An Indole-2-Carboxamide Derivative, LG4, Alleviates Diabetic Kidney Disease Through Inhibiting MAPK-Mediated Inflammatory Responses

Qian, Jianchang; Yin, Sihui; Lin, Yuanyuan; Wang, Zhe; Shu, Shengqiang; Mou, Zhenxin; Xu, Mingjiang; Chattipakorn, Nipon; Liu, Zhiguo; Liang, Guang

doi:10.2147/jir.s308353

Cited by 3 publications

(3 citation statements)

References 38 publications

(46 reference statements)

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“…Inflammatory response is a risk factor for glomerulosclerosis and tubulointerstitial fibrosis by inducing extracellular matrix deposition and proliferation and differentiation of myofibroblasts. Thus, blocking renal inflammation may be a strategy for treating diabetic nephropathy 49 . The local infiltration of inflammatory cells in kidney is related to many inflammatory factors, such as IL-6, IL-1β and so on.…”

Section: Discussionmentioning

confidence: 99%

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

Gao

Jiang

et al. 2022

Sci Rep

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Immune cells play an important role in the development of inflammation in type 1 diabetes mellitus, so we want to explore the changes of CD4+ T cells and macrophages in vivo, which can provide an experimental basis for immunotherapy based on CD4+ T cells and macrophages. The intraperitoneal injection of streptozocin was used to induce a type 1 diabetes mellitus mouse model; the blood glucose, body weight, and the expression of inflammatory factors in the kidney were measured. Immunohistochemistry was applied to determine and analyze the infiltration of CD4+ T cells and macrophages in the spleen, pancreas, and kidney. The subtypes of macrophages in the kidney and CD4+ T cells in the spleen were analyzed by flow cytometry. Our study suggests that CD4+ T cells and macrophages increase, while the inflammatory immune response system is activated in the development of T1DM. CD4+ T cells positively correlated with macrophages in the pancreas and kidney of T1DM. CD4+ T cells turn to pro-inflammatory subtypes in the spleen of T1DM, while macrophages turn to pro-inflammatory subtypes in the kidney of T1DM. Therefore, regulation of CD4+ T cells and macrophages may be a potential target for T1DM and kidney complications.

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Section: Discussionmentioning

confidence: 99%

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

Gao

Jiang

et al. 2022

Sci Rep

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“…The MAPK signaling pathway is an important signaling pathway in the DKD process. Drugs have been shown to prevent oxidative stress damage in DKD‐affected renal tissue by regulating the p38 MAPK signaling pathway (Qin et al, 2019) and alleviating DKD by inhibiting the MAPK‐mediated inflammatory response (Qian et al, 2021). According to some studies (Deb et al, 2017), hyperglycemia increased phospho‐p65 or phospho‐CREB and CBP bindings, as well as cAMP production and PKA activity.…”

Section: Discussionmentioning

confidence: 99%

Material basis and action mechanism of Euryale Ferox Salisb in preventing and treating diabetic kidney disease

Yang

Guo

et al. 2022

Journal of Food Biochemistry

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The aim of this study was to determine the chemical structure and mechanism of action of Euryale ferox Salisb (ES) in the prevention and treatment of diabetic kidney disease (DKD). The TCMSP, SymMap V2, CTD, DisGeNET, and GeneCards databases were searched for ES components, targets, and DKD targets using the network pharmacology method to identify common drug‐disease targets. PPI analysis was used to identify hub genes, which were then followed by DKD clinical relevance, GO, KEGG analysis, and transcription factor prediction. Finally, molecular docking was performed. We discovered 24 components of ES and 72 objectives of ES, 9 of which were clinically relevant and primarily regulated by transcription factors such as HNF4A and PPARG. They are involved primarily in signal transduction, inflammatory responses, TNF regulation, apoptosis, MAPK, and other signaling pathways. The main components are oleic acid targeting the protein encoded by PPARA, LPL, FABP1, and vitamin E binding the protein encoded by MAPK1, TGFB1. In general, this approach provides an effective strategy in which ES acts primarily against DKD through oleic acid and vitamin E, targeting the protein encoded by PPARA, LPL, FABP1, MAPK1 to regulate TNF, apoptosis, MAPK, and other signaling pathways. Practical applications Euryale ferox Salisb (ES) is well known for its use in medicine and food. Furthermore, ES contains many nutrients, whose pharmacological properties, including antidepressant, antioxidant, and anti‐diabetic action, have been extensively demonstrated by numerous studies. In this article, through network pharmacology combined with clinical correlation analysis and molecular docking, the target and mechanism of ES in the treatment of diabetic kidney disease (DKD) were discussed, which clarified its mechanism at the molecular level. Provides a reference for the further development and utilization of ES.

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“…Additionally, in vivo and in vitro data showed that LG4 could improve anti-inflammatory effects by suppressing the phosphorylation of JNK and ERK and by activating NF-κB signaling. However, the renal protective activity of DKD in type 2 diabetic mice needs further study ( Qian et al, 2021 ). Tropisetron, a synthetic indole drug, has been used to inhibit chemotherapy-induced vomiting in clinic.…”

Section: Introductionmentioning

confidence: 99%

Indole-Based Small Molecules as Potential Therapeutic Agents for the Treatment of Fibrosis

et al. 2022

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Indole alkaloids are widely distributed in nature and have been particularly studied because of their diverse biological activities, such as anti-inflammatory, anti-tumor, anti-bacterial, and anti-oxidant activities. Many kinds of indole alkaloids have been applied to clinical practice, proving that indole alkaloids are beneficial scaffolds and occupy a crucial position in the development of novel agents. Fibrosis is an end-stage pathological condition of most chronic inflammatory diseases and is characterized by excessive deposition of fibrous connective tissue components, ultimately resulting in organ dysfunction and even failure with significant morbidity and mortality. Indole alkaloids and indole derivatives can alleviate pulmonary, myocardial, renal, liver, and islet fibrosis through the suppression of inflammatory response, oxidative stress, TGF-β/Smad pathway, and other signaling pathways. Natural indole alkaloids, such as isorhynchophylline, evodiamine, conophylline, indirubin, rutaecarpine, yohimbine, and vincristine, are reportedly effective in organ fibrosis treatment. In brief, indole alkaloids with a wide range of pharmacological bioactivities are important candidate drugs for organ fibrosis treatment. The present review discusses the potential of natural indole alkaloids, semi-synthetic indole alkaloids, synthetic indole derivatives, and indole-contained metabolites in organ fibrosis treatment.

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An Indole-2-Carboxamide Derivative, LG4, Alleviates Diabetic Kidney Disease Through Inhibiting MAPK-Mediated Inflammatory Responses

Cited by 3 publications

References 38 publications

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

Material basis and action mechanism of Euryale Ferox Salisb in preventing and treating diabetic kidney disease

Indole-Based Small Molecules as Potential Therapeutic Agents for the Treatment of Fibrosis

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