MPO Levels Research Articles

Preemptive vs preventive coadministration of ibuprofen L-arginine and dexamethasone in lower third molar surgeries: a randomized controlled trial

To compare the effect of different preemptive and preventive analgesia strategies involving oral coadministration of ibuprofen-arginine (770 mg)-Ib-Ar and dexamethasone (8 mg)-DX, and their respective placebos (P-Ib-Ar and P-DX), four evaluation groups on inflammatory and laboratory parameters, impact on quality of life, pain catastrophizing perception and sleep quality related after lower third molar surgery. A randomized split-mouth, triple-blind, controlled clinical trial was conducted with 48 volunteers. They were allocated depending on the use of Ib-Ar or DX, 1 hour before surgery or immediately postoperatively, discriminating the groups: G1 (Ib-Ar + DX), G2 (Ib-Ar + P-DX), G3 (P-Ib-Ar + DX), and G4 (P-Ib-Ar + P-DX). Pain peaks occurred after 2 h (P-Ib-Ar groups) (P = .003), while the other groups showed peak pain after 4 h (P < .05). Regarding the edema: groups treated with placebos measurements significantly reduced without returning to baseline (P < .001). Regarding laboratory parameters: MPO and MDA levels, the G1 group (P < .001) was the only one showing significant reduction. The use of preemptive and preventive analgesia strategies of Ib-Ar and DX showed that the combined use delayed peak pain, with no difference in edema and trismus. The benefit of coadministration of both strategies was superior to isolated use of drugs.

Natural zinc-rich oyster peptides ameliorate DSS-induced colitis via antioxidation, anti-inflammation, intestinal barrier repair, microbiota modulation, and SCFA accumulation

Natural oyster zinc-rich peptide (OZP) was extracted and purified. The higher zinc concentration in natural OZP may be closely related to the high zinc affinity of amino acids containing Lys, His, Cys, Val, Arg and Ser residues. FTIR analysis indicated that amino, amide, carboxyl and carbonyl groups may contribute to the binding sites for zinc and peptides. Administration of OZP ameliorated the symptoms of DSS-induced ulcerative colitis (UC) in mice, including weight loss, colonic damage, mucosal edema, goblet cell exhaustion and crypt disappearance. Natural OZP suppressed oxidative stress by significantly reducing the level of NO, MDA and MPO as well as increasing SOD activity. The anti-inflammatory effects of OZP were associated with the inhibition of TLR4/NF-κB pathways by diminishing NF-κB, TLR4, COX-2, iNOS, TNF-α, IL-6 and IFN-γ and elevating IL-10. By promoting mucus secretion, repairing goblet cells and enhancing the expression of tight junction proteins including occludin, claudin-1 and ZO-1, natural OZP maintained the intestinal barrier function. Furthermore, natural OZP regulated the microbial composition by remarkedly enhancing the beneficial microbial abundance like Faecalibaculum, Odoribacter and Anaerostipes, which in turn led to a significant increase in SCFA production. Collectively, natural OZP exerted the synergistic capacity to protect against DSS-induced UC by improving antioxidation and anti-inflammation, repairing intestinal barrier and modulating intestinal microbiota and SCFA.

High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis

To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury (IRI) and its regulatory role in IRI. C57BL/6 mice were divided into sham operation group, IRI (induced by clamping the renal artery) model group, IRI+DMSO treatment group, and IRI+SN-011 treatment group. Serum creatinine and blood urea nitrogen of the mice were analyzed, and pathological changes in the renal tissue were assessed with PAS staining. RT-qPCR, ELISA, Western blotting, and immunohistochemistry were used to detect the expression levels of STING, KIM-1, Bcl-2, Bax, caspase-3, TLR4, P65, NLRP3, caspase-1, CD68, MPO, IL-1β, IL-6, and TNF-α in the renal tissues. In the cell experiment, HK-2 cells exposed to hypoxia-reoxygenation (H/R) were treated with DMSO or SN-011, and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR, Western blotting or flow cytometry. In C57BL/6 mice, renal IRI induced obvious renal tissue damage, elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1, STING, TLR4, P65, NLRP3, caspase-1, caspase-3, Bax, CD68, MPO, IL-1β, IL-6, and TNF-α, and reduction of Bcl-2 expression level. Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes. In HK-2 cells, H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate, which was significantly lowered by treatment with SN-011. Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Ameliorative effects of probiotic Limosilactobacillus fermentum and Enterococcus lactis isolated from cameroonian traditionally processed milk and palm wine against chronic constriction injury induced neuropathic pain in mice

