Potent Anti-inflammatory Effects Research Articles

Liver-X receptor β-selective agonist CE9A215 regulates Alzheimer's disease-associated pathology in a 3xTg-AD mouse model.

In Alzheimer's disease (AD), tau pathology is closely associated with disease progression. Therefore, therapeutics that alleviate tau pathology are essential. Liver-X receptor (LXR) has garnered interest as a potential target for the treatment of AD. We previously investigated the potent anti-allergic and anti-inflammatory effects of inotodiol, hereafter referred to as CE9A215, in various disease models. In this study, we explored the potential of CE9A215 as a treatment for AD. CE9A215 preferentially activated LXRβ (EC50 <10 nM), with no significant activation observed for LXRα at concentrations up to 1000 nM. Pharmacokinetic analysis confirmed that CE9A215 crosses the blood-brain barrier and accumulates in the brain. Moreover, CE9A215 modulated the expression of ABCA1, APOE, SREBP-1c and AQP4 in the brains of wild-type and LXR α/β knockout mice in LXRβ-dependent manner. The efficacy of CE9A215 on AD-related pathologies was evaluated using 3xTg-AD mice. CE9A215 exerted both prophylactic and therapeutic effects on AD-associated behaviors and pathologies, including reductions in amyloid-β, phosphorylated tau, and neuroinflammation in the hippocampus. Transcriptomic analysis revealed that CE9A215 induced significant changes in genes associated with tau pathology, particularly in pathways related to protein phosphorylation and PI3K/AKT signaling. Our findings suggest that CE9A215 could be a promising therapeutic candidate for AD, particularly in mitigating tau hyperphosphorylation and related AD pathologies.

Enhanced inflammatory and oxidative response mitigation by acetyl-L-carnitine in a rat model of pelvic inflammatory disease.

Acetyl-L-carnitine (ALC) is known for its potent antioxidant and anti-inflammatory properties. This research aimed to investigate the properties of ALC in combating pelvic inflammatory disease (PID) in a rat model. PID, a consequence of sexually transmitted infections in females, can impact the fallopian tubes and uterus, leading to complications. This study is a randomized control preclinical experiment. A total of 24 reproductively mature Sprague Dawley female rats were randomly and equally assigned (n = 4 per group) to six cohorts: control, PID, low-dose prophylactic, high-dose prophylactic, and low-dose therapeutic and high-dose therapeutic groups. PID was induced by injecting the rat cervix with a multi-pathogen solution. Acetyl-L-carnitine, 100 mg/kg (once a day), was orally administered to rats in the low-dose prophylactic group, while 200 mg/kg (once a day) to the high-dose prophylactic group, starting 1 day prior to induction of PID. The therapeutic groups were given similar doses of ALC 1 day after the PID model was confirmed. Samples from the right upper genital tract were collected for ELISA and antioxidant assays, while the left upper genital tract samples underwent histopathological analysis. According to the results, the ALC-treated groups showed a decreased level of cytokines (IL-1β, TNF-α) and oxidative stress markers (catalase, lipid peroxidation) when compared to the PID group. Histopathological examinations revealed that ALC treatment reduced the infiltration of neutrophils and lymphocytes in the uterus compared to the PID group. It was concluded that ALC showed potential antioxidant and anti-inflammatory effects in PID and, therefore, could be used as a possible option for the treatment of PID.

Therapeutic Potential of Arimoclomol Nanomicelles: In Vitro Impact on Alzheimer's and Parkinson's Pathology and Correlation with In Vivo Inflammatory Response.

This study investigates the potential of arimoclomol-loaded nanomicelles for the treatment of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as their anti-inflammatory properties. Arimoclomol, a coinducer of heat shock proteins (HSPs), has shown clinical promise in mitigating protein misfolding, a hallmark of these diseases. In this work, arimoclomol nanomicelles significantly reduced the aggregation of β-amyloid (Aβ1-42) and α-synuclein (α-syn), key pathological proteins in Alzheimer's and Parkinson's. Additionally, the nanomicelles demonstrated potent anti-inflammatory effects, reducing leukocyte and neutrophil counts in an acute inflammation model. These results suggest that arimoclomol nanomicelles could enhance clinical outcomes by targeting both neurodegenerative and inflammatory processes, offering a promising therapeutic strategy for long-term disease management.

