Cyclooxygenase Research Articles

Floral Fusion: Unravelling the Potent Blend of Ixora coccinea and Rhododendron arboreum for Health and Safety Benefits.

Ixora coccinea and Rhododendron arboreum are known for their traditional medicinal uses due to their diverse phytochemicals and pharmacological effects, which have attracted the interest of many researchers. This study aims to evaluate the antioxidant, anti-inflammatory, and cytotoxic effects of their combined extracts. In vitro antioxidant activity against reactive oxygen species (ROS) was measured using the ferric-reducing ability of plasma (FRAP), nitric oxide (NO), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays, while anti-inflammatory effects were assessed via the membrane stabilization method. Docking studies were performed to evaluate the interaction of phytochemicals - anthocyanins, quercetin, and ursolic acid, which are present in these plants - with nuclear factor kappa B (NF-κB), cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2). Standard protocols were used to evaluate embryotoxicity using the brine shrimp model and cytotoxicity using the zebrafish model, which is crucial for determining safe clinical dosages. The analysis revealed diverse bioactive compounds, including anthocyanins, quercetin, and ursolic acid. The formulation effectively inhibited ROS production at lower concentrations (inhibitory concentration 50%, or IC50 value ~2.8 µg/mL), indicating their potential for managing oxidative stress. Quercetin demonstrated the strongest interaction with all tested proteins, particularly NF-kB. Cytotoxicity and embryotoxicity assays revealed a dose-dependent effect (lethal concentration 50%, or LC50 value 82.4 µg/mL), with no adverse effects on developing embryos at the tested doses (5-80 µg/mL), suggesting the extracts are safe for clinical use, even during pregnancy. The combined extracts of I. coccinea and R. arboreum exhibit potent antioxidant and anti-inflammatory effects without causing cytotoxic or embryotoxic effects, even at higher concentrations. This indicates their potential for safe clinical application in treating oxidative and inflammatory diseases.

Activation Pathways of Murine Macrophages by Lipophosphoglycan from Strains of Leishmania major (FV1 and LV39).

Lipophosphoglycan (LPG) is an important Leishmania virulence factor. It is the most abundant surface glycoconjugate in promastigotes, playing an important role in the interaction with phagocytic cells. While LPG is known to modulate the macrophage immune response during infection, the activation mechanisms triggered by this glycoconjugate have not been fully elucidated. This work investigated the role that LPGs purified from two strains of Leishmania major (FV1 and LV39) play in macrophage activation, considering the differences in their biochemical structures. Bone marrow-derived macrophages from BALB/c mice were stimulated with 10 μg/mL purified LPG from the LV39 and FV1 strains. We then measured the production of nitric oxide (NO) and cytokines, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the activation of MAPK pathways. LPG from the LV39 strain, which has longer poly-galactosylated side chains, induced a more pro-inflammatory profile than that from the FV1 strain. This included higher production of NO, TNF-α, and PGE2, and increased expression of COX-2 and iNOS. Additionally, the phosphorylation of ERK-1/2 and JNK was elevated in macrophages exposed to LPG from the LV39 strain. No difference in IL-10 production was observed in cells stimulated by both LPG. Thus, intraspecific structural differences in LPG contribute to distinct innate immune responses in macrophages.

The Impact of Wharton's Jelly-derived Exosomes on the Production of Inflammatory Mediators from HIG-82 Synoviocytes.

Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton's jelly (Wj) derived from the umbilical cord (UC), has gained popularity. While mesenchymal stem cells (MSCs) derived from Wj show promise in restoring articular cartilage, they also have some limitations. Recent studies have indicated that exosomes isolated from acellular Wj may offer advantages under certain conditions. To investigate the anti-inflammatory properties of exosomes isolated from Wj in synoviocytes. Decellularization of Wj was performed using sterile umbilical cords obtained from patients. Next, the exosomes were isolated from Wj using ultracentrifugation. After characterizing the exosomes, they were co-cultured with inflammatory synovial fibroblast cells (HIG-82) for 24 hours. Then, the gene expression levels and protein contents of some important inflammatory mediators including metalloproteinase-13 (MMP-13), cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) were measured in the cells using real-time PCR and ELISA tests, respectively. The expression levels of MMP-13, COX-2, and iNOS genes were significantly reduced in the cultured cells treated with exosomes compared to untreated cells. Moreover, the content of MMP-13, COX-2, and iNOS proteins were significantly lower in the supernatant of the cultured cells compared to the control. Wj-derived exosomes exhibit notable anti-inflammatory properties, which can help mitigate inflammation in the synovial environment of joints. However, further research is required to fully understand their benefits and potential applications in treating osteoarthritis.