Ethnopharmacological relevanceFermented milk and palm wine are regularly used by several ethnic groups in Cameroon in traditional treatment rituals for infections, inflammatory, cardiovascular disorders, and even metabolic diseases such as diabetes, hypercholesterolemia etc. Reports from many studies have demonstrated that fermented milk and palm wine are potential sources of probiotic bacteria. However, the capacity of probiotics isolated from these natural sources to alleviate neuropathic pain has not been experimentally tested. Aim of the studyThis study aimed at investigating the ameliorative potential of lactic acid bacteria isolated from palm wine and traditional fermented cow milk on the chronic constriction injury (CCI) induced neuropathic pain in mice. Materials and methodsPour plating technique on De Man Rogasa (MRS) agar was utilised for isolation of lactic acid bacteria from fermented cow milk and palm wine, and identified using the 16S r RNA gene sequencing. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve. These bacteria were orally administered at different concentrations to Balb/c mice by gavage for 14 consecutive days. Cold allodynia, mechanical hyperalgesia and exploratory behaviour were evaluated on day 0, 7th and 14th respectively. The total level of calcium, oxidative stress markers and myeloperoxidase were also quantified in the sciatic nerve homogenate. Cyclooxygenase-2(COX-2) and cytokine profile were determined from serum. ResultsLactic acid bacteria were isolated from fermented cow milk and palm wine and two isolates were chosen according to their probiotic potentials and identified as strain of Limolactobacillus fermentum and Enterococcus lactis. Their 16 S rRNA gene sequences were deposited in NCBI genbank with accession number of OP896078 and OR619545, respectively. Pretreatment with Limosilactobacillus fermentum and Enterococcus lactis significantly alleviated mechanical hyperalgesia and cold allodynia with similar effect to the reference drug, morphine. These two isolates ameliorated CCI induced neuropathic pain by increasing antioxida776nts (GSH, CAT and SOD, P < 0.01) and decreasing pro-oxidants (MDA and NO, P < 0.01). Also, they inhibited the release of proinflammatory cytokines (IL-1β, TNF-α, IFN-γ, and IL-6; P < 0.01) and IL-10 level was significantly (P < 0.01) increased when compared to the negative control. Treatment with these bacteria significantly dropped the level of total calcium (P < 0.01), COX-2 (P < 0.01) and MPO (P < 0.01) when compared with the negative control. ConclusionThe neuroprotective potentials of these selected lactic acid bacteria against CCI induced neuropathic pain may be attributed to their anti-oxidant, anti-inflammatory properties and reduced calcium deposition in sciatic nerve.

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats

ObjectiveThe hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. MethodsThirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Resultsα-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. ConclusionResveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

Mild hypothermia pretreatment improves hepatic ischemia-reperfusion injury: A systematic review and meta-analysis of animal experiments.

Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.

The double-layer emulsions loaded with bitter melon (Momordica charantia L.) seed oil protect against dextran sulfate sodium-induced ulcerative colitis in mice

In this study, a whey protein isolate (WPI)-chitooligosaccharide (COS) stabilized bitter melon (Momordica charantia L.) seed oil emulsions (WC-BSOE) were prepared using the electrostatic layer-by-layer self-assembly technique, and their modulating effects on ulcerative colitis (UC) were investigated in dextran sulfate sodium (DSS)-induced UC mice model. The stability and releasing ability of WC-BSOE under simulated gastrointestinal digestion condition and their acute toxicity were also investigated. The results showed that WC-BSOE was stable to droplet aggregation in the simulated gastric and intestinal fluids and exhibited sustained release profile during gastrointestinal transit, evidenced by the measurement of particle size, polydispersity index, zeta-potential and released free fatty acids contents. Moreover, WC-BSOE had no toxic effects on BALB/c mice within the dose range of 40,000 mg/kg body weight (BW), and treatment with WC-BSOE at a dosage of 15 mg/kg BW effectively relieved DSS-induced UC symptoms in mice. Furthermore, WC-BSOE could improve the IL-4 and IgA contents in serum, as well as up-regulate the occludin and ZO-1 expressions and down-regulate MPO, MDA and ROS levels in colon tissues of colitis mice, and it also elevated the diversity and relative abundances of Firmicutes, Bacteroides, and Lactobacillus in the intestinal microbiota. These findings indicated that WC-BSOE exerted protective effects in UC through decreasing proinflammatory cytokines, increasing tight junction proteins, suppressing oxidative stress, and regulating intestinal microbiota. Collectively, this study suggested WC-BSOE might be developed as a promising dietary supplement for UC protection.

