Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo

Liu, Dandan; Su, Jiarui; Lin, Jiashan; Qian, Gang; Chen, Xingxiang; Song, Suquan; Huang, Kehe

doi:10.1016/j.ijbiomac.2018.08.156

Cited by 40 publications

(31 citation statements)

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“…LBP was observed to significantly promote the production of ROS in a dose-dependent manner and also inhibit the LPS-induced ROS overproduction (Figure 3d and Figure S10). Other studies have shown that polysaccharides can enhance the body's antibacterial, antiviral and antitumor capabilities, while avoiding the excessive production of inflammatory factors that damage tissues and organs [37,38]. This set of results suggests that appropriate amounts of LBP have the potential not only to be used as an immunostimulator to enhance the immune response, but also to prevent immune damage caused by excessive activation of macrophages.…”

Section: Immunomodulatory Activities Of Lbp In Vitromentioning

confidence: 82%

Immunomodulatory Effects of Lycium barbarum Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level

et al. 2020

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Lycium barbarum L. is a widely used functional food and medicinal herb in Asian countries. L. barbarium polysaccharides (LBP) are considered as one of the major medicinal components of L. barbarium fruit and exhibits a wide range of biological activities. Here, we investigated the immunomodulatory effects of LBP and its uptake behaviors at the cellular level. LBP was prepared by water extraction and ethanol precipitation, and divided into two fractions based on the molecular weight distribution by ultrafiltration (LBP > 10 kDa and LBP < 10 kDa). The physicochemical properties of LBP and LBP fractions were well characterized. The LBP > 10 kDa fraction greatly enhanced the viability of macrophages RAW264.7 cells and induced cell polarization, but had weak effects to other tested tumor cell lines and normal cell line. This fraction could regulate the production of NO, TNF-α, IL-6 and ROS in RAW264.7 cells, suggesting both pro-inflammatory and anti-inflammatory effects. The dye-labeled LBP could be internalized into all tested cell lines and accumulated in lysosomes. The internalization of LBP in RAW264.7 cells is mainly through the clathrin-mediated endocytosis pathway. The Caco-2 intestinal transport experiment demonstrated that the dye labeled LBP could be transported through the Caco-2 cell monolayer (mimic intestinal epithelium) through clathrin-mediated endocytosis. These results demonstrate the immunomodulatory effects of LBP and its effective uptake by macrophages and intestine.

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Section: Immunomodulatory Activities Of Lbp In Vitromentioning

confidence: 82%

Immunomodulatory Effects of Lycium barbarum Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level

et al. 2020

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“…RT-qPCR was performed using the StepOnePlus Real-Time PCR System (Applied Biosciences) as previously described [50]. Total RNA was isolated from the cells using an RNA Extraction Kit (Takara, Japan) and then reverse-transcribed to cDNA using the PrimeScript RT Master Mix Kit (Takara, Japan).…”

