Hederasaponin C inhibits LPS‐induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF‐κB/NLRP3 signaling pathway DOI Creative Commons
Shan Han, Siyuan Li,

Jilang Li

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(12), P. 5974 - 5990

Published: Oct. 1, 2023

Abstract Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) one of the main active components Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti‐inflammatory activity. However, protective effect against lipopolysaccharide (LPS)‐induced AKI in mice remains unclear. Therefore, we investigated LPS‐induced renal inflammation underlying molecular mechanisms. Herein, using MTT LDH assays to assess both cell viability activity; dual staining techniques identify different death patterns; conducting immunoblotting, QRT‐PCR, immunofluorescence analyses evaluate levels protein mRNA expression; employing docking, SPR experiments, CETSA investigate interaction between TLR4; studying effects AKI. The results indicate that inhibits expression TLR4 activation NF‐κB PIP2 signaling pathways, while simultaneously suppressing NLRP3 inflammasome. In animal models, ameliorated diminished inflammatory response level markers. These findings suggest has potential as therapeutic agent mitigate sepsis‐related

Language: Английский

Oxidized Low-Density Lipoprotein and Its Role in Immunometabolism DOI Open Access
Negin Mosalmanzadeh, Brandt D. Pence

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11386 - 11386

Published: Oct. 23, 2024

Modified cholesterols such as oxidized low-density lipoprotein (OxLDL) contribute to atherosclerosis and other disorders through the promotion of foam cell formation inflammation. In recent years, it has become evident that immune responses inflammatory molecules OxLDLs depend on cellular metabolic functions. This review examines known effects OxLDL immunometabolism in several diseases. We additionally provide context relationship between aging/senescence identify gaps literature our current understanding these areas.

Language: Английский

Citations

4

Caffeine Has Different Immunomodulatory Effect on the Cytokine Expression and NLRP3 Inflammasome Function in Various Human Macrophage Subpopulations DOI Open Access

Elek Gergő Kovács,

Ahmad Alatshan,

Marietta M. Budai

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(7), P. 2409 - 2409

Published: July 14, 2021

Besides its well-known psychoactive effects, caffeine has a broad range of actions. It regulates several physiological mechanisms as well modulates both native and adaptive immune responses by various ways. Although is assumed to be negative regulator inflammation, the effect on secretion pro- anti-inflammatory cytokines highly controversial. Macrophages are major mediators inflammatory responses; however, subpopulations develop different effects ranging from initiation resolution inflammation. Here we report comparative analysis two human monocyte-derived macrophages differentiated in presence macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage (GM-CSF), resulting M-MΦs GM-MΦs, respectively. We showed that although TNF-α was downregulated LPS-activated MΦ subtypes caffeine, IL-8, IL-6, IL-1β expression Nod-like receptors enhanced M-MΦs, while it did not change GM-MΦs. (1) altered adenosine receptor expression, (2) changed Akt/AMPK/mTOR signaling pathways, (3) inhibited STAT1/IL-10 axis M-MΦs. hypothesized these alterations play an important modulatory role upregulation NLRP3 inflammasome-mediated following treatment.

Language: Английский

Citations

25

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage DOI Open Access
Yuan Zhang, Wanpeng Yu,

Christopher Flynn

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(24), P. 5251 - 5251

Published: Dec. 9, 2022

The pathophysiological process of intracerebral hemorrhage (ICH) is very complex, involving various mechanisms such as apoptosis, oxidative stress and inflammation. As one the key factors, inflammatory response responsible for pathological acute brain injury associated with prognosis patients. Abnormal or dysregulated responses after ICH can aggravate cell damage in injured tissue. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome a multiprotein complex distributed cytosol, which be triggered by multiple signals. NLRP3 activated ICH, thus promoting neuroinflammation aggravating edema. In addition, there evidence that gut microbiota crucial activation inflammasome. plays role variety CNS disorders. Changes diversity species affect through release cytokines. turn, composition influenced Thereby, regulation microbe–gut–brain axis via may serve novel idea protecting against secondary (SBI) Here, we review recent on functions well their interactions, during ICH.

Language: Английский

Citations

18

Itaconate Attenuates Neuroinflammation and Exerts Dopamine Neuroprotection in Parkinson’s Disease through Inhibiting NLRP3 Inflammasome DOI Creative Commons

Guoqing Sun,

Rui Zhang, Chengxiao Liu

et al.

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(9), P. 1255 - 1255

Published: Sept. 16, 2022

Parkinson’s disease (PD) is a common age-associated neurodegenerative motor disorder, which mainly caused by dopaminergic neuron loss in the substantia nigra. This study aimed to evaluate function and underlying molecular mechanism of itaconate PD. PD models were established vivo vitro using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1-methyl-4-phenylpyridinium (MPP+), respectively. Pole rotarod tests applied coordination mice. The expression tyrosine hydroxylase (TH) MPTP-induced mice MPP+ revulsive cell model detected Western blotting immunofluorescence. inflammatory factors level was quantitative real-time polymerase chain reaction. content superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) nigra, striatum, SH-SY5Y cells analyzed. Moreover, apoptosis determined terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining flow cytometry. apoptosis- Nod-like receptor family protein 3 (NLRP3) inflammasome-associated proteins measured Itaconate attenuated deficits inhibited dopamine neuronal damage, response, oxidative stress, MPTP-caused model. Additionally, notably repressed activation NLRP3 inflammasome. research demonstrated that could attenuate neuroinflammation exert neuroprotection through inhibiting

Language: Английский

Citations

17

Hederasaponin C inhibits LPS‐induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF‐κB/NLRP3 signaling pathway DOI Creative Commons
Shan Han, Siyuan Li,

Jilang Li

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(12), P. 5974 - 5990

Published: Oct. 1, 2023

Abstract Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) one of the main active components Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti‐inflammatory activity. However, protective effect against lipopolysaccharide (LPS)‐induced AKI in mice remains unclear. Therefore, we investigated LPS‐induced renal inflammation underlying molecular mechanisms. Herein, using MTT LDH assays to assess both cell viability activity; dual staining techniques identify different death patterns; conducting immunoblotting, QRT‐PCR, immunofluorescence analyses evaluate levels protein mRNA expression; employing docking, SPR experiments, CETSA investigate interaction between TLR4; studying effects AKI. The results indicate that inhibits expression TLR4 activation NF‐κB PIP2 signaling pathways, while simultaneously suppressing NLRP3 inflammasome. In animal models, ameliorated diminished inflammatory response level markers. These findings suggest has potential as therapeutic agent mitigate sepsis‐related

Language: Английский

Citations

11