Trace Element Chromium-D-Phenylalanine Complex: Anti-Inflammatory and Antioxidant Insights from In Vivo and In Silico Studies.

The biological significance of trace elements such as chromium extends beyond basic cellular functions, influencing key processes like inflammation and oxidative stress. In this study, we explore the anti-inflammatory and antioxidant potential of a trace element complex, Chromium-D-phenylalanine (Cr(D-Phe)₃), through in vivo and in silico approaches. Anti-inflammatory activity was assessed using a carrageenan-induced paw oedema model in rats, coupled with histopathological and biochemical analyses. The antioxidant effects of Cr(D-Phe)₃ were evaluated by measuring reduced glutathione (GSH), lipid peroxidation (LPO), and tumour necrosis factor-alpha (TNF-α) as a marker of inflammation. Furthermore, molecular docking and dynamics simulations were conducted to elucidate the compound's binding affinity and stability with cyclooxygenase enzymes. Cr(D-Phe)₃ exhibited significant anti-inflammatory activity, with the 40μg/kg dose achieving 34.40% (p < 0.001) oedema inhibition, comparable to diclofenac sodium (42.40%). Treatment with Cr(D-Phe)₃ restored GSH levels (+ 62.10%, p < 0.001), reduced LPO (24.72%, p < 0.001), and lowered TNF-α (31.73%, p < 0.001) in carrageenan injected rats, demonstrating potent antioxidant and anti-inflammatory effects. Molecular docking revealed strong binding affinities between Cr(D-Phe)₃ and COX enzymes, suggesting its potential mechanism of action in modulating inflammatory pathways. This study highlights the potential of Cr(D-Phe)₃ as a chromium-based trace element complex with anti-inflammatory and antioxidant properties. These findings warrant further preclinical investigations to elucidate its full pharmacological potential and applications in managing inflammatory conditions.

Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2.

Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus. However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects requires further elucidation. To identify new sesquiterpene lactones from C. intybus, and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties. Identification of sesquiterpene lactones from C. intybus using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis. We identified 3 new sesquiterpene lactones and 15 known analogues from C. intybus. SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation in vitro. In vivo, 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal. 8-Deoxylactucin, the sesquiterpene lactone of C. intybus, exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.

Selected Plant Extracts Regulating the Inflammatory Immune Response and Oxidative Stress: Focus on Quercus robur

Background/Objectives: Inflammation is a vital response of the immune system, frequently linked to the development and progression of numerous chronic and autoimmune diseases. Targeting inflammation represents an attractive strategy to prevent and treat these pathologies. In this context, many pathways, including pro-inflammatory cytokines secretion, NFκB activation, reactive oxygen species (ROS) production, inflammasome activation and arachidonic acid metabolism could be highlighted and addressed. Several plant materials have traditionally been used as effective and non-harmful anti-inflammatory agents. However, well-established scientific evidence is lacking, and their mechanisms of action remain unclear. The current article compares the effects of seven plant extracts, including Quercus robur L. (Oak), Plantago lanceolata L. (narrowleaf plantain), Plantago major L. (broadleaf plantain), Helichrysum stoechas L. (immortelle or helichrysum), Leontopodium nivale alpinum Cass. (edelweiss), Medicago sativa L. (alfafa) and Capsella bursa-pastoris Moench (shepherd’s purse) on different inflammatory pathways. Results: All of the plant extracts significantly affected ROS production, but their action on cytokine production was more variable. As the Quercus robur extract showed the highest efficacy in our models, it was subsequently assessed on several inflammatory signaling pathways. Quercus robur significantly decreased the secretion of IFNγ, IL-17a, IL-12, IL-2, IL-1β and IL-23 in stimulated human leucocytes, and the expression of TNFα, IL-6, IL-8, IL-1β and CXCL10 in M1-like macrophages. Additionally, a significant reduction in PGE2 secretion, COX2, NLRP3, caspase1 and STAT3 expression and NFκB p65 phosphorylation was observed. Conclusions: Our results clearly indicate that Quercus robur has a potent anti-inflammatory effect, making it a promising candidate for both the treatment and prevention of inflammation and related diseases, thereby promoting overall well-being.

