Potent Anti-inflammatory Effects Research Articles

Canagliflozin exerts anti-inflammatory and antioxidant effects in the heart and skin tissues: Biochemical and histopathological assessment in a model of accelerated aging induced by D-galactose in mice

Canagliflozin was assessed for its anti-inflammatory and antioxidant effects as an anti-aging drug in animal models. 50 Swiss albino male mice were divided into five groups; all groups received their intervention using gastric gavage; group 1 received normal saline for 14 weeks; group 2 received induction by D-galactose 200 mg/kg/day for seven weeks; and group 3 to 5 received the same induction for seven weeks, followed by another seven weeks of investigated drugs; group 3 received Vitamin C (100 mg/kg/day); group 4 received canagliflozin (3 mg/kg/day); and group 5 received canagliflozin (1 mg/kg/day). At the end of 14 weeks, all animals were euthanasiad, and heart and skin tissue were harvested for further analysis. Canagliflozin at both 1 and 3 mg/kg was successful in reducing the levels of inflammatory mediators (TNF-alpha and IL6), reducing levels of MDA, increasing the levels of SOD, and increasing the levels of collagen-1 and elastin in skin tissue. Additionally, 3 mg/kg Canagliflozin showed a better effect compared to 1 mg/kg regarding its effect on IL6, SOD, and elastin. Histopathologically, treatment with both doses of Canagliflozin attenuates abnormalities induced by D-galactose (bizarre, irregular, and hyperchromatic nuclei). Canagliflozin exhibits potent antioxidant and anti-inflammatory effects in living organisms, effectively prevents cardiac and skin damage generated by D-galactose, and possibly reduces aging.

UPLC-MS/MS-based metabolomics combined to chemometrics reveal the anti-inflammatory metabolites of African Marigold (Tagetes erecta L.) flowers

African Marigold (Tagetes erecta L.) is widely recognized for its ornamental value and therapeutic properties, particularly its anti-inflammatory potential. This study employs UPLC-MS/MS-based metabolomics combined with chemometric analysis to identify bioactive metabolites contributing to the anti-inflammatory effects of T. erecta flowers. The flowers were fractionated using hexane, methylene chloride, ethyl acetate, and butanol, and a total of 79 metabolites were identified across the fractions, including flavonoids, phenolic acids, tannins, quinic acids, terpenoids, alkaloids, and amino acids. The anti-inflammatory efficacy of each fraction was assessed in vitro by evaluating their impact on the expression of four pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and IFN-γ) in LPS-stimulated leukocytes using PCR. Orthogonal Projections to Latent Structures was employed to determine the key metabolites contributing to the observed bioactivity. The analysis revealed that the methylene chloride and ethyl acetate fractions exhibited the most potent anti-inflammatory effects, primarily due to the presence of flavonoids and phenolic acids. Notably, disyringic acid hexoside, ellagic acid, gallic acid, p-coumaric acid, and quercetagetin dimethyl ether were identified as major anti-inflammatory agents based on their high correlation coefficients with cytokine inhibition and their substantial concentrations within the active fractions. These findings underscore the importance of selecting appropriate extraction solvents to isolate specific bioactive compounds and provide a deeper understanding of the metabolite profiles that contribute to the anti-inflammatory properties of T. erecta flowers.

Complement factor H-related protein 5 alleviates joint inflammation and osteoclast differentiation by disrupting RANK-JNK signaling in collagen antibody-induced arthritis mouse model