Differential Effect of Omega-3 Fatty Acids on Platelet Inhibition by Antiplatelet Drugs In Vitro.

The omega-3 polyunsaturated fatty acids (PUFAs) Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) exert multiple cardioprotective effects, influencing inflammation, platelet activation, endothelial function and lipid metabolism, besides their well-established triglyceride lowering properties. It is not uncommon for omega-3 PUFAs to be prescribed for hypertriglyceridemia, alongside antiplatelet therapy in cardiovascular disease (CVD) patients. In this regard, we studied the effect of EPA and DHA, in combination with antiplatelet drugs, in platelet aggregation and P-selectin and αIIbβ3 membrane expression. The antiplatelet drugs aspirin and triflusal, inhibitors of cyclooxygenase-1 (COX-1); ticagrelor, an inhibitor of the receptor P2Y12; vorapaxar, an inhibitor of the PAR-1 receptor, were combined with DHA or EPA and evaluated against in vitro platelet aggregation induced by agonists arachidonic acid (AA), adenosine diphosphate (ADP) and TRAP-6. We further investigated procaspase-activating compound 1 (PAC-1) binding and P-selectin membrane expression in platelets stimulated with ADP and TRAP-6. Both DHA and EPA displayed a dose-dependent inhibitory effect on platelet aggregation induced by AA, ADP and TRAP-6. In platelet aggregation induced by AA, DHA significantly improved acetylsalicylic acid (ASA) and triflusal's inhibitory activity, while EPA enhanced the inhibitory effect of ASA. In combination with EPA, ASA and ticagrelor expressed an increased inhibitory effect towards ADP-induced platelet activation. Both fatty acids could not improve the inhibitory effect of vorapaxar on AA- and ADP-induced platelet aggregation. In the presence of EPA, all antiplatelet drugs displayed a stronger inhibitory effect towards TRAP-6-induced platelet activation. Both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though they had no effect on P-selectin expression induced by ADP or TRAP-6. The antiplatelet drugs exhibited heterogeneity regarding their effect on P-selectin and αIIbβ3 membrane expression, while both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though had no effect on P-selectin expression induced by ADP or TRAP-6. The combinatory effect of DHA and EPA with the antiplatelet drugs did not result in enhanced inhibitory activity compared to the sum of the individual effects of each component.

AILDE Computer-Aided Discovery of Novel Ibuprofen-Coumarin Antitumor Lead Compounds Targeting Cyclooxygenase-2.

Starting from three ibuprofen-coumarin hit compounds, we designed 18 derivative compounds targeting cyclooxygenase-2 (COX-2) by introducing different substituents onto them by using the computational auto in silico ligand directing evolution (AILDE) method. After synthesizing and testing the activity, we found that 6 representative compounds have micromolar enzyme inhibitory activity against COX-2. Additionally, 16 compounds have shown certain inhibitory activity in cervical cancer cells. Among these compounds, 6c (IC50 = 0.606 μM, HeLa) and 7g (IC50 = 0.783 μM, HeLa) have exhibited excellent activity, which is approximately 10 times better than the commercial drug gefitinib. According to molecular simulation results, the halogen atoms of 6c and 7g on the coumarin ring can form halogen bonds with COX-2, which significantly improves their activity compared to their hit compounds 6a and 7a. However, the key interactions were lost in binding with COX-1. The calculation results revealed that the two compounds are selective COX-2 inhibitors, with potential selectivity indexes of 6-fold and 5-fold, respectively. The cell-based activity of compounds 6c and 7g toward HEK293 cells demonstrates that our compounds possess an acceptable safety toward normal cells. The results indicate that 6c and 7g can serve as potential lead compounds for further lucubrate.