Puerarin inhibits Staphylococcus aureus-induced endometritis through attenuating inflammation and ferroptosis via regulating the P2X7/NLRP3 signalling pathway.

Endometritis is one of the important causes of infertility. Puerarin (PU) can inhibit oxidative stress and reduce inflammation; however, it is unclear whether PU has a protective effect on the endometritis. In our study, we used Staphylococcus aureus to induce mouse endometritis. The PU group (100 mg/kg PU) and the S. aureus + PU group received daily intraperitoneal injection of PU (25, 50 or 100 mg/kg PU). The results showed that S. aureus significantly increased the levels of MPO, TNF-α, IL-1β and IL-6 in uterine tissue, and increased the expression of p-p65 and p-IκBα proteins in uterine tissue to induce endometritis in mice (p < 0.05). Furthermore, it has been found that S. aureus promotes the occurrence of ferroptosis by reducing GSH and ATP content, increasing MDA and iron content and reducing GPX4 and SLC7A11 protein expression levels (p < 0.05). S. aureus significantly increase the expression of NLRP3, ASC, caspase-1 and P2X7 proteins in uterine tissue (p < 0.05). However, PU obviously reduced the inflammatory response and reversed the changes of ferroptosis and the expression of P2X7 receptor/NLRP3 pathway associated proteins of the uterus induced by S. aureus (p < 0.05). Taken together, these findings emphasize the protective effect of PU on endometritis by regulating the P2X7 receptor/NLRP3 signalling pathway and inhibiting ferroptosis.

Borax attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/ROS balance in acrylamide-induced neurotoxicity in rainbow trout

Acrylamide (ACR) can have adverse environmental effects because of its multiple applications. Relevant scientific literatures of the existence of ACR residues in foods following processing steps have raised concern in the biochemistry, chemistry and safety of this vinyl substance. The interest has focused on the hepatotoxicity of ACR in animals and humans and on the ACR content mitigation and its detoxification. Borax (BX), as a naturally occurring antioxidant featured boron compound, was selected in this investigation to assess its possible neuro-protective potential against ACR-induced neurotoxicity. Nrf2 axis signaling pathways and detoxification response to oxidative stress after exposure to ACR in brains of rainbow trout, and the effect of BX application on reducing ACR-induced neurotoxicity were investigated. Rainbow trout were acutely exposed to ACR (12.5 mg/L) alone or simultaneously treated with BX (0.75 mg/L) during 96h. The exposed fish were sampled at 48th and 96th and oxidative stress response endpoints, 8-OHdG, Nrf2, TNF-α, caspase-3, in addition to IL-6 activities and the levels of AChE and BDNF in brain tissues of rainbow trout (Oncorhynchus mykiss) were evaluated. Samples showed decreases in the levels of ACR-mediated biomarkers used to assess neural toxicity (SOD, CAT, GPx, AChE, BDNF, GSH), increased levels of MDA, MPO, DNA damage and apoptosis. ACR disrupted the Nrf2 pathway, and induced neurotoxicity. Inhibited activities’ expressions under simultaneous administration experiments, revealed the protective effects of BX against ACR-induced toxicity damage. The obtained data allow the outline of early multi-parameter signaling pathways in rainbow trout

Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury by modulating heat shock protein A12B to inhibit the toll-like receptor 4/nuclear factor-kappa B signaling pathway