RvE1/ChemR23 facilitates hematoma clearance and promotes M2 polarization of macrophages/microglia in intracerebral hemorrhage.

Previous studies have demonstrated the potent anti-inflammatory effects of RvE1 in various diseases, and recent research has shown that it can also promote macrophage phagocytosis. Given that hematoma clearance is crucial for intracerebral hemorrhage (ICH) treatment, while neuroinflammation significantly influences secondary injury, we hypothesize that RvE1/ChemR23 activation, by modulating the polarization of macrophages/microglia, promotes hematoma resolution and alleviates neuroinflammatory responses after ICH. A total of 125 WT C57BL/6 and 67 ChemR23-/- male mice were used. Western blot and immunofluorescence staining assessed the temporal and spatial expression of ChemR23 after ICH. T2WI, T2*WI and behavioral tests were obtained to assess the protective effect of the RvE1/ChemR23 pathway in ICH. Additionally, co-staining of M1 (iNOS) or M2 polarization (Arg-1) markers with Iba-1 was used to explore the polarization status of macrophages/microglia in the perihematomal region. Finally, Akt phosphorylation was validated as a downstream mediator of the RvE1/ChemR23 pathway using an Akt inhibitor. ChemR23 is mainly expressed in activated microglia and infiltrating macrophages, with expression peaking 5-7 days post-ICH. Activation of the RvE1/ChemR23 pathway promotes hematoma resolution, reduces brain edema, and improves neurological deficits in ICH. These effects are likely mediated by promoting M2 polarization of macrophages/microglia after ICH. Furthermore, the use of an Akt inhibitor can counteract the protective effects of RvE1 in ICH. Our study provides the first evidence of the protective role of RvE1/ChemR23 signaling in ICH. This pathway might offer novel therapeutic targets for the clinical management of ICH.

Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.

We aimed to understand the potential therapeutic and anti-inflammatory effects of the phosphodiesterase-4 (PDE4) inhibitor roflumilast in models of pulmonary infection caused by betacoronaviruses. Mice were infected intranasally with murine hepatitis virus (MHV-3) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Roflumilast was given to MHV-3-infected mice therapeutically at doses of 1mg/kg or 10mg/kg, or prophylactically at 10mg/kg. In SARS-CoV-2-infected mice, roflumilast was given therapeutically at a dose of 10mg/kg. Lung histopathology, chemokines (CXCL-1 and CCL2), cytokines (IL-1β, IL-6, TNF, IFN-γ, IL-10 and TGFβ), neutrophil immunohistochemical staining (Ly6G+ cells), macrophage immunofluorescence staining (F4/80+ cells), viral titration plaque assay, real-time PCR virus detection, and blood cell counts were examined. Therapeutic treatment with roflumilast at 10mg/kg reduced lung injury in SARS-CoV-2 or MHV-3-infected mice without compromising viral clearance. In MHV-3-infected mice, reduced lung injury was associated with decreased chemokines levels, prevention of neutrophil aggregates and reduced macrophage accumulation in the lung tissue. However, the prophylactic treatment strategy with roflumilast increased lung injury in MHV-3-infected mice. Our findings indicate that therapeutic treatment with roflumilast reduced lung injury in MHV-3 and SARS-CoV-2 lung infections. Given the protection induced by roflumilast in inflammation, PDE4 targeting could be a promising therapeutic avenue worth exploring following severe viral infections of the lung.

Potential Transformation of Food Resveratrol: Mechanisms and Biological Impact

Resveratrol is a naturally occurring phenolic compound found in foods like grapes, berries, and peanuts. It has attracted substantial interest for its potential human health benefits, including antioxidant and anti-inflammatory effects. Research indicates that resveratrol may contribute to cardiovascular health, protect cognitive function, and exhibit anticancer properties. However, various factors such as pH levels, exposure to light, specific enzymes, and metal ions can alter its chemical structure, affecting its biological activities. These reactions can lead to the formation of different metabolites and polymers, which may affect the stability and bioactivity of resveratrol. This review examines the transformation of resveratrol from its natural sources to its consumption by humans. Additionally, we explore the biological activities of the resulting compounds of resveratrol transformations.

