TLR4-IN-C34 protects against acute kidney injury via modulating TLR4/MyD88/NF-κb axis, MAPK, and apoptosis.

DOAJ (DOAJ: Directory of Open Access Journals), Journal Year: 2022, Volume and Issue: 25(11), P. 1334 - 1340

Published: Nov. 1, 2022

Acute kidney injury (AKI) is a major component of isoproterenol (ISO) induced cardiorenal syndrome. In this study, we investigated the effect TLR4-IN-C34 as toll-like receptor (TLR)-4 inhibitor on ameliorating ISO-induced AKI and possible molecular underlying pathways.The study included 4 groups: control group, ISO group (rats received 100 mg/kg in 2 doses 24 hr apart, SC), ISO+C341 ISO+C343 groups 1 or 3 respectively twice one hour before each injection, IP).Obtained results showed that injection prior to decreased serum creatinine level (P<0.05). Renal tissue histopathologic changes were markedly by TLR4-IN-C34. relative expression MAPK MyD88 mRNA significantly both compared with Furthermore, TLR-IN-C34 lowered inflammatory cytokines IL-8, IL-1β, IL-12 renal levels Immunostained sections marked decrease NF-κb positive cells addition apoptotic marker Bax (P<0.05) two tested On other hand, antiapoptotic Bcl-2 was increased.It can be concluded ameliorates through anti-inflammatory anti-apoptotic effects modulation TLR4 signaling pathways.

Language: Английский

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Gadolinium-Based Magnetic Resonance Theranostic Agent with Gallic Acid as an Anti-Neuroinflammatory and Antioxidant Agent

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 204 - 204

Published: Feb. 5, 2024

Studies in the field have actively pursued incorporation of diverse biological functionalities into gadolinium-based contrast agents, aiming at amalgamation MRI imaging and therapeutic capabilities. In this research, we present development Gd-Ga, an anti-neuroinflammatory MR agent strategically designed to target inflammatory mediators for comprehensive diagnosis targeted lesion treatment. Gd-Ga is a gadolinium complex composed 1,4,7-tris(carboxymethylaza)cyclododecane-10-azaacetylamide (DO3A) conjugated with gallic acid (3,4,5-trihydroxybenzoic acid). Upon intravenous administration LPS-induced mouse models, demonstrated remarkable three-fold increase signal-to-noise (SNR) variation compared Gd-DOTA, particularly evident both cortex hippocampus 30 min post-MR monitoring. In-depth investigations, vitro vivo, properties revealed significantly reduced protein expression levels pro-inflammatory LPS group. The alignment between silico predictions phantom studies indicates that acts as by directly binding MD2. Additionally, robust antioxidant activity was confirmed its effective scavenging NO ROS. Our collective findings emphasize immense potential theranostic complex, where polyphenol serves anti-inflammatory drug, presenting exceptionally efficient platform treatment neuroinflammation.

Language: Английский

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Regulation of microglia inflammation and oligodendrocyte demyelination by Engeletin via the TLR4/RRP9/NF-κB pathway after spinal cord injury

Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107448 - 107448

Published: Oct. 10, 2024

Microglia polarization is crucial for neuroinflammatory response after spinal cord injury (SCI). Small molecule compounds and hub genes play an important role in regulating microglia polarization, reducing oligodendrocyte demyelination SCI. In this study, suitable data sets were used to screen genes, Western blot Immunofluorescence (IF) experiments confirm the expressions of proteins related SDAD1, RRP9 NF-κB pathways under LPS/SCI conditions. Engeletin (ENG) reduced inflammation vivo vitro via or signaling pathways. addition, ENG binds membrane receptor Toll-like 4 (TLR4) through small molecule-protein docking. COIP experiment protein-protein docking revealed interaction (PPI) between SDAD1. By gene knock-down (KD) / overexpression (OE) experiments, SDAD1 can regulate inflammatory ribosome biogenesis pathway. analysis showed that CU increased expression pathway TLR1/2, while C34 decreased TLR4. These results suggest reduce TLR4/RRP9(SDAD1)/NF-κB we demonstrated apoptosis could be influenced by regulation tissue inflammation. conclusion, study found Rrp9/Sdad1 compound ENG, which control microglia, further explored mechanism demyelination, has theoretical significance.

Language: Английский

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The novel anti-neuroinflammatory functional food CCL01, a mixture of Cuscuta seed extracts and Lactobacillus paracasei NK112

Food & Function, Journal Year: 2022, Volume and Issue: 13(14), P. 7638 - 7649

Published: Jan. 1, 2022

The medical herbal mixture (CCL01) including Cuscuta seeds and Lactobacillus paracasei NK112 has inhibitory effect on LPS-induced microglial inflammation may be a potential functional food for neuroinflammation-related diseases.

Language: Английский

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Correlation between nicotine dependence and inflammatory biomarkers in Thai smokers: Eight weeks of synbiotic intervention

IAES International Journal of Artificial Intelligence, Journal Year: 2022, Volume and Issue: 11(4), P. 1414 - 1414

Published: Aug. 25, 2022

<span>Cigarette smoke contains thousands of man-made substances, and many may contribute to addiction inflammation. This study examined the effect synbiotics on Fagerstrom test for nicotine dependence (FTND) inflammatory markers in Thai smokers. 14 smokers with a Nicotine Dependence Test scores 4 or higher no pregnancy lactation history participated this study. We gave them surveys about FTND continued blood tests Lipopolysaccharide (LPS), lactulose mannitol ratios (LMR), Quinolinic acid (QA), 5-hydroindoleacetic (5-HIAA) record marker levels leaky gut information. Pearson's R-values LPS LMR were 0.444 -0.465. showed positive correlation negative gut, but both relationships weak due gut. The R² coefficient was 0.197, p = 0.112, 0.217, </span><em><span>p</span></em><span> 0.001. FTND, LMR, QA significantly reduced, while 5-HIAA elevated. Further investigation is needed determine association between smoking In conclusion, improved permeability, </span>

Language: Английский

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