Reactive Oxygen Species Scavenger Research Articles

Orally Administered ZnxCeyO2/Se Hydrogel with Effective Antioxidant Activity for Treating Inflammatory Bowel Disease by Inhibiting Ferroptosis.

Oxidative stress leads to intestinal barrier damage, which induces immune responses to occur and further promotes oxidative stress exacerbating inflammatory bowel disease (IBD). In this work, the multifunctional ZnxCeyO2/Se (ZCSO) nanozyme wrapped with acid-resistant calcium alginate hydrogel designed for oral administration is prepared. The ZCSO nanozyme can promote the activation of the Nrf2 oxidative stress pathway, then significantly improve the efficiency of scavenging reactive oxygen species (ROS) and up-regulate the protein expression of glutathione peroxidase 4 (GPx4), which is closely related to the inhibition of ferroptosis. In addition, the ZCSO nanozyme inhibiting the growth of some pathogenic bacteria proliferating due to oxidative stress shows a positive regulation of the intestinal flora and reduces the secretion of pro-inflammatory factors and the levels of inflammatory macrophages, achieving the significant preventive and delayed therapeutic effect of colitis mice. Consequently, the distinctive properties of ZCSO nanozyme render it a promising candidate for the treatment of IBD by effectively scavenging ROS, thereby interrupting the detrimental cycle between oxidative stress and immune response, ultimately promoting the proliferation of epithelial cells to reestablish the integrity of the intestinal mucosal barrier.

Ethylene-Mediated RsCBF2 and RsERF18 Enhance Salt Tolerance by Directly Regulating Aquaporin Gene RsPIP2-1 in Radish (Raphanus sativus L.).

Salt stress is a major environmental factor limiting the production and quality of plants worldwide. Radish (Raphanus sativus L.), one of the most important root crops, is susceptible to salt stress worldwide. Plasma membrane intrinsic proteins (PIPs) have been identified to play a crucial role in regulating plants' salt tolerance. However, the underlying molecular regulatory mechanisms involved in salt stress tolerance are largely unknown. Here, a salt-induced water transport gene RsPIP2-1 associated with the regulatory mechanisms in response to salt stress was clarified in radish. Overexpression of RsPIP2-1 had high-water channel and H2O2 transport activity in Xenopus laevis oocytes and yeast, and it also conferred prominently salt tolerance through promoting reactive oxygen species (ROS) scavenging and enhancing antioxidant enzyme activity in transgenic radish. Moreover, yeast one-hybrid (Y1H) was used to screen the upstream regulators of RsPIP2-1, and two ethylene-responsive transcription factors including RsCBF2 and RsERF18 were identified. Y1H, dual-luciferase assay (DLA) and electrophoretic mobility shift assays (EMSA) showed that these two genes could active the transcription of RsPIP2-1 by directly binding to the DRE/CRT element and GCC-box element in its promoter. In addition, the salt tolerance and the expression levels of these two transcription factors could be significantly upregulated when treated with exogenous application of an ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), while the plants' resistance as well as the expression patterns could be reduced when exposure to the inhibitor of ethylene action (AgNO3), suggesting that RsCBF2 and RsERF18 positively regulated the salt tolerance in a manner of dependent on ethylene synthesis pathway. Taken together, these findings uncover a novel transcriptional regulatory module based on the RsCBF2/RsERF18-RsPIP2-1 underlying salt tolerance in radish and could provide new insights into the salt-tolerant vegetable crop breeding programs.

Synergistic Effect of ROS and p38 MAPK in Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.

The adverse effects of titanium dioxide nanoparticles (TiO2 NPs) on the integrity of the blood-testis barrier (BTB) are widely recognized. However, the underlying mechanisms remain incompletely understood. The integrity of the BTB is imperative for the preservation of male reproductive health. TM4 cells, which are major component of the BTB, play a critical role in its integrity. The apoptosis of TM4 cells is closely associated with the disruption of the BTB. Therefore, we selected TM4 cells as experimental models to investigate the apoptosis induced by TiO2 NPs and the underlying mechanisms. Cell viability, excessive production of reactive oxygen species (ROS), activation of p38 mitogen-activated protein kinase (MAPK) pathway, and apoptosis-related protein expression levels were determined under various concentrations (50, 100, 150, and 200 μg/mL) of TiO2 NPs exposure. The results indicate that TiO2 NPs induced the overproduction of ROS and activated the p38 MAPK signaling pathway, which subsequently led to apoptosis. The ROS scavenger N-acetylcysteine (NAC) was able to suppress the activation of p38 MAPK pathway induced by TiO2 NPs, while the p38 MAPK inhibitor SB203580 mitigated TiO2 NPs-induced ROS overproduction and subsequent apoptosis, suggesting an interplay between ROS overproduction and p38 MAPK pathway activation. In summary, TiO2 NPs induced mitochondrial apoptosis via the ROS-p38 MAPK axis. A positive feedback regulatory mechanism exists between the two processes, promoting apoptosis in TM4 cells through a synergistic effect.

