Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats

Lai, Liangxue; Chen, Yun-Xia; Tian, Xiaoxia; Li, Xujiong; Zhang, Xiaojing; Lei, Jingwen; Bi, Yanghui; Bu-wu, Fang; Song, Xiantao

doi:10.1016/j.ejphar.2015.08.040

Cited by 69 publications

(35 citation statements)

References 37 publications

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“…Toll-like receptors (TLRs), as an important mediator of cerebral ischemic injury, have played an important role in the initial activation of immune cell responses. Studies found that artesunate could significantly reduce the expressions of TLR4 and myeloid differentiation factor 88 (MyD88) in lipopolysaccharide-stimulated proinflammatory responses and experimental hepatic fibrosis, which serves as the underline mechanism for the anti-inflammation effect of artesunate [59–61]. So, artesunate probably has the effect of inhibiting the activation of immune cell responses in cerebral ischemic injury.…”

Section: Effect Of Artesunate On Central Nervous System Diseasesmentioning

confidence: 99%

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Zuo

Liu

et al. 2016

BioMed Research International

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Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future.

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Section: Effect Of Artesunate On Central Nervous System Diseasesmentioning

confidence: 99%

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Zuo

Liu

et al. 2016

BioMed Research International

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“…Artesunate (ART), a small molecule derived from Artemisinin extracted from the traditional Chinese herb Artemisia annua, markedly inhibits the progression of hepatic fibrosis by downregulating matrix metalloproteinases 2 and 9 in rats induced by bovine serum albumin [ 22 ]. However, only few published studies have investigated the anti-fibrogenic properties of ART [ 23 , 24 ]. In myelodysplastic syndrome (MDS) cells (SKM-1 cells), ART regulates apoptosis by inhibiting the expression of downstream targets of Wnt/β-catenin signaling pathway, such as c-Myc and cyclin D1 [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells

Bai

Wang

et al. 2018

BMC Pharmacol Toxicol

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BackgroundAn increasing number of studies are investigating the effects of Chinese medicine on hepatic fibrosis, but only few studies have examined the anti-fibrogenic properties of Artesunate (ART). The aim of the present study was to explore the anti-fibrotic effects of ART on LX-2 cells, the human HSC cell line, and to determine potential molecular mechanisms via the focal adhesion kinase (FAK)/ protein kinase B (Akt)/ β-catenin pathway.MethodsLX-2 cells were stimulated with different concentration of ART (0, 12.5, 25 and 50 μg/ml) for 12, 24, 48 or 72 h, their proliferation was analyzed using the Cell Counting Kit-8 (CCK-8) assay. LX-2 cells were treated with different doses of ART (0, 12.5, 25 and 50 μg/ml) for 24 h, their apoptosis was measured using flow cytometry, the levels of mRNAs encoding collagen I or α-smooth muscle actin (α-SMA) were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the levels of key proteins in the FAK/Akt/β-catenin signaling pathway were assessed by western blotting. Specific inhibitors of FAK were added to the LX-2 cells cultures to explore the potential signaling.ResultsExposing LX-2 cells to ART efficiently inhibited their proliferation, significantly promoted early apoptosis in a dose-dependent manner, and markedly downregulated the mRNA expression of α-SMA and collagen I. In addition, ART, similar to FAK inhibitor PF562271 significantly inhibited the FAK/Akt/β-catenin signaling pathway by reducing the levels of phosphorylated FAK, Akt and GSK-3β.ConclusionsOur present study shows that ART could regulate the proliferation, apoptosis and activation of LX-2. Meanwhile, the anti-fibrogenic mechanisms of ART was correlated with FAK/Akt/β-catenin pathway. Future research should verify and extend these findings, as well as explore other molecules and therefore serve as useful therapeutic targets.

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“…Toll-like receptors (TLRs) are reported to play an important role in regulation of innate and adaptive immune responses and are related to inflammatory liver diseases [ 13 ]. TLR4, a critical transmembrane recognition receptor, is associated with development of non-alcoholic steatohepatitis [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tetrahydropalmatine Prevents High-Fat Diet-Induced Hyperlipidemia in Golden Hamsters (Mesocricetus Auratus)

et al. 2018

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BackgroundHyperlipidemia is a major cause of atherosclerotic cardiovascular disease. Tetrahydropalmatine (THP) can exhibit hepatoprotective, anti-arrhythmic, and anti-inflammatory activities. The mechanism of THP on the hyperlipidemia remains unknown; therefore, the present study explored the role of THP in hyperlipidemia.Material/MethodsWe established an animal model of hyperlipidemia by high-fat diet (HFD) feeding. Blood samples were obtained for determination of serum cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), pro-inflammatory cytokines, and CYP7A1 expression. Histology was performed and inflammation was detected in the liver using hematoxylin-eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA and protein levels of TLR4 and TRAF-6 were determined by quantitative real-time PCR (qPCR) and Western blot, respectively.ResultsTHP suppressed hepatic lipid accumulation and reduced serum levels of TC, TG, LDL-c, and HDL-c in HFD-fed golden hamsters. THP increased cholesterol 7 α-hydroxylase (CYP7A1) expression and prevented inflammation by the limited reduction in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions in serum and liver. THP slightly increased the ratio of the body/liver weight. THP inhibited the mRNA and protein levels of Toll-like receptor 4 (TLR4) and TNF-receptor associated factor-6 (TRAF-6).ConclusionsThese results suggest that THP attenuates hyperlipidemia by multiple effects, including hepatoprotective and anti-inflammatory effects. Moreover, THP also suppressed the expressions of TLR4 and TRAF-6 in golden hamsters.

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Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats

Cited by 69 publications

References 37 publications

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Artesunate may inhibit liver fibrosis via the FAK/Akt/β-catenin pathway in LX-2 cells

Tetrahydropalmatine Prevents High-Fat Diet-Induced Hyperlipidemia in Golden Hamsters (Mesocricetus Auratus)

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