Luteolin ameliorates LPS-induced acute liver injury by inhibiting TXNIP-NLRP3 inflammasome in mice

Wang, Xiaohui; Wang, Lu; Dong, Renchao; Huang, Kai; Wang, Changyuan; Gu, Jiangning; Luo, Haifeng; Liu, Kexin; Wu, Jingjing; Sun, Huijun; Meng, Qiang

doi:10.1016/j.phymed.2021.153586

Cited by 66 publications

(43 citation statements)

References 27 publications

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“…Our results showed that LUT treatment significantly inhibited the expression of TXNIP and the NLRP3 inflammasome constituent proteins (NLRP3, caspase-1, and ASC). This is consistent with similar results by Wang et al [ 16 ]. This illustrates that LUT exerts bladder-protective effects by inhibiting the TXNIP/NLRP3 axis.…”

Section: Discussionsupporting

confidence: 94%

“…The regulating effect of the TXNIP/NLRP3 axis on oxidative stress has been widely reported [ 16 ]. In order to study the mechanism of LUT improving CYP-induced cystitis, we used western blot to study the expression changes of TXNIP/NLRP3 before and after LUT treatment.…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies have shown that LUT can reduce the damage caused by heavy metal cobalt to the hearts and kidneys of rats through its anti-inflammatory and antioxidant effects mediated by the NF-кB/Kim-1 pathway [ 15 ]. Wang et al found that LUT can reduce inflammation, cell necrosis, and oxidative stress caused by lipopolysaccharide through the TXNIP-NLRP3 axis [ 16 ] and achieve a protective effect on the liver. In lower urinary tract diseases, LUT also shows a certain therapeutic effect.…”

Section: Introductionmentioning

confidence: 99%

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Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Zhang

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Hemorrhagic cystitis is an important complication of cyclophosphamide chemotherapy, and current therapies for the disease are limited. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. This study aims to explore the protective effect of LUT on CYP-induced acute cystitis in rats. Female Sprague-Dawley rats were randomly assigned to the control (CON) group, CON + LUT group, CYP group, and CYP + LUT group. A single intraperitoneal injection of CYP was administered to establish an acute hemorrhagic cystitis model. HE staining was performed to detect the degree of bladder tissue damage, and TUNEL staining was performed to count apoptotic cells. Oxidative stress indicators were measured using commercial kits, and bladder surgery was performed to assess urinary function. The levels of inflammatory cytokines, apoptosis-related indicators, TXNIP/NLRP3 pathway, and NF-κB pathway were detected by western blot. We found that LUT treatment reduced bladder bleeding, congestion, and edema caused by CYP. Compared with the CYP + LUT group, the level of apoptosis was more highly expressed in the CYP group. We also found that caspase-3, caspase-8, and Bax were significantly upregulated and Bcl-2 was downregulated after LUT treatment. In addition, LUT inhibited the activation of NF-κB signal pathway in the rat bladder tissue after CYP exposure. LUT treatment can also reduce the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) and TXNIP in the bladder. Finally, LUT can reduce the increase in the urination frequency and maximum urination pressure caused by cystitis. These results indicate that LUT displays effective anti-inflammatory, antioxidant, and antiapoptotic properties in CYP-induced acute hemorrhagic cystitis rats by inhibiting the TXNIP/NLRP3 and NF-κB pathways. LUT may be a potent therapeutic agent for the prevention and treatment of hemorrhagic cystitis.

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Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Zhang

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“… 42 Increased IL‐6 in serum has been found in LPS‐induced ALF and IL‐6 has been reported to induce liver injury by several mechanisms such as NF‐κB and miR‐455‐3p/PI3K signaling pathways. 43 , 44 It has been documented that in hepatocytes, IL‐6 is one of the most important triggers of the acute phase protein expression which contributes to the control of inflammation at systemic levels. 45 , 46 Of note, monocytes/macrophages are crucial determinants for acute liver injury and consequent uncontrolled immune activation brings about sepsis as well as organ failure.…”

Section: Discussionmentioning

confidence: 99%

Blockade of mIL‐6R alleviated lipopolysaccharide‐induced systemic inflammatory response syndrome by suppressing NF‐κB‐mediated Ccl2 expression and inflammasome activation

