Anti-inflammatory Mechanisms Research Articles

Natural medicine can substitute antibiotics in animal husbandry: protective effects and mechanisms of rosewood essential oil against Salmonella infection

Aniba rosaeodora essential oil (RO) has been traditionally used in natural medicine as a substitute for antibiotics due to its notable antidepressant and antibacterial properties. Salmonella, a prevalent pathogen in foodborne illnesses, presents a major challenge to current antibiotic treatments. However, the antibacterial efficacy and mechanisms of action of RO against Salmonella spp. remain underexplored. This study aims to elucidate the chemical composition of RO, evaluate its antibacterial activity and mechanisms against Salmonella in vitro, and further delineate its anti-inflammatory mechanisms in vivo during Salmonella infection. Gas chromatography-mass spectrometry (GC-MS) was utilized to characterize the chemical constituents of RO. The antibacterial activity of RO was assessed using minimal inhibitory concentration (MIC) and time-kill assays. Various biochemical assays were employed to uncover the potential bactericidal mechanisms. Additionally, mouse and chick models of Salmonella infection were established to investigate the prophylactic effects of RO treatment. RO exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with an MIC of 4 mg·mL−1 for Salmonella spp. RO treatment resulted in bacterial damage through the disruption of lipid and purine metabolism. Moreover, RO reduced injury and microbial colonization in infected mice and chicks. RO treatment also modulated the host inflammatory response by inhibiting proinflammatory pathways. In conclusion, our findings demonstrate that RO is effective against Salmonella infection, highlighting its potential as an alternative to antibiotics for antibacterial therapy.

Anti-inflammatory effects of polydeoxyribonucleotide and adipose tissue-derived mesenchymal stem cells in a canine cell model of osteoarthritis.

A relatively new therapeutic agent for osteoarthritis (OA), polydeoxyribonucleotide (PDRN), shows potential in treating human OA due to its regenerative and anti-inflammatory effects. However, studies on PDRN for canine OA are limited, and no study has investigated their use with mesenchymal stem cells (MSCs) conventionally used for OA treatment. This study aimed to evaluate the potential of PDRN and explore its combined effect with adipose tissue-derived MSCs (AdMSCs) in treating canine OA. To study the impact of PDRN, canine chondrocytes, synoviocytes, and AdMSCs were exposed to various PDRN concentrations, and viability was assessed using cell counting kit-8. The OA model was created by treating chondrocytes and synoviocytes with lipopolysaccharide, followed by treatment under three different conditions: PDRN alone, AdMSCs alone, and a combination of PDRN and AdMSCs. Using real-time quantitative polymerase chain reaction, the anti-inflammatory effects and mechanisms were investigated by quantitatively assessing pro-inflammatory cytokines, collagen degradation markers, adenosine A2a receptor (ADORA2A), and nuclear factor-kappa B. PDRN alone and combined with AdMSCs significantly reduced the expression of pro-inflammatory cytokines and collagen degradation markers in an OA model. PDRN promoted AdMSC proliferation and upregulated ADORA2A expression. AdMSCs exhibited comprehensive anti-inflammatory effects through paracrine effects, and both substances reduced inflammatory gene expression through different mechanisms, potentially enhancing therapeutic effects. The results indicate that PDRN is a safe and effective anti-inflammatory material that can be used independently or as an adjuvant for AdMSCs. Although additional research is necessary, this study is significant because it provides a foundation for future research at the cellular level.

Saffron and its major constituents against neurodegenerative diseases: A mechanistic review

