Search Results (5,726)

Alpha-1 antitrypsin deficiency (AATD) represents a paradigmatic genetic disorder with well-characterized hepatic manifestations but relatively underexplored pulmonary implications. While liver involvement has been extensively reviewed, the underlying mechanisms of lung disease progression remain poorly understood, particularly regarding immunological pathways and inflammatory processes. The pathophysiology involves defective alpha-1 antitrypsin (AAT) production, including AAT variants that induce neutrophil elastase activity, causing progressive alveolar destruction and sustained inflammation, leading to emphysema, as one of the main components of chronic obstructive pulmonary disease (COPD). AATD and smoking represent major risk factors for COPD, the third leading cause of death worldwide at present. In AATD patients, neutrophils, which constitute the majority of circulating leukocytes, become dysregulated. Under normal conditions, cells perform essential functions, including phagocytosis and neutrophil extracellular trap formation (NETosis); in AATD, however, they accumulate excessively in alveolar spaces due to impaired elastase control. The accumulation of Z-AAT polymers within epithelial cells creates a pathological cycle, acting as chemoattractants that sustain pro-inflammatory responses and contribute to chronic obstructive pulmonary disease development. In addition, monocytes, representing a smaller fraction of leukocytes, migrate to inflammatory sites and differentiate into macrophages while secreting AAT with anti-inflammatory properties. However, in PiZZ patients, this protective mechanism fails, as polymer accumulation within cells reduces both AAT secretion and the number of protective human leukocyte antigen(HLA)-DR-monocyte subsets. In particular, macrophages demonstrate remarkable plasticity, switching between pro-inflammatory M1 (classically activated macrophages) and tissue-repairing M2 (alternatively activated macrophages) phenotypes based on environmental cues. In AATD, this adaptive capability becomes compromised due to intracellular polymer accumulation, leading to impaired phagocytic function and dysregulated cytokine production and ultimately perpetuating chronic inflammation and progressive tissue damage. Recent advances in induced pluripotent stem cell (iPSC) technology have facilitated alveolar epithelial cell (AEC) generation, in addition to the correction of AATD mutations through gene editing systems. Despite the limitations of AAT correction, iPSC-derived organoid models harboring AATD mutations can deliver important insights into disease pathophysiology, while gene editing approaches help demonstrate causality between specific mutations and observed phenotypes. Therefore, in this review, we investigated recent studies that can serve as tools for gene editing and drug development based on recently developed iPSC-related technologies to understand the pathogenesis of AATD. Full article

Feline infectious peritonitis (FIP) is a progressive and often fatal disease caused by a virulent biotype of feline coronavirus (FCoV). Although antiviral treatments are now available, relapse and resistance remain ongoing concerns. This study investigates the therapeutic potential of P. indusiatus, a medicinal mushroom, for its antiviral and anti-inflammatory activities against FIP. The main protease (FIPV M^pro) of feline infectious peritonitis virus (FIPV) was recombinantly expressed and purified to facilitate enzyme inhibition screening. P. indusiatus exhibited the strongest FIPV M^pro inhibitory activity among the 17 mushroom extracts tested (69.2%), showing a notable level of inhibition relative to standard antiviral agents such as lopinavir and ritonavir. To assess its anti-inflammatory potential, PBMCs derived from healthy cats and FIP-associated effusions (FIP fluid) were cultured and stimulated with LPS to induce inflammation. In healthy PBMCs, P. indusiatus significantly reduced nitrite levels, with effects similar to dexamethasone. However, PBMCs from FIP fluid, already in an activated state, showed no additional response. Notably, this study is the first to successfully isolate and culture PBMCs from FIP fluid, providing a new platform for future immunological research. These findings suggest that P. indusiatus possesses both antiviral and anti-inflammatory properties, positioning it as a potential dual-action therapeutic candidate for FIP. Further investigation into cytokine signaling pathways is warranted to clarify its mechanisms of action and advance future therapeutic development. Full article

