The hepatoprotective effects of Sedum sarmentosum extract and its isolated major constituent through Nrf2 activation and NF-κB inhibition

Wang, Guowei; Zhang, Xiaolong; Wu, Qinghua; Jin, Yong-Biao; Ning, Chun-Tao; Wang, Rui; Mao, Jingxin; Chen, Min

doi:10.1016/j.phymed.2018.09.023

Cited by 28 publications

(15 citation statements)

References 21 publications

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“…Studies have shown that the Hedgehog signaling pathway can activate the P13K/Akt pathway. P13K and its downstream molecule Akt are involved in NF-kB activity regulation, and they activate nuclear transcription factors, such as NF-kB, promote the production of several pro-inflammatory cytokines [34,38], and induce or sustain inflammation [6]. In the present study, LPS/D-GalN-induced liver tissues showed increased activity of the Hedgehog signaling pathway, which activated the P13K/Akt pathway, leading to increased liver injury and liver inflammation.…”

Section: Discussionsupporting

confidence: 48%

“…Acute liver injury was significantly alleviated, and the survival rate of the mice increased. Studies have shown that SS can prevent the occurrence of D-GalN/ LPS-induced acute liver injury by regulating antiinflammatory and anti-apoptosis mechanisms [33,34], but the specific mechanism is unclear. Therefore, we further explored the protective mechanisms of SS extract on LPS and D-GalN-induced acute liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence and development of acute liver injury are closely related with the activation of HMGB1, which can cause the excessive release of inflammatory mediators by triggering the downstream TLR4/NF-κB signaling pathway [34], leading to liver injury. miR-124 can transregulate the activity of HMGB1/TLR4/ NF-κB inflammatory pathways [39].…”

Section: Discussionmentioning

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RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway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: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…Drug-induced liver injury causes abnormalities in biomarkers in serum and the morphology of tissues. ALT, AST, ALP, TBIL, and DBIL are all important biochemical indicators for the diagnosis of liver injury in clinical trials [19]. In the present study, BUE significantly increased the serum levels of ALT, AST, ALP TBIL, and DBIL, indicating that liver injury was induced by BUE.…”

Section: Discussionsupporting

confidence: 60%

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Wang

Dong

Zhang

et al. 2019

Toxins

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Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.

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“…In this study, we found that SA diminished ICAM-1 expression and continuously To further understand the mechanism by which SA attenuated acute lung inflammation, the most well-known signaling pathways including NF-κB and Nrf2 signaling pathways were considered and tested on RAW264.7 cells. NF-κB (p50/p65 heterodimer) is sequestered by IκB and stays in inactive form unless the stimulus is given, and once it happens, IκB will be phosphorylated and NF-κB will dissociate and accumulate into the nucleus, continuing to regulate inflammatory cytokine genes transcription and expression (Li et al, 2019;Wang et al, 2019). Nrf2 signaling is a typical pathway of antioxidative stress mechanisms in cellular defense system.…”

Section: Discussionmentioning

confidence: 99%

Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF‐κB and Nrf2 signaling pathways

Huang

Fan

Zou³

et al. 2020

Phytotherapy Research

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Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPSinduced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.

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The hepatoprotective effects of Sedum sarmentosum extract and its isolated major constituent through Nrf2 activation and NF-κB inhibition

Cited by 28 publications

References 21 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

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis

Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF‐κB and Nrf2 signaling pathways

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