Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation and apoptosis

Jamali-Raeufy, Nida; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Keimasi, Sara; Goudarzi, Mina

doi:10.1016/j.jchemneu.2019.101709

Cited by 47 publications

(30 citation statements)

References 52 publications

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“…Multiple studies have reported that the active components of saffron, including quercetin, kaempferol, isorhamnetin, crocetin, crocin I, crocin II, safranal, and picrocrocin exhibit anti-apoptotic and antiin ammatory properties [42][43][44][45][46][47][48]. The above results suggest that CASP3, IL6, and MAPK8 are at the core of the PPI network, consistent with the literature, there were closely related to neuronal apoptosis and neuroin ammation of PD [49][50][51].…”

Section: Molecular Dockingsupporting

confidence: 88%

Predication of the Underlying Protective Effect of Saffron on Parkinson's Disease via Network Pharmacology and Molecular Docking

Gong

Hao

et al. 2021

Preprint

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BackgroundReports indicate that saffron originated from Iran then introduced into mainland China through the earlier established trans-Tibet trade routes in ancient China. Based to the theory of traditional Chinese medicine, saffron functions by promoting blood circulation and removing blood stasis, cooling blood and detoxification, as well as relieving depression for tranquilization. Modern medical research has demonstrated several properties of saffron including antitumor, antidepressant, enhancement of immunity, cardioprotection. Notably, recent studies introduce that saffron has a neuroprotective effect, specifically in the treatment of Parkinson's disease in recent years. Nevertheless, the underlying molecular mechanism remains elusive so far. As such, this study aims to predict the underlying mechanism of saffron on Parkinson's disease through network pharmacology and molecular docking.MethodsA functional-based network pharmacology and molecular docking model was constructed for dissecting the underlying mechanism of saffron on Parkinson's disease. Based on the Traditional Chinese Medicine System Pharmacology database (TCMSP) and the literature reviews, the putative targets of Saffron were collected. Further, the interaction networks of Drug- candidate compounds targets-Therapeutic targets-Disease were mined using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted and the String database was used to analyze the protein interaction network. Finally, Molecular docking was used to predict the interaction between the components in Saffron and key targets by MOE 2014.09 software.ResultsA total of 9 candidate compounds from saffron corresponding to 52 therapeutic targets of Parkinson's disease were identified. The neuroprotective effect of saffron in the treatment of PD was attributed to the strong binding between crocin (including crocin I and crocin II) as well as key targets including CASP3, IL6, and MAPK8. Additionally, the auxiliary neuroprotective effects might have originated from quercetin, kaempferol, isorhamnetin, crocetin, safranal, and picrocrocin because of their slightly weaker binding capacity to the key targets.ConclusionSaffron exhibits a synergistic effect via multiple targets and pathways in the treatment of Parkinson's disease and our systemic pharmacological analysis provides a basis for the clinical application and in-depth study of saffron.

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Section: Molecular Dockingsupporting

confidence: 88%

Predication of the Underlying Protective Effect of Saffron on Parkinson's Disease via Network Pharmacology and Molecular Docking

Gong

Hao

et al. 2021

Preprint

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“…Studies have proved that isorhamnetin can protect human RPE cells from oxidative stress-induced cell death, which is related to the activation of the PI3K/Akt signal pathway [ 22 ], so it can prevent the imbalance of oxidative stress caused by diabetic retinopathy. Other studies have shown that isorhamnetin can significantly reduce pain, blood sugar levels, and anti-inflammatory effects [ 23 ]. These also help to improve the pathological changes 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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“…27 Isorhamnetin, a 3-O-methylated metabolite of quercetin, possesses a wide variety of biological effects, including neuroprotective, anti-inflammatory, antioxidant, antiapoptotic, etc. 28 Ishola I et al demonstrated that isorhamnetin improves recognition and spatial memory in mice with scopolamine-induced amnesia. Moreover, they showed that this flavonoid enhanced antioxidant defense, reduced acetylcholinesterase activity and increased brain-derived neurotrophic factor (BDNF) levels in the hippocampus and the prefrontal cortex in mice with this model of memory impairment.…”

Section: Effect Of Gbse On % Sa In Y-maze Testmentioning

confidence: 99%

An experimental study on phytochemical composition and memory enhancing effect of Ginkgo biloba seed extract

Tomova

Doncheva

Bakova

et al. 2021

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Introduction: The Ginkgo biloba L. tree is considered as one of the oldest species on Earth. It is known as a “living fossil” dating back approximately 200 million years. Both the leaves and seeds of this tree have been used for millennia in traditional Chinese medicine. Aim: To study the phytochemical profile of Gingko biloba seed extract (GBSE) and its memory enhancing effects. Materials and methods: Liquid chromatography with mass detection (LC-MS) was performed for phytochemical analyses of the extracts. For the in vivo experiments, male Wistar rats were divided randomly into 5 groups (n=8): saline; piracetam;  GBSE 50; 100, and 200 mg/kg b.w. Y-maze, T-maze, step-down passive avoidance and novel object recognition test (NORT) were performed. The observed parameters were: percentage of spontaneous alternations (% SA), working memory index, latency of reaction and recognition index, respectively. Statistical analysis was done using SPSS 19. Results: LC-MS analysis showed the presence of the flavonoids quercetin, kaempferol and isorhamnetin (as aglycones), the ginkgolides A, B, C, J, and bilobalide. In Y-maze task, the groups treated with 50 and 100 mg/kg of GBSE significantly increased the % SA during the memory test compared to saline (p<0.05). In T-maze test, the three experimental groups with GBSE significantly increased the working memory index in comparison with that of the control group (p<0.05). In step-down test, the animals receiving 100 mg/kg b.w. GBSE, notably increased the latency during both retention tests (p<0.05 and p<0.01, respectively). In NORT, only the animals with the middle dose of GBSE ameliorated the recognition index when compared to saline (p<0.05). Conclusions: GBSE enhances spatial working memory, recognition memory, and short- and long-term recall in naïve rats due to the synergic effects of detected flavonoids and terpene lactones on brain functions. The brain structures involved are probably the hippocampus and prefrontal cortex.

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Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation and apoptosis

Cited by 47 publications

References 52 publications

Predication of the Underlying Protective Effect of Saffron on Parkinson's Disease via Network Pharmacology and Molecular Docking

Predication of the Underlying Protective Effect of Saffron on Parkinson's Disease via Network Pharmacology and Molecular Docking

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

An experimental study on phytochemical composition and memory enhancing effect of Ginkgo biloba seed extract

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