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Life-threatening medical conditions characterized by high morbidity and mortality rates, where the inflammatory process plays a crucial role in lung tissue damage, especially in models induced by lipopolysaccharide (LPS). Heat shock protein A12B (HSPA12B) has strong anti-infammatory properties However, it is unknown whether increased HSPA12B is protective against LPS-induced ALI. And Dexmedetomidine (DEX) is a potent α2-adrenergic receptor (α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. This study utilized bioinformatics analysis and an LPS-induced ALI model to explore how DEX alleviates lung injury by modulating HSPA12B and inhibiting the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Results indicate that HSPA12B overexpression and DEX pre-treatment markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) in the BALF, and the levels of NO, MDA,SOD and MPO in the lung. Moreover, HSPA12B overexpression and DEX pre-treatment significantly reduces lung injury and inflammation levels by upregulating HSPA12B and inhibiting the activation of the TLR4/NF-κB signaling pathway. On the contrary, when the expression of HSPA12B is inhibited, the protective effect of DEX pre-treatment on lung tissue is significantly weakened.In summary, our research demonstrated that the increased expression of AAV-mediated HSPA12B in the lungs of mice inhibits acute inflammation and suppresses the activation of TLR4/NF-κB pathway in a murine model of LPS-induced ALI. DEX could enhance HSPA12B and inhibit the initiation and development of inflammation through down-regulating TLR4/NF-κB pathway.These findings highlight the potential of DEX as a therapeutic agent for treating ALI and ARDS, offering new strategies for clinical intervention.

Pericopsis laxiflora (Baker) stem bark extract is protective against carbon tetrachloride-induced acute liver damage by modulation of oxidative stress and inflammation

The present study aimed to investigate the hepatoprotective activity of the hydroethanolic (HSE) and methanolic extracts (MSE) of Pericopsis laxiflora stem bark on carbon tetrachloride-induced hepatotoxicity in rats. The stem bark of P. laxiflora was extracted with 50% ethanol and methanol. Hepatoprotective activities were assessed using the CCl4 model and tested against extracts at 100, 250, and 500 mg/kg bwt. Biochemical, antioxidant enzymes and proinflammatory cytokines in liver homogenate were assayed. Treatment with HSE and MSE resulted in a significant increase in SOD, CAT, and GSH levels and a significant decrease in MDA and MPO levels in livers of CCl4 treated rats. There was also restoration of liver biomarkers and pro-inflammatory cytokines to near-normal levels. The present investigation suggests P. laxiflora extracts possess good hepatoprotective properties. This could be attributed in part to the inhibitory effect of the extracts on oxidative stress and the suppression of proinflammatory cytokines.

Protective effect of soluble dietary fiber from Rosa roxburghii Tratt residue on dextran sulfate sodium-induced ulcerative colitis by regulating serum metabolism and NF-κB pathway in mice.

Ulcerative colitis (UC) refers to an idiopathic chronic inflammatory bowel disease that starts with inflammation of the intestinal mucosa. Dietary fiber plays a crucial role in maintaining the normal architecture of the intestinal mucosa. In this study, the protective effect and potential mechanism of soluble dietary fiber from Rosa roxburghii Tratt residue (SDFR) on dextran sulfate sodium (DSS)-induced UC mice were explored. The results revealed that SDFR could ameliorate body weight loss and pathological injury, improve the structure and crypt destruction in colon in DSS-induced mice. Moreover, the levels of NO, IL-1β, TNF-α, MPO and protein expression of iNOS and COX-2 were decreased after administration of SDFR. Notably, nontargeted metabolomics analysis indicated that there were significant differences in 51 potential metabolites in serum between the DSS and control groups. SDFR intervention could regulate aberrant alterations of these metabolites and mitigate UC via regulating metabolic pathways, including arachidonic acid and glycerophospholipid metabolism. This study provides novel evidence that SDFR could be used as a potential modulator to relieve UC. Also, the results provide a theoretical basis for the utilization of byproducts in Rosa roxburghii Tratt fruit processing. © 2024 Society of Chemical Industry.

Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health.

The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings. The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease-free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty-six NG participants age-matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead-based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2-way analysis of variance (ANOVA) with a post-hoc Tukey's test. Our findings showed that EG had a greater gingival index than NG and was healthy (p<0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p<0.001), CCL3 (p<0.05), and IL-1B (p<0.001) than NG. In contrast, NG had increased levels of MIF (p<0.05), Fractalkine (p<0.001), angiogenin (p<0.05), C3a (p<0.001), BMP-2 (p<0.001), OPN (p<0.05), RANKL (p<0.001), and MMP-13 (p<0.001) than EG. Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG.