BackgroundNeurodegeneration has been recognized as the main pathophysiological alteration in the majority of brain-related diseases. Despite contemporary attempts to provide acceptable medicinal therapies, the conclusion has not been much beneficial. Besides, the complex pathophysiological mechanisms behind neurodegenerative diseases (NDDs) urge the needs for finding novel multi-target agents. Accordingly, saffron with major active constituents and as multi-targeting agents have shown beneficial effects in modulating NDDs with higher efficacy and lower side effects. PurposeThe present study provides a systematic and comprehensive review of the existing in vitro, in vivo, and clinical data on the effectiveness, and signaling pathways of saffron and its key phytochemical components in the management of NDDs. The need to develop novel saffron delivery systems is also considered. MethodsStudies were identified through systematic and comprehensive searches in Science Direct, PubMed, and Scopus databases through April 30, 2024. The whole saffron major constituents (e.g., saffron, crocin, crocetin, picrocrocin, and safranal) and NDDs (e.g., neuro*, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Huntington*, Parkinson*, Alzheimer*, and brain) were selected as keywords to find related studies. In the systematic analysis, 64 articles were directly included in the current study. Additional reports were added within a comprehensive review. ResultsSaffron and its active metabolites crocin, crocetin, safranal, and picrocrocin have shown acceptable efficacy in managing NDDs like Alzheimer's disease, Parkinson's disease, Attention deficit hyperactivity disorder, depression, and other NDDs via modulating apoptotic (e.g., caspases, Bax/Bcl-2, cytochrome c, and death receptors), inflammatory (e.g., NF-κB, IL-1β, IL-6, TNF-α, and COX-2), and oxidative strass (e.g., Nrf2, GSH, GPx, CAT, SOD, MDA, ROS, and nitrite) signaling pathways. The presented in vitro, in vivo, and clinical evidences showed us a better future of controlling NDDs with higher efficacy, while decreasing associated side effects with no significant toxicity. Additionally, employing novel delivery systems could increase the efficacy of saffron phytoconstituents to resolve the issues pharmacokinetic limitations. ConclusionSaffron and its major constituents employ anti-inflammatory, anti-apoptotic and antioxidant mechanisms in modulating several dysregulated-signaling pathways in NDDs. However, further research is necessary to elucidate the precise underlying mechanisms in exploring the feasibility of using saffron active compounds against NDDs. More studies should focus on dose-response relationships, long-term effects, highlighting key mechanisms, and designing more well-controlled clinical trials. Additionally, developing stable and cost-benefit novel delivery systems in future works helps to remove the pharmacokinetic limitations of saffron major constituents.

Sulfated polysaccharide from Apostichopus japonicus viscera exhibits anti-inflammatory properties in vitro and in vivo

Polysaccharides from sea cucumbers are known for their biological activities, but little is known about those from sea cucumber viscera. The present study isolated a sulfated polysaccharide (SCVP-2) from the viscera of Apostichopus japonicas, which had a molecular weight of 209.1 kDa. SCVP-2 comprised 66.3 % total sugars, 2.1 % uronic acid, 4.5 % proteins, and 25.5 % sulfate groups, containing glucosamine, galactosamine, glucose, galactose, and fucose. FT-IR and NMR analyses identified SCVP-2 as a fucoidan sulfate with sulfation patterns of the fucose branches as Fuc2S, Fuc4S, and Fuc0S. SEM and AFM analyses showed irregular clusters and linear conformations. SCVP-2 demonstrated strong anti-inflammatory properties both in vitro and in vivo. In lipopolysaccharide (LPS)-induced inflammation in macrophage RAW264.7 cells, SCVP-2 significantly reduced nitric oxide (NO) and cytokine secretion (IL-1β, IL-6, TNF-α). Additionally, it downregulated the expression of these cytokine genes. Furthermore, the anti-inflammatory mechanism of SCVP-2 was related to the inhibition of the MAPKs and NF-κB pathways. SCVP-2's anti-inflammatory capacity was confirmed in acute inflammation models, including xylene-induced ear swelling and acetic acid-induced peritoneal capillary permeability, and in high-fat diet-induced systemic low-grade chronic inflammation. In conclusion, SCVP-2 exhibits significant anti-inflammatory activity, suggesting its potential for development as a functional food ingredient or therapeutic agent for inflammation-related diseases.

Identification and molecular mechanism of the anti-inflammatory effect of sea cucumber peptides: Network pharmacology, molecular docking and animal experiments

Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which there is currently no efficacious therapeutic drug with fewer side effects. Therefore, the development of approaches for the prevention of UC from natural food sources is urgently needed. In this study, mice were pre-fed with sea cucumber peptides prior to dextran sodium sulfate (DSS) induction. Results showed that sea cucumber peptides decreased pro-inflammatory cytokine (IL-4 and IL-10) levels and remissions of main clinic symptoms in a dose-dependent manner. The composition of peptides was identified, and the anti-inflammatory molecular mechanism was evaluated by silico prediction. The molecular weight of the peptides was 243–1800 Da and composed of 3–18 amino acid residues. Online activity assessment and molecular docking prediction revealed that tripeptides of FGI, FLI, FLL, GFL, GFM, IGF and LDF exhibited strong anti-inflammatory activity. Particularly, LDF showed the highest potency, with a binding energy of −5.37 kJ/mol. Network pharmacology analysis of UC related diseases indicated that active peptides interact with colitis disease targets, primarily proto-oncogene tyrosine-protein kinase Src (SRC), E3 ubiquitin-protein ligase XIAP (XIAP) and angiotensin-converting enzyme (ACE). The results suggest that sea cucumber peptides have potential as a novel nutraceutical option for colitis relief.

