Effects of Artesunate prevent nephritis via the Toll-like receptor 4/nuclear factor-κB signaling pathway in rats

Abstract

The active ingredient in Artemisia carvifolia, artemisinin, may alleviate inflammation and toxicity. Artemisinin and its derivatives are first‑line anti‑malarial drugs currently, which have rapid effects on fever caused by malaria parasites with fewer side effects. The present study investigated the effects of Artesunate in a mouse nephritis model. Mice were injected intraperitoneally with 500 µl pristine to induce nephritis, and were treated with 28.8 mg/kg Artesunate. Subsequently, proteinuria, renal function, and tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 levels were assessed to evaluate the effects of Artesunate on nephritis. Western blot analysis was used to measure the protein expression levels of α‑smooth muscle actin (SMA), TLR4, myeloid differentiation primary response gene 88 (MyD88), NF‑κB p65 and transforming growth factor (TGF)‑β1 to investigate the underlying mechanisms of Artesunate on nephritis. The results demonstrated that Artesunate reduced proteinuria and preserved renal function in nephritis mice. Artesunate attenuated TNF‑α and IL‑6 levels, suppressed α‑SMA, TLR4, MyD88, NF‑κB p65 and TGF‑β1 protein expression, and decreased caspase‑3 activity in nephritis mice. These results indicated that the effects of Artesunate may prevent nephritis and inhibit inflammation via the TLR4/NF‑κB signaling pathway in mice. Therefore, Artesunate may be a potential therapeutic agent to prevent nephritis.

Artesunate promotes the proliferation of neural stem/progenitor cells and alleviates Ischemia-reperfusion Injury through PI3K/Akt/FOXO-3a/p27kip1 signaling pathway

“…ART is widely used in clinical practice and is recommended by the World Health Organization for the treatment of malaria, especially for cerebral and falciparum malaria [16]. ART has been intensively investigated due to its potential functions involved in anti-tumor [4], immune regulation [5], inhibition of inflammation [6], and treatment of type I diabetes [7]. An animal model of subarachnoid hemorrhage has been established in our previous study, and the data revealed that ART could protect the blood-brain barrier by activating sphingosine 1 phosphate receptor 1/phosphatidylinositol 3 kinase (S1pR/PI3K) signaling pathway [8].…”

“…The proliferation of endogenous NSPCs triggered by trauma or ischemia, is not sufficient enough to induce neural repair, which could contribute to permanent disability in stroke patients [3]. Artesunate (ART) is a watersoluble derivative of artemisinin, which has been intensively investigated due to its potential functions involved in anti-tumor [4], immune regulation [5], inhibition of inflammation [6], and treatment of type I diabetes [7]. Our previous study using an established animal model of subarachnoid hemorrhage revealed that ART could protect the blood-brain barrier AGING by activating sphingosine 1 phosphate receptor 1/phosphatidylinositol 3 kinase (S1pR/PI3K) signaling pathway [8].…”

The Therapeutic Effect of Artemisinin and Its Derivatives in Kidney Disease

“…For LN mice, it has been reported that treatment with ARSs could decrease interferon-gamma (IFN-g), tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) in serum, and blocked intercellular adhesion molecule-1 (ICAM-1), fractalkine, NF-kB signaling pathway in renal (Dong et al, 2003;Li et al, 2006;Wang et al, 2010;You et al, 2014;Liang et al, 2018). A similar effect was observed in the nephritis and septic AKI models Wan and Li, 2017;Liu et al, 2019). Also, ARSs were reported to inhibit disease progression via downregulating renal monocyte chemoattractant protein 1 (MCP-1) expression in LN, IgAN, and septic AKI models (Mi et al, 2009;Jin et al, 2009;Ma et al, 2009;Liu et al, 2019).…”

Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

“…Artemisinins downregulated the levels of MMP2 and TIMP-2 whilst up-regulating E-cadherin in hepatocarcinoma cells lines ( Zhao, Zhang, Xu, & Wang, 2017 ). Artesunate has been shown to upregulate the expression of adhesion molecules integrin β1 and neural cell adhesion molecule (NCAM) in embryonal rhabdomyosarcoma cells, thereby reducing migration and invasion ( Wan & Li, 2017 ).…”

“…The anti-inflammatory effects of artesunate have also been investigated in animal models of myocardial ischaemia, acute lung injury and nephritis ( Efferth et al, 2007 ; Liu et al, 2018 ; Wan & Li, 2017 ; Zhao et al, 2017 ). In a rat model of transient myocardial ischemia, artesunate conferred myocardial protection via inhibition of glycogen synthase kinase- 3β, inhibition of NF-κB, activation of endothelial NOS, activation of the STAT3 (SAFE) pathway and activation of the PI3K/Akt/ERK 1/2 (RISK) pathway ( Khan et al, 2018 ).…”