Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimers disease DOI Creative Commons
Zhi Tang,

Tong-Tong Sha,

Yun-sheng WANG

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Introduction Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer′s disease (AD). Isoliquiritigenin, a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on stress. Here, we assessed neuroprotective isoliquiritigenin streptozotocin-injected mouse model. Method Molecular docking analysis performed for with mTOR ERK2. The mice (n = 27, male) were intracerebroventricularly injected streptozotocin, treated (intraperitoneal, 2 days) using Morris water maze. Oxidative stress, tau phosphorylation, synaptic impairment evaluated cortex hippocampal tissues by biochemical assays immunofluorescence staining. Results Isoliquiritigenin treatment mitigated spatial memory capacity alleviated phosphorylation at Ser396; production reactive oxygen species; fission proteins Mfn1 Mfn2; neuronal loss; (PSD95, SNAP25). reduced levels Ser2448 ERK1/2 T202/Y204 upregulated level GSK-3βSer9 hippocampus mice. Conclusion In conclusion, our findings suggest that ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, decreasing ERK activity increasing GSK-3β activity.

Language: Английский

Nitroxidative Stress, Cell—Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain DOI Open Access
Álvaro José Chávez Silva, Mário Sérgio Lima de Lavor

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2050 - 2050

Published: Feb. 26, 2025

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative nitrosative stress, an imbalance between reactive oxygen nitrogen species (ROS/RNS) antioxidant defenses, plays crucial role in its pathophysiology. While are essential for physiological functions, excessive levels can cause cellular component neuronal dysfunction pain. This review highlights the complex interactions species, systems, cell signaling, neuropathic We discuss roles ROS/RNS detrimental effects oxidative stress. Furthermore, we explore potential manganese porphyrins, compounds with properties, as promising therapeutic agents mitigate stress alleviate pain by targeting key pathways involved Further research is needed fully understand their managing human non-human animals.

Language: Английский

Citations

0
Electroacupuncture Inhibits NLRP3-Mediated Microglial Pyroptosis to Ameliorate Chronic Neuropathic Pain in Rats DOI Creative Commons

Wenyun Kui,

Yanan Li,

Zhen Gu

et al.

Journal of Pain Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1115 - 1129

Published: March 1, 2025

Patients with neuropathic pain (NP), caused by injury or disease of the somatosensory nervous system, usually suffer from severe pain. Our previous studies revealed that electroacupuncture (EA) stimulation could effectively improve NP. However, underlying mechanisms EA have not been fully clarified. This study aimed to investigate specific in alleviating NP, focusing on pyroptosis. Chronic Constriction Injury (CCI) model was established male Sprague-Dawley rats. CCI rats were treated at acupoints GV20 and ST36 or/with NOD-like receptor protein 3 (NLRP3) antagonist MCC950. treatment administered for successive 14 days 7 after surgery. The mechanical withdrawal threshold (MWT) paw latency (PWL) performed during experiment. At end experiment, spinal cord segments serum collected, ELISA detected expression inflammatory factors, immunofluorescence microglia neuron cells pyroptosis biomarkers, Western blot NLRP3 pathway. significantly alleviated hypersensitivity increasing MWT PWL. Moreover, reduced levels pro-inflammatory cytokines IL-1β TNF-α tissue. Mechanistically, pyroptosis-related proteins, including NLRP3, N-GSDMD, Cleaved Caspase-1, IL-18 as well downregulated EA, indicating attenuated phenotype NP In particular, co-expression Caspase-1 N-GSDMD rather than neuronal astrocytic within Pharmacological inhibition inflammasome MCC950 alleviates CCI-induced while blocking EA's effect anti-pyroptosis These findings demonstrate ameliorates neuroinflammation relieve chronic suppressing activation microglia. may serve a viable therapy

Language: Английский

Citations

0
Natural Products in the Treatment of Neuroinflammation at Microglia: Recent Trend and Features DOI Creative Commons

Chi–Su Yoon

Cells, Journal Year: 2025, Volume and Issue: 14(8), P. 571 - 571

Published: April 10, 2025

Natural products (NPs) are considered to be the oldest medicine in human history and numerous NPs have been investigated search for therapeutic agents various diseases. Neurodegenerative diseases such as dementia, Parkinson's, Alzheimer's, Huntington's disease increasing following extension of lifespans. Neuroinflammation is a key factor genesis several neurodegenerative diseases; therefore, many studies focused on finding therapeutics reduction neuroinflammation. Microglia cells found central nervous system (CNS) these play crucial role regulation neuroinflammation; thus, importance microglia research has recognized. This review focuses recent trends neuroinflammatory regulators by using NPs.

Language: Английский

Citations

0
Research Progress of Flavonoids in Spinal Cord Injury: Therapeutic Mechanisms and Drug Delivery Strategies DOI
Shizhe Li, Shutao Gao, Yukun Hu

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Spinal cord injury (SCI) is a serious neurological disease with an extremely high disability rate. Most patients show loss of motor and sensory functions below the level injury. Current treatment protocols are based on early surgical decompression pharmacotherapy. However, efficacy these interventions suboptimal. Due to its complex pathophysiological mechanisms difficulty central nervous system (CNS) regeneration, exploring effective therapeutic remains daunting. Flavonoids secondary metabolites unique plants that have attracted attention in recent years for their potential now commonly used inflammation, tumors, other diseases. For SCI, related studies still exploring; some compounds, such as quercetin, fisetin, hesperetin, shown good anti-inflammatory anti-apoptotic properties, which help restore function injured spinal cord. flavonoids exhibit certain disadvantages, including poor solubility, low bioavailability, inability achieve long-term controlled release. Some proposed drug delivery strategies-including nanoparticles, hydrogels, collagen scaffolds-to enhance efficacy. In this paper, we summarize strategies SCI by searching relevant literature propose future research directions provide new ideas multimodal SCI.

Language: Английский

Citations

0
Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimers disease DOI Creative Commons
Zhi Tang,

Tong-Tong Sha,

Yun-sheng WANG

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Introduction Tau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimer′s disease (AD). Isoliquiritigenin, a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on stress. Here, we assessed neuroprotective isoliquiritigenin streptozotocin-injected mouse model. Method Molecular docking analysis performed for with mTOR ERK2. The mice (n = 27, male) were intracerebroventricularly injected streptozotocin, treated (intraperitoneal, 2 days) using Morris water maze. Oxidative stress, tau phosphorylation, synaptic impairment evaluated cortex hippocampal tissues by biochemical assays immunofluorescence staining. Results Isoliquiritigenin treatment mitigated spatial memory capacity alleviated phosphorylation at Ser396; production reactive oxygen species; fission proteins Mfn1 Mfn2; neuronal loss; (PSD95, SNAP25). reduced levels Ser2448 ERK1/2 T202/Y204 upregulated level GSK-3βSer9 hippocampus mice. Conclusion In conclusion, our findings suggest that ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, decreasing ERK activity increasing GSK-3β activity.

Language: Английский

Citations

0