P1339 CJRB-201, a promising candidate for microbiome-based therapy with potent anti-inflammatory effects in Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal condition characterized by immune dysregulation driven by microbiome dysbiosis, with a reduction of beneficial bacteria such as Faecalibacterium, a dominant commensal bacterium comprising 5-10% of the human gut microbiome. Its depletion is a hallmark of Crohn's disease and other autoimmune-related conditions, making it an emerging candidate as a next-generation probiotic. Methods CJRB-201 was selected using our BI platform (Ez-Mx), based on more than 500 metagenomic datasets from IBD patients and healthy controls. The immune regulatory efficacy of CJRB-201 was evaluated through in vitro and ex vivo assays, focusing on key cytokine ratios (IL-10/IL-1β, IL-10/TNF, IL-10/IFN-γ) in macrophages and T cells. The induction of T regulatory (T reg) cell populations was evaluated ex vivo and in germ-free (GF) mice. Three pathogenetically different IBD animal models (DSS-induced, IL-10 KO GF, T cell transfer) were examined to assess its efficacy. Lastly, the SHIME system (Simulator of the Human Intestinal Microbial Ecosystem) was applied to test various fibers that promote the growth of CJRB-201. Results Among 34 tested anti-inflammatory strains, including those from CJ Bioscience, 4D Pharma, and our Ez-Mx platform, CJRB-201 emerged as one of the most effective. Notably, CJRB-201 and its conforming species showed the highest induction of T reg populations ex vivo among the sixty Faecalibacterium strains, primarily driven by its cell pellet form rather than the supernatant. Administration of CJRB-201 resulted in successful colonization in the colon of GF mice, leading to an enhanced T reg cell population. In the three IBD models with both preventative and therapeutic approaches, CJRB-201 demonstrated significant improvements across five key disease features (body weight, disease activity index, colon length, histopathology, and inflammatory markers such as cytokines and fecal lipocalin-2). Interestingly, CJRB-201 outperformed other potential single and consortia strains and demonstrated efficacy comparable to the α-IL-12p40 antibody, particularly in the T cell transfer model (Figure 1). Lastly, we identified the fiber that stabilizes the engraftment of CJRB-201 in the SHIME system. Conclusion CJRB-201 exhibits superior anti-inflammatory efficacy in multiple immune assays and IBD animal models, significantly improving preclinical and inflammatory markers. Given its ability to enhance T reg populations and the promising potential of the identified fiber in supporting its colonization, CJRB-201 holds strong promise as a microbiome-based therapeutic for IBD patients.

Advances in Research on Marine Natural Products for Modulating the Inflammatory Microenvironment.

In recent years, marine natural products (MNPs) have emerged as crucial sources of lead compounds for the advancement of anti-inflammatory drugs due to their abundant diversity, complexity, and distinctiveness. Inflammatory microenvironments (IMEs) are pervasive pathological features in the etiology of various chronic diseases, referring to the localized milieu or ecosystem where inflammatory responses occur, and they play a pivotal role in the onset and progression of inflammatory diseases. Uncontrolled IMEs can lead to dysregulation of inflammatory mediators within signaling pathways, thereby exerting detrimental effects on human health and even contributing to the development of inflammatory diseases such as cancer. Currently, inflammation treatment predominantly relies on chemical drugs. Nevertheless, these existing therapies are constrained by their numerous side effects and slow remission of symptoms. Consequently, there is an urgent need for the discovery and development of new drugs that exhibit minimal side effects while exerting potent anti-inflammatory effects. This article extensively explored the activities and mechanisms of MNPs (covering studies from 2010 to 2024) regulating key signaling pathways and inflammatory mediators in the IME, which establishes a theoretical basis for the further development of anti-inflammatory drugs.

Biochemical strategy-based hybrid hydrogel dressing-mediated in situ synthesis of selenoproteins for DFU immunity-microbiota homeostasis regulation.