BackgroundComplement Factor H-Related protein 5 (CFHR5) belongs to the factor H/CFHR family and regulates the complement system by modulating factor H’s inhibitory activity against C3b. Despite its known role, the impact of CFHR5 on autoimmune arthritis and its relationship to pathophysiological changes in arthritis and bone loss remain unclear. This study aimed to assess the effect of CFHR5 on aggressive osteoclast activity and arthritis using a murine model of collagen antibody-induced arthritis (CAIA). MethodsThe effect of recombinant CFHR5 protein (rCFHR5) on arthritis were evaluated in CAIA. The mice were divided into three group and intraperitoneally treated with rCFHR5, methotrexate (MTX) as positive control or PBS as negative control. In the CAIA mouse model, the rCFHR5-treated group significantly reduced the incidence and clinical arthritis equivalent to the MTX group. Clinical arthritis scores, incidence and body weight were measured, and histological analysis of ankle joints was performed by Hematoxylin and Eosin (H&E) and Safranin O − Fast green (SOFG), Tartrate-resistant acid phosphatase (TRAP) staining and Immunohistochemistry. Moreover, to investigate the rCFHR5 role, we isolated murine osteoclast precursor cells (OCPs) from each group, induced osteoclasts with M−CSF and RANKL, and performed TRAP and F-actin staining. To verify the mechanism, mRNA and protein analyses were performed in OCPs. ResultsHistological examination of ankle joints revealed substantial reductions in synovial hyperplasia, bone marrow inflammation, bone erosion, cartilage destruction and TRAP-positive cells in the rCFHR5 group compared to the vehicle group. The ankle joints of the rCFHR5 group showed markedly decreased expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6). Mechanically, treatment with rCFHR5 inhibited RANKL-mediated osteoclast differentiation from OCPs and disrupted the RANK-JNK signaling. These findings demonstrate that treatment with rCFHR5 attenuates joint inflammation and reduces osteoclast differentiation, indicating its potential anti-inflammatory effect in autoimmune arthritis models.

Promising Anti-Inflammatory Properties of Ursolic Acid Isolated from Atylosia goensis.

Indigenous plants are plant species that are native to a specific region and have evolved naturally and adapted to local environmental conditions over a long period. This study aimed to explore the anti-arthritic effects of Atylosia goensis, an indigenous plant species in the Western Ghats of India. An ethanolic extract of Atylosia goensis was obtained using the Soxhlet extraction method, which revealed a diverse array of phytochemicals through liquid chromatography-mass spectroscopy (LC-MS). Key compounds, including fatty acids, sterols, and potential health-beneficial compounds, were identified, and one prominent phytoconstituent, ursolic acid, was spectroscopically characterized using 1H NMR, 13C NMR, and mass spectrometry. The research also examined the anti-inflammatory activity and in-vitro and in-vivo anti-arthritic activity of ethanolic extract. The ethanol extract exhibited notable inhibition of Cox-2, indicating potential anti-inflammatory effects. The in vivo anti-arthritic activity of ursolic acid was evaluated at different doses (200 and 400 mg/kg) over a 24-day period. Ursolic acid significantly reduced joint edema, particularly at higher doses, thereby emphasizing its anti-inflammatory properties. Biomarker analysis revealed dose-dependent attenuation of disease-associated biomarker levels, supporting the potential therapeutic efficacy of ursolic acid in arthritis management. Moreover, the hepatoprotective potential of ursolic acid was evident in biochemical parameters, including SGPT, SGOT, and ALP levels. Both doses of ursolic acid effectively mitigated liver dysfunction induced in the disease control group, demonstrating its protective role in liver health. Histopathological assessments corroborated these findings, indicating a reduction in inflammatory areas following ursolic acid treatment, especially at higher doses. This experimental work provides valuable information on the therapeutic potential of Atylosia goensis and ursolic acid, emphasizing their roles in anti-inflammatory and hepatoprotective applications. This study contributes to the understanding of plant-derived compounds for potential pharmaceutical use in the management of inflammatory and arthritic conditions.

Effects of Opuntia stricta var. dillenii Extracts Obtained from Prickly Pear and an Industrial By-Product on Maturing Pre-Adipocytes.