Dai

Zhang

et al. 2022

MedComm

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Systemic inflammatory response syndrome (SIRS) is characterized by dysregulated cytokine release, immune responses and is associated with organ dysfunction. IL‐6R blockade indicates promising therapeutic effects in cytokine release storm but still remains unknown in SIRS. To address the issue, we generated the human il‐6r knock‐in mice and a defined epitope murine anti‐human membrane‐bound IL‐6R (mIL‐6R) mAb named h‐mIL‐6R mAb. We found that the h‐mIL‐6R and the commercial IL‐6R mAb Tocilizumab significantly improved the survival rate, reduced the levels of TNF‐α, IL‐6, IL‐1β, IFN‐γ, transaminases and blood urea nitrogen of LPS‐induced SIRS mice. Besides, the h‐mIL‐6R mAb could also dramatically reduce the levels of inflammatory cytokines in LPS‐treated THP‐1 cells in vitro. RNA‐seq analysis indicated that the h‐mIL‐6R mAb could regulate LPS‐induced activation of NF‐κB/Ccl2 and NOD‐like receptor signaling pathways. Furthermore, we found that the h‐mIL‐6R mAb could forwardly inhibit Ccl2 expression and NLRP3‐mediated pyroptosis by suppressing NF‐κB in combination with the NF‐κB inhibitor. Collectively, mIL‐6R mAbs suppressed NF‐κB/Ccl2 signaling and inflammasome activation. IL‐6R mAbs are potential alternative therapeutics for suppressing excessive cytokine release, over‐activated inflammatory responses and alleviating organ injuries in SIRS.

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“…Furthermore, there is evidence that β -carotene can reduce skin inflammation by inhibiting the expression of inflammatory factors and reducing the activity of MMP9 in the ox-AD mouse model [ 28 ]. Luteolin could inhibit lipid-induced liver inflammation by reducing the expression of IL-10 and IL-6 and play a protective role in the male C57BL/6 mice liver and primary mouse hepatocytes [ 29 ]. To investigate the effect of autophagy and apoptosis on NDV replication after NDV infection in chicken tissues and cells, researchers found that decreasing cleavage of caspase 3 can enhance autophagy and promote cell survival and NDV replication [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Strategy for Exploring the Pharmacological Mechanism of Honeysuckle (Lonicer japonica Thunb.) against Newcastle Disease

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Newcastle disease causes huge economic losses in the global poultry industry. An efficient treatment is needed to deal with the variable immunogenicity of the Newcastle disease virus (NDV). This study utilized network pharmacology to study the potential therapeutic targets of Honeysuckle (Lonicer japonica Thunb.) against Newcastle disease. Methods. Venny online analysis was used to analyze the potential overlapping targets of Honeysuckle and Newcastle disease. Hub genes were obtained using the STRING database and Cytoscape 3.8.2 software. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis using the DAVID online tool were performed on these targets. Results. Twenty-five overlapping targets were identified. The PPI network construction results included 23 nodes of 25 genes and 95 edges. It was found that the IL-6 node had the largest degree. STAT1 and IRF1, CASP9, and CASP3 had the same as well as strongest interaction strengths. GO functions, such as “cytokine activity,” had a regulatory effect on NDV. The “Toll-like receptor signaling Pathway” “Nod-like receptor signaling pathway,” “RIG-I-like receptor signaling pathway,” and “Apoptosis,” which were obtained using KEGG analysis, also indicated that these pathways can act on NDV to enhance immune function. Conclusions. In this study, the potential targets and mechanisms of action of Honeysuckle against Newcastle disease were explored through network pharmacology, which provided a theoretical basis for the treatment of Newcastle disease and provided new ideas for the development of traditional Chinese medicine for the poultry industry.

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Luteolin ameliorates LPS-induced acute liver injury by inhibiting TXNIP-NLRP3 inflammasome in mice

Cited by 66 publications

References 27 publications

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Luteolin Improves Cyclophosphamide-Induced Cystitis through TXNIP/NLRP3 and NF-κB Pathways

Blockade of mIL‐6R alleviated lipopolysaccharide‐induced systemic inflammatory response syndrome by suppressing NF‐κB‐mediated Ccl2 expression and inflammasome activation

Network Pharmacology-Based Strategy for Exploring the Pharmacological Mechanism of Honeysuckle (Lonicer japonica Thunb.) against Newcastle Disease

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