Gynura procumbens is a commonly adopted medicinal plant native to the tropical regions of East and Southeast Asia and is well recognized for its significant therapeutic potential. Traditionally used in herbal medicine, it has been employed to manage various conditions, including hypertension, diabetes, renal disorders, constipation, and inflammation. Its leaves are particularly rich in flavonoids—such as astragalin, kaempferol, quercetin, myricetin, and rutin—which are associated with anti-glycaemic, anticancer, antihypertensive, antimicrobial, and antioxidant activities. These bioactive constituents form the basis of the broad pharmacological profile of the plant. Emerging studies also suggest a potential role for G. procumbens in the management of infertility, further broadening its therapeutic scope. This review provides a concise overview of its phytochemical constituents, taxonomic classification, and current pharmacological evidence, highlighting its potential as a valuable candidate for novel drug development. Full article

This study investigated the anti-inflammatory effects of Rubus parvifolius leaf (RPL) extract, and its phytochemical composition was characterized using LC-MS/MS and HPLC analyses. In an inflammation model using HaCaT keratinocytes, treatment with RPL extract led to a significant reduction in inflammatory markers, indicating strong anti-inflammatory activity. Phytochemical analysis revealed that the extract is rich in flavonoids, with quercetin 3,7-diglucoside (12.73 mg/g DW) as the most abundant compound, followed by hirsutrin (4.74 mg/g DW) and ellagic acid (1.58 mg/g DW). Kaempferol 3-O-glucuronide was detected in lower amounts (0.31 mg/g DW), and tiliroside was present only in trace levels. These compounds are well known for their antioxidant and anti-inflammatory properties, suggesting that RPL extract may exert multiple beneficial effects on skin health. Collectively, these findings support the potential of RPL extract as a natural therapeutic agent for managing skin inflammation, particularly in conditions such as atopic dermatitis, with its efficacy likely attributed to the high levels of quercetin 3,7-diglucoside, hirsutrin, and ellagic acid. However, the present work was confined to in vitro experiments, and the mechanistic pathways were not experimentally validated. Future in vivo studies are needed to confirm these findings. Full article

Hamamelis virginiana (witch hazel) is traditionally used in dermatology for its antibacterial and anti-inflammatory effects. However, the number of studies on its chemical composition and potentials in skin protection remains limited. This study aimed to investigate the qualitative and quantitative composition of polyphenolic compounds in the leaves and bark of the plant, as well as to explore their antioxidant, anti-inflammatory, and extracellular matrix (ECM)-protective activities in skin-relevant cell models. Human dermal fibroblasts and keratinocytes were exposed to oxidative and inflammatory stimuli and pretreated with leaf and bark extracts. ROS levels, antioxidant enzyme activity (SOD, GPx, CAT), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and inhibition of collagenase, hyaluronidase, and elastase were assessed. Both extracts strongly reduced ROS levels, enhanced SOD activity, and significantly decreased pro-inflammatory cytokines. Bark extract also exhibited potent inhibitory activity against collagenase and elastase. UPLC-DAD-MS analysis revealed that both plant parts contained high levels of tannins; however, the leaf extract showed a more diverse composition, including more complex tannin forms and a significant amount of flavonoids from the quercetin and kaempferol class. In conclusion, H. virginiana leaf and bark extracts demonstrate multifunctional antioxidant and anti-inflammatory properties, supporting their potential use in cosmeceuticals and dermatological formulations targeting skin aging and inflammation. Full article

Background/Objectives: Systemic toxicities to key organs like the heart, liver, and kidneys impair the efficacy of chemotherapy in cancer treatment. These toxicities are caused by oxidative stress, inflammation, mitochondrial malfunction and ferroptosis, causing clinical morbidity and possibly impaired adherence to treatment. This review, also, examines how magnesium, selenium, zinc and vitamin D protect against chemotherapy-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. Methodology: A complete literature search of PubMed (MEDLINE), Scopus, Cochrane Library and Embase was used to synthesize data till 29 June 2025. Studies included randomized and non-randomized trials, cohort studies, case series (≥3 patients), and relevant systematic reviews. To contextualize pathways, preclinical in vivo and in vitro studies were studied independently. Patients undergoing systemic chemotherapy and magnesium, selenium, zinc or vitamin D therapies were eligible. Supplementation’s safety and organ-specific toxicity were investigated. Results: Magnesium protected against cisplatin-induced nephrotoxicity via modulating renal transporters and oxidative defenses across chemotherapy regimens. Selenium supplementation has strong antioxidant and anti-inflammatory characteristics, especially in avoiding cardiac and hepatic injury, although its nephroprotective potential was formulation-dependent. Zinc’s activity was connected to metallothionein-mediated redox stabilization, inflammatory regulation, and cardiac and hepatic resilience. Vitamin D and its analogs reduced cardiotoxicity and nephrotoxicity through mitochondrial preservation and immunomodulatory signaling. Conclusions: To date, magnesium, selenium, zinc, and vitamin D have been shown to reduce chemotherapy-related organ toxicities. Preclinical studies are promising, but randomized clinical trials are needed to prove therapeutic effectiveness and oncologic safety. Full article