Mechanism Actions of Coniferyl Alcohol in Improving Cardiac Dysfunction in Renovascular Hypertension Studied by Experimental Verification and Network Pharmacology.

Renovascular hypertension (RH), a secondary hypertension, can significantly impact heart health, resulting in heart damage and dysfunction, thereby elevating the risk of cardiovascular diseases. Coniferol (CA), which has vascular relaxation properties, is expected to be able to treat hypertension-related diseases. However, its potential effects on cardiac function after RH remain unclear. In this study, in combination with network pharmacology, the antihypertensive and cardioprotective effects of CA in a two-kidney, one-clip (2K1C) mice model and its ability to mitigate angiotensin II (Ang II)-induced hypertrophy in H9C2 cells were investigated. The findings revealed that CA effectively reduced blood pressure, myocardial tissue damage, and inflammation after RH. The possible targets of CA for RH treatment were screened by network pharmacology. The interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling pathways were identified using a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The inflammatory response was identified using a Gene Ontology (GO) enrichment analysis. Western blot analysis confirmed that CA reduced the expression of IL-17, matrix metallopeptidase 9 (MMP9), cyclooxygenase 2 (COX2), and TNF α in heart tissues and the H9C2 cells. In summary, CA inhibited cardiac inflammation and fibrohypertrophy following RH. This effect was closely linked to the expression of MMP9/COX2/TNF α/IL-17. This study sheds light on the therapeutic potential of CA for treating RH-induced myocardial hypertrophy and provides insights into its underlying mechanisms, positioning CA as a promising candidate for future drug development.

Shedding Light on the COVID-19 Pandemic: Placental Expression of Cell Biomarkers in Negative, Vaccinated, and Positive Pregnant Women.

Background: We investigated the expression of inflammation, placental development, and function markers, including cluster of differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2), to shed light on the controversy regarding the impact of the COVID-19 epidemic on fetal development and pregnancy outcomes. Methods: We immunohistochemically analyzed placental tissue from 170 patients (65 COVID-positive and unvaccinated women; 35 Pfeizer-vaccinated and COVID-negative women; and 70 COVID-negative and unvaccinated women, without any other associated pathology) for particularities in the expression of these three molecules. Results: CD44 expression was highest in COVID-negative and unvaccinated women, moderate in COVID-positive cases, and lowest in vaccinated and COVID-negative women. OPN expression was highest in COVID-negative and Pfeizer-vaccinated cases, moderate in COVID-negative and unvaccinated cases, and lowest in COVID-positive cases. COX-2 expression was increased in COVID-negative and unvaccinated women, modestly elevated in COVID-positive and unvaccinated cases, and lowest in vaccinated cases. Conclusions: These findings reflected an alteration in the placental structure and consequent function due to altered expression of the three studied molecules.

Unraveling the Potential of Mononuclear Zn(II) and Cu(II) Schiff Base Metal Complexes: Microwave‐Aided Synthesis, Theoretical Analysis and Application in Biomimetic Catalysis, CT‐DNA Interaction, and In Vitro Biological Assays

ABSTRACTGiven the widespread and diverse effects of transition metal ions such as copper and zinc in multiple biological processes, this research endeavor addresses herein the microwave‐aided synthesis of two novel tetradentate ONNO (L1) and tridentate NNO (L2) donor Schiff base ligands derived from 4,5‐dimethyl‐1,2‐phenylenediamine and 4‐bromo‐2‐hydroxybenzaldehyde in a 1:2 ratio and from 4,5‐dimethyl‐1,2‐phenylenediamine and 5‐methoxy‐2‐hydroxybenzaldehyde in a 1:1 ratio, with their respective zinc, ZnL1(1) and ZnL2(3), and copper, CuL1(2) and CuL2(4), Schiff base metal complexes, which are comprehensively characterized utilizing physiochemical and analytical techniques, along with geometry optimization using the DFT approach. Spectrophotometric analyses have been used to assess the biomimetic activity in the conversion of 3,5‐DTBC to 3,5‐DTBQ with turnover numbers 53.4 and 78 h−1 in methanol for 2 and 4, whereas the zinc complexes are found to be ineffective. With CT‐DNA, possible modes of interaction with the synthesized complexes have been explored using absorption spectroscopy, where the associated binding constants ranged between 1.541 × 105 and 2.186 × 105 M−1. EtBr‐bound DNA was used in the fluorescence quenching experiments with Stern–Volmer constant (Ksv) values in the range 4.084 × 104 and 3.402 × 104 M−1, showing a stronger association with CT‐DNA. The compounds' ability to inhibit bacterial strains was also examined in vitro, as well as their ability to reduce inflammation, through the protein denaturation method and the DPPH assay for antioxidant activity have been performed. Furthermore, molecular docking simulations have been carried out to obtain a deeper comprehension of the molecular‐level interactions with CT‐DNA and cyclooxygenase‐2 (COX‐2).

