate polymerisation of various monomers. EXPERIMENTAL (or Materials and Methods): In this study, hydrogels based on poly(methacrylic acid) were prepared through eco-friendly method by using enzyme/hydrogen peroxide (HP)/ascorbic acid (AA) as initiator. Two groups of the samples were prepared: in the first group peroxidase isolated from potato peel waste (with activity of 0.8 IU) was used in the initiation system, whereas in the second group peroxidase isolated from soya bean coats (with activity of 0.8 IU) was employed in the initiation system. The amounts of HP and AA in both series were 40 µL and 10 mg, respectively. Anti-inflammatory drugs, dexamethasone (5 mg/mL) and diclofenac (4.5 mg/mL) were encapsulated in the first and the second group of the PMAA samples, respectively. Anti-inflammatory effect of the PMAA hydrogels with encapsulated drugs were tested on the Bovine Chondrocytes cells. RESULTS AND DISCUSSION: Results showed that the level of pro-inflammatory mediators NO and IL-8 decreased. The PCR analysis showed that the proinflammatory TNα, IL-6 genes expression level decreased, the matrix catabolism MMP1 and MMP3 genes expression level decreased and the fibrotic COL2 and ACAN genes expression level increased. CONCLUSIONS: The study showed that the PMAA hydrogels have anti-inflammatory effect and have potential for treatment of the inflammation processes. [ABSTRACT FROM AUTHOR]

Context: Muntingia calabura L. (Muntingiaceae) exerts antioxidant and anti-inflammatory activities, thus, it might be a good hepatoprotective agent. Objective: This study investigates the effect of methanol extract of M. calabura leaves (MMCL) on hepatic antioxidant and anti-inflammatory activities in CCl4-induced hepatotoxic rat. Materials and methods: Sprague Dawley rats (n = 6) were treated (p.o.) with 10% DMSO (Groups 1 and 2), 50 mg/kg N-acetylcysteine (Group 3) or, 50, 250, or 500 mg/kg MMCL (Groups 4–6) for 7 consecutive days followed by pretreatment (i.p.) with vehicle (Group 1) or 50% CCl4 in olive oil (v/v) (Groups 2–6) on day 7th. Plasma liver enzymes and hepatic antioxidant enzymes and pro-inflammatory cytokines concentrations were measured while liver histopathology was examined. Results: MMCL, at 500 mg/kg, significantly (p

Polygonum odoratum var. Pakphai has been used in traditional Thai medicine for the treatment of flatulence and constipation and to relieve the inflammation caused by insect bites. Quercetin (Q), which is abundant in plant-based foods, has been found to exert anti-inflammatory properties. This study evaluated the anti-inflammatory activity of P. odoratum ethanolic extract in RAW264.7 macrophage cells. Leaves were extracted with 50% ethanol, phenolics and flavonoids were then analyzed using UHPLC-QTOF-MS and HPLC-DAD. RAW264.7 cells were induced with lipopolysaccharides (LPSs). They were then treated with the extract and prostaglandin E2 (PGE2), and interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-α) concentrations were determined. Levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6 and TNF-α mRNAs were analyzed using qRT-PCR. Chemical analysis demonstrated that the extract was abundant with Q while also containing catechin, gallic acid, epicatechin gallate and coumarin. The extract increased the viability of RAW264.7 cells and dose-dependently decreased nitric oxide production, PGE2, IL-6 and TNF-α levels in the medium from the LPS-induced RAW264.7 cell culture. Consistently, COX-2, iNOS, IL-6 and TNF-α mRNA levels were decreased in a concentration-dependent manner (p < 0.05). Thus, the quercetin-rich ethanolic extract derived from P. odoratum var Pakphai leaves can exert anti-inflammatory activity in LPS-induced RAW264.7 cells through a reduction of the pro-inflammatory mediator response.