Acute inflammation is frequently triggered by pathogen infections and contributes to host mortality. In this study, a new exopolysaccharide (ObEPS) was isolated from the moss endophyte Ovatospora brasiliensis and characterized for its structure and biological activity. Monosaccharide composition analysis revealed that ObEPS was mainly composed of galactose, glucose, mannose, and glucuronic acid. Multi-angle light scattering and conformation analysis showed a molar mass of 10⁵–10⁶ Da and a compact chain conformation. In vitro experiments showed that ObEPS markedly inhibited nitric oxide production and reduced pro-inflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In a systemic Candida albicans infection model, ObEPS combined with fluconazole significantly reduced fungal colony-forming units (CFUs)/g kidney from 3.8 × 10⁵ to 0.1 × 10⁵, with the reduction of pro-inflammatory cytokine levels and tissue damage compared with the EPS-free groups suffering from C. albicans infection. Overall, these findings indicate that ObEPS has potent anti-inflammatory activity and may serve as a promising natural adjunct for mitigating infection-associated inflammatory damage. Full article

Propolis contains abundant flavonoid and phenolic compounds, whose composition and concentration vary significantly in different geographical origins, thereby affecting its bioactive properties including anti-inflammatory, antioxidant, and antimicrobial activities. In this study, the flavonoid and phenolic content in the ethanol extract of propolis (EEP) from Henan (HN) and Shandong (SD) provinces was quantitatively analyzed, and the results showed that concentrations of both bioactive components in HN were slightly higher than those in SD. The non-targeted metabolomics technology was further employed to analyze the components of EEP, and a total of 10683 metabolites were detected. In the comparison between the samples of HN and SD, there were a total of 1436 differential metabolites, with 553 decreased and 883 increased in the HN sample. Among them, there were 205 differential metabolites related to flavonoids and phenols, with 108 decreased and 97 increased in the HN sample. However, a greater number of carboxylic acids and derivatives, fatty derivatives and organooxygen metabolites were found at higher relative levels in the HN sample. As a result, the EEP of the HN sample was selected to investigate its inhibitory effect on inflammation in lipopolysaccharide (LPS)-induced BV2 microglia cells. The results showed that LPS promoted the M1 polarization of BV2 microglia. However, treatment with EEP at concentrations of 10 µg/mL, 5 µg/mL, and 2.5 µg/mL could partially restore the cell morphology to its non-activated state. Meanwhile, LPS stimulation increased the protein levels of IL-1β, IL-6 and TNF-α significantly, as well as the relative gene expression levels of IL-1β, IL-6, TNF-α, COX-2, iNOS and TLR4. After treatment with the EEP, the expression levels of these three proteins and six genes were significantly decreased. These findings revealed that EEP effectively inhibited the M1 polarization of LPS-induced BV2 cells and decreased the expression of inflammatory factors, indicating its potential as a therapeutic agent for neuroinflammation. Full article

Amelanchier Medik. (Rosaceae) is a genus of perennial, deciduous shrubs and trees distributed across temperate and boreal regions of the Northern Hemisphere. Traditionally, Native American communities used fruits, leaves, bark, and roots to treat digestive ailments, fevers, colds, inflammation, and to promote general well-being. Scientific investigation began with molecular studies in 1946 and phytochemical research in 1978, with research activity on some Amelanchier species increasing substantially between 2010 and 2025. Fruits are rich in phenolic compounds—particularly flavonoids and anthocyanins—along with triterpenes, carotenoids, vitamins, and minerals. Pharmacological studies of selected species report antioxidant, anti-inflammatory, anticancer, antidiabetic, antibacterial, and antiviral activities. Despite extensive chemical profiling in several members of the genus, the biological and toxicological properties of Amelanchier remain insufficiently explored, and clinical evidence is lacking. This review synthesizes recent findings on the phytochemistry, medicinal applications, and biological effects of Amelanchier species, linking traditional knowledge with modern research and highlighting priorities for future biomedical investigation. Full article