Anti-inflammatory activity and molecular docking studies of the hydromethanolic leaf extract of Baphia longipedicellata brumitt in rats

Background: Almost all Baphia species of the Fabaceae family have a long history in traditional China due to their potent anti-inflammatory properties Baphia longipedicellata (B. longipedicellata) is a relatively novel plant comprised mainly of stigmasterol, which has a rich history in Chinese medicine and is a principal active component in numerous Chinese herbs such as maidong, the banxia-baizhu-tianma decoction and Qingfengteng which are all native to China and well known for its use in inflammatory diseases, asthma and diabetes management.Aim of the study: The study was meticulously designed to evaluate the anti-inflammatory activity of Baphia longipedicellata in rats. What sets this study apart is its unique approach to predicting the mechanism of anti-inflammatory action through docking studies.Materials and Methods: Preliminary phytochemical screening and oral acute toxicity were carried out for the hydromethanolic extract of Baphia longipedicellata (HMBL). Phytocompounds in the extract were identified using high-performance Liquid Chromatography (HPLC). Carrageenan and egg albumin-induced paw edema models in rats were evaluated to ascertain the extract's anti-inflammatory potential.Molecular docking experiments were carried out to evaluate the binding affinity of HPLC-selected compounds to cyclooxygenase-2 (COX-2) and tumour necrosis Factor-alpha (TNF-alpha).Results and Discussion: Preliminary phytochemical screening revealed the presence of saponin, tannins, cardiac glycosides, alkaloids, terpenoids, etc. Results obtained from this study showed that the LD50 was greater than 2000 mg/kg, and there were no observable toxic effects or mortality following its acute exposure.HPLC of HMBL profiled, Curcumin, Lutein, Stigmasterol, Beta-Sitosterol, Chrysarobin, Quercetin, and Napabucasin,HMBL extract at all treatment doses showed a significant reduction in both carrageenan and egg albumin-induced hind paw edema in a dose-dependent manner, comparable to the standard drug Diclofenac. Peak anti-oedematogenic activity was observed at the 6th-hour post-carrageenan injection with 28.50, 42.06, and 36.90 % inhibition for HMBL (100, 200, or 400 mg/kg) and 5th-hour post-egg-albumin injection with 61.22, 66.88, and 48.06 % inhibition.The molecular docking study showed that all the isolated HPLC compounds inhibited COX-2 and TNF-alpha.Conclusion Ultimately, the hydro-methanolic leaf extract of B. longipedicellata exhibits potent anti-inflammatory activity via COX 2 and TNF-alpha inhibition. Thus, it would be a viable phytotherapeutic option for treating inflammatory conditions.

Resveratrol Protects Müller Cells Against Ferroptosis in the Early Stage of Diabetic Retinopathy by Regulating the Nrf2/GPx4/PTGS2 Pathway.