Hydrogel Containing Bismuth Molybdate Nanosheets with Piezoelectricity and Nanoenzyme Activity for Promoting Osteoblast Responses.

The development of piezoelectric biomaterials with the capability to produce electrical signals and scavenge reactive oxygen species (ROS) is a novel strategy for stimulating osteoblast responses and promoting bone regeneration. Herein, tungsten (W), iridium (Ir), and ruthenium (Ru) codoped bismuth molybdate (4(W/Ru/Ir)-BMO) nanosheets with improved piezoelectricity and enzyme-like (CAT-like and SOD-like) activities were constructed by using the hydrothermal method. A composite hydrogel of oxidized sodium alginate/gelatin (OSA/GEL) and 4(W/Ru/Ir)-BMO (OSA/GEL/4-B) was also prepared. Due to the presence of 4(W/Ru/Ir)-BMO, OSA/GEL/4-B exhibited not only piezoelectricity but also enzyme-like activities. Under ultrasound (US), OSA/GEL/4-B generated electrical signals that significantly promoted the proliferation and osteogenic differentiation of bone marrow stromal cells. Furthermore, the piezoelectric effect of OSA/GEL/4-B improved the CAT-like (production of oxygen) and SOD-like (scavenger of ROS) activities. The improved piezoelectricity of 4(W/Ru/Ir)-BMO was attributed to the codoping of W, Ir, and Ru ions, which resulted in lattice distortion and enhanced crystal asymmetry, which produced electrical signals for regulating the osteogenic microenvironment. Moreover, the improvement of enzyme-like activities was attributed to the enhanced piezoelectric effect by the codoping of W, Ir, and Ru ions, which generated a piezoelectric field triggered by US that accelerated electron transfer for alleviating cellular oxidative stress and provided an antioxidant microenvironment for osteoblast responses. This piezoelectric hydrogel may provide a novel pathway for promoting osteogenic differentiation and bone regeneration.

OsHDAC1 deacetylates the aldehyde dehydrogenase OsALDH2B1, repressing OsGR3 and decreasing salt tolerance in rice.

Salt stress poses a significant challenge to the growth and productivity of rice (Oryza sativa L.). Histone deacetylases (HDACs) play a vital role in modulating responses to various abiotic stresses. However, how OsHDAC1 responds to salt stress remains largely unknown. Here, we report that OsHDAC1 decreases salt tolerance in rice through post-translational modification of metabolic enzymes. Specifically, the rice OsHDAC1 RNAi lines exhibited enhanced resilience to salt stress, while plants overexpressing OsHDAC1 were notably more sensitive. OsHDAC1 interacts with the aldehyde dehydrogenase (ALDH) OsALDH2B1 and deacetylates it at K311 and K531, triggering ubiquitin-proteasome-mediated degradation of OsALDH2B1. OsALDH2B1 can directly target OsGR3, which encodes a type of glutathione reductase critical for reactive oxygen species (ROS) scavenging. Compared with wild-type plants, OsALDH2B1-overexpressing plants exhibited higher OsGR3 expression levels and increased salt resistance, whereas OsALDH2B1 RNAi lines showed reduced OsGR3 expression and lower salt resistance. Collectively, our data suggest that salt stress down-regulates OsHDAC1, resulting in an increase in the acetylation level of OsALDH2B1, which in turn stabilizes OsALDH2B1 and promotes its activity in the regulation of OsGR3 transcription. This OsHDAC1/OsALDH2B1/OsGR3 regulatory module represents an alternative pathway for governing salt stress adaptation in rice.