Section: Methodsmentioning

confidence: 99%

Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury

Wang

et al. 2019

Preprint

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23Porcine epidemic diarrhea virus (PEDV) is a highly contagious pathogenic virus that 24 causes severe diarrhea and dehydration in pigs of all ages. Deoxynivalenol (DON), the 25 most abundant trichothecene in food and feed, causes vomit and diarrhea in animals 26 and human. However, whether DON exposure could affect PEDV infection remains 27 unknown. Herein, we investigated the impacts of DON on entry and replication of 28 PEDV, morbidity situation of piglets and the mechanisms involved. In vivo, twenty-29 seven piglets infected naturally with PEDV were randomly divided into three groups, 30 receiving the basal diet containing 0, 750 and 1500 μg/kg DON, respectively. We 31 observed significant increases in the diarrhea rates, the villous injury of jejunums and 32 the PEDV proliferation of duodenum, jejunum, ileum and mesenterium of piglets in 33 experimental groups compared with control. Additionally, the autophagosome-like 34 vesicles and the autophagy-related protein expressions were also increased in 35 experimental groups. In vitro, we observed that, approximately 2 hrs post-infection, 36 0.1, 0.5 and 1.0 μM DON promoted PEDV entry (P < 0.05) in IPEC-J2s and resulted 37 in tight junction protein occludin internalization. Knockdown of occludin and 38 CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of autophagy-induced 39 occludin internalization in DON-promoted PEDV entry. We also observed that, 24 hrs 40 post-infection, a significant increase in PEDV replication after 0.1, 0.5 and 1.0 μM 41 DON treatment, along with the induction of a complete autophagy. Specifically, 42 deletion of LC3B indicated a crucial role of autophagy in DON-promoted PEDV . CC-BY 4.0 International license author/funder. It is made available under aThe copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/852608 doi: bioRxiv preprint 3 43 replication. Pretreatment with SB202190, a p38 signaling inhibitor, abolished the 44 induction of autophagy. Furthermore, downregulation of type I interferon revealed that 45 DON contributed PEDV to escape innate immune. Mechanistically, DON-caused 46 innate immune escape was related to the upregulation of LC3B, which further inhibited 47 STING phosphorylation. Taken together, DON could promote PEDV infection by 48 inducing occludin internalization and innate immune escape via triggering p38-49 mediated autophagy.50 Author summary 53 Porcine epidemic diarrhea (PED), a devastating enteric disease, leads to catastrophic 54 economic loss to the global pig industry. Its primary pathogen is the coronavirus PED 55 virus (PEDV). Growing evidence indicates that pathogen infection is not the only factor 56 of PED outbreaks, other non-infectious factors is also related to this disease. We 57 guessed some ubiquitous substances, such as deoxynivalenol (DON), that lead to pig 58 intestinal epithelial cell stress might encourage the progress and spread of PED. In the 59 present study, the weaning piglets infected naturally with PEDV and the IPEC-J2 cell 60 lin...

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“…Tissue samples were fixed in 10% neutral buffered formalin, sectioned at a thickness 4 μm and processed for paraffin embedding. Hematoxylin and eosin (H&E) staining, Masson staining, and immunohistochemical analysis were used according to standard procedures 24 .…”

Section: Histopathological and Immunohistochemical Analysismentioning

confidence: 99%

Nontoxic concentration of ochratoxin A decreases the dosage of cyclosporine A to induce chronic nephropathy model via autophagy mediated by toll-like receptor 4

Hou

Lin

et al. 2020

Cell Death Dis

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Cyclosporine A (CsA) extracted from the products of fungal fermentation is used to develop a chronic nephropathy model. However, it has numerous side effects. Ochratoxin A (OTA) is a mycotoxin that induces renal injury. We developed a chronic nephropathy model to lessen the side effects of CsA by administration of nontoxic dosage of OTA, and investigated the underlying mechanism. C57BL/10 wild-type mice, toll-like receptor 4 (TLR4) −/− mice, and HK-2 cells were used in this study. The nontoxic dosage (0.25 mg/kg, qod) of OTA could significantly decrease the dosage of CsA from 30 to 20 mg/kg per day, and combination of them induced chronic nephropathy model and alleviated the side effects of onefold CsA in vivo, including cardiotoxicity, hepatotoxicity, and immunosuppression. The nontoxic concentration (0.5 μg/ml) of OTA could significantly decrease the concentration of CsA from 10 to 6 μg/ml that induced cytotoxicity, oxidative stress, and nephrotoxicity in vitro. Nontoxic concentration of OTA and low dosage of CsA activated TLR4 and autophagy. These toxic effects induced by OTA and CsA could be reversed by knockdown of TLR4 and autophagy inhibitor 3-methyladenine in vitro. Furthermore, the renal injury and autophagy induced by OTA and CsA could be attenuated in TLR4 −/− mice. It suggested that a chronic nephropathy model had been successfully developed by administration of nontoxic concentration of OTA and low dosage of CsA via TLR4-mediated autophagy. The side effects of current model were significantly lesser than those of the previous model induced by onefold CsA. It provided a new tool for exploring the pathogenesis and treatment of chronic kidney disease.

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Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo

Cited by 40 publications

References 38 publications

Immunomodulatory Effects of Lycium barbarum Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level

Immunomodulatory Effects of Lycium barbarum Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level

Deoxynivalenol Promotes Porcine Epidemic Diarrhea Virus Infection and Aggravates Gut Barrier Injury

Nontoxic concentration of ochratoxin A decreases the dosage of cyclosporine A to induce chronic nephropathy model via autophagy mediated by toll-like receptor 4

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