Esculin prevents Lipopolysaccharide/D-Galactosamine-induced acute liver injury in mice

Liu, Aiyun; Shen, Yongbin; Du, Ya-Ju; Chen, Jing; Pei, Feng‐Hua; Fu, Weiran; Jian, Qiao

doi:10.1016/j.micpath.2018.10.003

Cited by 41 publications

(29 citation statements)

References 24 publications

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Section: Introductionmentioning

confidence: 99%

“…Intraperitoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) is a convenient method of constructing model mice with acute liver injury [7]. LPS, a major component of endotoxins secreted by Gramnegative bacteria, causes apoptosis and necrosis of hepatocytes by stimulating the release of inflammatory factors from immune cells, including macrophages [7]. D-GalN inhibits the synthesis of biomacromolecules, such as RNA and protein, by consuming uridine triphosphate in the liver, thereby causing liver inflammation and diffused necrosis of hepatocytes [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…LPS, a major component of endotoxins secreted by Gramnegative bacteria, causes apoptosis and necrosis of hepatocytes by stimulating the release of inflammatory factors from immune cells, including macrophages [7]. D-GalN inhibits the synthesis of biomacromolecules, such as RNA and protein, by consuming uridine triphosphate in the liver, thereby causing liver inflammation and diffused necrosis of hepatocytes [7,8]. The synergistic effect of LPS and D-GalN causes the liver cells of experimental animals to die within a short time, and the liver physiological function becomes seriously impaired.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

Hao

Liu

et al. 2020

BMC Complement Med Ther

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Background: Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)induced acute liver injury in mice and the mechanism of such effects.Methods: Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 μg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice.Results: Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h.Conclusions: S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

Hao

Liu

et al. 2020

BMC Complement Med Ther

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“…Additionally, esculin showed wide pharmacological activities against different diseases, such as cognitive impairment in experimental diabetic nephropathy where it exhibited a strong anti-inflammatory activity marked by the suppressed p38 MAPK and JNK [142]. In models of streptozotocin-induced renal damage in diabetic mice [143], cold-restrained stress and pylorus ligation-induced ulcer [144], ethanol-induced gastric lesion [145], and LPS/D-galactosamine-induced acute liver injury [146], esculin significantly ameliorated inflammation evidenced by the suppressed TNF-α, IL-1β, and MPO. Li et al reported the protective role of esculin against LPS-induced macrophages and endotoxin shock in mice and NO production in vitro.…”

Section: Urolithin Amentioning

confidence: 99%

“…Pertaining to the impact of esculin on Nrf2 activation, Liu et al have shown that esculin attenuated acute liver injury in mice induced by LPS/D-galactosamine and reduced pathological symptoms of acute hepatic injury via suppression of NF-κB expression as well as activation of Nrf2/HO-1 signaling [146]. Another study by Kim et al reported that esculin activated Nrf2/ARE signaling in macrophages [148].…”

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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Chinese medicine in the treatment of autoimmune hepatitis: Progress and future opportunities

Liu

Han

et al. 2022

Anim Models and Exp Med

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Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease occurring in individuals of all ages with a higher incidence in females and characterized by hypergammaglobulinemia, elevated serum autoantibodies and histological features of interface hepatitis. AIH pathogenesis remains obscure and still needs in‐depth study, which is likely associated with genetic susceptibility and the loss of immune homeostasis. Steroids alone and in combination with other immunosuppressant agents are the primary choices of AIH treatment in the clinic, whereas, in some cases, severe adverse effects and disease relapse may occur. Chinese medicine used for the treatment of AIH has proven its merits over many years and is well tolerated. To better understand the pathogenesis of AIH and to evaluate the efficacy of novel therapies, several animal models have been generated to recapitulate the immune microenvironment of patients with AIH. In the current review, we summarize recent advances in the study of animal models for AIH and their application in pharmacological research of Chinese medicine‐based therapies and also discuss current limitations. This review aims to provide novel insights into the discovery of Chinese medicine‐originated therapies for AIH using cutting‐edge animal models.

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Esculin prevents Lipopolysaccharide/D-Galactosamine-induced acute liver injury in mice

Cited by 41 publications

References 24 publications

RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Chinese medicine in the treatment of autoimmune hepatitis: Progress and future opportunities

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