Earlier studies reported that long-term treatment with thymoquinone (TQ) at a high dose (20 mg/kg) exerts a cardioprotective effect against isoproterenol (ISO)-triggered myocardial infarction (MI) in rats. In the present study, we tested the hypothesis that TQ, as a potent molecule, can exhibit cardioprotective effects at the lower dose for a short-term regimen. The rats were administered with TQ (5 mg/kg, intraperitoneal) at the 4 h interval for 2 days. ISO (100 mg/kg/day, subcutaneous) was given for 2 days to produce MI. ISO challenge results in deformation in ECG wave front, elevated left ventricular (LV) end-diastolic pressure, and reduced LVdP/dtmax and LVdP/dtmin. The levels of the cardiac biomarker in serum, such as creatine kinase MB, alanine aminotransferase, and aspartate aminotransferase, were increased. In the myocardium, a rise in malonaldehyde and decreased superoxide dismutase, glutathione, and catalase contents were observed. Furthermore, increased levels of tumor necrotic factor-α, interleukin-6, and interleukin-1β were observed in the myocardium. TQ pretreatment significantly normalized alterations in hemodynamic parameters, strengthened the antioxidant defense system, and decreased the contents of pro-inflammatory cytokines and hepatic enzymes as compared to the ISO group. Based on the results, TQ appears to be cardioprotective at low doses, and effective even administered for a shorter duration.

Rheumatoid arthritis (RA) is associated with joint damage. For treatment, non-steroidal anti-inflammatory drugs (NSAIDs), steroidal agents, and immune-suppressants are used. Their side-effects require a safe and effective natural alternative. Thirty-six male albino rats, half kept under observation for 1 week (group I) and others for 2 weeks (group II) were used. Each group was subdivided into: normal (A), RA (B), and oral mandarin-peel extract (MPE) treated (C). Ankle diameter, serum levels of RF, interleukin (IL)-1β, TNFα, IL-4, IL-10, liver homogenates malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) were measured together with the histopathological examination. MPE treatment was associated with increased serum IL-4, IL-10, liver homogenates GSH, and SOD, and decreased ankle diameter, serum RF, IL-1β, TNFα, liver homogenates MDA, NO, inflammatory cell infiltrate, and necrosis. Two weeks' treatment was better. MPE has useful effects in alleviating the disturbed ankle diameter, serum pro- and anti-inflammatory mediators, oxidative stress, and ankle joint histopathology in rheumatic rats. [ABSTRACT FROM AUTHOR]

BackgroundThe ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.ObjectivesThe study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation.SettingDepartment of Pathogenic Biology and Immunology, Medical School of Southeast UniversitySubjectsMice with down-regulated/up-regulated PPARγ activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls.InterventionsAcute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPARγ is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPARγ. PPARγ activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA.Measures and Main ResultsWe find that during IgG-IC-induced acute lung inflammation, PPARγ expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPARγ activation reduces IgG-IC-mediated pro-inflammatory mediators’ production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPARγ. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters.ConclusionDuring IgG-IC-stimulated acute lung inflammation, PPARγ activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPARγ-Egr-1-pro-inflammatory mediators axis by PPARγ agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury.

Background: The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown. Objectives: The study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation. Setting: Department of Pathogenic Biology and Immunology, Medical School of Southeast University Subjects: Mice with down-regulated/up-regulated PPARγ activity or down-regulation of Early growth response protein 1 (Egr-1) expression, and the corresponding controls. Interventions: Acute lung inflammation is induced in the mice by airway deposition of IgG-IC. Activation of PPARγ is achieved by using its agonist Rosiglitazone or adenoviral vectors that could mediate overexpression of PPARγ. PPARγ activity is suppressed by application of its antagonist GW9662 or shRNA. Egr-1 expression is down-regulated by using the gene specific shRNA. Measures and Main Results: We find that during IgG-IC-induced acute lung inflammation, PPARγ expression at both RNA and protein levels is repressed, which is consistent with the results obtained from macrophages treated with IgG-IC. Furthermore, both in vivo and in vitro data show that PPARγ activation reduces IgG-IC-mediated pro-inflammatory mediators' production, thereby alleviating lung injury. In terms of mechanism, we observe that the generation of Egr-1 elicited by IgG-IC is inhibited by PPARγ. As an important transcription factor, Egr-1 transcription is substantially increased by IgG-IC in both in vivo and in vitro studies, leading to augmented protein expression, thus amplifying IgG-IC-triggered expressions of inflammatory factors via association with their promoters. Conclusion: During IgG-IC-stimulated acute lung inflammation, PPARγ activation can relieve the inflammatory response by suppressing the expression of its downstream target Egr-1 that directly binds to the promoter regions of several inflammation-associated genes. Therefore, regulation of PPARγ-Egr-1-pro-inflammatory mediators axis by PPARγ agonist Rosiglitazone may represent a novel strategy for blockade of acute lung injury. [ABSTRACT FROM AUTHOR]

Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis. The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms. The rats were immunized by intradermal injection of complete Freund's adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses. The LD50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1β), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p < 0.01 or p < 0.05). The ER significantly decreased NO (3.91 ± 0.61 µmol/L), IL-6 (75.67 ± 16.83 pg/mL) and malondialdehyde (MDA) (2.28 ± 0.32 nmol/mL) contents and clearly increased IFN-γ (2082 ± 220.93 pg/mL) and superoxide dismutase (SOD) (601.98 ± 38.40 U/mL) levels. The ES and EL did not reverse the changes in some indicators. All the extracts alleviated inflammatory cell infiltration and synovial cell proliferation. Among them, the ER was the most pronounced. ER exerts the most promising effects, as shown by inhibiting the releases of inflammatory cytokines and enhancing antioxidant capacity, which provides a scientific basis for further research on C. serratus and its clinical applications. [ABSTRACT FROM AUTHOR]

Sesamin, one of the most abundant lignans in sesame seeds and oils, is well known for neuroprotective activity. However, its effects on toll-like-receptor 4 (TLR4), the key innate immune receptor implicated in microglia activation and neuroinflammation has not been reported. Our study demonstrated that sesamin significantly diminished LPS-stimulated TLR4 expression result in the reduction of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in BV2 microglia by suppressing JNK and NF-κB pathway. While conditioned medium from LPS-stimulated microglia-induced PC12 cell death, sesamin pre-treatment on microglia abrogated the cytotoxic effects of pro-inflammatory mediators. Our result also demonstrated the direct effect of sesamin in ameliorating PC12 cell death induced by activated microglial-conditioned medium. These results suggested that sesamin alleviated inflammation-induced neurodegeneration via inhibition of TLR4 expression and microglial activation resulting in diminishing the neurotoxicity effect. Sesamin might be a potential agent for neurodegenerative diseases prevention.

Abstract Autoimmune disease management presents a significant challenge to medical science. Environmental factors potentially increase the risk of developing inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. Among various environmental stresses, cigarette smoke and hypoxia have both been reported to lead to an enhanced risk of inflammatory and autoimmune diseases. In this review, we shed light on all reported mechanisms whereby cigarette smoke and a hypoxic environment can induce inflammatory and autoimmune diseases and discuss how hypoxic conditions influence the cigarette smoke-induced threat of inflammatory and autoimmune disease development. Cigarette smoke and hypoxia both lead to increased oxidative stress and production of reactive oxygen species and other free radicals, which have various effects including the generation of autoreactive pro-inflammatory T cells and autoantibodies, reductions in T regulatory (Treg) cell activity, and enhanced expression of pro-inflammatory mediators [e.g., interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-8 (IL-8)]. Accordingly, smoking and hypoxic environments may synergistically act as potent environmental risk factors for inflammatory and autoimmune diseases. To our knowledge, no studies have reported the direct association of cigarette smoke and hypoxic environments with the risk of developing inflammatory and autoimmune diseases. Future studies exploring the risk of autoimmune disease development in smokers at high altitudes, particularly military personnel and mountaineers who are not acclimatized to high-altitude regions, are required to obtain a better understanding of disease risk as well as its management.