Baicalin promotes liver regeneration after acetaminophen-induced liver injury by inducing NLRP3 inflammasome activation

Shi, Liang; Zhang, Shaobo; Huang, Zhenlin; Hu, Feifei; Zhang, Tianyu; Wei, Mengjuan; Bai, Qingshun; Lü, Bin; Ji, Lili

doi:10.1016/j.freeradbiomed.2020.05.012

Cited by 57 publications

(29 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, acetaminophen overdose is the most frequent cause of acute liver failure in the United States and many European countries (Larson et al, 2005;Yano et al, 2014). Severe liver injury, along with increasing expressions of NLRP3 and IL-1β, occurred in acetaminophen-treated mice liver or liver cell lines Lv et al, 2020;Samra et al, 2020;Shi et al, 2020). Imaeda et al (2009) found that genetic deficiencies in NLRP3 inflammasome components (NLRP3, ASC, and caspase-1) provided protection from acetaminophen-induced mice death and liver injury.…”

Section: Acetaminophen-induced Liver Injurymentioning

confidence: 99%

“…Liver regeneration has drawn a lot of attention in the study of DILI (Bhushan and Apte, 2019;Clemens et al, 2019). A recent study showed that baicalin promoted liver regeneration via inducing Nrf2 accumulation in cytoplasm, thus causing NLRP3 inflammasome activation after acetaminophen-induced acute liver injury in mice (Shi et al, 2020). It seems that the NLRP3 inflammasome activation partly acted as a compensatory regulation in the process of acetaminophen hepatotoxicity.…”

Section: Phytochemicals That Treat Drug-induced Liver Injurymentioning

confidence: 99%

See 1 more Smart Citation

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

Wei

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Drug-induced toxicity, which impairs human organ function, is a serious problem during drug development that hinders the clinical use of many marketed drugs, and the underlying mechanisms are complicated. As a sensor of infections and external stimuli, nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a key role in the pathological process of various diseases. In this review, we specifically focused on the role of NLRP3 inflammasome in drug-induced diverse organ toxicities, especially the hepatotoxicity, nephrotoxicity, and cardiotoxicity. NLRP3 inflammasome is involved in the initiation and deterioration of drug-induced toxicity through multiple signaling pathways. Therapeutic strategies via inhibiting NLRP3 inflammasome for drug-induced toxicity have made significant progress, especially in the protective effects of the phytochemicals. Growing evidence collected in this review indicates that NLRP3 is a promising therapeutic target for drug-induced toxicity.

show abstract

Section: Acetaminophen-induced Liver Injurymentioning

confidence: 99%

Section: Phytochemicals That Treat Drug-induced Liver Injurymentioning

confidence: 99%

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

Wei

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…However, there are still uncertainties regarding the signaling pathways that underlie acetaminophen hepatotoxicity. Two outstanding uncertainties are the contributions of the NLRP3 inflammasome and IL-4 signaling pathways (Yoon et al 2016 ; Jaeschke 2018 ; Shi et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Diacerein counteracts acetaminophen-induced hepatotoxicity in mice via targeting NLRP3/caspase-1/IL-1β and IL-4/MCP-1 signaling pathways

Elshal

Abdelmageed

2022

Arch. Pharm. Res.

View full text Add to dashboard Cite

The current study aims at repurposing the anti-arthritic drug diacerein (DCN) for the treatment of acetaminophen hepatotoxicity and investigating the potential underlying mechanisms. Mice were randomly divided into six groups receiving either no treatment (control group), 20 mg/kg DCN i.p, 400 mg/kg acetaminophen i.p, DCN 4 h before acetaminophen, DCN 2 h after acetaminophen, or 400 mg/kg N-acetylcysteine (NAC) i.p, 2 h after acetaminophen. Biomarkers of liver dysfunction, oxidative stress, and apoptosis were assessed. Hepatic necroinflammatory changes were evaluated along with hepatic expression of NF-κB and caspase-1. The levels of NLRP3, IL-1β, IL-4, MCP-1, and TNF-α in the liver, as well as CYP2E1 mRNA expression, were measured. Diacerein significantly reduced biomarkers of liver dysfunction, oxidative stress, hepatocyte necrosis, and infiltration of neutrophils and macrophages whether administered 4 h before or 2 h after acetaminophen. Further, the effects were comparable to those of NAC. Diacerein also counteracted acetaminophen-induced hepatocellular apoptosis by increasing Bcl-2 and decreasing Bax and caspase-3 expression levels. Moreover, DCN normalized hepatic TNF-α and significantly decreased NF-κB p65 expression. Accordingly, DCN can prevent or reverse acetaminophen hepatotoxicity in mice, suggesting potential utility as a repurposed drug for clinical treatment.

show abstract

“…Moreover, the systems pharmacology study showed that quercetin, wogonin, luteolin, baicalein, corynoline were the active components with the high content in PDL. Previous studies have demonstrated that baicalin 48 , 49 or wogonoside, 50 which have high contents in PDL, affect anti-inflammation by modulating the NLRP3 inflammasome signaling. The contents of wogonin and corynoline are also high in PDL, which rank closely followed by baicalin and wogonoside.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid

Tian

Bao

et al. 2021

ACS Omega

View full text Add to dashboard Cite

Pudilan antiphlogistic oral liquid (PDL) is a commercial traditional Chinese medicine widely used in the treatment of a variety of inflammatory diseases. However, the specific mechanisms of PDL’s anti-inflammatory effects have not been fully understood. In this research, five classic inflammatory models and a network pharmacology-based strategy were utilized to evaluate its anti-inflammatory efficacy and elucidate its multicomponent and multitarget mode of the anti-inflammatory mechanism. A systems pharmacology approach was carried out via a holistic process of active compound screening, target acquisition, network construction, and further analysis. The potential component–target-associated anti-inflammatory mechanisms of PDL were further verified both in vivo and in vitro . The results showed that PDL exhibited a proven anti-inflammatory effect on multiple types of inflammatory models, including β-hemolytic streptococcus-induced acute pharyngitis, LPS-induced acute lung injury, xylene-induced ear swelling, carrageenan-induced paw edema, and acetic acid-induced capillary permeability-increasing models. Systems pharmacology analysis predicted 45 ingredients of PDL that interact with 185 targets, of which 38 overlapped with the inflammation-related targets. Furthermore, KEGG pathway analysis showed that the predicted targets were mainly involved in hypoxia-inducible factor (HIF)-1, tumor necrosis factor (TNF), nuclear factor kappa-B (NF-κB), and NOD-like receptor (NLR) pathways. Both in vivo and in vitro experiments clarified that PDL has anti-inflammatory potency by inhibiting PI3K and p38 phosphorylation and activating the NLRP3 inflammasome. Our results suggested that PDL has an efficient and extensive anti-inflammatory effect, and its anti-inflammatory mechanisms may involve multiple inflammatory-associated signaling pathways, including HIF-1- and TNF-mediated pathways and NLRP3 inflammasome activation.

show abstract

Baicalin promotes liver regeneration after acetaminophen-induced liver injury by inducing NLRP3 inflammasome activation

Cited by 57 publications

References 35 publications

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

Diacerein counteracts acetaminophen-induced hepatotoxicity in mice via targeting NLRP3/caspase-1/IL-1β and IL-4/MCP-1 signaling pathways

Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid

Contact Info

Product

Resources

About