Chronic consequences of diabetes that are most commonly encountered are diabetic foot ulcers (DFUs), driven by microbiota-immune system dyshomeostasis, eventually leading to delayed wound healing. Available therapies, such as systemic or topical administration of anti-inflammatory or antimicrobial agents, are limited due to antibiotic resistance and immune dysfunction. Herein, a hybrid hydrogel dressing is developed as the artificial bioadhesive barrier at wound sites to maintain microbial and immunological homeostasis locally and have potent anti-inflammatory effects. Specifically, Zero-valent selenium nanoparticles are synthesized and encapsulated into the alginate-polyacrylamide interpenetrating hydrogel networks, during which trehalose is adopted to modify the network defects. Besides, as an anti-adhesion agent, trehalose has shown the ability to prevent immune degradation by reducing bacteria binding to HUVECs. The obtained hybrid hydrogel dressing serves as a physical barrier against microbiome invasion, further regulates the composition of the wound microbiome to restore microbial immune homeostasis at the wound site, and cooperatively relieves DFU-associated symptoms. Meanwhile, the hydrogel dressing can synthesize selenoproteins in situ based on biochemical strategies and significantly reduce the secretion of proinflammatory cytokines. The proposed biochemical strategy based on the hybrid hydrogel dressings can efficiently restore microbiota-immune homeostasis in the wounds, presenting a promising approach for DFU therapy in clinics.

Evaluation of the anti-inflammatory, antioxidant and wound healing effects of pterostilbene in human gingival fibroblasts in vitro.

We aimed to investigate the wound-healing, antioxidant, and anti-inflammatory effects of pterostilbene (PTS) on human gingival fibroblasts (GF). Different concentrations of PTS were applied to GFs and cell viability was evaluated by MTT assay. GFs were stimulated by lipopolysaccharide (LPS) and the study groups were determined as LPS, LPS + 1μM PTS, LPS + 10μM PTS, and control. The most effective PTS concentrations were applied in a wound-healing model, with cell counts in the wound area assessed at 0, 24, 48, and 72h. The effect of PTS on the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), basic fibroblast growth factor (bFGF), and collagen type I (COL I) was assessed at 24 and 48h by ELISA. The data was statistically analyzed. Our results showed that PTS had a dose-dependently negative effect on wound healing and cell proliferation at 10μM concentration, but not at low concentration (1μM). PTS exhibited a potent anti-inflammatory effect by reducing IL-6 and TNF-α levels, while also enhancing antioxidant activity, as evidenced by increased GSH-Px levels in the LPS + 1μM PTS group (P < 0.05). According to our results, PTS could be a potential and promising substance with anti-inflammatory and antioxidant effects on LPS-stimulated GF. Therefore our results have merit in terms of providing pioneering data for future studies.

Design and synthesis of phenylthiophosphoryl dichloride derivatives and evaluation of their antitumour and anti-inflammatory activities.

Tumours and inflammation are serious risks to human health and are importantly regulated by the gas signalling molecule hydrogen sulphide. In this work, we report the rational design and synthesis of H2S donor molecules based on phenylthiophosphoryl dichloride nuclei and assess their efficacy against tumours and inflammation. We predicted its potential anticancer targets based on network pharmacology and then verified the inhibitory effect of the active compound S11 on the pathway PI3K/AKT by enzyme inhibition and molecular docking assay. In addition, compound S11 exhibited a potent anti-inflammatory effect on macrophages, effectively reducing the levels of inflammatory mediators TNF-α, IL-10 and HO-1. Compound S11 can be used as a new chemical entity for the discovery of new anti-cancer drugs or anti-inflammatory drugs.

Phlorofucofuroeckol-A: A Natural Compound with Potential to Attenuate Inflammatory Diseases Caused by Airborne Fine Dust.

Background and Objectives: Persistent exposure to airborne fine dust (FD) particles contributing to air pollution has been linked to various human health issues, including respiratory inflammation, allergies, and skin diseases. We aimed to identify potential seaweed anti-inflammatory bioactive reagents and determine their effects on systemic inflammatory responses induced by FD particles. Materials and Methods: While exploring anti-inflammatory bioactive reagents, we purified compounds with potential anti-inflammatory effects from the seaweed extracts of Ecklonia cava, Ecklonia stolonifera, and Codium fragile. Structural analyses of the purified compounds siphonaxanthin (Sx), fucoxanthin (Fx), dieckol (Dk), and phlorofucofuroeckol-A (PFF-A) were performed using NMR and LC-MS/MS. Results: Notably, these compounds, especially PFF-A, showed significant protective effects against FD-induced inflammatory responses in RAW 264.7 cells without cytotoxicity. Further investigation of inflammatory-associated signaling demonstrated that PFF-A inhibited IL-1β expression by modulating the NF-κB/MAPK signal pathway in FD-induced RAW 264.7 cells. Additionally, gene profiling revealed the early activation of various signature genes involved in the production of inflammatory cytokines and chemokines using gene profiling. Treatment with PFF-A markedly reduced the expression levels of pro-inflammatory and apoptosis-related genes and even elevated the Bmp gene families. Conclusions: These results suggested that PFF-A is a potential natural therapeutic candidate for managing FD-induced inflammatory response.