Potential active fractions and constituents in the flowers of Trollius chinensis Bunge responsible for treating acute pharyngitis

Ethnopharmacological relevanceTrollius chinensis Bunge has a long history of use in China as traditional Chinese medicine and functional tea for the treatment of respiratory infections, such as pharyngitis, tonsillitis and bronchitis. Pharyngitis can impact the entire throat and adjacent lymphoid tissues, and may lead to significant systemic complications. However, the active components and mechanism of Trollius chinensis Bunge for treating acute pharyngitis remains unclear. Aim of the studyTrollius chinensis Bunge is recognized in China both as a medicinal herb and a functional tea. Research into its properties aimed to establish its effectiveness against pharyngitis and to pinpoint the active components and mechanism. Materials and methodsA 70% ethanol extract from the herb was prepared, which was refined using chromatography through a column containing D101 macroporous resin and varying ethanol solutions. The efficacy of the initial and refined extracts was tested using a rat model of ammonia-induced acute pharyngitis. Pathological examination, HE staining and ELISA were applied to screen activity fraction. The compounds were isolated by silica gel, sephadex LH-20 column chromatography and semi-preparative HPLC chromatography from active fraction. All of the isolated compounds were assessed for anti-inflammatory activity by acting on LPS-induced RAW 264.7 macrophage cells in vitro. Cytotoxicity of compounds was detected by CCK-8 assay. The Griess reaction was applied to evaluate the inhibitory effects of isolated compounds on NO production in RAW 264.7 cells induced by LPS. TNF-α, IL-6, IL-1β and PGE2 levels in macrophage supernatant were detected by ELISA. Molecular docking and western blot analysis were applied to study the anti-inflammatory mechanism of active compound. ResultsThe fraction extracted with 30% ethanol proved particularly effective, significantly reducing pharyngitis symptoms. This was evidenced by decreased levels of cytokines (TNF-α, IL-6, IL-1β and PGE2) and visible improvements in the pharyngeal tissue histology. In pursuit of pharyngitis treatments, 23 phenolic acids and 13 flavonoids were isolated from the 30% ethanol fraction and identified using spectral analysis. Of these, three were newly discovered compounds and eight were first-time isolates from the Trollius genus. These compounds were further investigated for their ability to suppress nitric oxide production in RAW 264.7 cells triggered by lipopolysaccharide. Compounds 3, 19, and 26 exhibited strong anti-inflammatory properties. HPLC analysis of the 30% ethanol fraction revealed that orientin was the predominant component, accounting for 44.4% of this fraction. Western blot analysis demonstrated that orientin reduced the expression levels of the protein p-p65 relative to p65, p-IκBα relative to IκBα and iNOS, indicating an anti-inflammatory effect potentially through the modulation of the NF-κB signaling pathway. ConclusionThe finding of this study provided strong support for the use of T. chinensis as a potential functional food for treating pharyngitis.

Nano-cubosomes of the phyto-active principle in Withania somnifera: LC-MS-NMR, anti-microbial, and insights of the anti-neuropathic and anti-inflammatory mechanism

