The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis

Pu, Zhichen; Sui, Bangzhi; Wang, Xingwen; Wang, Wusuan; Xie, Haiyang

doi:10.1016/j.phymed.2023.154753

Cited by 11 publications

(3 citation statements)

References 64 publications

(87 reference statements)

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“…TLR4 and NF-κB are widely recognized for their crucial roles in innate immunity and orchestration of inflammatory responses ( Shao et al, 2020 ; Gudowska-Sawczuk and Mroczko, 2022 ; Zhou et al, 2023 ). Dysregulation of TLR4/NF-κB/NLRP3 signals have been implicated in various diseases that are primarily associated with dysfunction of the defense system and inflammation ( He et al, 2022 ; Pu et al, 2023 ). It is known that activated macrophages are usually divided into M1-like and M2-like macrophages, which are individually involved in proinflammatory and anti-inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Zhang,

Huang,

Chen

et al. 2024

Front. Pharmacol.

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IntroductionAlcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury.MethodsC57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury.ResultsTreatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice.ConclusionAdministration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut–liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

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Section: Discussionmentioning

confidence: 99%

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Zhang,

Huang,

Chen

et al. 2024

Front. Pharmacol.

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“…Five small molecules were screened in the second round, and three small molecules were obtained from a literature review. Luteolin (LUT) and dehydroandrographolide (DA) with antipyroptosis effects, 30 and 1-piperazineethanol,α-[(1,3-benzodioxol-5-yloxy)methyl]-4-(2-methoxyphenyl) (M2) with good antagonistic effects on aflatoxin B 1 (AFB 1 ) toxicity 31 were selected as candidate drugs and their inhibitory effects on trp53inp1 protein expression were detected by WB. Finally, four small molecules with significant inhibitory effects were used in the third round of small molecules to detect the subsequent antipyroptosis effects.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

Xu,

Wu,

Zhao

et al. 2024

J. Agric. Food Chem.

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Multiple compounds are related to the development of liver injury, such as toxins, drugs, and environmental pollutants. Although there are reports that the T-2 toxin can cause liver injury, its toxic mechanism remains unclear, which further impedes the development of effective antidotes. In this study, CRISPR-Cas9 genome-wide screening technology was used to identify transformation-related protein 53 inducible nuclear protein 1 (trp53inp1) as a toxic target of the T-2 toxin. Mechanism studies have shown that the T-2 toxin induced pyroptosis of macrophages (J774A.1 cells) by activating the trp53inp1/NF-κB/NLRP3/GSDMD-N pathway, leading to a subacute liver injury. Also, the new drug berberine (BER) identified through virtual screening significantly alleviated the subacute liver injury by competitively binding trp53inp1 via His224; the effect was better than those of the positive control drugs N-acetylcysteine (NAC) and disulfiram (DSF). In summary, the above results indicate that trp53inp1 is a key target for T-2 toxin to induce subacute liver injury and that inhibiting macrophage pyroptosis is a new method for treating liver injury. In addition, this study provides a new method and strategy for the discovery of key disease targets and the search for effective drugs.

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“…Ubiquitination and deubiquitination modifications are essential types of protein post-translational modification (PTM), playing crucial regulatory roles in inflammatory signaling [ 10 ]. It has been reported that these modifications can directly or indirectly regulate the activation or degradation of NLRP3 inflammasomes, thereby intervening in the development of various inflammation-related diseases [ 11 , 12 ]. Therefore, this review discusses the regulation of NLRP3 inflammasome activation by ubiquitination and deubiquitination modifications, their intervention in inflammation-related diseases, and the potential mechanisms associated with these processes.…”

Section: Introductionmentioning

confidence: 99%

The roles of ubiquitination and deubiquitination of NLRP3 inflammasome in inflammation-related diseases: A review

Tang,

Geng,

Wang

et al. 2024

Biomol Biomed

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The inflammatory response is a natural immune response that prevents microbial invasion and repairs damaged tissues. However, excessive inflammatory responses can lead to various inflammation-related diseases, posing a significant threat to human health. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a vital mediator in the activation of the inflammatory cascade. Targeting the hyperactivation of the NLRP3 inflammasome may offer potential strategies for the prevention or treatment of inflammation-related diseases. It has been established that the ubiquitination and deubiquitination modifications of the NLRP3 inflammasome can provide protective effects in inflammation-related diseases. These modifications modulate several pathological processes, including excessive inflammatory responses, pyroptosis, abnormal autophagy, proliferation disorders, and oxidative stress damage. Therefore, this review discusses the regulation of NLRP3 inflammasome activation by ubiquitination and deubiquitination modifications, explores the role of these modifications in inflammation-related diseases, and examines the potential underlying mechanisms.

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The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis

Cited by 11 publications

References 64 publications

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway

Inhibition of Macrophage Pyroptosis─A New Therapeutic Strategy to Alleviate T-2 Toxin-Induced Subacute Liver Injury by Directly Competing with the Key Target

The roles of ubiquitination and deubiquitination of NLRP3 inflammasome in inflammation-related diseases: A review

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