The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-κB signaling

Jiang, Yuchen; Yang, Liman; Yang, Xiaojing; Yin, Sihui; Zhuang, Fei; Liu, Zhiguo; Wang, Yi; Liang, Guang; Qian, Jianchang

doi:10.1016/j.bbrc.2020.03.016

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Relevant findings have been shown in other reports. For example the development of DN was associated with lipopolysaccharide-induced inflammation (Jiang et al, 2020), gut microbiota dysbiosis (Fernandes et al, 2019), and oxidative stress (Gerardo Yanowsky-Escatell et al, 2020), which were partially in line with our findings. Notably, a previous study indicated the crosstalk between inflammation and oxidative stress mechanisms in DN pathogenesis (Samsu, 2021).…”

Section: Discussionsupporting

confidence: 89%

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

QIAN,

REN,

ZHAO

et al. 2023

Biocell

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Background: Diabetic nephropathy (DN) is a serious complication of diabetes with rising prevalence worldwide. We aimed to explore the anti-DN mechanisms of the compound celastrol derived from the medicinal plant Tripterygium wilfordii. Methods: Celastrol-related targets were obtained from Herbal Ingredients' Targets (HIT) and GeneCards databases. DN-related targets were retrieved from GeneCards, DisGeNET, and Therapeutic Targets Database (TTD). A Protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using ClusterProfiler. The cytoHubba plugin was used to select the top 10 hub targets. Molecular docking was performed employing PyMOL and AutoDock software. Cell counting kit-8 (CCK-8) and flow cytometry assays were used to detect the viability and apoptosis of NRK-52E cells, respectively. The mRNA expression levels of mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and AKT serine/threonine kinase 1 (AKT1) in NRK-52E cells were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We obtained sixty-six overlapping targets of celastrol and DN. GO and KEGG analyses demonstrated that the core targets of celastrol and DN were mainly involved in the inflammatory and immune response, oxidative stress, advanced glycation end products (AGEs) and their receptors (RAGEs) (AGE-RAGE), TNF, interleukin 17 (IL-17), and MAPK signaling pathways. Finally, based on the good binding activity with celastrol, MAPK3, TNF, and AKT1 were identified as the foremost targets of celastrol. We observed that celastrol enhanced the viability of high glucose (HG)-treated NRK-52E cells and inhibited apoptosis in the in vitro assays. Moreover, celastrol decreased the mRNA expression levels of MAPK3, TNF, and AKT1 in high glucose (HG)-treated NRK-52E cells. Conclusion: Celastrol may treat DN by targeting APK3, TNF, and AKT1 and regulating inflammatory responses and oxidative stress through the AGE-RAGE, TNF, IL-17, and MAPK signaling pathways.

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Section: Discussionsupporting

confidence: 89%

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

QIAN,

REN,

ZHAO

et al. 2023

Biocell

View full text Add to dashboard Cite

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“…In addition, TSF was found to suppress the TLR4/c-Jun N-terminal kinase (JNK) and NF- κ B signaling pathways in the kidneys. This suppression resulted in a decrease in microalbuminuria and serum creatinine levels, as well as the inhibition of moderate expansion of the kidney thylakoid matrix, luminal dilatation, and tubular interstitium of rats with DKD induced by STZ and uninephrectomy [ 215 ]. Furthermore, a purified preparation of anthraquinone-glycosides derived from rhubarb, which are monomeric compounds found in rhubarb, has been shown to reduce inflammation in individuals with DM [ 216 ] ( Table 1 ).…”

Section: The Role Of Gut Microecological Interventions In Retarding T...mentioning

confidence: 99%

Role of Gut Microbiota, Immune Imbalance, and Allostatic Load in the Occurrence and Development of Diabetic Kidney Disease

Han,

Zheng,

et al. 2023

Journal of Diabetes Research

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Diabetic kidney disease (DKD) is a prevailing complication arising from diabetes mellitus. Unfortunately, there are no trustworthy and efficacious treatment modalities currently available. In recent times, compelling evidence has emerged regarding the intricate correlation between the kidney and the gut microbiota, which is considered the largest immune organ within the human physique. Various investigations have demonstrated that the perturbation of the gut microbiota and its associated metabolites potentially underlie the etiology and progression of DKD. This phenomenon may transpire through perturbation of both the innate and the adaptive immunity, leading to a burdensome allostatic load on the body and ultimately culminating in the development of DKD. Within this literature review, we aim to delve into the intricate interplay between the gut microbiota, its metabolites, and the immune system in the context of DKD. Furthermore, we strive to explore and elucidate potential chemical interventions that could hold promise for the treatment of DKD, thereby offering invaluable insights and directions for future research endeavors.

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The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-κB signaling

Cited by 2 publications

References 23 publications

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

Study of molecular mechanisms underlying the medicinal plant Tripterygium wilfordii-derived compound celastrol in treating diabetic nephropathy based on network pharmacology and molecular docking

Role of Gut Microbiota, Immune Imbalance, and Allostatic Load in the Occurrence and Development of Diabetic Kidney Disease

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