Lion’s Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential—A Narrative Review

Hericium erinaceus, commonly known as lion’s mane mushroom, has gained increasing scientific interest due to its rich composition of bioactive compounds and diverse health-promoting properties. This narrative review provides a comprehensive overview of the nutritional and therapeutic potential of H. erinaceus, with a particular focus on its anti-inflammatory, antioxidant, and antimicrobial activities. A structured literature search was performed using databases such as PubMed, Scopus, Science Direct, Web of Science, Science Direct, and Google Scholar. Studies published in the last two decades focusing on H. erinaceus’ bioactive compounds were included. The chemical composition of H. erinaceus includes polysaccharides, terpenoids (hericenones and erinacines), and phenolic compounds, which exhibit potent antioxidant effects by scavenging reactive oxygen species (ROS) and inducing endogenous antioxidant enzymes. Additionally, H. erinaceus shows promising antimicrobial activity against bacterial and fungal pathogens, with potential applications in combating antibiotic-resistant infections. The mushroom’s capacity to stimulate nerve growth factor (NGF) synthesis has highlighted its potential in preventing and managing neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Advances in biotechnological methods, including optimized cultivation techniques and novel extraction methods, may further enhance the bioavailability and pharmacological effects of H. erinaceus. Despite promising findings, clinical validation remains limited. Future research should prioritize large-scale clinical trials, the standardization of extraction methods, and the elucidation of pharmacokinetics to facilitate its integration into evidence-based medicine. The potential of H. erinaceus as a functional food, nutraceutical, and adjunct therapeutic agent highlights the need for interdisciplinary collaboration between researchers, clinicians, and regulatory bodies.

Self-disassembling nanoparticles as oral nanotherapeutics targeting intestinal microenvironment

Inspired by the survival strategies of pyomelanin-producing microbes, we synthesize pyomelanin nanoparticles (PMNPs) from homogentisic acid- γ-lactone via auto-oxidation and investigate their biomedical potential. PMNPs possess distinct physicochemical properties, including reactive oxygen species scavenging and microenvironment-responsive self-disassembly. Under intestinal conditions, PMNPs self-disassemble and penetrate the nanoscale pores of the mucin layer. In an inflammatory bowel disease model, orally administered PMNPs withstand gastric acidity and, in their solubilized form, interact with macrophages and epithelial cells. They significantly reduce reactive oxygen species levels, exert anti-inflammatory effects, and restore gut microbiota composition. Compared to conventional nanoparticles and 5-aminosalicylic acid, PMNPs exhibit greater therapeutic efficacy. Clinical symptoms and intestinal inflammation are alleviated, and the gut microbiota is restored to near-normal levels. These findings underscore the therapeutic potential of PMNPs for inflammatory bowel disease treatment and suggest broader biomedical applications.

A Versatile Immune Protective Armor to Enhance the Regenerative Potential of Exogenous Stem Cells.

Host immune rejection has long been recognized as a major contributor to the poor survival rates of exogenous stem cells (ESCs). In this study, we present a simple and versatile strategy to protect ESCs from host immune system insults by developing a protective "armor." This armor was designed using tannic acid (TA), leveraging its strong affinity for biomacromolecules and its anti-inflammatory properties. Prior to implantation, the armor can be readily applied to the surface of individual ESCs, cell aggregates, cell sheets, or cell-laden hydrogel systems by simply immersing them in a TA solution for several seconds, without additional processing steps. The TA-based armor effectively modulates the acute inflammatory response during the initial days postimplantation by scavenging reactive oxygen species (ROS), thereby creating an ESCs-friendly immune microenvironment. This was evidenced by reduction in the infiltration of pro-inflammatory immune cells and the secretion of pro-inflammatory cytokines. Consequently, the survival of engrafted ESCs was significantly enhanced, with preserved stemness and immunomodulatory functions. The regenerative potential of ESCs was further demonstrated in a rat periodontal defect model. These findings provide a novel approach for enhancing the regenerative performance of ESCs and offer a straightforward and versatile strategy to shield ESCs from host immune rejection.

Tissue-Adhesive, Antibacterial, and Antioxidant Hydrogel Sealant for Sealing Colorectal Anastomotic Leakage and Preventing Postoperative Adhesion.