Blended ƙ-carrageenan and xanthan gum hydrogel containing ketoprofen-loaded nanoemulsions: Design, characterization, and evaluation in an animal model of rheumatoid arthritis.

This study reports the preparation of hydrogels (HG) made with xanthan gum (XG) and ƙ-carrageenan (KC) polysaccharides containing ketoprofen (KET)-loaded nanoemulsions (NK) and their evaluation in a rheumatoid arthritis (RA) model. The nano-based HGs exhibited nanometric-sized droplets (~ 100nm), an acidic pH (5.10-6.83), drug content above 85%, a suitable spreadability factor, and pseudoplastic flow behavior. The most promising blend (HGCX 2:1) demonstrated sustained KET release, reaching 81.44 ± 6.11% after 5h, and superior drug concentration in the skin layers (237.91 ± 41.0µg/g). The formulation was selected due to its enhanced bioadhesiveness, with the HG-NK formulation showing the highest bioadhesion force and occlusion factor. RA was induced by complete Freund's adjuvant (CFA) intraplantar injection into the left hind paw of male and female Swiss mice. Treatments with HGs were applied to the animals' dorsal region for 7days. Notably, HG-NK demonstrated remarkable efficacy, reversing mechanical sensitivity in male mice and significantly reducing thermal sensitivity in both genders. Moreover, HG-NK provided a significant reduction in paw edema (52-fold in males, 27-fold in females) and inflammatory markers, such as myeloperoxidase activity (32-fold in males, 14-fold in females) and lipid peroxidation (2.5-fold in males, twofold in females). The formulation also promoted greater permeation of KET across the skin. These findings underscore the significant reduction in inflammatory markers by the HG-NK formulation, highlighting its potent anti-inflammatory effects and potential as a promising therapeutic strategy for managing RA.

Size effect-based improved antioxidant activity of selenium nanoparticles regulating Anti-PI3K-mTOR and Ras-MEK pathways for treating spinal cord injury to avoid hormone shock-induced immunosuppression

Spinal cord injury (SCI) is a critical condition affecting the central nervous system that often has permanent and debilitating consequences, including secondary injuries. Oxidative damage and inflammation are critical factors in secondary pathological processes. Selenium nanoparticles have demonstrated significant antioxidative and anti-inflammatory properties via a non-immunosuppressive pathway; however, their clinical application has been limited by their inadequate stability and functionality to cross the blood-spinal cord barrier (BSCB). This study proposed a synthesis method for ultra-small-diameter lentinan Se nanoparticles (LNT-UsSeNPs) with significantly superior reactive oxygen species (ROS) scavenging capabilities compared to conventional lentinan Se nanoparticles (LNT-SeNPs). These compounds effectively protected PC-12 cells from oxidative stress-induced cytotoxicity, alleviated mitochondrial dysfunction, reduced apoptosis. In vivo studies indicated that LNT-UsSeNPs efficiently penetrated the BSCB and effectively inhibited the apoptosis of spinal neurons. Ultimately, LNT-UsSeNPs directly regulated the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK signaling pathways by regulating selenoproteins to achieve non-immunosuppressive anti-inflammatory therapy. Owing to their ultra-small size, LNT-UsSeNPs exhibited strong spinal barrier penetration and potent antioxidative and anti-inflammatory effects without compromising immune function. These findings suggest that LNT-UsSeNPs are promising candidates for further development in nanomedicine for the effective treatment of SCI.Graphical abstract

Uses of Cyclohexan-1,3-diones to Synthesis Xanthenes Derivatives with Anti-proliferative Activity Against Cancer Cell Lines and their Inhibitions Toward Tyrosine Kinases.