Withania somnifera (W. somnifera) has a long history of safety in the amelioration of neuro-active ailments. The current study aims to explore Withania somnifera phyto-active principle anti-microbial, ant-neuropathic, and anti-inflammatory activities, and to modify these activities utilizing nano-cubosomes exploiting their mechanisms of action. Bio-guided fractionation technique was utilized, to identify the most phyto-active compound, using LC-MS-NMR online technique and biological models of diabetes, neuropathy, and inflammation. In-vitro antibacterial activity was also monitored. The HbA1c, in-vivo antioxidant (serum-catalase, TBARS, and GSH), serum insulin, and pro-inflammatory serum cytokines (TNF alpha, IL-six, and IL-ten) levels have been assessed to establish the anti-neuropathic and anti-inflammatory mechanisms. The nano-cubosomal formulations (CUB 1–3) were utilized to improve the W. somnifera most active compound efficacy. W. somnifera has shown ten major peaks; coagulin Q (10.2 %), dihydrowithanolide A (2.4 %), dihydrowithaferin D (1.8 %), physagulin D (7.6 %), withanoside V (2.3 %), withanolide A (WDA, 10.3 %), withafrin A (4.9 %), withaferin D (7.7 %), withanone 9 (9.9 %), withanolide D (4.8 %). The bio-guided fractionation technique utilizing LC-MS-NMR technique has proved that withanolide A (WDA) is the most phyto-active compound in W. somnifera. The latter has shown better results than WDA, which might be due to other effective compounds in Ws. However, CUB 3 (WDA nano-cubosomes dispersion) has shown more prominent anti-diabetic, anti-neuropathic, anti-inflammatory, and anti-bacterial potentials than Ws and WDA. Thus, CUB 3 modified WDA activity, and improved its efficacy. The normalization of HbA1c levels, increased insulin secretagogue potential, and the amelioration of the oxidative-stress may be the underlying Ws, WDA, and CUB 3 antidiabetic neuropathy mechanism. Moreover, the Ws, WDA, and CUB 1–3 anti-inflammatory mechanism might be due to the amelioration of the pro-inflammatory serum cytokines (decreasing TNF alpha and IL-six levels and increasing IL-ten). Thus, CUB 3 might be a powerful tool in augmenting Withania somnifera activity as an oral drug-delivery system and improving its efficacy against neuropathy and inflammation.

A multifunctional nanoplatform with dual-targeted antibacterial and cascaded immunomodulatory strategy for the treatment of bacterial keratitis

Bacterial keratitis (BK) is a serious ocular infection and frequently cause irreversible damage to the corneal tissue and even blindness. Current clinical treatments using antibiotics achieve unsatisfactory outcomes due to the lower bioavailability, high risks of drug resistance and limited therapeutic functions. To address these challenges, we proposed a dual-targeted antibacterial and cascaded immunomodulatory therapy strategy, constructing a multifunctional nanoplatform (HPBH@GLA/AMP) using the 3-aminophenylboric acid (NBA) and hyaluronic acid (HA) co-modified hollow polydopamine (HPDA) to serve as a functional nanocarrier (HPBH) for loading antimicrobial peptide (AMP) and glycyrrhizic acid (GLA). The HPBH@GLA/AMP presented excellent targeting and bactericidal performance to Pseudomonas aeruginosa (P. aeruginosa), coupled with its capacity to alleviate the bacteria-triggered excessive immune response via an ingenious cascaded immunoregulatory process. Notably, the study of underlying anti-inflammatory mechanism revealed that the functional nanocarrier of HPDA could effectively scavenge the reactive oxygen species (ROS) for controlling early inflammatory responses, while inhibit the expression of late mediator high mobility group box 1 (HMGB1) chemokine through released GLA. Specially, the duel-targeted characteristic enabled this nanoplatform to recognize both the bacteria and inflammatory cells precisely and aggregate the location where bacteria and/or inflammatory cells exist persistently, effectively increased the therapeutic concentration of drugs. Featuring the antibacterial synergistic yet sequential regulation for the inflammatory response, the HPBH@GLA/AMP achieved satisfactory therapeutic effects in a BK mouse model in vivo. This study provides a bright prospect for clinical treatment of refractory bacterial keratitis (BK) and even extended to other immunotherapy in infectious disease.

A comparison of the safety and efficacy of tapinarof and roflumilast topical therapies in the management of mild-to-moderate plaque psoriasis.

Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles. This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment. Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects. Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs. Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice.

Application of Proteomics Technology Based on LC-MS Combined with Western Blotting and Co-IP in Antiviral Innate Immunity.

As an interferon-stimulating factor protein, STING plays a role in the response and downstream liaison in antiviral natural immunity. Upon viral invasion, the immediate response of STING protein leads to a series of changes in downstream proteins, which ultimately leads to an antiviral immune response in the form of proinflammatory cytokines and type I interferons, thus triggering an innate immune response, an adaptive immune response in vivo, and long-term protection of the host. In the field of antiviral natural immunity, it is particularly important to rigorously and sequentially probe the dynamic changes in the antiviral natural immunity connector protein STING caused by the entire anti-inflammatory and anti-pathway mechanism and the differences in upstream and downstream proteins. Traditionally, proteomics technology has been validated by detecting proteins in a 2D platform, for which it is difficult to sensitively identify changes in the nature and abundance of target proteins. With the development of mass spectrometry (MS) technology, MS-based proteomics has made important contributions to characterizing the dynamic changes in the natural immune proteome induced by viral infections. MS analytical techniques have several advantages, such as high throughput, rapidity, sensitivity, accuracy, and automation. The most common techniques for detecting complex proteomes are liquid chromatography (LC) and mass spectrometry (MS). LC-MS (Liquid Chromatography-Mass Spectrometry), which combines the physical separation capability of LC and the mass analysis capability of MS, is a powerful technique mainly used for analyzing the proteome of cells, tissues, and body fluids. To explore the combination of traditional proteomics techniques such as Western blotting, Co-IP (co-Immunoprecipitation), and the latest LC-MS methods to probe the anti-inflammatory pathway and the differential changes in upstream and downstream proteins induced by the antiviral natural immune junction protein STING.