Surgical treatment of colorectal diseases typically involves excising the diseased portion of the bowel and anastomosing the remaining sections to reestablish continuity. Surgical suturing has limitations in preventing anastomotic leakage and postoperative adhesion. To address these challenges, a tissue-adhesive, antibacterial, and antioxidant hydrogel is designed to cover and seal colorectal anastomotic wounds. The hydrogel is formed in situ by simply mixing oxidized hyaluronic acid, adipic acid dihydrazide-modified hyaluronic acid, ε-poly-l-lysine, and tannic acid. The hydrogel exhibits a rapid gelation rate and self-healing ability. Compared with commercial fibrin glue, the hydrogel has superior tissue-adhesive strength and wound sealing performance. The hydrogel displays potent reactive oxygen species scavenging ability and antibacterial activity against both Gram-positive and Gram-negative bacteria. The hydrogel also exhibits good biodegradation and biocompatibility. In a cecum-abdominal wall adhesion model in rats, the hydrogel attaches firmly to the injured tissues and serves as a physical barrier to prevent adhesion formation. In anastomotic leakage models after colon resection in rats and rabbits, the hydrogel effectively seals the anastomotic leakage, prevents postoperative adhesion, and promotes anastomotic healing. Thus, this multifunctional hydrogel has strong clinical potential for preventing anastomotic leakage and adhesion formation after colorectal surgery.

Zn‐DHM Nanozymes Enhance Muscle Regeneration Through ROS Scavenging and Macrophage Polarization in Volumetric Muscle Loss Revealed by Single‐Cell Profiling

Abstract Volumetric muscle loss (VML) is a severe condition in which the loss of skeletal muscle surpasses the body's intrinsic repair capabilities, leading to irreversible functional deficits and potential disability, with persistent inflammation and impaired myogenic differentiation. To address these challenges, a novel zinc‐dihydromyricetin (Zn‐DHM) nanozyme with superoxide dismutase (SOD)‐like activity is developed, designed to neutralize excessive reactive oxygen species (ROS) and restore oxidative balance. Zn‐DHM mitigates oxidative stress and promotes polarization of macrophages from the proinflammatory M1 phenotype to the anti‐inflammatory M2 phenotype, thereby reducing chronic inflammation and creating a conducive environment for muscle repair. Further, Zn‐DHM significantly enhances the myogenic differentiation of C2C12 cells, accelerating wound healing processes. These studies confirm the biosafety and low toxicity of Zn‐DHM. As per a murine tibialis anterior VML model, Zn‐DHM effectively suppresses inflammation and markedly improves skeletal muscle repair outcomes. Single‐cell RNA sequencing reveals that Zn‐DHM treatment increases the expression of M2 macrophage markers and enhances the proliferation and differentiation capacity of muscle stem cells (MuSCs). In addition, intercellular communication analysis reveals interactions between MuSCs and macrophages in the Zn‐DHM treatment group, suggesting that these interactions may drive tissue regeneration through the activation of the GAS and Notch signaling pathways.

Engineered Exudate Trap with Programmable Enrichment and Force‐Controlled Therapy Pump toward Diabetic Burn Personalized Treatment

AbstractPersonalized treatment is an effective approach that provides customized therapeutic regimens. However, existing personalized treatment strategies often require complex designs, which are challenging to implement and susceptible to failure. By virtue of the widespread mechanical environment in the human body, a force‐controlled therapy pump is reported for controlled release and individualized therapy. Similar to a fish trap, the pump is composed of a hydrophobic trammel film with random microfibers, a hydrophobic cover film with aligned microfibers, and an inner hydrophilic sponge loaded with bletilla striata polysaccharide‐confined nano cerium oxide (BCe). BCe possesses excellent reactive oxygen species (ROS) scavenging ability (, H2O2, and ·OH) due to the small cerium oxide particle size (2.6 ± 0.8 nm) and high Ce3+ ratio (66.19%). The trap programmatically enriches exudate and enables force‐controlled release of BCe through massage (0.1–1.38 N), achieving personalized treatment as a therapy pump. The inflammatory phase is shortened by blocking TNF and NF‐κB signaling pathways, while activating the PI3K‐AKT signaling pathway associated with cell migration and angiogenesis. The healing rate of diabetic burn wounds (92.3%) surpasses that of the commercial drug. This strategy is suitable for treatments in mechanically induced environments, offering a reference for personalized medicine.

Zearalenone Depresses Lactation Capacity Through the ROS-Mediated PI3K/AKT Pathway.

