Madecassoside prevents acute liver failure in LPS/D-GalN-induced mice by inhibiting p38/NF-κB and activating Nrf2/HO-1 signaling

Wang, Wei; Wu, Lingling; Li, Qing; Zhang, Zhuo; Xu, Liba; Lin, Caixia; Gao, Ling; Zhao, Kaili; Liang, Fei; Zhang, Qing; Jiang, Weizhe

doi:10.1016/j.biopha.2018.04.162

Cited by 40 publications

(28 citation statements)

References 48 publications

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“…Three mechanisms are reported in the studies: asiatic acid can reduce the level of pro-apoptotic factors (B-cell lymphoma 2(Bcl-2) ↑, Bcl-2-associated X protein(Bax) ↓, caspase-3 ↓), and related inflammation factors (TGF-β1 ↓, TNF-α ↓, IL-6 ↓, IL-1β ↓), and increase the level of anti-oxidative stress factors (SOD ↑, GSH-Px ↑, CAT ↑, GST ↑, GSH ↑) ( Xiao et al, 2017 ; Siddique et al, 2017 ; Wei et al, 2018 .). The study on madecassoside found that it could ameliorate drug-induced acute liver failure by reducing inflammation (TNF-α ↓, IL-1β ↓, IL-6 ↓, iNOS ↓, COX-2 ↓) and oxidative stress (SOD ↑, CAT ↑, GPx ↑, Nrf2 ↑, HO-1 ↑) ( Wang W. et al, 2018 ). Oral administration of the four components of C. asiatica could attenuate colitis in mice, but it’s mainly madecassoside acid, the active form of madecassoside, when topically administered in the colon, weakened colitis by regulating Th17/Treg balance via affecting the PPARγ/AMPK/ACC1 pathway ( Xu et al, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

Sun

et al. 2020

Front. Pharmacol.

177

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Centella asiatica (also known as Centella asiatica (L.) Urb. or Gotu kola) is a traditional Chinese medicine with extensive medicinal value, which is commonly used in Southeast Asian countries. This study aimed to summarize the effects of C. asiatica and its main components on neurological diseases, endocrine diseases, skin diseases, cardiovascular diseases, gastrointestinal diseases, immune diseases, and gynecological diseases, as well as potential molecular mechanisms, to study the pathological mechanism of these diseases based on the changes at the molecular level. The results showed that C. asiatica and its triterpenoids had extensive beneficial effects on neurological and skin diseases, which were confirmed through clinical studies. They exhibited anti-inflammatory, antioxidative stress, anti-apoptotic effects, and improvement in mitochondrial function. However, further clinical studies are urgently required due to the low level of evidence and lack of patients.

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Section: Resultsmentioning

confidence: 99%

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

Sun

et al. 2020

Front. Pharmacol.

177

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“…TNF-α and IL-1β are the most representative pro-inflammatory cytokines in inflammatory factors, and many studies have also shown that IL-1β and TNF-α play key roles in the development and maintenance of inflammation, while inflammatory cytokines are horizontally increased, which is related to liver disease [ 36 , 37 ]. Inflammatory mediators such as TNF-α are up-regulated and might induce liver damage via multiple cytotoxic mechanisms [ 38 ]. TNF-α can induce pleiotropic cytokines produced by a variety of physiological and pathological conditions [ 39 ].…”

Section: Discussionmentioning

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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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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“…Acute liver injury mice model was induced as described by Wang et al (2018). Briefly, mice were randomly divided into 6 groups ( n = 6 per group): (1) Normal (0.4% CMC), (2) Model (3 mg/kg LPS), (3) LPS+T11-L (2.8 mg/kg, Low dose), (4) LPS+T11-M (14 mg/kg, Middle dose), (5) LPS+T11-H (28 mg/kg, High dose), (6) LPS+PA (Prednisone acetate, PA as a positive control, 1.3 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways

et al. 2018

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Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only regulates oxidative stress response, but also represses inflammation by regulating cytokines production and cross-talking with NF-κB signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of this study is to clarify the regulating effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS-stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines production (TNF-α, IL-6 and IL-1β). The antioxidant responsive element (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD, histopathology and neutrophils/macrophages filtration) and the underlying protection mechanisms of ALI amelioration (Nrf2 and NF-κB signaling pathway) of T11. Firstly, the results showed that T11 can not only effectively decrease the productions of inflammatory cytokines (TNF-α, IL-6 and IL-1β), ROS and NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11 could dramatically decrease the oxidative stress responses (SOD and MDA) and inflammation (histopathology, neutrophils/macrophages filtration, TNF-α, IL-6 and IL-1β production) in LPS-induced ALI in BALB/c mice. Finally, the results implied that T11 could dramatically increase Nrf2 protein expression and decrease p-TAK1, p-IκBα and NF-κB protein expression both in vivo and in vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced oxidative stress and inflammation by regulating Nrf2 and NF-κB signaling pathways in vitro and in vivo, which offers a novel insights for the application of TwHF in clinical.

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Madecassoside prevents acute liver failure in LPS/D-GalN-induced mice by inhibiting p38/NF-κB and activating Nrf2/HO-1 signaling

Cited by 40 publications

References 48 publications

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

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

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways

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