Suppressing NLRP3 activation and PI3K/AKT/mTOR signaling ameliorates amiodarone-induced pulmonary fibrosis in rats: a possible protective role of nobiletin

Tabaa, Manar Mohammed El; Tabaa, Maram Mohammed El; Elgharabawy, Rehab M.; Abdelhamid, Walaa

doi:10.1007/s10787-023-01168-2

Cited by 12 publications

(3 citation statements)

References 44 publications

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“…The HCV-mediated activation of the NLRP3 inflammasome in macrophages may play an important role in the onset of liver fibrosis, since it secretes IL-1β, which in turn regulates TGF-β1 release. Although both chemoattractant molecules are master regulators of fibrogenic processes, TGF-β1 also activates the PI3k/Akt/mTOR pathway, a crucial pathway upregulated in HCC [40,41]. Targeting NLRP3 inflammasome activation might be a valid approach to both reduce HCV-infected cell death and diminish the activation of fibrogenic processes that lead to cancer.…”

Section: Chronic Viral Hepatitis C (Hcv)mentioning

confidence: 99%

NLRP3 Inflammasome in Acute and Chronic Liver Diseases

Sayaf,

Battistella,

Russo

2024

IJMS

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NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity.

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Section: Chronic Viral Hepatitis C (Hcv)mentioning

confidence: 99%

NLRP3 Inflammasome in Acute and Chronic Liver Diseases

Sayaf,

Battistella,

Russo

2024

IJMS

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“…According to Huang et al., they have proved in mice that the drug, hispolon, can provide protection for pulmonary cells through inhibition of PI3K/Akt/mTOR, further resisting inflammation and oxidative stress under diabetic environments ( 226 ). Moreover, the chemical ingredients such as syringic and ascorbic acids, as well as nobiletin, have also been found to suppress autophagic cell death by downregulating the PI3K/Akt/mTOR pathway to prevent possible injuries to the lungs ( 227 , 228 ). As for pyroptosis, several small molecules targeting the essential sites have already been developed to deal with conditions of multiple diseases.…”

Section: Interactions Of Multiple Forms Of Non-apoptotic Pcds In Diab...mentioning

confidence: 99%

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products

Dai,

Zhou,

Qiao

et al. 2023

Front. Endocrinol.

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Diabetes mellitus (DM) is a chronic metabolic disorder that affects multiple organs and systems, including the pulmonary system. Pulmonary dysfunction in DM patients has been observed and studied for years, but the underlying mechanisms have not been fully understood. In addition to traditional mechanisms such as the production and accumulation of advanced glycation end products (AGEs), angiopathy, tissue glycation, oxidative stress, and systemic inflammation, recent studies have focused on programmed cell deaths (PCDs), especially the non-apoptotic ones, in diabetic pulmonary dysfunction. Non-apoptotic PCDs (NAPCDs) including autophagic cell death, necroptosis, pyroptosis, ferroptosis, and copper-induced cell death have been found to have certain correlations with diabetes and relevant complications. The AGE–AGE receptor (RAGE) axis not only plays an important role in the traditional pathogenesis of diabetes lung disease but also plays an important role in non-apoptotic cell death. In this review, we summarize novel studies about the roles of non-apoptotic PCDs in diabetic pulmonary dysfunction and focus on their interactions with the AGE–RAGE axis.

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“…A previous study has reported that nobiletin exhibited a protective effect on lipopolysaccharide-induced ALI by inhibiting nuclear factor-kappa B activation and inflammatory response (10). Accumulating evidence also supports the protective effect of nobiletin in lung disease (11); nevertheless, little is known regarding its impact on lung injury induced by HS. In addition, nobiletin can attenuate hypoxia-induced placental damage by modulating the p53 signaling pathway to inhibit apoptosis of placental cells (12).…”

Section: Introductionmentioning

confidence: 95%

Nobiletin ameliorates heatstroke-induced acute lung injury by inhibiting ferroptosis via p53/SLC7A11 pathway

Chen,

Xie,

Peng

et al. 2023

Shock

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The molecular mechanism for nobiletin’s protective effect against heatstroke-induced acute lung injury (HS-ALI) remains largely unknown. Previous research has demonstrated that ferroptosis is an important pathogenic event in HS-ALI. Nobiletin is a natural polymethoxylated flavonoid. Herein, we investigated the potential contribution of nobiletin to HS-ALI by inhibiting ferroptosis. Heat stress was used to induce HS-ALI in mice, and MLE-12 cells were stimulated by heat stress in vitro. Nobiletin was administrated by gavage for 2 hours before HS induction. Biochemical kits, immunofluorescence staining, and western blotting were performed on the markers of ferroptosis. Our results showed that nobiletin administration significantly attenuated HS-induced lung injury and ferroptosis. Moreover, nobiletin pretreatment significantly reversed HS-induced p53 upregulation in vivo and in vitro. Pretreatment with a p53 agonist, Tenovin-6 partly abolished the protective effect of nobiletin in mice with HS-ALI. Meanwhile, p53 knockdown significantly increased GPX4 and SLC7A11 expression levels compared to the HS group in HS-induced MLE-12 cells. Subsequently, nobiletin ameliorated HS-induced MLE-12 cells ferroptosis by activating the SLC7A11/GPX4 pathway, while p53 overexpression effectively abolished the protective effect of nobiletin. Taken together, our findings reveal that nobiletin attenuates HS-ALI by inhibiting ferroptosis through the p53/SLC7A11 pathway, indicating it to be a potential therapeutic agent for HS-ALI prevention and treatment.

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Suppressing NLRP3 activation and PI3K/AKT/mTOR signaling ameliorates amiodarone-induced pulmonary fibrosis in rats: a possible protective role of nobiletin

Cited by 12 publications

References 44 publications

NLRP3 Inflammasome in Acute and Chronic Liver Diseases

NLRP3 Inflammasome in Acute and Chronic Liver Diseases

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products

Nobiletin ameliorates heatstroke-induced acute lung injury by inhibiting ferroptosis via p53/SLC7A11 pathway

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