Protective Role of Melatonin Against Abamectin-Induced Biochemical, Immunohistochemical, and Ultrastructural Alterations in the Testicular Tissues of Rats.

Abamectin is one of the most widely used pesticides due to its strong insecticidal and anthelmintic activities. Melatonin is a neurohormone with potent antioxidant, anti-apoptotic, and anti-inflammatory effects. This study aimed to investigate the potential ameliorative effects of melatonin against abamectin-induced testicular toxicity in rats. Twenty-four rats were divided into four groups: control group (1 mL/kg/day corn oil), melatonin-treated group (10 mg/kg/day), abamectin-treated group (0.5 mg/kg/day), and melatonin plus abamectin-treated group. Test substances were administered via oral gavage once daily for 28 days. While MDA and 8-OHdG levels increased in the testicular tissue of rats treated with abamectin, SOD, CAT, GPx, and GST enzyme activities decreased significantly. While interleukin-17 levels, TNF-α, and caspase3 expression increased in the testicular tissue, acetylcholinesterase activity decreased. At the same time, serum gonadotropins (luteinizing and follicle-stimulating hormones) and testosterone levels decreased. Light microscope examinations of testicular tissues revealed severe histopathological changes, such as atrophic hyalinized seminiferous tubules, basement membrane irregularity, degeneration, spermatogenic cell loss, and necrosis. Electron microscopy examinations revealed large vacuoles in Sertoli and spermatogenic cells, swelling and vacuolization in mitochondria, lysosomal structures, and increased pyknotic nuclei. In contrast, melatonin supplementation significantly ameliorated abamectin-induced testicular toxicity in rats through antioxidant, antiapoptotic, and anti-inflammatory mechanisms.

New anti-inflammatory mechanism of glucocorticoids uncovered

Glucocorticoids (GCs) are potent anti-inflammatory drugs. A new study by Auger et al. found that GCs increase itaconate, an anti-inflammatory tricarboxylic acid (TCA) cycle intermediate, by promoting movement of cytosolic pyruvate dehydrogenase (PDH) to mitochondria. Itaconate was sufficient for mediating the anti-inflammatory effects of GCs in mice, overriding the notion that nuclear glucocorticoid receptor (GR) are necessary for inflammation inhibition.

Engeletin attenuates the inflammatory response via inhibiting TLR4-NFκB signaling pathway in Crohn's disease-like colitis

Ethnopharmacological relevanceSmilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal for treating various inflammatory conditions. Engeletin1 (ENG) is one of the most abundant bioactive compounds found in Smilax glabra rhizome, with anti-inflammatory, antioxidant, and ulcer-preventing activities.Aim of the study: The purpose of this study was to investigate the ability of ENG to alleviate inflammatory symptoms and improve epithelial barrier integrity utilize a 2,4,6-trinitrobenzene sulfonic acid2 (TNBS)-induced murine model in Crohn's disease3 (CD)-like colitis, and to characterize the underlying anti-inflammatory mechanisms of action. Materials and methodsA colitis model was established in BALB/c mice and treated with ENG for 7 days. RAW264.7 macrophages were pre-treated with ENG and lipopolysaccharide4 (LPS) stimulation. The mice's weight and colon length were assessed. qPCR and Western blotting were used to analyze gene expression and TLR4-NFκB pathway. Flow cytometry was used to analyze the polarization states of the macrophages. ResultsTreatment with ENG was sufficient to significantly alleviate symptoms of inflammation and colonic epithelial barrier integrity in treated mice. Significant inhibition of TNF-α, IL-1β, and IL-6 expression was observed following ENG treatment in vivo and in vitro. ENG was also determined to be capable of inhibiting the expression of iNOS and CD86, inhibited M1 macrophage polarization in vitro, as well as the TLR4-NFκB signaling pathway. Molecular docking showed a highly stable binding between ENG and TLR4. ConclusionENG has been proven to alleviate inflammation and ameliorate the damage of epithelial barrier in CD-like colitis. ENG also suppressed the M1 macrophages polarization and the inhibited inflammatory cytokines. TLR4-NFκB signaling pathway, especially TLR4, may be the target of ENG. These data offer a new insight into the therapeutic mechanisms of ENG.