Opuntia stricta var. dillenii, a member of the Cactaceae family, produces a fruit known as prickly pear. This fruit is rich in bioactive compounds, including betalains and phenolic compounds, which play an important role in health promotion due to their antioxidant and anti-inflammatory properties. This study aims to investigate the impact of prickly pear extracts obtained from the whole fruit, peel, pulp, and an industrial by-product (bagasse) on the differentiation of 3T3-L1 pre-adipocytes. During the differentiation process, 3T3-L1 pre-adipocytes were treated with prickly pear extracts at concentrations ranging from 10 to 100 μg/mL from day 0 to day 8 post-induction. Moreover, the potential mechanisms justifying the observed effects were assessed by RT-PCR. All extracts led to an increase in both triacylglycerol accumulation and cell number. In conclusion, the analysed extracts demonstrated adipogenic effects in 3T3-L1 maturing pre-adipocytes by increasing the expression of the c/ebp-β, srebf-1, and c/ebp-α genes. Additionally, a potential anti-inflammatory effect was observed through the upregulation of adiponectin.

3-Deazaneplanocin A (DZNep): A Drug That Deserves a Second Look.

The emerging data compiled during the past five years on 3-deazaneplanocin (DZNep) provide compelling evidence to reevaluate this drug as a better alternative over the specific catalytic inhibitors of histone methyl transferases (HTMs). The indirect mechanism of DZNep via inhibition of AdoHcy-ase, once considered a liability due to possible side effects, has now shown to be rather beneficial as additional pathways targeted by DZNep are important contributors to its superior anticancer properties. Furthermore, DZNep has demonstrated the ability to induce proteasomal degradation of its target and reduce toxicity in combination with well-established antitumor therapies in animal models. In addition, DZNep has shown important effects in suppressing fibrosis and inflammation in liver, kidney, peritoneum, and airways. Finally, inhibition of mRNA m6A methylation by DZNep suppresses the synthesis of the viral genome in SARS-Cov-2 infection and promises to have important therapeutic value when combined with its potent antiviral efficacy and anti-inflammatory effects.

Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4

IntroductionProcesses that generate systemic inflammation are strongly associated with neurodegenerative diseases. This study aimed to explore the potential anti-oxidative and anti-inflammatory effects of fasudil and its role in modulating aquaporin-4 (AQP-4) to improve cognitive impairment in a systemic inflammation model induced by lipopolysaccharide (LPS). Methodfourty C57BL/6 mice were assigned to four groups, including sham, LPS, sham+fasudil, and LPS+fasudil). Intraperitoneal LPS was given (500 μg/kg/day) at hours 0, 24, 48, and 72, and fasudil (30 mg/kg) administered intraperitoneal injections 2 hours after LPS injection. The open field, Y-maze, and Novel object tasks was used to assess learning and memory. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the hippocampus also measured as markers of oxidative stress and inflammation. Furthermore, the expression of AQP-4 measured in the intact and experimental groups. ResultsThe results showed that Fasudil significantly improved memory and anxiety behavior induced by LPS in the open field maze, spatial recognition memory in the Y-maze, and performance in the novel object recognition task. It also mitigates hippocampal MDA and SOD levels. Additionally, fasudil ameliorated LPS-induced hippocampal levels of TNFα and IL-10 and increased hippocampal levels of AQP-4 expression in mice. ConclusionOur results suggest that fasudil in the LPS model of systemic inflammation could improve cognition by suppressing oxidative stress and inflammation and increasing AQP-4 protein expression. These findings highlighted the potential of fasudil as a neuroprotective agent. However, further research is required to fully understand its neuroprotective properties in the treatment of neurodegenerative disorders.

Evaluation of protective potency of coconut oil-based probiotic against antibiotic-induced compromised gastrointestinal attributes and associated complications in Swiss albino mice