The effects of zearalenone (ZEA), a fungal toxin in food and feed, remain unclear on the mammary gland and lactation. This study examines ZEA-induced damage in lactating mice and bovine mammary epithelial cells (MAC-T), focusing on the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in regulating cell proliferation and apoptosis. The results demonstrated that exposure to ZEA at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg) reduced lactation in female mice and slowed weight gain in their offspring. Hematoxylin and eosin (HE) staining and CSNK immunofluorescence staining of mammary tissue confirmed ZEA-induced mammary gland damage in vivo. Further analysis using PCNA immunohistochemistry and fluorescent TUNEL staining revealed that ZEA promoted apoptosis and decreased the proliferative capacity of mammary tissues. In vitro, 20 μM ZEA decreased MAC-T cell proliferation, increased apoptosis and oxidative stress, inhibited PI3K/AKT signaling, and decreased κ-casein (CSNK) expression. Pretreatment with a reactive oxygen species (ROS) scavenger (NAC) or PI3K/AKT activator (740-Y-P) reversed these effects, with NAC specifically restoring PI3K/AKT activity inhibited by ZEA. Overall, this study concludes that ZEA induces MAC-T cell apoptosis and disrupts proliferation via the ROS-mediated PI3K/AKT pathway, ultimately impairing lactation function. These findings highlight potential targets for managing ZEA contamination in food and its impact on lactation.

Development of Akkermansia Muciniphila Membrane‐Coated Mesoporous Silica Nanoparticles with a Cerium Oxide Core for Inflammatory Bowel Disease Treatment

AbstractWhile convenient for patient compliance, the efficacy of oral treatments for inflammatory bowel disease (IBD) is often compromised by the dynamic and harsh chemical environment of the gastrointestinal tract, presenting challenges for effective therapeutic management. The pathological complexity of IBD frequently involves multiple factors such as oxidative stress, immune dysregulation, gut microbiome abnormality, and inadequate drug bioavailability, among others. To address these challenges, this project develops an oral nanomedicine platform based on mesoporous silica nanoparticles with a cerium oxide core, further coated with an outer membrane (OM) derived from Akkermansia muciniphila (Akk), a beneficial bacteria naturally present in the human gut. This novel nanocomplex, termed “OM‐CeMeso,” is evaluated for its enhanced stability, reactive oxygen species (ROS) scavenging capacity, and ability to restore microbiota homeostasis. This project demonstrates that the silica‐based nanomaterials’ acid‐resistant yet base‐degradable properties significantly improved stability in a murine IBD model. The incorporation of cerium oxide nanoparticles (CeO2 NPs) added further benefits by enhancing ROS scavenging. Notably, the Akk‐derived OM coat also increases the diversity and abundance of beneficial gut microbiota. These complementary and integrated functions lead to significant symptom alleviation in murine IBD models while avoiding any unwanted toxicity.

Aging Impairs Implant Osseointegration Through a Novel Reactive Oxygen Species-Hypoxia-Inducible Factor 1α/p53 Axis.

Enhancing bone-vessel coupling to form high-quality vascular-rich peri-implant bone is crucial for improving implant prognosis in elder patients. Notably, hypoxia-inducible factor 1α (HIF1α) is known to promote osteogenesis-angiogenesis coupling; however, this effect remains to be investigated in aged bone owing to the dual effect of HIF1α in different aged organs. In this study, HIF1α inhibitor or activator was applied to aged mice and their bone mesenchymal stem cells (BMSCs) to investigate the effects and inner mechanism of HIF1α on the peri-implant osteogenesis and angiogenesis in senescent status. Cell senescence, along with osteogenic and angiogenic abilities of aged BMSCs, was detected, respectively. Meanwhile, a femur implant implantation model was constructed on aged mice, and the bone-vessel coupling of peri-implant bone was observed. Mandibular bone morphology was also detected to further provide evidence for clinical oral implantation. Furthermore, p53 expression was examined invivo and in vitro following HIF1α intervention. A reactive oxygen species (ROS) scavenger was also adopted to further investigate the roles of ROS in the HIF1α-p53 axis. Results showed that the suppression of HIF1α alleviated senescence and osteogenesis-angiogenesis coupling of aged BMSCs, while its activation aggravated these effects. The mandible phenotype and bone-vessel coupling in aged peri-implant bone also changed accordingly upon regulation of HIF1α. Mechanistically, p53 changed in the same direction as HIF1α invivo and in vitro. Moreover, the ROS scavenger reversed the HIF1α-p53 relationship and weakened the effect of HIF1α inhibitor on peri-implant bone improvement. In conclusion, in aged mice, highly expressed HIF1α impaired peri-implant bone-vessel coupling and implant osseointegration through p53, and accumulated ROS was a prerequisite for HIF1α to positively regulate p53. These findings provide new insights into the role of HIF1α and the ROS-HIF1α/p53 signaling axis, offering potential therapeutic targets to improve implant outcomes in elderly patients.