Preclinical evaluation of Janus Kinase inhibitors in atopic dermatitis: Insights from an oxazolone-induced mouse model

Abstract Atopic dermatitis (AD) is a prevalent inflammatory skin condition affecting a substantial proportion of the population. However, the lack of robust preclinical evidence of Janus kinase (JAK) inhibitors in AD treatment necessitates the development of more effective therapies, including those repurposed from other indications. Thus, we aimed to establish a preclinical evaluation system targeting JAK inhibitors to explore their effectiveness and mechanism of action in AD mouse model. We utilized an oxazolone (OXA)-induced AD mouse model to assess the effects of JAK inhibitors. Ear thickness, IgE and MPO levels were measured regularly. At the end of study, spleen weights were measured, and ear tissues were processed for cytokine analysis and pathological evaluation. Additionally, flow cytometry was utilized to analyze immune cells in auricular draining lymph nodes (DLN). Following OXA challenge, temporal changes in the immune system were observed, characterized by increased pro-inflammatory cytokines, immune cell infiltration in auricular DLN, and elevated IgE and MPO levels. Treatment with JAK inhibitors led to a reduction in AD-associated features and resulted in decreased immune cell infiltration and alterations in specific molecular features. Our study successfully established a preclinical mouse model for AD, facilitating a comprehensive understanding of skin inflammation, immunomodulation, and the pharmacodynamics of test articles in the context of AD.

Molecular docking, dynamics, and preclinical experimental studies identify Morin hydrate as a potent PPAR-γ and NRF-2 transcription factor agonist that mitigates colon inflammation

Introduction: Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a vital role in regulating intestine inflammation. PPAR-γ is highly expressed in the adipose tissue and the colon. The nuclear erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) system protects cells from oxidative stress and inflammation. Therefore, PPAR-γ and Nrf2 ligands offer a drug-targeting system that can be exploited to treat inflammatory bowel diseases (IBDs), especially ulcerative colitis. IBD prevalence is on the rise globally. Current mainstream therapies for IBD offer protection but with many side effects; therefore, up to 30% of IBD patients turn to alternate therapy using bioactive phytochemicals. Morin hydrate, a naturally occurring bioflavonoid in many fruits, stems, and leaves of the Moraceae family plant, possesses potent anti-inflammatory properties. The docking studies reveal that it is a potent activator of the PPAR-γ and Nrf2 transcription factors. Therefore, in this study, we investigated the role of morin hydrate modulating colon epithelial PPAR-γ transcription in colon inflammation. Aim: Therefore, this study aims to investigate morin hydrate’s anti-inflammatory properties using both in vivo and in vitro models of colon inflammation. Methodology: C57BL/6J black mice were administered 2% dextran sodium sulfate (DSS) morin hydrate administered at concentrations of 25 &amp; 50mg/kg body for in vivo studies. The DAI, colon length, MPO, and histology changes were determined. Proinflammatory cytokines (IL-1β, IL-6, TNF-α, &amp; IL17A) were measured using ELISA and mRNA using real-time PCR. PPAR-γ and Nrf2 expression and phosphoNF-κB/NF-κB expression were estimated. HT-29 cells were cultured in DMEM media and were stimulated using TNF-α (1ng/ml). Different concentrations of morin hydrate were treated to HT-29 cells to determine a safe dose range for further in vitro experiments by estimating cell toxicity assay. CXCL-1, IL-8, and mRNA levels were determined using real-time PCR after morin hydrate co-treatment. Morin hydrate effect on PPAR-γ and Nrf2 promoter activity was determined using full-length promoter transfection studies. Results: Morin treatment significantly ( p&lt;0.01) decreased DAI, MPO level, and restored colon length dose-dependently in the treated group. Histological scoring for colonic inflammation was significantly ( p&lt;0.001) improved upon morin treatment. Morin treatment also inhibited the proinflammatory cytokines (IL-1β, IL-6, TNF-α, &amp; IL17A) significantly ( p&lt;0.01) both at protein and mRNA levels. Morin significantly inhibited COX-2 and iNOS both at protein and mRNA levels and also decreased tissue nitrite levels. Morin also activated PPAR-γ protein expression NRF2 nuclear translocation and inhibited NF-κB expression in DSS-administered mice. Morin significantly decreased antioxidant surrogate markers superoxide dismutase (SOD) and catalase activity. Morin significantly ( p&lt;0.01) decreased proinflammatory cytokine (CXCL-1 &amp; IL-8) mRNA expression when HT-29 cells were challenged with TNF-α. Morin also increased PPAR-γ and Nrf2 promoter activity. Conclusion: Morin hydrate is a potent PPAR-γ and Nrf2 transcription factor activator that mitigates colon inflammation through its anti-inflammatory and antioxidant activities. This is supported from UAE University grant, fund number 12R006 and 12R169. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Dietary Inosine 5'-Monophosphate Supplementation on the Growth Performance and Salinity and Oxidative Stress Resistance of Gibel Carp (Carassius auratus gibelio).