Background: Antibiotic-induced gastrointestinal toxicity is a major concern globally. The gut-organ axis has been explicitly studied, and hence, any damage to the gut ecosystem directly or indirectly manifests into compromised multi-organ functions. Therefore, the present study was designed to explore the protective potency of coconut oil-probiotic (C-PRO) against antibiotic-induced compromised gastrointestinal attributes and associated complications. Methods: Animals were divided into 5 groups (n=6). Normal saline was given to the control group; the antibiotic cocktail was given to the antibiotic group. In the treatment group, low and high doses of C-PRO were given post-antibiotic treatment. In the per se group, only a high dose of C-PRO was given. After 28 days, animals were studied for neurobehavioral parameters and scarified. Blood and organs were collected and stored for histopathological, immune histochemical, and biochemical analysis. Results: Antibiotic treatment reduced body weight, increased oxidative stress, and caused histopathological damage to the stomach, duodenum, colon, brain, heart, liver, lungs, kidney, spleen, and testis. It also altered biochemical parameters such as lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), albumin, creatinine, urea, uric acid, and blood urea nitrogen (BUN). Additionally, Antibiotic exposure in mice exhibited depressive-like behaviour and declined cognitive function. The treatment with a low dose of C-PROs showed negligible protective effect, whereas a high dose of C-PRO effectively reversed the structural, biochemical, and neurobehavioral attributes toward normal. Conclusions: We conclude that the synergistic effect of coconut oil and probiotics, which have potent antioxidant and anti-inflammatory effects, might be responsible for multidimensional protective effects against compromised gastrointestinal attributes and associated complications.

Antioxidant effect and inhibitory effect on nitric oxide production of sea mustard fractions from Busan, Korea

We investigated the chemical characteristics and nitric oxide (NO) production and antioxidant effects of sea mustard (Undaria pinnatifida) fractions obtained from Taejongdae in Busan, Korea. Dried sea mustard was extracted using different solvents, and antioxidant effects was evaluated based on the radical scavenging and DNA oxidation assays and the effect on reactive oxygen species (ROS) production. Total phenolic content was significantly higher in the 85% aq. MeOH fraction than that in the other factions. The 85% aq. MeOH fraction was more effective in scavenging free radicals than other fractions, as assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2.2'-azino-bis (3-ethylbenothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS) assays (P<0.05). All sea mustard fractions decreased H2O2-induced cellular ROS production compared to the control (P<0.05), however, the 85% aq. MeOH fraction exhibited the greatest inhibitory effect on ROS production among all fractions. Moreover, the 85% aq. MeOH fraction significantly inhibited genomic DNA oxidation. In addition, we measured NO levels to determine the potential anti-inflammatory effects of fractions from sea mustard and observed the highest level of activity in case of the 85% aq. MeOH fraction. These results indicated that the antioxidant effects of sea mustard are associated with its higher phenol content. This study proposes that processed food products supplemented with sea mustard can be developed into functional foods to promote the health of the local populations.

Evaluation of antioxidant and anti-inflammatory properties, bioactive compound profiling, and molecular mechanisms of a multicomponent Thai herbal formulation

BackgroundMedicinal plants have long been used as dietary supplements to reduce the risk of chronic diseases, inflammation, cancer, and metabolic syndromes. Traditional remedies possess therapeutic properties, making them promising candidates for further investigation and potential pharmaceutical development. Aim of the studyThis study aimed to evaluate the efficacy of Belog Plus (BP), a polyherbal product containing five Thai medicinal plants: Citrus aurantifolia, Cannabis sativa, Tiliacora triandra, Alpinia galanga, and Piper nigrum, combined with safflower seed oil. This study focused on quantifying the total phenolic content (TPC) and total flavonoid content (TFC), and identifying key herbal biomarkers that contribute to its therapeutic properties. In addition to assessing the antioxidant and anti-inflammatory potential of the plant extracts, the study explored the molecular mechanisms underlying their anti-inflammatory activity, offering a comprehensive understanding of BP's efficacy. MethodsThe ethanolic extract of BP and its components were assessed for antioxidant potential using DPPH, FRAP, and H2O2 induced oxidative stress. The anti-inflammatory activity was evaluated using the Griess reaction assay, and the mechanisms were explored through mRNA and protein expression analysis. The TPC and TFC were measured using the Folin–Ciocalteu (F–C) assay and the aluminium chloride colorimetric assay, respectively, while herbal biomarkers were identified using LC-MS/MS analysis. ResultsThe results revealed that the ethanolic extract of BP (6.25–100 µg/ml) exhibited a potent anti-inflammatory effect through nitric oxide inhibition (IC50 24.4 μg/ml) and significantly reducing the expression of inflammatory genes iNOS, COX-2, IL-6, and TNF-α. Additionally, it significantly reduced the expression of inflammatory proteins iNOS and COX-2 at concentrations of 6.25–25 µg/ml. Among the individual components, C. aurantifolia, A. galanga, and P. nigrum showed potent anti-inflammatory effects with IC50 values of 35.7, 6.5, and 23.3 μg/ml, respectively. The TPC and TFC results demonstrated significant levels of phenolic (80.6 µg GAE/mg) and flavonoid (47.4 µg catechin/mg) compounds. Additionally, the LC-MS/MS analysis identified a variety of bioactive compounds known for their anti-inflammatory properties. ConclusionThese findings support BP's potential use as a dietary supplement to mitigate the risk of chronic inflammatory diseases, with its ethanolic extract containing bioactive phenolic and flavonoid compounds that significantly suppress iNOS and COX-2 protein expressions.

