Search

Fibrotic kidney injury from hepatocarcinogenesis seriously impacts treatment effect. Astragaloside IV (AS-IV), an extract of Astragalus membranaceus, has several pharmacological activities, which are useful in the treatment of edema and fibrosis. Nrf2/HO-1 is a key antioxidant stress pathway and help treatment of kidney injury. Smad3 phosphorylation is implicated in hepatocarcinogenesis. Our previous study clarified that Smad3 is differentially regulated by different phosphorylated forms of Smad3 on hepatocarcinogenesis. Therefore, we investigated the contribution of AS-IV on the therapy of kidney fibrosis from hepatocarcinogenesis. And the focus was on whether the phosphorylation of Smad3 and the regulation of Nrf2/HO-1 pathway were involved during AS-IV therapy and whether there is an effect of Nrf2 knockout on the phosphorylation of Smad3. We performed TGF-β1 stimulation on HK-2 cells and intervened with AS-IV. Furtherly, we investigated renal injury of AS-IV on Nrf2 knockout mice during hepatocarcinogenesis and its mechanism of action. On the one hand, in vitro results showed that AS-IV reduced the ROS and α-SMA expression of HK-2 by promoting the expression pSmad3C/p21 of and Nrf2/HO-1 and suppressed the expression of pSmad3L/PAI-1. On the other hand, the in vivo results of histopathological features, serological biomarkers, and oxidative damage indicators showed that Nrf2 knockout aggravated renal injury. Besides, Nrf2 deletion decreased the nephroprotective effect of AS-IV by suppressing the pSmad3C/p21 pathway and promoting the pSmad3L/PAI-1 pathway. The experimental results were as we suspected. And we identify for the first time that Nrf2 deficiency increases renal fibrosis from hepatocarcinogenesis and attenuates the therapeutic effects of AS-IV via regulating pSmad3C/3L signal pathway. [ABSTRACT FROM AUTHOR]

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin–eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV), one of the major compounds extract from Astragalus membranaceus, has shown attractive anti-cancer effects in certain malignancies. Oxidative stress (OS) is considered as a crucial factor in promoting the progression of hepatocellular carcinoma (HCC). In response to OS, nuclear factor erythroid 2-related factor 2 (Nrf2) upregulates and induces heme oxygenase 1 (HO-1) to combat oxidative damages. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) activates p21 to resist HCC progression, while the phosphorylation of the linker region of Smad3 (pSmad3L) up-regulates c-Myc transcription to exert promoting effect towards HCC. This study aimed to explore whether AS-IV suppresses migration and invasion of human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-β1/Smad3 pathways. HuH-7 cells were induced with TGF-β1 (9 or 40 pM) to establish HCC model in vitro and pretreated with AS-IV at different concentration (5, 10, and 20 μM) for 24 h. Cell proliferation, migration, invasion, and intracellular reactive oxygen species (ROS) of HuH-7 cells were measured. The expression of Nrf2, pSmad3C, Nrf2/pNrf2, HO-1, pSmad3C/3L, c-Myc, and p21 were detected. Exposure of HuH-7 cells to TGF-β1 enhanced the cell proliferation, migration, invasion, and ROS production. Pretreatment with AS-IV (5, 10, and 20 μM) significantly reduced the cell proliferation, migration, invasion, and ROS production in HuH-7 cells. Furthermore, AS-IV increased the expressions of Nrf2/pNrf2, HO-1, pSmad3C, and p21, meanwhile reduced the expressions of pSmad3L and c-Myc. In conclusion, our study suggested that AS-IV inhibit HuH-7 cells migration and invasion, which related to activate Nrf2/HO-1 pathway, up-regulation pSmad3C/p21 pathway, and down-regulation pSmad3L/c-Myc pathway. The present research supports the notion that AS-IV may be a latent agent for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium–treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition. [ABSTRACT FROM AUTHOR]