Hecogenin exhibits anti-arthritic activity in rats through suppression of pro-inflammatory cytokines in Complete Freund’s adjuvant-induced arthritis

Ingawale, Deepa K.; Patel, Snehal S.

doi:10.1080/08923973.2017.1405439

Cited by 21 publications

(13 citation statements)

References 52 publications

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“…Macrophages activation in turn activate the proinflammatory cytokines such as TNF-a and IL-6 [41]. Arthritic index score is also increased to significant extent in CFA induced rats [42] and nimbolide treatment reduced the arthritic index score.…”

Section: Discussionmentioning

confidence: 96%

Evaluation of antiarthritic activity of nimbolide against Freund’s adjuvant induced arthritis in rats

Cui

Wang

Bian

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Nimbolide, a triterpenoid isolated from flower of neem tree possess various therapeutic properties. The objective of the study was to assess the anti-arthritic activity of nimbolide in arthritis induced rats. Nimbolide (20 mg/kg per day) was given orally to arthritic rats induced with Complete Freund's Adjuvant and changes in paw volume, body weight, organ indices (thymus and spleen), arthritic score, biochemical parameters and proinflammatory cytokines levels were determined. Histopathological analysis was also performed. Western blot analysis was also performed. Rats treated with nimbolide displayed marked reduction in arthritic score, organ indices, volume of paw, edema formation, along with substantial enhancement in body weight. Histopathological findings showed significant reduction in destruction of joints and inflammation following nimbolide treatment. The protective action of arthritic rats treated with nimbolide was also substantiated by molecular and biochemical studies. The results of the study show that nimbolide treatment has markedly enhanced health and reduced inflammation via lessening the proinflammatory cytokines expression in arthritic rats. Hence, nimbolide may be used as a potent therapeutic drug in treating rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 96%

Evaluation of antiarthritic activity of nimbolide against Freund’s adjuvant induced arthritis in rats

Cui

Wang

Bian

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Although the two aforementioned drugs have been reported to be associated with the treatment of ICH, the mechanisms underlying their therapeutic actions still require further research. In addition, we found that hecogenin has an anti-inflammatory effect that may contribute to the treatment of ICH (Ingawale, Mandlik & Patel, 2019; Ingawale & Patel, 2016; Ingawale & Patel, 2018).…”

Section: Discussionmentioning

confidence: 89%

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis

Liu

Zhang

Chen

et al. 2019

PeerJ

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BackgroundBecause of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH.MethodsThe dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model.ResultA total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential.ConclusionIn this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.

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“…Although the two aforementioned drugs have been reported to be associated with the treatment of ICH, the mechanisms underlying their therapeutic actions still require further research. In addition, we found that hecogenin has an antiinflammatory effect that may contribute to the treatment of ICH (Ingawale et al 2019;Ingawale & Patel 2016;Ingawale & Patel 2018).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis (v0.2)"

2019

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Background.Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH. Methods. The GSE24265 dataset, consisting of data from 4 perihematomal brain tissues and 7 contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a P-value of < 0.05 set as cutoffs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a P-value of < 0.05 set as the cutoff. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model. Result. A total of 59 up-regulated genes and 8 down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokinecytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential. Conclusion. In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.

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Hecogenin exhibits anti-arthritic activity in rats through suppression of pro-inflammatory cytokines in Complete Freund’s adjuvant-induced arthritis

Cited by 21 publications

References 52 publications

Evaluation of antiarthritic activity of nimbolide against Freund’s adjuvant induced arthritis in rats

Evaluation of antiarthritic activity of nimbolide against Freund’s adjuvant induced arthritis in rats

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis

Peer Review #1 of "Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis (v0.2)"

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