The Galloyl Group Enhances the Inhibitory Activity of Catechins against LPS-Triggered Inflammation in RAW264.7 Cells.

The galloyl group in catechins was confirmed to be crucial for their health benefits. However, whether the catechins' galloyl group had a contribution to their anti-inflammation remains unclear. This study investigated the anti-inflammation properties and mechanisms of catechins in RAW264.7 cells by using ELISA, fluorometry, flow cytometer, Western blot, and molecular docking. Results showed that the galloyl group enhanced the inhibitory abilities of catechins on inflammatory cytokines (NO, PGE2, IL-1β, and TNF-α) and ROS release in LPS-induced cells. This suppression was likely mediated by delaying cells from the G0/G1 to the S phase, blocking COX-2 and iNOS via the TLR4/MAPK/NF-κB pathway with PU.1 as an upstream target. The research proved that the existence of galloyl groups in catechins was indispensable for their anti-inflammatory capacities and offered a theoretical basis for the anti-inflammatory mechanism of galloylated catechins. Future research is needed to verify the anti-inflammatory effects of catechins in various sources of macrophages or the Caco-2/RAW264.7 cell co-culture system.

Anti-Allergic and Anti-Inflammatory Signaling Mechanisms of Natural Compounds/Extracts in In Vitro System of RBL-2H3 Cell: A Systematic Review.

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway.

Comprehensive landscapes of the causal network between immunity and sarcopenia.

Inflammaging, an immune status characterized by a sustained increase in pro-inflammatory markers and a decline in anti-inflammatory mechanisms, is a critical risk factor in the development of sarcopenia. Landscapes of the causal relationships between immunity and sarcopenia are needed to understand the mechanism of sarcopenia and provide novel treatments comprehensively. We used Mendelian Randomization (MR) as the basic method in this study. By setting immune proteins, immune cells, and sarcopenia as exposures and outcomes alternatively, and then combining them in different directions, we potentially estimated their causal relationships and directions and subsequently mapped the comprehensive causal landscape based on this information efficiently. To further understand the network, we developed a method based on rank-sums to integrate multiple algorithms and identify the key immune cells and proteins. More than 1,000 causal relationships were identified between immune cell phenotypes, proteins, and sarcopenia traits (p < 0.05), and the causal maps of these linkages were established. In the threshold of FDR < 0.05, hundreds of causal linkages were still significant. The final comprehensive map included 13 immune cell phenotypes and 8 immune proteins. The star factors in the final map included EM CD8br %CD8br, EM DN (CD4- CD8-) %DN, SIRT2, and so on. By reading the landscapes in this study, we may not only find the factors and the pathways that have been reported and proven but also identify multiple novel immunity cell phenotypes and proteins with enriched upstream and downstream pathways.

Photothermal Catalytic Reduction and Bone Tissue Engineering Towards a Three-in-One Therapy Strategy for Osteosarcoma.

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.

Phytochemical Composition Antioxidant and Anti-Inflammatory Activity of Artemisia dracunculus and Artemisia abrotanum.

This study aimed to investigate the antioxidant and anti-inflammatory activities mechanism of Artemisia dracunculus (A. dracunculus) and Artemisia abrotanum (A. abrotanum) ethanol extracts in acute rat inflammation induced in Wistar male rats with turpentine oil. The characterization of the polyphenolic compounds in the extracts was conducted using UV-Vis and Fourier-transform infrared spectroscopy and high-performance liquid chromatography coupled with mass spectrometry techniques. The antioxidant activity of the extracts was evaluated in vitro by DPPH, FRAP, H2O2, and NO scavenging tests and in vivo by measuring the total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), 8-hydroxy-deoxyguanosine (8-Oxo-dG), advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitric oxide (NO), 3-nitrotyrosine (3NT), and total thiols (SH). Inflammation was evaluated by measuring nuclear factor-kB-p65 (NfkB-p65) and NLRP3 inflammasome activation with IL-1β, IL-18, and gasdermin D. Liver and renal toxicity was determined following transaminases (ALT and AST), creatinine, and urea. The experimental results indicated that A. dracunculus and A. abrotanum ethanol extracts have moderate in vitro antioxidant activity and had in vivo antioxidant activity and an anti-inflammatory effect by NfkB-p65, IL-1b, IL-18, and gasdermin D serum level reduction. The antioxidant activity correlated with the chemical composition of the extracts. These results bring evidence-based use of A. dracunculus and A. abrotanum's in traditional and contemporary medicine.

