Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 501 - 501

Published: Feb. 23, 2024

Stroke is a major contributor to global mortality and disability. While reperfusion essential for preventing neuronal death in the penumbra, it also triggers cerebral ischemia-reperfusion injury, paradoxical injury primarily caused by oxidative stress, inflammation, blood–brain barrier disruption. An burst inflicts marked cellular damage, ranging from alterations mitochondrial function lipid peroxidation activation of intricate signalling pathways that can even lead cell death. Thus, given pivotal role stress mechanisms reinforcement antioxidant defence system has been proposed as protective approach. Although this strategy proven be successful experimental models, its translation into clinical practice yielded inconsistent results. However, should considered availability numerous molecules with wide range chemical properties affect extent injury; several groups molecules, including polyphenols, carotenoids, vitamins, among other compounds, mitigate damage intervening multiple at various stages. Multiple trials have previously conducted evaluate these using melatonin, acetyl-L-carnitine, chrysanthemum extract, edaravone dexborneol, saffron, coenzyme Q10, oleoylethanolamide, treatments. Therefore, multi-antioxidant therapy emerges promising novel therapeutic option due potential synergistic effect provided simultaneous roles individual compounds.

Language: Английский

---

Quercetin, a natural flavonoid, protects against hepatic ischemia–reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Hepatic ischemia–reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes the pathogenesis of by promoting inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in immunity cells protected from injury. However, search inhibitors continues. This study aims evaluate whether quercetin, natural flavonoid, can inhibit mitigate IRI. established murine model cellular efficacy quercetin. Quercetin effectively alleviated IRI-induced tissue necrosis inflammation. found during IRI, cleavage GSDMD occurred macrophages, but not other non-parenchymal cells. inhibited macrophages. Moreover, we quercetin blocked ASC assembly formation NLRP3 inflammasomes AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed interaction between Caspase-8, which mechanism complex inflammasome formation. Overexpression Caspase-8 abolished anti-pyroptosis effect signaling. Furthermore, hepatoprotective activity was reduced myelocytic GSDMD-deficient mice. Our findings suggest has beneficial effects on could attenuate target inhibition via Caspase-8/ASC interaction. recommend might serve as targeted approach prevention personalized treatment perioperative patients.

Language: Английский

---

Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway

Inflammation, Journal Year: 2024, Volume and Issue: 47(5), P. 1616 - 1633

Published: Feb. 27, 2024

Language: Английский

---

Polyphyllin I alleviates neuroinflammation after cerebral ischemia–reperfusion injury via facilitating autophagy-mediated M2 microglial polarization

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: May 14, 2024

Abstract Microglial activation and polarization play a central role in poststroke inflammation neuronal damage. Modulating microglial from pro-inflammatory to anti-inflammatory phenotype is promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), steroidal saponin, shows multiple bioactivities various diseases, but potential function PPI ischemia not elucidated yet. In our study, influence on ischemia–reperfusion injury was evaluated. Mouse middle artery occlusion (MCAO) model oxygen–glucose deprivation reoxygenation (OGD/R) were constructed mimic vivo vitro. TTC staining, TUNEL RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test foot-fault open-field Morris water maze performed study. We found that alleviated neuroinflammation, improved functional recovery mice after MCAO. modulated towards M2 MCAO post OGD/R Besides, promoted autophagy via suppressing Akt/mTOR signaling microglia, while inhibition abrogated effect OGD/R. Furthermore, facilitated autophagy-mediated ROS clearance inhibit NLRP3 inflammasome reactivation by nigericin abolished microglia polarization. conclusion, post-stroke neuroinflammation tissue damage increasing Our data suggested had ischemic stroke treatment.

Language: Английский

---

Extracellular Matrix-Mimicking Hydrogel with Angiogenic and Immunomodulatory Properties Accelerates Healing of Diabetic Wounds by Promoting Autophagy

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

The management of diabetic wounds faces significant challenges due to the excessive activation reactive oxygen species (ROS), dysregulation inflammatory response, and impaired angiogenesis. A substantial body evidence suggests that aforementioned diverse factors contributing delayed healing may be associated with autophagy. Impaired autophagy leads endothelial fibroblast dysfunction impedes macrophage phenotypic transformation. This disruption hinders angiogenesis extracellular matrix deposition, ultimately culminating in wound healing. Therefore, biomaterials possessing regulatory functions hold potential for clinical applications enhancing wounds. hybrid multifunctional hydrogel (GelMa@SIS-Qu) has been developed, comprising methacrylamide gelatin (GelMa), a small intestine submucosal acellular (SIS), quercetin nanoparticles, which demonstrates capability promote promotion not only reduces ROS levels cells enhances their antioxidant activity but also mitigates ROS-induced cell apoptosis, thereby promoting Furthermore, facilitates transformation macrophages from M1 phenotype M2 phenotype. study investigates distinctive mechanisms GelMa@SIS-Qu proposes promising therapeutic strategy treating diabetes-related

Language: Английский

---

NO-releasing double-crosslinked responsive hydrogels accelerate the treatment and repair of ischemic stroke

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction blood vessels at lesion site. Here, biocompatible in situ hydrogel platform was designed to target multiple pathogenic post-stroke, including anti-inflammation, anti-oxidant, promotion angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond microenvironment damage site mediate delivery nitric oxide (NO) ISO-1 (inhibitor macrophage migration inhibitory factor, MIF). demonstrated good biocompatibility scavenge reactive oxygen species (ROS) inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), MIF. In mouse model, hydrogels, when situated within cerebral infarction characterized by weak acidity elevated ROS release, would release anti-inflammatory nanoparticles rapidly exert an effect. Concurrently, NO sustained facilitate angiogenesis provide neuroprotective effects. Neurological function significantly improved treated mice assessed modified neurological severity score, rotarod test, open field test. These findings indicate held promise for alleviate injury responding brain's microenvironment.

Language: Английский

---

Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes

Bioactive Materials, Journal Year: 2025, Volume and Issue: 47, P. 152 - 169

Published: Jan. 22, 2025

Language: Английский

---

Identification of Novel Biomarkers for Ischemic Stroke Through Integrated Bioinformatics Analysis and Machine Learning

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Jan. 25, 2025

Language: Английский

---

Esculentoside H reduces the PANoptosis and protects the blood-brain barrier after cerebral ischemia/reperfusion through the TLE1/PI3K/AKT signaling pathway

Experimental Neurology, Journal Year: 2024, Volume and Issue: 379, P. 114850 - 114850

Published: June 12, 2024

Language: Английский

---

A Systematic Review: Quercetin—Secondary Metabolite of the Flavonol Class, with Multiple Health Benefits and Low Bioavailability

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12091 - 12091

Published: Nov. 11, 2024

The main goal of this systematic review on the flavonol class secondary metabolite quercetin is to evaluate and summarize existing research quercetin's potential health benefits, therapeutic properties, effectiveness in disease prevention treatment. In addition evaluating for drug development with fewer side effects lower toxicity, type attempts collect scientific evidence addressing roles as an antioxidant, anti-inflammatory, antibacterial, anticancer agent. first part, we analyze various flavonoid compounds, focusing their chemical structure, classification, natural sources. We highlight most recent biological activities reported literature. Among these pay special attention quercetin, detailing its physicochemical process biosynthesis plants. also present sources emphasize such antioxidant anti-inflammatory effects. Additionally, discuss methods enhance bioavailability, analyzing latest effective delivery systems based quercetin.

Language: Английский

---