NF‐κB and AMPK/PI3K/Akt signaling pathways are involved in the protective effects of <scp><i>Platycodon grandiflorum</i></scp> saponins against acetaminophen‐induced acute hepatotoxicity in mice

Leng, Jing; Wang, Zi; Fu, Chenglin; Zhang, Jing; Ren, Shengxiang; Hu, Jun‐Nan; Jiang, Shuang; Wang, Ying‐Ping; Chen, Chen; Li, Wei

doi:10.1002/ptr.6160

Cited by 58 publications

(37 citation statements)

References 48 publications

(66 reference statements)

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“…In addition, CCl4 exposure upregulated the expression level of toll-like receptor 4 (TLR4) [ 52 ]. Similarly, previous reports also confirmed that MAPKs as a large family of seine/threonine kinases can also largely mediate the inflammatory signaling from the cell surface to nucleus [ 53 , 54 ]. Therefore, in the present work, the analysis of AP-1 expression in TLR4-MAPKs signal pathway will easily understand the protective effect of maltol on CCl 4 induced liver injury.…”

Section: Discussionsupporting

confidence: 62%

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The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

et al. 2018

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The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

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Section: Discussionsupporting

confidence: 62%

“…Hoechst 33258 staining was performed by using 5-μm thick tissue sections, and this was performed as described above [ 53 ]. Briefly, we randomly selected four sections in each group, and they were rehydrated by xylene and aqueous alcohol solutions carefully, and then were washed by PBS three times before being stained by the dye.…”

Section: Methodsmentioning

confidence: 99%

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

et al. 2018

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“…Platycodon grandiflorum (PG) has been used as an oriental herbal medicine native to East Asia (Korea, China, and Japan). It has various beneficial effects such as anti-inflammatory [12] and antibacterial [13] activities, improvement of liver function [14], and enhancement of cognitive ability [15]. In particular, platycodin D and platycodin D3 as main active ingredients of PG have anti-inflammatory activities, as it was shown to mitigate the inflammatory response induced by lipopolysaccharides (LPS) in RAW 264.7 (a macrophage cell line) cells [16].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of fermentedPlatycodon grandiflorumextract through NF-κB signaling in RAW 264.7 cells

Park

Lee

2020

Nutr Res Pract

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BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG), an oriental herbal medicine, has been known to improve liver function, and has both anti-inflammatory and antimicrobial properties. However, little is known about the immune-enhancing effects of PG and its mechanism. In this study, we aimed to investigate whether fermented PG extract (FPGE), which has increased platycodin D content, activates the immune response in a murine macrophage cell line, RAW 264.7. MATERIALS/METHODS: Cell viability was determined by Cell Counting Kit-8 assay and the nitric oxide (NO) levels were measured using Griess reagent. Cytokine messenger RNA levels of were monitored by quantitative reverse transcription polymerase chain reaction. To investigate the molecular mechanisms underlying immunomodulatory actions of FPGE in RAW 264.7 cells, we have conducted luciferase reporter gene assay and western blotting. RESULTS: We found that FPGE treatment induced macrophage cell proliferation in a dosedependent manner. FPGE also modulated the expression of NO and pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The activation and phosphorylation levels of nuclear factor kappa B (NF-κB) were increased by FPGE treatment. Moreover, 5-aminoimidazole-4-carboxamide ribonucleotide, an activator of AMP-activated kinase (AMPK), significantly reduced both lipopolysaccharides-and FPGE-induced NF-κB reporter gene activity. CONCLUSIONS: Taken together, our findings suggest that FPGE may be a novel immuneenhancing agent acting via AMPK-NF-κB signaling pathway.

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“…Liver disease is common and often life-threatening. 1 Carbon tetrachloride (CCl 4 ), 2 paracetamol 3 and lipopolysaccharide 4 may cause acute liver injury. The occurrence of liver injury may be related to viral infection, alcohol and drugs.…”

Section: Introductionmentioning

confidence: 99%

<p>Sinomenine Attenuates Acetaminophen-Induced Acute Liver Injury by Decreasing Oxidative Stress and Inflammatory Response via Regulating TGF-β/Smad Pathway in vitro and in vivo</p>

Chen

Wang

Jiao

et al. 2020

DDDT

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Introduction: Liver disease is common and often life-threatening. Sinomenine (SIN) is an active ingredient extracted from Sinomenium acutum. This study investigated the protective effect and mechanism of sinomenine (SIN) on acetaminophen (APAP)-induced liver injury from in vitro and in vivo. Methods: In vivo experiments, mice were randomly divided into six groups (n=10): control group, model group, SIN (25 mg/kg) group, SIN (50 mg/kg) group, SIN (100 mg/kg) group and SIN (100 mg/kg) + SRI-011381 group. Alanine transaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP) were detected. The pathological lesion was measured by HE staining. Apoptosis was measured by TUNEL staining. In vitro experiments, BRL-3A cells were treated with APAP (7.5 mM) and then subjected to various doses of SIN (10, 50 and 100 μg/mL) at 37°C for 24 h. Inflammatory factors and oxidative stress index were measured by ELISA. The expression of proteins was detected by Western blot. Results: The results showed that compared with the control group, the levels of ALT, AST and ALP in the serum of APAP-induced mice were significantly increased, followed by liver histological damage and hepatocyte apoptosis. Besides, APAP reduced the activity of SOD and GSH-Px, while increasing the content of MDA and LDH. Notably, APAP also promoted the expression of NLRP3, ASC, caspase-1 and IL-1β. Interestingly, SIN treatment dose-dependently reduced APAP-induced liver injury and oxidative stress, inhibited the activation of NLRP3 inflammasomes, and reduced the levels of inflammatory cytokines. In vitro studies have shown that SIN treatment significantly reduced the viability of BRL-3A cells and oxidative stress and inflammation. In addition, the Western blotting analysis showed that SIN inhibited the activation of TGF-β/Smad pathway in a dose-dependent manner in vitro and in vivo. These effects were significantly reversed by TGF-β/Smad activator SRI-011381 or TGF-β overexpression. Discussion: The study indicates that SIN attenuates APAP-induced acute liver injury by decreasing oxidative stress and inflammatory response via TGF-β/Smad pathway in vitro and in vivo.

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NF‐κB and AMPK/PI3K/Akt signaling pathways are involved in the protective effects of Platycodon grandiflorum saponins against acetaminophen‐induced acute hepatotoxicity in mice

Cited by 58 publications

References 48 publications

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

Immunomodulatory effects of fermentedPlatycodon grandiflorumextract through NF-κB signaling in RAW 264.7 cells

<p>Sinomenine Attenuates Acetaminophen-Induced Acute Liver Injury by Decreasing Oxidative Stress and Inflammatory Response via Regulating TGF-β/Smad Pathway in vitro and in vivo</p>

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