The potential therapeutic role of itaconate and mesaconate on the detrimental effects of LPS-induced neuroinflammation in the brain

Despite advances in antimicrobial and anti-inflammatory treatment, inflammation and its consequences remain a major challenge in the field of medicine. Inflammatory reactions can lead to life-threatening conditions such as septic shock, while chronic inflammation has the potential to worsen the condition of body tissues and ultimately lead to significant impairment of their functionality. Although the central nervous system has long been considered immune privileged to peripheral immune responses, recent research has shown that strong immune responses in the periphery also affect the brain, leading to reactive microglia, which belong to the innate immune system and reside in the brain, and neuroinflammation. The inflammatory response is primarily a protective mechanism to defend against pathogens and tissue damage. However, excessive and chronic inflammation can have negative effects on neuronal structure and function. Neuroinflammation underlies the pathogenesis of many neurological and neurodegenerative diseases and can accelerate their progression. Consequently, targeting inflammatory signaling pathways offers potential therapeutic strategies for various neuropathological conditions, particularly Parkinson’s and Alzheimer’s disease, by curbing inflammation. Here the blood–brain barrier is a major hurdle for potential therapeutic strategies, therefore it would be highly advantageous to foster and utilize brain innate anti-inflammatory mechanisms. The tricarboxylic acid cycle-derived metabolite itaconate is highly upregulated in activated macrophages and has been shown to act as an immunomodulator with anti-inflammatory and antimicrobial functions. Mesaconate, an isomer of itaconate, similarly reduces the inflammatory response in macrophages. Nevertheless, most studies have focused on its esterified forms and its peripheral effects, while its influence on the CNS remained largely unexplored. Therefore, this study investigated the immunomodulatory and therapeutic potential of endogenously synthesized itaconate and its isomer mesaconate in lipopolysaccharide (LPS)-induced neuroinflammatory processes. Our results show that both itaconate and mesaconate reduce LPS-induced neuroinflammation, as evidenced by lower levels of inflammatory mediators, reduced microglial reactivity and a rescue of synaptic plasticity, the cellular correlate of learning and memory processes in the brain. Overall, this study emphasizes that both itaconate and mesaconate have therapeutic potential for neuroinflammatory processes in the brain and are of remarkable importance due to their endogenous origin and production, which usually leads to high tolerance.

Unlocking the Insightful Antidiabetic Effects of Lemongrass (Cymbopogon citratus): A Comprehensive Review

Lemongrass (Cymbopogon citratus) has emerged as a noteworthy contender in traditional medicine for its aromatic and therapeutic attributes, yet its potential as an antidiabetic agent remains largely unexplored in the literature. To address this gap, this study endeavors to provide a comprehensive overview of lemongrass role in diabetes management and the underlying pathways involved. Rich in bioactive compounds such as citral, flavonoids, and essential oils, lemongrass boasts a diverse array of medicinal properties. Research indicates its capability to modulate blood glucose levels, improve insulin sensitivity, and fortify pancreatic β-cell function primarily through antioxidant and anti-inflammatory mechanisms. Animal studies have demonstrated substantial reductions in fasting blood glucose and enhanced glucose tolerance, ascribed to heightened insulin signaling and inhibition of carbohydrate metabolism enzymes. Additionally, lemongrass exhibits a positive impact on lipid profiles, thereby mitigating cardiovascular risks associated with diabetes. Limited human trials have corroborated these findings, showcasing improvements in glycemic control and lipid metabolism following lemongrass consumption. In conclusion, lemongrass emerges as a promising adjunctive therapy for diabetes management, owing to its natural composition and multifaceted mechanisms. Nonetheless, further investigation, particularly through rigorous clinical trials, is imperative to determine optimal dosages, long-term safety, and efficacy, thereby facilitating its seamless integration into conventional diabetes treatment protocols.