The aim of this study was to investigate the anti-ferroptotic effect of resveratrol (RSV) on retinal Müller cells (RMCs) in the early stages of diabetic retinopathy (DR) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/prostaglandin-endoperoxide synthase 2 (PTGS2). The retina was obtained from normal and diabetic Sprague-Dawley rats or wild-type and Nrf2 knockout (KO) diabetic mice, with or without RSV (10mg/kg/d) treatment for 12weeks. RMCs transfected with or without SiNrf2 were cultured with high glucose and RSV (20mM). The retinal neurofunctional changes were measured by electroretinogram (ERG). The retinal inner nuclear layer cell mitochondrial morphological changes were detected by transmission electron microscopy. The cell viabilities were measured by cell counting kit-8 (CCK-8) assay. The levels of Fe2+, malonic dialdehyde (MDA), and glutathione (GSH) were measured by colorimetric method. The expression of Nrf2, GPx4, and PTGS2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry. In vivo, RSV inhibited retinal neurofunctional changes and mitochondrial morphological changes; decreased Fe2+, MDA, and PTGS2; and increased GSH, Nrf2, and GPx4 in retina of DM rats. In vitro, RSV decreased MDA and PTGS2 and increased cell viability, GSH, Nrf2, and GPx4. In vivo and vitro, the role of Nrf2-regulated signaling pathway in anti-ferroptosis by RSV was further confirmed using Nrf2 KO mice and pre-transfected SiNrf2 in RMCs. These findings indicated that RSV is a potential therapeutic option for DR and that Nrf2/GPx4/PTGS2 plays a role in the anti-ferroptosis mechanism of RSV on RMCs.

The Biological Effects and Mechanisms of Fisetin on Hepatotoxicity, Liver Injury, and Liver Fibrosis: A Systematic Review

Background: Liver disease is a common cause of death worldwide. Objectives: This study aims to investigate the effects and mechanisms of Fisetin on hepatotoxicity, liver injury, and liver fibrosis. Methods: We adhered to the PRISMA 2020 guidelines in this systematic review. Our search used MeSH keywords encompassed Embase, PubMed, Web of Science, Scopus, and Cochrane Library for articles published before March 2, 2024. Relevant data was extracted from the publications, meticulously recorded in a standard form, and subsequently reviewed for outcomes and mechanisms. Results: Fisetin protects hepatocytes from oxidative stress by neutralizing free radicals (O2 −and H2O2), reduces oxidative stress, prevents lipid peroxidation, and increases endogenous antioxidants. It also reduces inflammation via lowering the production of tumor necrosis factor α (TNF-α), interleukins (IL)1α, IL-6, IL-18, IL-1β suppressing nuclear factor kappa B (NF-κB) activation, and cyclooxygenase- 2 (COX-2), inducible nitric oxide synthase (iNOS) inhibition, reducing monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor 1 (PAI-1), NLR family pyrin domain-containing 3 (NLRP3) inflammasome and interferon-gamma (IFN‐γ). Moreover, it inhibited apoptosis-modulated enzyme activity and detoxification enzymes via modulating the activity of cytochrome P450 and Phase II detoxification enzymes. Fisetin prevented fibrosis by inhibiting the activation of hepatic stellate cells (HSCs), attenuating extracellular matrix (ECM) remodeling-associated genes, and suppressing transforming growth factor-β (TGF-β) signaling pathway and attenuating collagen production. It decreased lipid accumulation and liver function tests. Conclusion: In vivo and in vitro studies indicated that Fisetin can enhance detoxification, attenuate liver injury, and reduce fibrosis, which helps maintain liver health.

Ameliorative effect of diclofenac in rotenone corneal kindling model of drug-resistant epilepsy: Edge of dual COX and KMO inhibition

Epilepsy affects millions of people worldwide, about one-third patients with epilepsy exhibits resistance to available antiseizures medications, known as drug-resistant epilepsy (DRE). Mitochondrial dysfunction has been implicated as a hallmark in drug-resistant epilepsy via activation of microglial kynurenine 3-monooxygenase (KMO) and cyclooxygenase (COX) enzymes, leading to neuroinflammation and oxidative stress. Diclofenac, an equipotent non selective cyclooxygenase inhibitor, has inhibitory action on KMO enzyme and has also shown anti-inflammatory and antioxidant properties in animal models of epilepsy. These properties make it a suitable candidate for amelioration of DRE. However, its potential in drug-resistant epilepsy remained unexplored till date. In this study, dose dependent effect of diclofenac (5 mg/kg, 10 mg/kg, 20 mg/kg) has been explored in rotenone corneal kindling model of mitochondrial DRE. The results of our study revealed the induction of drug resistance to antiseizure medications and induced kynurenine 3-monooxygenase activity in rotenone corneal kindled epileptic mice in comparison to naive mice. Treatment of rotenone corneal kindled epileptic mice with diclofenac resulted in a significant decrease in drug resistance to antiseizure medications as evident by a reduction in seizure score in the treatment groups as compared to control group, in post-treatment resistance validation. The kynurenine 3-monooxygenase inhibitory activity (as evidenced by decreased levels of neurotoxic quinolinic acid) and the antioxidant effect (as evident by significantly reduced oxidative stress) in the diclofenac treated groups, emerged as a major contributor for its ameliorative action. Findings of this study suggests, diclofenac can be used as an adjunct therapy in amelioration of drug-resistant epilepsy.

