Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Wu, Song; Lin, Wei; Du, Yanwei; Wang, Yimei; Jiang, Shuang

doi:10.1016/j.intimp.2018.07.027

Cited by 120 publications

(76 citation statements)

References 42 publications

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“…Our previous study demonstrated, for the first time, that ginsenoside CK could improve the depressive-like behavior in rats with CUMS (chronic unpredictable mild stress)-induced depression, which may be related to the regulation of hippocampal and prefrontal cortical neurotransmitters [6]. In addition, our series of studies on ginsenoside CK also found that it could alleviate kidney damage in diabetic nephropathy rats by inhibiting NF-jB and NLRP3 inflammasome signalling pathways [7]. Therefore, given the available experimental evidence, we speculate that ginsenoside CK may attenuate central inflammation by inhibiting NLRP3 inflammasome of the central nervous system, which may be another mechanism of the antidepressant effect of CK.…”

Section: Introductionmentioning

confidence: 73%

Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Tang

et al. 2019

Biotechnology & Biotechnological Equipment

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Depression, a mood disorder characterized by persistently low mood and feeling of sadness, has been a more and more serious problem today. NLRP3 (the NACHT, LRR and PYD domainscontaining protein 3) inflammasome-mediated central inflammation is recently considered to contribute to the pathology of depression. Based on previous findings that ginsenoside compound K (CK), a ginsenoside metabolite, exhibited antidepressant effects in rats, here we studied whether the antidepressant effects of CK are associated with inhibiting the oxidative stress, NLRP3 inflammasome or inflammatory cytokine in hippocampus of mice exposed to chronic unpredictable mild stress (CUMS). CK (3, 10 and 30 mg/kg) was intragastrically administered for 4 weeks. The depression-like behaviors, oxidative stress parameters, inflammatory cytokines and NLRP3 expression in the hippocampus were evaluated. The results showed that after 4 weeks of administration, CK (30 mg/kg) alleviated the depressant-like behaviors, including shorter immobility time in both the forced swimming test and the tail suspension test, and increased the sucrose preference. In addition, the levels of IL-1b, IL-18 in the hippocampus were significantly decreased in CK-treated groups. The western blot and immunohistochemistry results revealed that the expression levels of NLRP3 inflammasome components (NLRP3 and cleaved caspase-1) were down-regulated in hippocampus of CK-treated mice. These results demonstrate that the antidepressant effect of CK is, at least partially, associated with suppression of oxidative stressinduced NLRP3 inflammasome activation and inhibition of the release of corresponding inflammatory cytokines in the hippocampus.

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Section: Introductionmentioning

confidence: 73%

Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Tang

et al. 2019

Biotechnology & Biotechnological Equipment

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“…AMPK also ameliorates the NF-κB related inflammatory response through activation of SIRT1 and PGC-1α [9,10]. SIRT1 suppresses NF-κB by deacetylation of p65 and decreases priming of NLRP3 protein [10]. One previous study suggested that SIRT1 decreased activation of NLRP3 inflammasome in vitro [10].…”

Section: Discussionmentioning

confidence: 99%

“…AMPK has some physiological effects on mitochondrial biogenesis and glucose metabolism. AMPK also ameliorates the NF-κB related inflammatory response through activation of SIRT1 and PGC-1α [9,10]. SIRT1 suppresses NF-κB by deacetylation of p65 and decreases priming of NLRP3 protein [10].…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1 suppresses NF-κB by deacetylation of p65 and decreases priming of NLRP3 protein [10]. One previous study suggested that SIRT1 decreased activation of NLRP3 inflammasome in vitro [10]. Furthermore, SIRT1 was found to preserve podocyte function by regulating claudin-1, which induces podocyte effacement and albuminuria [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…Renal function was examined by measurement of urinary albumin/creatinine ratio (ACR), plasma creatinine, and blood urea nitrogen (BUN). To measure the degree of urinary albumin excretion, spot urine samples were collected by bladder massage at the initial (0-4 week), mid (4-8 week), and late (8)(9)(10)(11)(12) week) stages of the experiment. Urinary albumin excretion was determined according to bromocresol green (BCG) albumin quantification method using a commercial albumin assay kit (Bioassay, Hayward, CA, USA).…”

Section: Renal Function Testmentioning

confidence: 99%

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Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

Park¹,

Lee²,

Kim³

et al. 2020

Antioxidants

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads to morphological and functional changes in kidney. A previous study showed a protective effect of Lespedeza bicolor extract (LBE) on endothelial dysfunction induced by methylglyoxal glucotoxicity. We aimed to investigate whether LBE ameliorated renal damage through regulation of NLRP3 inflammasome-dependent hyper-inflammation in T2DM mice. After T2DM induction by a high fat diet and low dose of streptozotocin (30 mg/kg), the mice were administered with different dosages of LBE (100 or 250 mg/kg/day) by gavage for 12 weeks. LBE supplementation ameliorated kidney dysfunction demonstrated by urine albumin-creatinine at a low dose and plasma creatinine, blood urea nitrogen (BUN), and glomerular hypertrophy at a high dose. Furthermore, a high dose of LBE supplementation significantly attenuated renal hyper-inflammation associated with NLRP3 inflammasome and oxidative stress related to nuclear factor erythroid 2-related factor 2 (Nrf-2) in T2DM mice. Meanwhile, a low dose of LBE supplementation up-regulated energy metabolism demonstrated by phosphorylation of adenosine monophosphate kinase (AMPK) and Sirtuin (SIRT)-1 in T2DM mice. In conclusion, the current study suggested that LBE, in particular, at a high dose could be used as a beneficial therapeutic for hyperglycemia-induced renal damage in T2DM.

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MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions

Zheng,

Zhang,

Wang

et al. 2024

Archiv der Pharmazie

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The NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.

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Protective effect of ginsenoside metabolite compound K against diabetic nephropathy by inhibiting NLRP3 inflammasome activation and NF-κB/p38 signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Cited by 120 publications

References 42 publications

Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions

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