Ovarian aging is characterized by mitochondrial dysfunction, oxidative stress, and inflammation. The development of adjunctive treatments that mitigate age-related subfertility is warranted. We examined the benefits of nutraceutical supplementation (FE; Fertility Enhancer) with mitochondrial antioxidants, anti-inflammatory agents, metabolic activators, vitamins and minerals, and amino acids on ovarian aging, metabolic activity, and reproductive success in young (Y; 6-month-old) and middle-aged (O; 11-month-old) female C57BL/6J mice. The mice were fed calorie- and macronutrient-matched diets w/wo the FE supplement for three months and harem mated twice. Daily FE supplementation promoted significant body re-composition, including loss of white adipose tissue (gWAT: −36% vs. CON, p < 0.001), gain of skeletal muscle (SkM: +67% vs. CON, p < 0.001), and improved SkM/gWAT ratio (+185% vs. CON, p < 0.001). Metabolic testing showed enhanced fat oxidation (+38%, p < 0.01) and energy expenditure (+7%, p = 0.051) in FE mice. Breeding and immunoblotting data demonstrated improved reproductive success (Y-CON: 44%, Y-FE: 89%, O-CON: 0%, O-FE: 18%) and a modest attenuation of ovarian aging markers in both FE groups. We surmise that a multi-ingredient supplement, such as the Fertility Enhancer, may improve body re-composition, metabolic activity, and markers of ovarian aging, thus enhancing reproductive health and fertility in females. Full article

Chelerythrine (CHE) is the main active component of Chelidonium majus L., possessing excellent antioxidant and anti-inflammatory properties. However, the protective effects of CHE against liver injury and its underlying mechanisms remain unclear. We aimed to investigate the effects of CHE on acute liver injury (ALI) and explore its underlying mechanisms. Mice were orally administered with or without CHE (15 and 30 mg/kg) treatment for 7 days, followed by a single intraperitoneal injection of acetaminophen (APAP, 350 mg/kg). After 24 h, serum, liver, and fecal samples were collected. Then, 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to investigate the protective effects of CHE against ALI. Finally, we elucidated the role of CHE in restoring gut microbiota and metabolic disorders in the context of ALI. The results showed that CHE significantly inhibited ALT and AST levels (p < 0.001). Furthermore, CHE counteracted APAP-induced alterations in IL-6, IL-1β, TNF-α, MPO, MDA, H₂O₂, CAT, SOD, and GSH (p < 0.05). These results indicate that CHE possesses antioxidant properties and inhibits inflammatory factors, thereby protecting the organism from APAP-induced ALI. CHE treatment significantly altered gut microbiota composition, particularly increasing levels of the beneficial bacterium Barnesiella intestinihominis (p < 0.05). In addition, CHE reversed metabolic disturbances and inhibited oxidative and inflammatory signaling pathways. These findings suggest that CHE is a natural hepatoprotective agent that prevents ALI by modulating gut microbiota, related metabolites, oxidative stress, and inflammation. This study provides new insights into CHE as a potential therapeutic approach for ALI. Full article

Undaria pinnatifida fucoidan (UPF), a sulphated polysaccharide derived from brown seaweed, has attracted scientific and clinical interest for its wide-ranging anti-inflammatory and neurodegenerative properties. A growing body of research shows that UPF inhibits NF-κB and MAPK signalling pathways, reduces pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), decreases ROS production, and suppresses iNOS and COX-2 activity, thereby mitigating oxidative and inflammatory damage in vitro. In vivo studies confirm these actions, demonstrating reduced systemic inflammation, promoted antioxidant defence, modulated gut microbiota composition, and improved production of beneficial microbial metabolites. In parallel, emerging evidence highlights UPF’s neuroprotective potential, characterised by protection against neuroinflammation and oxidative stress, the attenuation of amyloid-beta deposition, and improvement in neuronal function. Importantly, low- to medium-molecular-weight and highly sulphated UPF fractions consistently exhibit stronger bioactivities, suggesting a structural basis for its therapeutic potential. This review integrates mechanistic evidence from cellular, preclinical, and emerging clinical studies, highlighting UPF as a versatile marine-derived agent with therapeutic relevance for inflammatory and neurodegenerative diseases, and outlines future research directions toward clinical translation. Full article