An 88-day feeding trial was conducted to evaluate the effects of dietary inosine 5'-monophosphate (5'-IMP) on the growth performance and salinity and oxidative stress resistance in the juvenile gibel carp CAS III (Carassius auratus gibelio; initial body weight: 7.48 g). Four isonitrogenous and isoenergetic diets containing exogenous 5'-IMP were formulated. P1, P2, P3 and P4 were diets containing 5'-IMP at four concentrations (0, 1, 2 and 4 g kg-1). The four diets were randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, six fish per tank were netted randomly and placed into 12‱ saline water to test their response to salinity stress. The results indicated that the feed conversion rate was enhanced by dietary supplementation with 5'-IMP. The appetite, plasma neuropeptide Y level and feeding rate of the P3 group were lower than those in the control treatment group. Dietary supplementation with 5'-IMP improved the osmoregulatory adaptation of gibel carp under acute salinity stress. Six hours after the salinity stress treatment, in the dietary 5'-IMP treatment group, the plasma cortisol and K+ concentrations were lower and the Na+/K+-ATPase activity was greater than that in the control group. Dietary supplementation with 5'-IMP promoted the expression of the glucocorticoid receptors NKA-α1b and NKCC and retarded the expression of Hsp70 in P4-treated gill filaments and kidneys. Dietary supplementation with 5'-IMP resulted in a stable oxidative-stress-resistant phenotype characterized by increased levels of cellular antioxidants, including SOD, catalase, glutathione peroxidase, glutathione reductase and MPO. The above results of the current study demonstrate that supplementation of 5'-IMP can promote feed utilization and have positive influences on the salinity and oxidative stress resistance of gibel carp.

Protective effects of sinomenine against dextran sulfate sodium-induced ulcerative colitis in rats via alteration of HO-1/Nrf2 and inflammatory pathway.

Dextran Sulfate Sodium (DSS) induces ulcerative colitis (UC), a type of inflammatory bowel disease (IBD) that leads to inflammation, swelling, and ulcers in the large intestine. The aim of this experimental study is to examine how sinomenine, a plant-derived alkaloid, can prevent or reduce the damage caused by DSS in the colon and rectum of rats. Induction of ulcerative colitis (UC) in rats was achieved by orally administering a 2% Dextran Sulfate Sodium (DSS) solution, while the rats concurrently received oral administrations of sinomenine and sulfasalazine. The food, water intake was estimated. The body weight, disease activity index (DAI), colon length and spleen index estimated. Antioxidant, cytokines, inflammatory parameters and mRNA expression were estimated. The composition of gut microbiota was analyzed at both the phylum and genus levels in the fecal samples obtained from all groups of rats. Sinomenine treatment enhanced the body weight, colon length and reduced the DAI, spleen index. Sinomenine treatment remarkably suppressed the level of NO, MPO, ICAM-1, and VCAM-1 along with alteration of antioxidant parameters such as SOD, CAT, GPx, GR and MDA. Sinomenine treatment also decreased the cytokines like TNF-α, IL-1, IL-1β, IL-6, IL-10, IL-17, IL-18 in the serum and colon tissue; inflammatory parameters viz., PAF, COX-2, PGE2, iNOS, NF-κB; matrix metalloproteinases level such as MMP-1 and MMP-2. Sinomenine significantly (P < 0.001) enhanced the level of HO-1 and Nrf2. Sinomenine altered the mRNA expression of RIP1, RIP3, DRP3, NLRP3, IL-1β, caspase-1 and IL-18. Sinomenine remarkably altered the relative abundance of gut microbiota like firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia, and Actinobacteria. The results clearly indicate that sinomenine demonstrated a protective effect against DSS-induced inflammation, potentially through the modulation of inflammatory pathways and gut microbiota.