Assessment of cell death in the liver of Labeo rohita on exposure to an emerging contaminant aspirin: an immunofluorescent, flow cytometric and biochemical investigation.

Aspirin is one of the most frequently detected non-steroidal anti-inflammatory drugs in aquatic environments. Despite its prevalence, toxicity possessed by aspirin to non-target organisms like fish is poorly explored. In the present study, cell death induced by different concentrations of aspirin (1, 10, and 100µg/L) has been investigated in the liver of fish, Labeo rohita exposed for 28days. A significant increase (p < 0.05) in the density of caspase-3 positive cells in a dose and duration-dependent manner assessed through immunofluorescent staining indicates caspase-dependent pathway of cell death which may be either through intrinsic or extrinsic pathway. The flow cytometric analysis, in addition, revealed a significant (p < 0.05) decline in the live cells and an increase in apoptotic cells in the liver of fish exposed to aspirin. Cell death due to apoptosis is further indicated by a significant increase (p < 0.05) in the Kupffer cells and tumor necrosis factor-α. The decrease in the activity of cyclooxygenase (COX) enzyme significantly (p < 0.05) in all three exposure concentrations of aspirin suggests COX-dependent pathway of cell death. The present study provides in-depth insights into aspirin-induced cell death in the liver of fish at environmentally realistic concentrations.

Nano-pregabalin effectively mitigates Glut, CGRP and NE neurotransmitters abnormalities in the brain of gamma irradiated rats with reserpine-induced fibromyalgia model: Behavioral and neurochemical studies

AimsFibromyalgia (FM) is an idiopathic syndrome with painful burdensome symptoms. Radiotherapy is one of the main therapeutic modalities for treating various malignancies and there is a probable association between FM exacerbation and exposure to ionizing radiation. Based on that nanomedicines progressively being explored for their promising applications in medicine, the aim of the current study is to assess the possible therapeutic benefits of nanoform of pregabalin (N-PG) in managing FM symptoms during being exposed to ionizing radiation. Main methodsRats were allocated into four groups. First group served as control, the other three groups received gamma radiation (2 Gy/day) after 1 h of reserpine administration (1 ml/kg per day, s.c.) to induce FM for three successive days. On the next day, third and fourth groups received (30 mg/kg, p.o.) of PG and N-PG, respectively once daily for ten consecutive days. Tail flick test was performed and von Frey filaments were used to assess mechanical allodynia/hyperalgesia, and then rats were sacrificed to obtain brains. Key findingsN-PG effectively replenished reserpine effects and treated both allodynia and hyperalgesia, improved thermal allodynia, effectively recovered all neurotransmitters near to normal baseline, inhibited oxidative stress status via decreasing malondialdehyde (MDA), increasing glutathione (GSH) and superoxide dismutase (SOD), it had strong anti-inflammatory effect as verified by reducing both cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-kB) in addition to inhibition of intrinsic apoptosis through caspase-3 (casp-3) decrease and B-cell lymphoma-2 (Bcl-2) increase. Histopathological and immunohistochemical results confirmed the biochemical findings. SignificanceN-PG could be a promising drug for treating FM especially when there is urgent need to expose patient to ionizing radiation.

