Capsaicin alleviates acetaminophen-induced acute liver injury in mice

Zhan, Xiang; Zhang, Jianqiang; Chen, Hui; Liu, Liyuan; Zhou, Yiming; Zheng, Ting; Li, Suxiao; Zhang, Yanxiang; Zheng, Bing; Gong, Quan

doi:10.1016/j.clim.2020.108578

Cited by 23 publications

(10 citation statements)

References 34 publications

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“…Interestingly, promoting Bcl-2 protein expression can protect from APAP-induced apoptosis [ 41 ]. The present work demonstrated that acute dose of APAP caused a marked increase in the activity of caspase-3 as well as the expression of Bax with diminished expression of Bcl-2 [ 42 ], that DIA therapy restored these results in a dose-related manner. The anti-apoptotic effect of DIA has been reported previously in different tissues [ 12 , 22 , 23 , 30 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 81%

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

2022

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Background Acetaminophen (APAP) is a worldwide antipyretic as well as an analgesic medication. It has been extensively utilized during the outbreak of coronavirus 2019 (COVID-19). APAP misuse would lead to liver injury. Diacerein (DIA), an anthraquinone derivative, has antioxidant and inflammatory properties. Hence, this study attempted to evaluate the impact of DIA treatment on liver injury induced by APAP and its influence on nuclear factor-κB (NF-κB) /toll-like receptor 4 (TLR4)/high mobility group box-1(HMGB-1) signaling as well as the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) expression. Methods Male albino rats received 25 as well as 50 mg/kg/day DIA orally for seven days. One hour after the last administration, rats received APAP (1gm/kg, orally). For histopathological analysis, liver tissues and blood were collected, immunohistochemical (IHC) assay, biochemical assay, as well as quantitative real-time polymerase chain reaction (qRT-PCR). Results DIA markedly reduced liver injury markers and ameliorated histopathological changes. Moreover, DIA dose-dependently alleviated oxidative stress status caused by APAP administration along with inflammatory markers, including the level of interleukin-1 beta (IL-1β), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Furthermore, DIA downregulated protein levels as well as mRNA of HMGB-1, TLR4, NF-κB p65 expression, and enhanced PPAR-γ expression. Moreover, DIA ameliorated apoptotic (Bax) and caspase-3 expressions and increased the anti-apoptotic (Bcl2) expression. Conclusions This study demonstrated that DIA exerts anti-apoptotic, anti-inflammatory, and antioxidant properties against liver injury induced by APAP that is attributed to inhibition of the HMGB1/TLR4/NF-κB pathway, besides upregulation of the expression of PPAR-γ.

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Section: Discussionmentioning

confidence: 81%

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

2022

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“…Consistent with current results, our previous study also found CAP can protect against acetaminophen-induced acute liver injury by inhibiting HMGB1 expression. 19 NF-κB is a transcription factor important for HMGB1 synthesis; when activated, it translocates to the nucleus, binds to multiple target genes involved in injury and inflammation, and promotes their expression. 41 Our results show that the expression of NF-κB and HMGB1 increases in the LPS-induced ALI, while CAP pretreatment significantly inhibits the activation of NF-κB and HMGB1 release.…”

Section: Discussionmentioning

confidence: 99%

“…18 Furthermore, a recent study found that CAP exerts a protective effect on acetaminophen-induced acute liver injury by inhibiting the HMGB1/TLR4/NF-κB signaling pathway and hepatocyte apoptosis. 19 Lin et al reported that CAP can inhibit PI3K/ AKT/mTOR signaling in human nasopharyngeal carcinoma cells, thereby inducing autophagy and promoting caspase-3 activation and apoptosis. 20 Hence, CAP can inhibit inflammation by regulating cell signaling, and the pathogenesis of ALI is associated with uncontrolled inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Chen

Zhan

et al. 2021

JIR

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Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated from chili peppers, which has complex pharmacological properties, including beneficial effects against various diseases. The aim of this study was to investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the possible underlying mechanisms. Materials and Methods: ALI was induced by intranasal administration of LPS (0.5 mg/ kg), and CAP (1 mg/kg) injected intraperitoneally 3 days before exposure to LPS. Then, the histopathological changes were evaluated by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory cytokines in serum and lung tissue. The expressions of HMGB1/NF-κB, PI3K/AKT/mTOR signaling pathways and apoptosis-associated molecules were determined by Western blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL staining, and the expression and location of cleaved caspase-3 were detected by immunofluorescence analysis. Results: CAP pretreatment significantly protected mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content and pro-inflammatory cytokine levels, and significant increased superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear factor-kappa B (NF-κB) activation, and the PI3K/AKT/mTOR signaling pathway. Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX expression, and up-regulation of BCL-2. Conclusion: Our data demonstrate that CAP can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory responses and apoptosis through down-regulation of the HMGB1/NF-κB and PI3K/AKT/mTOR pathways.

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“…In the study, capsaicin significantly attenuated acute liver injury by improving MDA, SOD, and GSH levels. Mechanistically, it downregulated the expressions IL‐6, IL‐1β, and TNF‐α (pro‐inflammatory cytokines) via the HMGB1/TLR4/NF‐κB signaling axis and inhibited the hepatocyte apoptosis via reducing BAX, caspase 3, and cleaved caspase 3 levels (Zhan et al, 2020). In light of the above findings, it can be concluded that alkaloids have the potential to alleviate DILI via inhibiting inflammatory response, attenuating oxidative stress, and reducing hepatocyte apoptosis.…”

Section: Protecting the Liver: Potential Of Natural Products As Agent...mentioning

confidence: 99%

Unveiling the therapeutic promise of natural products in alleviating drug‐induced liver injury: Present advancements and future prospects

Singh,

Khan,

Siddique

2023

Phytotherapy Research

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Drug‐induced liver injury (DILI) refers to adverse reactions to small chemical compounds, biological agents, and medical products. These reactions can manifest as acute or chronic damage to the liver. From 1997 to 2016, eight drugs, including troglitazone, nefazodone, and lumiracoxib, were removed from the market due to their liver‐damaging effects, which can cause diseases. We aimed to review the recent research on natural products and their bioactive components as hepatoprotective agents in mitigating DILI. Recent articles were fetched via searching the PubMed, PMC, Google Scholar, and Web of Science electronic databases from 2010 to January 2023 using relevant keywords such as “natural products,” “acetaminophen,” “antibiotics,” “paracetamol,” “DILI,” “hepatoprotective,” “drug‐induced liver injury,” “liver failure,” and “mitigation.” The studies reveal that the antituberculosis drug (acetaminophen) is the most frequent cause of DILI, and natural products have been largely explored in alleviating acetaminophen‐induced liver injury. They exert significant hepatoprotective effects by preventing mitochondrial dysfunction and inflammation, inhibiting oxidative/nitrative stress, and macromolecular damage. Due to the bioavailability and dietary nature, using natural products alone or as an adjuvant with existing drugs is promising. To advance DILI management, it is crucial to conduct well‐designed randomized clinical trials to evaluate natural products' efficacy and develop new molecules clinically. However, natural products are a promising solution for remedying drug‐induced hepatotoxicity and lowering the risk of DILI.

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Capsaicin alleviates acetaminophen-induced acute liver injury in mice

Cited by 23 publications

References 34 publications

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

Diacerein ameliorates acetaminophen hepatotoxicity in rats via inhibiting HMGB1/TLR4/NF-κB and upregulating PPAR-γ signal

Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through the HMGB1/NF-κB and PI3K/AKT/mTOR Pathways

Unveiling the therapeutic promise of natural products in alleviating drug‐induced liver injury: Present advancements and future prospects

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