Protective effects of Moringa oleifera against acetic acid-induced colitis in rat: Inflammatory mediators’ inhibition and preservation the colon morphohistology

Moringa oleifera decoction is used in folk medicine to alleviate various gastrointestinal ailments and has been shown in several studies to exhibit diverse biological activities: antioxidant, anti-inflammatory, and myorelaxant on intestine strips. However, its protective effect on pro-inflammatory cytokines in colitis remains to be ascertained. We investigated Moringa oleifera leaf aqueous extract activities on a rat model of acetic acid-induced colitis. Thirty-six rats were divided in random into six groups, and received either distilled water (10 mL/kg), the aqueous leaf extract of Moringa oleifera (25, 50, and 100 mg/kg) or the reference drug Loperamide (5 mg/kg) for 20 days. Animal body weight and food intake were followed-up. Colitis was induced on day 15, and daily stool weight was followed up. Animals were sacrificed (day 21), serum concentrations of pro-inflammatory cytokines MPO, IL-6, and TNF-α were evaluated, and the colon and liver preserved for histological examinations. After one-week pre-treatment, a significant (P < 0.05) weight increase was observed. At day 20, the extract significantly (P < 0.01) prevented weight loss. Food intake decreased by 36.33% in the colitis control, and by 4.34% in the extract (100 mg/kg) treated animals (P < 0.01). Moringa oleifera (100 mg/kg, day 20) decreased stool weights to 4.75±0.3 g (P < 0.05). The extract decreased (P < 0.01) MPO level. At 100 mg/kg, it significantly (P < 0.05) reduced IL-6 –0.58 ± 0.14 against 0.85 ± 0.00 ng/L in the colitis control. At the same dose, TNF-α levels decreased to 417.96 ± 0.17 ng/L (P < 0.001). Moringa oleifera alleviated colitis symptoms by reducing stool emission, alleviating inflammation, and preserving colon and liver cytoarchitecture.

Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1β level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

Hydroethanolic extract and fractions of Pericopsis laxiflora stem bark protect against liver injury in Rat

Pericopsis laxiflora is a medicinal plant that is ubiquitous, especially in the tropical and savannah regions. It can be used in the treatment of hemorrhoids, rheumatism, abdominal pain treatment, diarrhoea, dysentery, fever, skin diseases, and jaundice. The present study investigated the protective effect of 50% hydroethanolic extract and fractions of Pericopsis laxiflora stem bark in lead-induced hepatotoxicity in rats. The development of liver injury has become a global issue and their treatment and management mostly result in more economic problems, especially in the African population.The stem bark of P. laxiflora was processed and 50 % hydroethanolic extract (HSE) was prepared. HSE was subjected to sequential fractionation with organic solvents: chloroform (CFHSE), ethyl acetate (EFHSE), and methanol (MFHSE), to obtain respective fractions. The residue was designated as aqueous fraction (AFHSE). Hepatoprotective activities of HSE and fractions (at 250 mg/kg) and Silymarin were assessed using the lead (as lead acetate; 50 mg/kg, i.p.). Body and organ weight changes, biochemical, hematological profile, oxidative stress parameters, and pro-inflammatory cytokines (TNF-α, TGF-β, NF кβ, and COX-2) in liver homogenate were measured. A histopathological examination of the liver was performed. Treatment with HSE and fractions resulted in a significant increase in relative organ weights, GSH, CAT, SOD, and levels and a significant decrease in MDA and MPO levels against Pb, as well as the restoration of liver biomarkers and pro-inflammatory cytokines (TNF-α, TGF-β, NF кβ, and COX-2) to near-normal levels. Biochemical data were corroborated by histological observations, with MFHSE recording the highest percentage of liver protection. The present investigation suggests that HSE possesses remarkable hepatoprotective properties and this can be attributed to the inhibitory effect on oxidative stress and suppression of pro-inflammatory cytokines.