Xanthene derivatives are a notable class of heterocyclic compounds widely studied for their significant biological impact. These molecules, found in both natural and synthetic forms, have attracted substantial scientific interest due to their broad spectrum of biological activities. The xanthene nucleus, in particular, is associated with a range of potential pharmaceutical properties, including antibacterial, antiviral, antiinflammatory, anticancer, and antioxidant effects. Their structural flexibility allows for modifications that can enhance specific biological functions, making them valuable candidates in medicinal chemistry and drug development. Multi-component reactions involving two equivalents of 5,5-dimethylcyclohexane-1,3-dione with aromatic aldehydes yield xanthene derivatives that are known for their biological activity. Additionally, fused xanthene derivatives are formed through subsequent heterocyclization reactions, resulting in compounds with a broad range of biological properties. Various xanthene derivatives incorporating thiophene and thiazole moieties were synthesized. Compounds 3a-c were further subjected to heterocyclization reactions to produce fused xanthene derivatives with additional heterocyclic components, enhancing their biological activity. The cytotoxic effects of the synthesized compounds were assessed across six cancer cell lines. Inhibition studies on c-Met kinase and the PC-3 cell line were conducted. Additionally, the compounds' inhibitory activity against tyrosine kinases was evaluated, and morphological changes in the A549 cell line were observed with the two most potent compounds. The synthesized heterocyclic compounds, derived from 5,5-dimethylcyclohexane-1,3-dione and related cyclohexanone derivatives, exhibited significant inhibitory effects across various cancer cell lines. Specifically, compounds 3b, 5c, 5d, 7b, 7c, 7d, 9a, 9b, 10b, 10c, 12c, 15b, 15c, 16b, 16c, 17c, 17d, 17e, and 17f demonstrated high levels of inhibition, indicating potential for further exploration of xanthene-based heterocyclic compounds to enhance anticancer properties.

Propolis from Mount Lawu: Dose-Dependent Antioxidant and Anti-Inflammatory Effects in a Rat Model of Wound Healing

Background: Chronic wounds present a significant healthcare challenge, necessitating the exploration of effective adjuvant therapies. Propolis, a natural product derived from beehives, has demonstrated antioxidant and anti-inflammatory properties. This study investigated the dose-dependent effects of Mount Lawu propolis extract on oxidative stress and inflammation in a rat model of wound healing. Methods: A completely randomized experimental design was employed using male rats (Rattus norvegicus). Granulation tissue wounds were induced, and the rats were treated with varying doses of ethanol extract of Mount Lawu propolis. Immunohistochemical analysis was performed to assess the expression of Malondialdehyde (MDA) and Interleukin-6 (IL-6) in the wound tissue. Results: The results demonstrated a significant dose-dependent decrease in MDA and IL-6 expression in the propolis-treated groups compared to the control group. The high-dose propolis group exhibited the most substantial reduction in both MDA and IL-6 levels. Conclusion: Mount Lawu propolis extract exhibits potent antioxidant and anti-inflammatory effects in a dose-dependent manner, suggesting its potential as an adjuvant therapy for chronic wound management.

Extraction and Processing of Bioactive Phytoconstituents from Widely Used South African Medicinal Plants for the Preparation of Effective Traditional Herbal Medicine Products: A Narrative Review.

Medicinal plants are sources of crude traditional herbal medicines that are utilized to reduce the risk of, treat, or manage diseases in most indigenous communities. This is due to their potent antioxidant and anti-inflammatory effects. It is estimated that about 80% of the population in developing countries rely on herbal traditional medicines for healthcare. This signifies the need for traditional herbal medicines, which are polyherbal formulations prepared by traditional health practitioners. This review examines preparatory steps to extract bioactive phytoconstituents and post-extraction processes to increase the potency of the extracted bioactive phytoconstituents. Achieving this will allow for the reduced use of plant materials and promote the sustainable use of the limited resource of medicinal plants, especially in our South African context. Electronic ethnobotanical books and online databases were used to find studies that focus on phytoconstituent extraction and post-extraction processing to enhance the potency of the extracted bioactive phytoconstituents. Modification of the extracted bioactive phytoconstituents to synthesize daughter compounds facilitates an enhancement in their potency and bioavailability. Based on the data collected through this review, the importance of understanding the properties of the targeted phytoconstituents is essential in selecting the required extraction method. This determines the quality and yield of extracted bioactive phytoconstituents.