Coriander-Derived Exosome-Like Nanovesicles Laden Hydrogel with Antioxidant Property Accelerates Wound Healing.

The oxidative balance and inflammatory responses play important roles in wound healing. Plant-derived exosome-like nanovesicles exhibit antioxidant or anti-inflammatory properties. However, their effects and underlying molecular mechanisms of action in wound healing remain unclear. Herein, coriander-derived exosome-like nanovesicles (CDENs) are isolated and characterized. It is found that the CDENs can be internalized by HaCaT cells and mouse skin tissue, promoting cell migration, scavenging reactive oxygen species (ROS) by increasing the expression of antioxidant enzymes, and effectively relieving inflammation. Furthermore, it designs a CDENs-based hydrogel with a sustained CDENs-release effect and excellent biocompatibility, and explored its potential for use in wound healing in vivo. During the different phases of wound healing, CDENs-hydrogel facilitated macrophage M2 polarization in the inflammation phase, promoted angiogenesis in the proliferation phase, and expedited collagen deposition in the remodeling phase. Mechanistically, through releasing CDENs, CDENs-hydrogel activated Nrf2 signaling pathway, which enhanced the antioxidant enzyme defense system and reduced the inflammatory response, ultimately accelerated wound healing process. This is the first report that CDENs-hydrogel holds great promise as a safe and effective alternative for clinical wound management.

Engineering dual-driven pro-angiogenic nanozyme based on porous silicon for synergistic acceleration of burn infected wound healing.

Engineering dual-driven pro-angiogenic nanozyme based on porous silicon for synergistic acceleration of burn infected wound healing.

Engineered silk fibroin bio-hybrid artificial graft with releasing biological gas for enhanced circulatory stability and surgical performance.

Engineered silk fibroin bio-hybrid artificial graft with releasing biological gas for enhanced circulatory stability and surgical performance.

The MYB transcription factor TaMYB30 enhances wheat resistance to sharp eyespot disease by scavenging ROS accumulation.

The MYB transcription factor TaMYB30 enhances wheat resistance to sharp eyespot disease by scavenging ROS accumulation.

Lutein-loaded multifunctional hydrogel dressing based on carboxymethyl chitosan for chronic wound healing.

Lutein-loaded multifunctional hydrogel dressing based on carboxymethyl chitosan for chronic wound healing.

Oral administration of Momordica charantia-derived extracellular vesicles alleviates ulcerative colitis through comprehensive renovation of the intestinal microenvironment

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease (IBD), accompanied by intense inflammation, oxidative stress, and intestinal microbiota dysbiosis. Current treatments using chemotherapeutic drugs or immunosuppressants have limited effectiveness and side effects. Therefore, the development of safe, effective, and multi-targeting therapies for IBD is of great importance. Momordica charantia exhibits antioxidant, anti-inflammatory, and intestinal microbiota-regulating properties, suggesting that Momordica charantia-derived extracellular vesicles (MCEVs) have the potential for UC management.ResultsWe extracted MCEVs using differential centrifugation and density gradient centrifugation. The results showed that MCEVs possessed high purity, even particle size, and excellent stability. In vitro, MCEVs were shown to inhibit macrophage inflammatory responses, scavenge reactive oxygen species (ROS), and protect cells from oxidative damage. Transcriptomics analysis revealed that MCEVs may alleviate mitochondria-dependent apoptosis by safeguarding the integrity of the mitochondrial structure and regulating the expression of apoptosis-related proteins. Furthermore, all components of MCEVs contributed to their pharmacological activity. In vivo, MCEVs had better retention in the inflamed colon and significantly alleviated UC through a comprehensive renovation of the intestinal microenvironment.ConclusionThese findings suggested that MCEVs own considerable potential as natural nanotherapeutics for UC treatment.Graphical abstract