Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung disorders associated with high morbidity and mortality. Dysregulation of the renin–angiotensin system (RAS) and proinflammatory pathways play an indispensable role in ALI progression. Aim This study aimed to investigate the protective potential of nobiletin (NOB) in mitigating ALI and hyperinflammatory lung injury. Material and Methods The study enrolled 32 male albino rats allocated into four groups: (Control, NOB, lipopolysaccharide [LPS], and NOB + LPS groups). Rats received NOB 20 mg/kg by oral gavage for 1 week; on the seventh day, a single dose of 15 mg/kg LPS was given by intranasal instillation. After 24 h of LPS administration, plasma and lung tissue samples were analyzed for inflammatory cytokines, mitochondrial complex‐I, oxidative stress markers, and molecular signaling pathways. Results NOB administration significantly downregulated miR‐200 expression, associated with ACE2 activation and attenuated AT1R‐mediated inflammatory responses. It also decreased NF‐κB and p38 MAPK signaling, reducing pulmonary and systemic levels of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), granulocyte monocyte‐colony stimulating factor (GM‐CSF), and interleukin‐17A (IL‐17A). Additionally, NOB improved the high mobility group box 1 (HMGB1)/NF‐κB/mammalian target of rapamycin (mTOR) pathway, and increased mitochondrial complex‐I may be consistent with improved tissue preservation. Conclusion NOB exerts protective effects against ALI by improving inflammatory cytokine, oxidative stress, miRNA‐200, mitochondrial complex‐I, and ACE2, highlighting its potential as a protective candidate for ALI and hyperinflammatory‐associated lung injury.
As medicinal plants offer promising alternatives to synthetic drugs, this study explored the ex vivo antioxidant and in vitro anti‐inflammatory capacities of Pithecellobium dulce leaf extracts, alongside the in vivo anti‐inflammatory potential of its bioactive flavonoid, afzelin, using experimental and computational approaches. In erythrocytes, 2,2 ′ ‐azobis(2‐amidinopropane)dihydrochloride (AAPH) induced a time‐dependent increase in hemolysis, malondialdehyde (MDA) formation, and depletion of cytosolic glutathione (GSH) and superoxide dismutase (SOD). The chloroform fraction (CHF) and ethyl acetate fraction (EAF) mitigated hemolysis and lipid peroxidation, enhanced GSH and SOD levels, lowered MDA levels compared with the AAPH group, and also protected P UC19 plasmid DNA from oxidative damage. In anti‐inflammatory assays, EAF and CHF inhibited heat‐induced red blood cell (RBC) lysis by 57.31% ± 0.80% and 51.39% ± 0.27% and egg albumin denaturation by 39.74% ± 0.77% and 37.20% ± 2.16%, respectively, compared with 61.52% ± 0.58% for acetylsalicylic acid. Afzelin (50 mg/kg body weight) reduced carrageenan‐induced paw edema by 56.16%, versus 70.83% for diclofenac sodium. Bioinformatics analysis identified 38 potential anti‐inflammatory protein targets of afzelin, of which 11 were further examined via molecular docking. Docking results revealed favorable binding energies for all targets, with the highest affinity observed for JAK3 (−9.60 kcal/mol) compared to native ligands. These computational results suggest that afzelin can form stable, energetically favorable interactions with multiple key proinflammatory proteins. Overall, these findings indicate that P. dulce leaf extracts possess significant antioxidant and anti‐inflammatory activities, and afzelin showed predicted interactions with multiple kinase and nonkinase inflammation‐associated proteins.
Background Monounsaturated fatty acid (MUFA) metabolism promotes cancer progression and survival by regulating membrane lipid composition, maintaining lipid homeostasis and preserving redox balance. A growing body of evidence indicates that altered MUFA metabolism promotes tumour growth while protecting cancer cells from ferroptosis. Aim This review summarises current knowledge on the contributions of MUFA metabolism to carcinogenesis, regulation of ferroptosis and treatment response across different cancers. Further, we discussed the emerging treatment strategies targeting MUFA metabolic pathways. Methods Relevant experimental and clinical studies investigating MUFA metabolism, lipid metabolic reprogramming, ferroptosis and therapeutic interventions in cancer were comprehensively reviewed and critically analysed. Results Enhanced de novo MUFA synthesis and incorporation into membrane phospholipids increase the MUFA‐to‐polyunsaturated fatty acid (PUFA) ratio, thereby reducing the availability of oxidation‐prone PUFAs, limiting lipid peroxidation, and protecting cancer cells from ferroptosis. MUFA‐driven membrane remodelling enhances membrane fluidity and activates oncogenic signalling pathways, including epithelial‐mesenchymal transition (EMT), cancer cell migration, invasion and metastasis. These effects are mediated by the dysregulated expression of key lipogenic enzymes and signalling pathways that reprogramme lipid metabolism to meet the metabolic demands of cancer cells. Multiple studies have shown that MUFA metabolism is a promising therapeutic target. Furthermore, the inhibition of stearoyl‐CoA desaturase‐1 (SCD1) and fatty acid synthase (FASN), key enzymes in MUFA metabolism, sensitises cancer cells to ferroptosis by enhancing lipid peroxidation. Conclusion MUFA metabolism is a key regulator of cancer progression and ferroptosis resistance. Targeting MUFA metabolic pathways is a promising therapeutic strategy. However, mechanistic studies are required to elucidate the molecular mechanisms underlying sensitivity to ferroptosis and to optimise clinical applications.
Alzheimer’s disease (AD) is a major global health challenge characterized by cognitive decline and neuronal degeneration driven by amyloid‐β (Aβ) aggregation and oxidative stress. Given the limited efficacy and adverse effects of current pharmacological therapies, food‐derived bioactive compounds have gained increasing attention as potential preventive strategies against neurodegenerative disorders. In this study, we investigated the neuroprotective effects of Holothuria leucospilota extracts using a transgenic Caenorhabditis elegans model of AD. Our results demonstrated that H. leucospilota hexane extract (HLHE) at 500 µg/mL significantly delayed Aβ‐induced paralysis and improved chemotaxis behavior. Consistently, HLHE treatment reduced Aβ deposition and decreased both high‐ and low‐molecular weights of Aβ oligomers, as determined by automated Western blot analysis. Additionally, HLHE also reduced reactive oxygen species (ROS) levels. Transcriptomic and RT‐qPCR analyses revealed that HLHE enhanced autophagic activity through the upregulation of bec-1 (autophagy initiation) and lysosomal genes ( cpr-1 , cpr-2 , and cpr-5 ). Furthermore, HLHE activated antioxidant defense pathways via the insulin/IGF‐1 signaling (IIS) axis, specifically upregulating genes associated with SKN‐1 pathway ( pmk-1 , skn-1 , gst-4 , and gst-10 ) and HSF‐1 pathway ( hsf-1 , hsp-16.1 , hsp-12.6 , and mtl-1 ). HLHE also promoted nuclear localization of SKN‐1 and increased expression of its downstream target gst-4 . Chemical analysis revealed that HLHE contained arachidonic acid (21.12%) and other bioactive lipid compounds as major constituents, suggesting a synergistic role in promoting autophagy and antioxidant responses. Collectively, this study suggests that HLHE confers neuroprotection against Aβ‐induced toxicity by activating autophagy and oxidative stress defense mechanisms, supporting its potential development as a food‐derived preventive or therapeutic agent for AD.