Anti-Inflammatory Activity and Wound Healing Ability of Coconut Oil Mouthwash on Gingival Fibroblast Cell In Vitro

Coconut oil-pulling therapy is used for maintaining oral health. The procedure has benefits for the prevention of oral disease, including dental caries, oral malodor, bleeding gums. However, virgin coconut oil (VCO) has unsatisfying oily taste. Therefore, coconut oil mouthwash (CoMW) was recently developed. This in vitro study aimed to evaluate the anti-inflammatory activity of coconut oil mouthwash consisting of 60% v/v virgin coconut oil (VCO), 30% v/v propylene glycol (PG), and 10% v/v distilled water on human gingival fibroblast (HGF) cells compared with the activity on murine macrophage (Raw 264.7) cells. The cytotoxicity of CoMW, 0.12% chlorhexidine gluconate (CHX), VCO, and PG was assessed. IC50 concentration of CoMW, CHX, and PG were 1:8 (v/v), 1:32 (v/v), and 1:16 (v/v), respectively. All tested concentrations of VCO had no impact on cell viability. Their anti-inflammatory effects of each IC50 concentration were further studied. Notably, the IC50 concentration of CHX also significantly inhibited nitric oxide production in lipopolysaccharide (LPS)- activated Raw 264.7 cells. Moreover, the IC50 concentrations of CoMW, VCO, PG, and CHX could suppress the interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) gene expressions in LPS-activated HGF cells, while also enhancing the cell migration of HGF cells as likely to the effect observed with the IC50 concentration of CHX. Wound healing ability of CoMW was also demonstrated after testing with a scratch assay. These findings indicated promising potential for coconut oil mouthwash as an effective agent in reducing inflammation and facilitating wound healing.

Disruption of the PGE2 synthesis / response pathway restrains atherogenesis in programmed cell death-1 (Pd-1) deficient hyperlipidemic mice.

Immune checkpoint inhibitors (ICIs) that target programmed cell death 1 (PD-1) have revolutionized cancer treatment by enabling the restoration of suppressed T-cell cytotoxic responses. However, resistance to single-agent ICIs still limits their clinical utility. Combinatorial strategies enhance the antitumor effects, but may also enhance the risk of immune related adverse effects of ICIs. Prostaglandin (PG) E2, formed by the sequential action of the cyclooxygenase (COX) and microsomal PGE synthase (mPGES-1) enzymes, acting via its E prostanoid (EP) receptors, EPr2 and EPr4, promotes lymphocyte exhaustion, revealing an additional target for ICIs. Thus, COX inhibitors and EPr4 antagonists are currently being combined with ICIs potentially to enhance antitumor efficacy in clinical trials. However, given the cardiovascular (CV) toxicity of COX inhibitors, such combinations may increase the risk particularly of CV AEs. Here, we compared the impact of distinct approaches to disruption of the PGE2 synthesis /response pathway- global or myeloid cell specific depletion of mPges-1 or global depletion of Epr4- on the accelerated atherogenesis in Pd-1 deficient hyperlipidemic (Ldlr KO) mice. All strategies restrained the atherogenesis. While depletion of mPGES-1 suppresses PGE2 biosynthesis, reflected by its major urinary metabolite, PGE2 biosynthesis was increased in mice lacking EPr4, consistent with enhanced expression of aortic Cox-1 and mPges-1. Deletions of mPges-1 and Epr4 differed in their effects on immune cell populations in atherosclerotic plaques; the former reduced neutrophil infiltration, while the latter restrained macrophages and increased the infiltration of T-cells. Consistent with these findings, chemotaxis by bone-marrow derived macrophages from Epr4 KO mice as impaired. in Epr4 depletion also resulted in extramedullary lymphoid hematopoiesis and inhibition of lipoprotein lipase activity (LPL) with coincident spelenomegaly, leukocytosis and dyslipidemia. Targeting either mPGES-1 or EPr4 may restrain lymphocyte exhaustion while mitigating CV irAEs consequent to PD-1 blockade.

Radical-Scavenging and Anti-inflammatory Activities of Fermented Eucheuma cottonii from Lombok