Osmanthus fragrans var. aurantiacus Makino is a traditional medicine for treating various diseases, including inflammation. In this study, we discovered the biological features of this plant by assessing antioxidative and anti-inflammatory activities. The GNPS-FBMN approach and in vitro assays guided the identification of active ingredients. As a result, one new compound and 17 other compounds were separated and identified. The structure of the new compound was established by CD spectrum and hydrolysis, followed by HPLC analysis. These compounds demonstrated antioxidative and anti-inflammatory activities. Western blotting clarified the active compound by inhibiting inflammation through COX-2 and iNOS enzymes and blocking the ERK 1/2 MAPK signaling. In silico approaches supported the binding affinity and dynamic features of the established complexes’ target inflammation. Our finding supports evidence from both experimental and in silico approaches that O. fragrans fractions and its constituents may be employed as potential therapeutic phytochemicals for treating inflammatory bowel diseases. Full article

Ketamine, a widely used anesthetic with emerging evidence suggesting neuroprotective and anti-inflammatory properties across various neurological disorders, is recognized for its NMDA receptor antagonism. It has been postulated to play a role in neuroprotection, due to its anti-inflammatory properties, and decrease microglial activation, as well as cytokines TNF and IL-6. Despite its established role, the extent of ketamine’s effects on neuroinflammation and neuroprotection remains to be fully elucidated. Here, we conducted a narrative review synthesizing current knowledge on ketamine’s operating mechanisms, including its modulation of synaptic plasticity, excitotoxicity, and cytokine release, alongside its therapeutic applications in traumatic brain injury, neurodegenerative diseases, psychiatric disorders, and pain management. For this narrative review, we searched the Medline, Embase, Scopus, Web of Science, and PubMed databases. Our findings indicate that ketamine reduces excitotoxicity and inflammation, which may contribute to neuroprotection in acute neurological injuries. These insights underscore ketamine’s potential as an adjunctive neuroprotective agent, warranting further clinical investigation to optimize its therapeutic utility across neurological and psychiatric contexts. Full article

Crohn’s disease is a chronic, idiopathic inflammatory bowel disease characterized by patchy, transmural inflammation that is influenced by genetic, environmental, and microbial factors. The NOD2 pathway mediates NFκB activation and pro-inflammatory cytokine production. In the SHIP–/– murine model of Crohn’s disease-like ileitis, macrophage-derived IL-1β production drives intestinal inflammation. SHIP reduces NOD2 signaling by preventing downstream interaction between RIPK2 and XIAP, leading us to hypothesize that blocking RIPK2 in SHIP–/– mice would ameliorate intestinal inflammation. We examined the effects of RIPK2 inhibition on pro-inflammatory cytokine production in SHIP+/+ and SHIP–/– macrophages and in mice, using the RIPK2 inhibitor, GSK2983559. We found that GSK2983559 blocked RIPK2 activation in SHIP+/+ and SHIP–/– bone marrow-derived macrophages (BMDMs), and reduced Il1b transcription and IL-1β production in (MDP+LPS)-stimulated SHIP–/– BMDMs. Despite the reduction of IL-1β production in BMDMs, in vivo treatment with GSK2983559 worsened intestinal inflammation and increased IL-1β concentrations in the ileal tissues of SHIP–/– mice. GSK2983559 only modestly reduced IL-1β in (MDP+LPS)-stimulated SHIP–/– peritoneal macrophages, and did not suppress pro-inflammatory cytokine production in response to TLR ligands in peritoneal macrophages from either SHIP+/+ or SHIP–/– mice. Taken together, our data suggest that although RIPK2 inhibition can block IL-1β production by (MDP+LPS)-stimulated macrophages in vitro, it is not an effective anti-inflammatory strategy in vivo, highlighting the limitations of targeting RIPK2 to treat intestinal inflammation in the context of SHIP deficiency. Full article