Physicochemical properties, antioxidant and anti-inflammatory activities of polysaccharides from lotus leaves by pectinase-assisted extraction

In order to improve the extraction yield of lotus leaf polysaccharide (LLP) and offer scientific foundation for utilization of LLPs in the food and pharmaceutical industries, pectinase-assisted extraction method was employed for the preparation of LLP. The chemical composition, physicochemical properties (e.g. rheological and thermal properties etc.), antioxidant and anti-inflammatory effects of LLP and its two purified fractions (LLP1 and LLP3) obtained using DEAE-52 and subsequent Sephadex G-100 column chromatography were also investigated. Antioxidant assays indicated that the polysaccharides had remarkable DPPH• and ABTS+• scavenging activities. In H2O2-induced RAW264.7 cells, LLPs showed marked protective effect on oxidative stress, reducing the MDA and ROS contents and increasing the CAT and SOD activities. LLPs were also found to effectively modulate the expressions of CAT, SOD1, Nrf-2, HO-1, NQO1 and Keap1 mRNA. Thus, the potent antioxidant effects of LLPs were achieved possibly by regulating the Keap1/Nrf-2/HO-1 signaling pathways. In lipopolysaccharide-treated RAW264.7 macrophages, LLPs reduced phagocytic ability, decreased release of NO, TNF-α, IL-1β and IL-6, and increased release of IL-10 and TGF-β1, indicating their potent anti-inflammatory effect. LLPs downregulated expressions of iNOS, IL-1β, IL-6, TNF-α, COX-2, and TLR-4 mRNA. Therefore, modulation of NF-κB signaling pathway is possibly the important anti-inflammatory mechanism of LLPs.

Lignans and phenols with potential anti-inflammatory effect from the stems of Mallotus paxii Pamp

Phytochemical investigation of the stems of Mallotus paxii Pamp. led to the isolation and identification of four new compounds, including three neolignans (1–3) and one phenol (13), along with eight known neolignans (4–12) and one known phenol (14). Their structures were determined by spectroscopic methods, including NMR, MS and ECD analyses. Bioassay demonstrated that malloapelin A (4) exhibited a most potent anti-inflammatory activity to NO release with IC50 value of 21.32 μM. Furthermore, malloapelin A (4) markedly decreased the secretion of TNF-α, iNOS, and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Investigating the Hepatic Response to Orlistat and White Tea in Rats on a High-Fat Diet.

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects.

Novel ophthalmic hyaluronic acid-hydrogel with curcumin nanoparticles for enhanced healing of ulcerative keratitis in rabbit model

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.

Cordyceps militaris Grown on Germinated Rhynchosia nulubilis (GRC) Encapsulated in Chitosan Nanoparticle (GCN) Suppresses Particulate Matter (PM)-Induced Lung Inflammation in Mice.

Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: TPP w/w ratio of 4:1; TPP pH 2) exhibited a zeta potential of +22.77 mV, suitable for GRC encapsulation. At different GRC concentrations, higher levels (60 and 120 mg/mL) led to increased negative zeta potential, enhancing stability. The optimal GRC concentration for maximum entrapment (31.4 ± 1.35%) and loading efficiency (7.6 ± 0.33%) of GRC encapsulated in CN (GCN) was 8 mg/mL with a diameter of 146.1 ± 54 nm and zeta potential of +30.68. In vivo studies revealed that administering 300 mg/kg of GCN significantly decreased the infiltration of macrophages and T cells in the lung tissues of PM-treated mice, as shown by immunohistochemical analysis of CD4 and F4/80 markers. Additionally, GCN ameliorated PM-induced lung tissue damage, inflammatory cell infiltration, and alveolar septal hypertrophy. GCN also decreased total cells and neutrophils, showing notable anti-inflammatory effects in the bronchoalveolar lavage fluid (BALF) from PM-exposed mice, compared to GRC. Next the anti-inflammatory properties of GCN were further explored in PM- and LPS-exposed RAW264.7 cells; it significantly reduced PM- and LPS-induced cell death, NO production, and levels of inflammatory cytokine mRNAs (IL-1β, IL-6, and COX-2). GCN also suppressed NF-κB/MAPK signaling pathways by reducing levels of p-NF-κB, p-ERK, and p-c-Jun proteins, indicating its potential in managing PM-related inflammatory lung disease. Furthermore, GCN significantly reduced PM- and LPS-induced ROS production. The enhanced bioavailability of GRC components was demonstrated by an increase in fluorescence intensity in the intestinal absorption study using FITC-GCN. Our data indicated that GCN exhibited enhanced bioavailability and potent anti-inflammatory and antioxidant effects in cells and in vivo, making it a promising candidate for mitigating PM-induced lung inflammation and oxidative stress.

Design, synthesis, and computational analysis (molecular docking, DFT, MEP, RDG, ELF) of diazepine and oxazepine sulfonamides: biological evaluation for in vitro and in vivo anti-inflammatory, antimicrobial, and cytotoxicity predictions.

We report the synthesis and extensive characterization of Diazepane and Oxazepane derivatives, followed by their biological evaluation. These compounds were assessed for in vitro and in vivo antimicrobial, anti-inflammatory, and anticancer activities. Among the synthesized molecules, compound 5b demonstrated remarkable antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis with MIC values of 20 and 40 μg/mL, respectively. Additionally, 5b exhibited potent anti-inflammatory effects both in vitro and in vivo. Advanced computational studies, including DFT, MEP, RDG, and ELF analyses, were performed to understand the electronic distribution and molecular interactions. The bioactivity and physicochemical properties of these derivatives were further predicted using PASS and pkCSM platforms, emphasizing their potential as promising lead molecules in drug development.

Endogenous glucocorticoids are required for normal macrophage activation and gastric Helicobacter pylori immunity.

Glucocorticoids are steroid hormones well known for their potent anti-inflammatory effects. However, their immunomodulatory properties are multifaceted. Increasing evidence suggests that glucocorticoid signaling promotes effective immunity and that disruption of glucocorticoid signaling impairs immune function. In this study, we conditionally deleted the glucocorticoid receptor (GR) in the myeloid lineage using the LysM-Cre driver (myGRKO). We examined the impact on macrophage activation and gastric immune responses to Helicobacter pylori, the best-known risk factor of gastric cancer. Our results indicate that, compared with wild type (WT), glucocorticoid receptor knockout (GRKO) macrophages exhibited higher expression of proinflammatory genes in steroid-free conditions. However, when challenged in vivo, GRKO macrophages exhibited aberrant chromatin landscapes and impaired proinflammatory gene expression profiles. Moreover, gastric colonization with H. pylori revealed impaired gastric immune responses and reduced T cell recruitment in myGRKO mice. As a result, myGRKO mice were protected from atrophic gastritis and pyloric metaplasia development. These results demonstrate a dual role for glucocorticoid signaling in preparing macrophages to respond to bacterial infection but limiting their pathogenic activation. In addition, our results support that macrophages are critical for gastric H. pylori immunity.NEW & NOTEWORTHY Signaling by endogenous glucocorticoids primes macrophages toward more robust responses to pathogens. Disruption of glucocorticoid signaling caused dysregulation of the chromatin landscape, blunted proinflammatory gene activation upon bacterial challenge, and impaired the gastric inflammatory response to Helicobacter pylori infection.

Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

Acute lung injury (ALI) is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide (AG), a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide (LPS)-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4 (TLR4)/Kelch-like ECH-associated protein 1(Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Molecular docking simulations identified the binding sites of AG on the TLR4 protein (Kd value: -33.5 kcal·mol-1), and these interactions were further corroborated by Cellular Thermal Shift Assay (CETSA) and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

Anti-viral Effects of Pavetta indica Methanolic Extract and Acyclovir on Behavioral and Biochemical Parameters in Streptozotocin-induced Alzheimer's Disease in Rats.

Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in β-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin. Wistar rats received acyclovir and Pavetta indica methanolic extract orally at different dose ranges (50, 150, 450 mg/kg) and (125, 250, 500 mg/kg), respectively. The standard therapy, Rivastigmine (2 mg/kg), was given orally. Intracerebroventricular-streptozotocin produced significant alternations in behavioral assessments, including locomotor activity test, Morris water maze test, and elevated plus maze test. Moreover, intracerebroventricular-streptozotocin ameliorated the antioxidant defense activity by decreasing levels of catalase, superoxide dismutase, and reduced glutathione while enhancing the oxidative stress markers, including malondialdehyde, and total nitrite levels. Finally, the main findings showed that intracerebroventricular-streptozotocin significantly increased the inflammatory marker, tumor necrosis factor-α, and disturbed neurotransmitter mediators, including levels of acetylcholinesterase, glutamate, and γ-amino butyric acid. In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

Topical Anti-Inflammatory Formulations from Medicinal Plant Extracts: Stability, Efficacy, and Cytokine Modulation in a Carrageenan-Induced Paw Edema Model

Background: Traditional anti-inflammatory drugs, like NSAIDs, often cause side effects, which has fueled interest in plant-based alternatives with fewer adverse effects. Medicinal plants such as turmeric (Curcuma longa), ginger (Zingiber officinale), frankincense (Boswellia serrata), ashwagandha (Withania somnifera), and gotu kola (Centella asiatica) are known for their bioactive compounds with anti-inflammatory properties. This study aimed to evaluate the anti-inflammatory efficacy of these plant extracts in topical formulations. Methods: Ethanol extracts of the selected plants were prepared and formulated into topical gel and cream forms. Stability testing was conducted over a 30-day period to confirm the formulations' consistency, color, and pH. Anti-inflammatory efficacy was assessed using a carrageenan-induced paw edema model in Wistar rats. The animals were divided into six groups, including control, standard drug (indomethacin), and plant-based formulations at two extract concentrations (5% and 10%). Edema reduction was measured using a plethysmometer, and serum cytokine levels (TNF-α and IL-6) were quantified via ELISA. Histopathological analyses of tissue samples further evaluated the anti-inflammatory effects. Results: Both gel and cream formulations demonstrated stability over 30 days. The 10% extract cream formulation achieved the highest reduction in paw edema (70%) and reduced inflammation levels comparable to indomethacin. The 10% extract gel showed similar results (65% reduction). Biochemical analysis revealed significant reductions in TNF-α and IL-6 levels, especially in the 10% cream and gel groups, aligning with histopathological findings that indicated reduced tissue damage and inflammatory cell infiltration in treated groups compared to controls. Conclusion: The findings suggest that these plant extracts possess potent anti-inflammatory effects when formulated into stable, topical products. The 10% extract cream formulation was particularly effective, offering a promising alternative for managing inflammation with fewer side effects.