Eucheuma cottonii, a widely cultivated seaweed from the Island of Lombok, Indonesia, contains various bioactive compounds. Its utilization, however, is mainly limited based on its high carbohydrate content. Nevertheless, plant fermentation using lactic acid bacteria is renowned for increasing bioactive compounds and enhancing bioactivities. This study unveiled the potential of Lactobacillus plantarum-fermented E. cottonii as a functional food. E. cottonii was fermented using L. plantarum for 24 h. The folin-Ciocalteau method was used to determine the total phenolic content. The antioxidant capacity was measured using a 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. Anti-inflammatory activity was carried out using cyclooxygenase (COX) inhibition assay against cervical cancer (HeLa) and colon cancer (WiDr) cells. Overall, fermentation successfully enhanced the bioactivities of E. cottonii. Fermented products exhibited higher antioxidant capacity than unfermented ones. Interestingly, the bioactivities only showed a moderate correlation with total phenolic content. Regarding anti-inflammatory activity, fermented extracts exhibited higher cyclooxygenase inhibition against HeLa cells, whereas no significant differences were observed between the fermented and unfermented products in WiDr cells. These findings indicate that L. plantarum-fermented E. cottonii holds promise to be a profitable functional food and has the potential to be utilized as an additional food therapy for cancer treatment. Keywords: Eucheuma cottonii; fermentation; Lactobacillus plantarum; antioxidant, anti-inflammation.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer.

Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Cyclooxygenase 2 and prostaglandin E2 in the genesis of pregnancy loss in cytomegalovirus infection

Prostaglandins (PGs), regulated by cyclooxygenase (COX) 2, play a significant role in the development of placental disorders in pathological pregnancy. A review of current literature reveals a lack of evidence demonstrating the involvement of PGs in the pathogenesis of early spontaneous miscarriages associated with cytomegalovirus (CMV) infection. The aim of this study was to investigate the levels of COX-2 and PG E2 in peripheral blood and determine their significance in predicting pregnancy loss during exacerbation of CMV infection at 7-8 weeks gestation.Materials and methods. The study involved 70 patients experiencing an exacerbation of chronic CMV infection at 7-8 weeks of gestation, with 36 patients presenting with a threatened miscarriage (main group) and 34 patients without signs of threatened miscarriage (comparison group). CMV infection was diagnosed based on the presence of M and G class antibodies using enzyme-linked immunosorbent assay (ELISA), as well as CMV DNA detected by polymerase chain reaction. COX-2 levels in mononuclear cell lysates were determined using the "Assay Designs, COX-2" (USA) test systems, and PG E2 concentrations in blood serum were measured using "Cloud-Clone Corp." (USA) kits.Results. Women with exacerbated CMV infection associated with spontaneous miscarriage at 7-8 weeks of gestation exhibited elevated concentrations of COX-2 (23.0±2.20 ng/mL) and PG E2 (850.10±35.0 pg/mL, p&lt;0.001) compared to pregnant women without threatened miscarriage (12.75±1.35 ng/mL and 42.0±2.80 pg/mL, respectively).Conclusion. The findings of this study underscore the significant role of elevated COX-2 and PG E2 concentrations in the pathogenesis of pregnancy loss during exacerbation of CMV infection at 7-8 weeks of gestation. The assessment of COX-2 and PG E2 levels should be considered as a predictive measure for the risk of pregnancy loss during exacerbation of CMV infection.

Erythropoietin Reduces Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Bleomycin-Induced Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial disease with unknown etiology and no effective cure, posing a great health burden to society. Erythropoietin (EPO) has been demonstrated to have protective roles in various tissues such as brain, spinal cord, heart, kidney and lung tissues. In this study, we investigate the specific anti-inflammatory, antioxidant and antiapoptotic effects of erythropoietin on lung tissue in a bleomycin-induced rat model of idiopathic pulmonary fibrosis. Recombinant human EPO or saline was injected, and the animals were monitored for 14 days after bleomycin instillation. Their hematocrit and serum EPO levels were determined. Histological and immunohistochemical analyses were performed. The extent of tissue injury, determined through morphometric analysis, was significantly decreased in size in animals treated with erythropoietin. An immunohistochemical analysis of the expression of cyclooxygenase-2 (COX-2), inducible synthase of nitric oxide (i-NOS), metalloproteinase-9 (MMP-9), erythropoietin receptor (EPO-R), and cytochrome-C (cyt-C) found these enzymes to be decreased in a statistically significant manner in animals treated with erythropoietin when compared to a non-treated group. The reduced expression of COX-2, i-NOS, MMP-9, EPO-R, and i-NOS in the lung tissues of animals treated with EPO indicates the anti-inflammatory, antioxidant and antiapoptotic action of erythropoietin, suggesting its potential therapeutic role in pulmonary fibrosis.