Protective effect of ginsenoside Rg5 against kidney injury via inhibition of NLRP3 inflammasome activation and the MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Zhu, Yanyan; Zhu, Chenhui; Yang, Haixia; Deng, Jianjun; Fan, Daidi

doi:10.1016/j.phrs.2020.104746

Cited by 110 publications

(67 citation statements)

References 54 publications

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“…In addition, given its capacity to increase the insulin-like growth factor-I (IGF-1), cepharanthine was shown to lower blood glucose and decrease insulin resistance [ 94 ]. Similar results were found for ginsenoside Rg5, whereby the kidneys of high-fat diet/streptozotocin-induced diabetic mice were able to decrease the expression levels of NLRP3, ASC and caspase-1, IL-1β and IL-18 as well as the expression of NF-kB and P38 MAPK phosphorylation, thus improving renal injury through the reduction in inflammation [ 103 ].…”

Section: Nutraceutical Compounds the Nlrp3 Inflammasome And Type supporting

confidence: 70%

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

Castejón-Vega

Giampieri

Álvarez-Suarez

2020

IJMS

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The macromolecular complex known as “inflammasome” is defined as an intracellular multi-protein complex composed of a sensor receptor (PRR), an adaptor protein and an effector enzyme (caspase-1), which oligomerize when they sense danger, such as how the NLR family, AIM-2 and RIG-1 receptors protect the body against danger via cytokine secretion. Within the NLR members, NLRP3 is the most widely known and studied inflammasome and has been linked to many diseases. Nowadays, people’s interest in their lifestyles and nutritional habits is increasing, mainly due to the large number of diseases that seem to be related to both. The term “nutraceutical” has recently emerged as a hybrid term between “nutrition” and “pharmacological” and it refers to a wide range of bioactive compounds contained in food with relevant effects on human health. The relationship between these compounds and diseases based on inflammatory processes has been widely exposed and the compounds stand out as an alternative to the pathological consequences that inflammatory processes may have, beyond their defense and repair action. Against this backdrop, here we review the results of studies using several nutraceutical compounds in common diseases associated with the inflammation and activation of the NLRP3 inflammasomes complex. In general, it was found that there is a wide range of nutraceuticals with effects through different molecular pathways that affect the activation of the inflammasome complex, with positive effects mainly in cardiovascular, neurological diseases, cancer and type 2 diabetes.

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Section: Nutraceutical Compounds the Nlrp3 Inflammasome And Type supporting

confidence: 70%

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

Castejón-Vega

Giampieri

Álvarez-Suarez

2020

IJMS

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“…Previous studies have confirmed that inflammasomes promote inflammation, and chronic inflammatory response triggered by a variety of immune cells is crucial for PM2.5‐induced pulmonary inflammation 4,5 . NOD‐like receptor protein 3 (NLRP3) inflammasome is an intracellular multi‐protein complex containing NLRP3, apoptotic speck protein (ASC), and pro‐caspase‐1 6 . When stimulated, the NLRP3 inflammasome promotes caspase‐1 activation and subsequently converting pro‐interleukin‐1β (IL‐1β) and pro‐IL‐18 into their mature bioactive forms.…”

Section: Introductionmentioning

confidence: 98%

PM2.5‐induced pulmonary inflammation via activating of the NLRP3/caspase‐1 signaling pathway

Jia

Liu

Guo

et al. 2020

Environmental Toxicology

106

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Particulate matter 2.5 (PM2.5)‐induced pulmonary inflammation has become a public concern in recent years. In which, the activation of the NLRP3/caspase‐1 pathway was closely related to the inflammatory response of various diseases. However, the promotion effect of the NLRP3/caspase‐1 pathway on PM2.5‐induced pulmonary inflammation remains largely unclear. Here, our data showed that PM2.5 exposure caused lung injury in the mice by which inflammatory cell infiltration occurred in lung and alveolar structure disorder. Meanwhile, the exposure of human bronchial epithelial cells (16HBE) to PM2.5 resulted in suppressed cell viability, as well as elevated cell apoptosis. Moreover, a higher level of inflammatory cytokine and activation of the NLRP3/caspase‐1 pathway in PM2.5‐induced inflammation mice models and 16HBE cells. Mechanistically, pretreatment with MCC950, a NLRP3/caspase‐1 pathway inhibitor, prevented PM2.5‐induced lung injury, inflammatory response, and the number of inflammatory cells in BALFs, as well as promoted cell viability and decreased inflammatory cytokine secretion. Collectively, our findings indicated that the NLRP3/caspase‐1 pathway serves a vital role in the pathological changes of pulmonary inflammation caused by PM2.5 exposure. MCC950 was expected to be the therapeutic target of PM2.5 inhalation mediated inflammatory diseases.

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“…Studies have shown that excessive ROS can promote the production of cytokines and transcription factors, ultimately leading to the synthesis and deposition of extracellular matrix and promoting the progression of renal fibrosis and end-stage renal failure in the early and late stages of DN [60,61]. The thioredoxin (TRX) system plays an important role in defending against oxidative stress [62] and is closely related to the NLRP3 inflammasome signaling pathway [63]. The TRX system consists of NADPH, TRXR, TRX, and TXNIP.…”

mentioning

confidence: 99%

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

Zhang

Tao

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of Astragalus membranaceus (Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats. Methods. Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (n=8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1β, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot. Results. In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs, IL-1β, and IL-18 expression and fibrosis indexes in the kidney of rats. Conclusion. AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.

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Protective effect of ginsenoside Rg5 against kidney injury via inhibition of NLRP3 inflammasome activation and the MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Cited by 110 publications

References 54 publications

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

Nutraceutical Compounds Targeting Inflammasomes in Human Diseases

PM2.5‐induced pulmonary inflammation via activating of the NLRP3/caspase‐1 signaling pathway

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

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