Uncovering the protective mechanism of Taohong Siwu decoction against diabetic retinopathy via HIF-1 signaling pathway based on network analysis and experimental validation

Wang, Lei; Li, Shuyan; Wang, Leilei; Lin, Kai; Du, Jialun; Wang, Miao; Zhang, Lei

doi:10.1186/s12906-020-03086-0

Cited by 13 publications

(7 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result of insulin resistance, glucose uptake, glycogen synthesis in skeletal muscle, and glycogen synthesis in the liver decrease, while hepatic gluconeogenesis increases [48]. HIF-1 is the transcription factor that enhances hypoxia adaption and relates to T2DM complications such as diabetic retinopathy [49] and diabetic foot ulcers [50]. e PI3K/Akt pathway is a multifunctional signaling pathway that is critical in the pathophysiology of diabetic nephropathy and is activated in high glucose-stimulated HKC cells [51].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

Tran

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global incidence. Panax ginseng has been used to treat T2DM in traditional medicine, with previous in vitro, in vivo, and clinical trial studies demonstrating its e cacy. is study aimed to determine the mechanism of P. ginseng in treating T2DM by network pharmacology. Methods. e bioactive compounds of P. ginseng and corresponding targets of P. ginseng-T2DM were retrieved across multiple databases. e proteinprotein interaction network was established using the STRING database and topological analysis helped identify the core target. Using the DAVID tool, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, we checked the binding of core targets and bioactive compounds using molecular docking. Results. e P. ginseng-T2DM networks mainly contained 22 bioactive compounds and 314 overlapping targets. e ve most signi cant core targets were SRC, STAT3, MAPK1, AKT1, and PIK3R1. ere were 244 GO terms and 95 KEGG pathways (adjusted p < 0.01) that were strongly correlated with diabetes-related signaling pathways, such as insulin resistance, the HIF-1 signaling pathway, the PI3K/Akt signaling pathway, the prolactin signaling pathway, the Rap1 signaling pathway, the Ras signaling pathway, the calcium signaling pathway, and the FoxO signaling pathway. Molecular docking results revealed that the top ve core targets had a high binding a nity with the bioactive compounds of P. ginseng. Conclusion. e bioactive compounds and targets in P. ginseng ameliorate T2DM by regulating insulin resistance and multiple signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

Tran

2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Additionally, lots of studies and experiments results have confirmed that downregulation of the VEGF and HIF1 signaling pathway could also prevent hypoxia-induced retinal angiogenesis [ 61 – 63 ]. One experiment demonstrated that HIF-1 signaling pathway had a protective effect on DR [ 64 ], and it is suggested that targeting the HIF-1 signaling pathway could be a therapeutic approach to prevent development of DR.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…TCM prescriptions, specific to the treatment of T2DM, for invigorating the spleen, resolving phlegm, tonifying the kidneys, and dehumidifying and activating the blood can help improve lipid metabolism, reduce fat accumulation in vivo, improve circulation, promote the use of nutrients in the body, increase the utilization of insulin in the muscles and other cells, and reduce insulin resistance. 12 The reduction of insulin resistance not only reduces blood sugar but also prevents the occurrence 13 of complications. It has a unique role to play in the treatment of T2DM in the field of TCM.…”

Section: Discussionmentioning

confidence: 99%

The Distribution Pattern of Traditional Chinese Medicine Syndromes in 549 Patients with Type 2 Diabetes

Zhang¹,

Liu²,

Liang³

et al. 2021

DMSO

View full text Add to dashboard Cite

Objective This study aimed to summarize the distribution pattern of traditional Chinese medicine (TCM) syndromes in patients with type 2 diabetes mellitus (T2DM). Methods The frequency, characteristics and distribution of all TCM syndromes of 549 patients with T2DM were analyzed. Results The average age of T2DM onset was higher in women than in men (ie, men experienced earlier onset). The distribution of TCM syndromes, in order of frequency, was as follows: damp-heat trapping spleen (including spleen deficiency and dampness, damp heat due to spleen deficiency, and qi weakness due to spleen deficiency) (58.29%), qi-yin deficiency (16.03%), deficiency of yin and excessive heat (12.93%), blood stasis in collaterals (9.41%), and yin-yang deficiency (3.21%). The physical intensity of patients’ occupational activity was mainly light (49.6%), followed by heavy (31.4%) and moderate (19.0%). Conclusion Damp-heat trapping spleen is the most common TCM syndrome in patients with T2DM, with damp heat due to spleen deficiency the most significant subtype. This syndrome tends to occur in people over the age of 60 and those undertaking too much or too little physical activity in their occupational activities. The traditional “three more and one less” symptoms do not adequately describe the clinical symptoms of T2DM.

show abstract

Uncovering the protective mechanism of Taohong Siwu decoction against diabetic retinopathy via HIF-1 signaling pathway based on network analysis and experimental validation

Cited by 13 publications

References 47 publications

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

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

The Distribution Pattern of Traditional Chinese Medicine Syndromes in 549 Patients with Type 2 Diabetes

Contact Info

Product

Resources

About