Kaempferol protects retinal ganglion ceils from high-glucose-induced injury by regulating vasohibin-1

Zhao, Lu; Sun, Junbo; Shi, Suqin; Xiao, Qin; Zhang, Keke; Xu, Jiangyan

doi:10.1016/j.neulet.2019.134633

Cited by 22 publications

(14 citation statements)

References 30 publications

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“…Kaempferol comes from HuangQi. Studies have confirmed that kaempferol can protect retinal ganglion cells from high glucose injury through ERK and VASH1 signaling pathways [ 17 ], and kaempferol can also protect human RPE cells from oxidative stress injury through its antioxidant activity and antiapoptosis function [ 18 ]. Other studies have shown that kaempferol inhibits the activation of the Src-Akt1-ERK1/2 signal pathway by targeting VEGF and PGF and thus inhibits the angiogenesis of human retinal endothelial cells [ 19 ], which may permit the treatment of neovascularization caused by diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

Zheng

2020

Evidence-Based Complementary and Alternative Medicine

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Aim of the Study. To study the mechanism of Compound-Xueshuantong Capsule in diabetic retinopathy treatment based on network pharmacology. Materials and Methods. The components with oral bioavailability ≥30% and drug similarity ≥0.18 were screened by the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the effective grouping of Compound-Xueshuantong Capsule was obtained. At the same time, the targets of each drug active component in the Compound-Xueshuantong Capsule were obtained by searching the TCMSP. The effective components and targets of the Compound-Xueshuantong Capsule were annotated by the UniProt database, and the disease treatment targets were searched by the GeneCards database. The disease treatment target is intersected with the drug target and the Wayne diagram is drawn by VennDiagram. The active ingredient targets of the intersection and Compound-Xueshuantong Capsule were inputted into Cytoscape 3.7.2 software to construct the active ingredient-target-disease interaction network. The above targets were inputted into the String database for protein-protein interaction network prediction. Finally, by using the DAVID database, GO and KEGG enrichment analysis was carried out to reveal the potential signal pathway of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment. Results. 93 active components of the Compound-Xueshuantong Capsule and 92 targets for treating diabetic retinopathy were screened. The main active components of the Compound-Xueshuantong Capsule in treating diabetic retinopathy were quercetin, luteolin, kaempferol, beta-sitosterol, isorhamnetin, and tanshinone IIa. The effect of the Compound-Xueshuantong Capsule on diabetic retinopathy may be related to IL6, EFGR, CASP3, and VEGFA. In addition, the treatment of diabetic retinopathy mainly involves in the regulation of nuclear receptors and transcription factors in vivo. The target of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment is significantly enriched in the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications. Conclusion. Compound-Xueshuantong Capsule can treat diabetic retinopathy through multitarget, multipathway, and multipathway regulation of the biomolecular network. The potential biological mechanism of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment may be related to the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications, but these findings still need to be confirmed by further clinical research.

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Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

Zheng

2020

Evidence-Based Complementary and Alternative Medicine

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“…In this study, ingredient-gene-pathway network shows that kaempferol is one of the core ingredients. Many experiments and findings have confirmed that kaempferol could protect retinal ganglion cells through regulating vasohibin-1 from high-glucose-induced injury [ 32 ] and prevent retinal pigment epithelial cell damage from oxidative stress [ 32 ]. Another study has indicated that kaempferol can inhibit VEGF and PGF expression and in vitro angiogenesis under high-glucose environment [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Mechanisms of Pollen Typhae in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking

Zhou

Jin

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the main bioactive compounds and investigate the underlying mechanism of Pollen Typhae (PT) against diabetic retinopathy (DR) by network pharmacology and molecular docking analysis. Methods. Bioactive ingredients and the target proteins of PT were obtained from TCMSP, and the related target genes were acquired from the SwissTargetPrediction database. The target genes of DR were obtained from GeneCards, TTD database, DisGeNET database, and DrugBank. The compound-target interaction network was established based on Cytoscape 3.7.2. The protein-protein interaction (PPI) network was constructed via STRING database and Cytoscape 3.7.2. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were visualized through DAVID database and Bioinformatics. Ingredient-gene-pathway network analysis was conducted to further screen the ingredients, target proteins, and pathways closely related to the biological mechanism on PT for DR, and molecular docking analysis was performed by SYBYL-X 2.1.1 software. Finally, the mechanism and underlying targets of PT in the treatment of DR were predicted. Results. A total of 8 compounds and 171 intersection targets were obtained based on the online network database. 7 main compounds were screened from compound-target network, and 53 targets including the top six key targets (PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR) were further acquired from PPI analysis. The 53 key targets covered 80 signaling pathways, among which PI3K-Akt signaling pathway, focal adhesion, Rap1 signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway were closely connected with the biological mechanism involved in the alleviation of DR by PT. Ingredient-gene-pathway network shows that AKTI, EGFR, and VEGFA were core genes, kaempferol and isorhamnetin were pivotal ingredients, and VEGF signaling pathway and Rap1 signaling pathway were closely involved in anti-DR. The docking results indicated that five main compounds (arachidonic acid, isorhamnetin, quercetin, kaempferol, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) had good binding activity with EGFR and AKT1 targets. Conclusion. The active ingredients in PT may regulate the levels of inflammatory factors, suppress the oxidative stress, and inhibit the proliferation, migration, and invasion of retinal pericytes by acting on PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR targets through VEGF signaling pathway, PI3K-Akt signaling pathway, Rap1 signaling pathway, and HIF-1 signaling pathway to play a therapeutic role in diabetic retinopathy.

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“…It promotes apoptosis and inhibits cell proliferation [77]. By regulating vasohibin-1 and ERK signaling, kaempferol prevents high glucose-induced injury in retinal ganglion cells [78]. In addition, kaempferol has a bonesparing effect via mTOR/PI3K/Akt signaling pathway [79,80].…”

Section: Pharmacological Actions Of Kaempferolmentioning

confidence: 99%

The Therapeutic Potential of Kaemferol and Other Naturally Occurring Polyphenols Might Be Modulated by Nrf2-ARE Signaling Pathway: Current Status and Future Direction

Hussain

Khan²,

Alsharif³

et al. 2022

Molecules

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Kaempferol is a natural flavonoid, which has been widely investigated in the treatment of cancer, cardiovascular diseases, metabolic complications, and neurological disorders. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor involved in mediating carcinogenesis and other ailments, playing an important role in regulating oxidative stress. The activation of Nrf2 results in the expression of proteins and cytoprotective enzymes, which provide cellular protection against reactive oxygen species. Phytochemicals, either alone or in combination, have been used to modulate Nrf2 in cancer and other ailments. Among them, kaempferol has been recently explored for its anti-cancer and other anti-disease therapeutic efficacy, targeting Nrf2 modulation. In combating cancer, diabetic complications, metabolic disorders, and neurological disorders, kaempferol has been shown to regulate Nrf2 and reduce redox homeostasis. In this context, this review article highlights the current status of the therapeutic potential of kaempferol by targeting Nrf2 modulation in cancer, diabetic complications, neurological disorders, and cardiovascular disorders. In addition, we provide future perspectives on kaempferol targeting Nrf2 modulation as a potential therapeutic approach.

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Kaempferol protects retinal ganglion ceils from high-glucose-induced injury by regulating vasohibin-1

Cited by 22 publications

References 30 publications

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

Investigating the Mechanisms of Pollen Typhae in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking

The Therapeutic Potential of Kaemferol and Other Naturally Occurring Polyphenols Might Be Modulated by Nrf2-ARE Signaling Pathway: Current Status and Future Direction

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