Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation

Xie, Yupeng; He, Qiu-Xiang; Chen, Hong; Lin, Zijiang; Xu, Yong; Yang, Chuang

doi:10.1016/j.ejphar.2019.172640

Cited by 68 publications

(37 citation statements)

References 34 publications

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“…What's more, Cao et al found that the expression of PI3K in depressed rats were attenuated signi cantly [104]. The study of Xie et al showed that Crocin can ameliorate depression via PI3K-Akt mediated suppression of in ammation [105], these studies illustrate the close connection between PI3K-Akt signaling pathway and depression.…”

Section: Discussionmentioning

confidence: 86%

Potential Molecular Mechanisms of JTW in the Treatment of Diabetes Mellitus and Depression Based on Network Pharmacology

Tang

et al. 2021

Preprint

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Background: The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. As a well-known traditional Chinese medicine (TCM), Jiao-tai-wan (JTW) has obvious hypoglycemic and antidepressant effects, but its specific targets and mechanisms are still unclear.Methods: The active compounds and corresponding targets of JTW were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). The GeneCards, the Online Mendelian Inheritance in Man (OMIM), the DrugBank and the Therapeutic Target Database (TTD) were used to collect targets of DM and depression. After sorting out the intersection targets of drugs and diseases, the Cytoscape software was used to perform a "Drug-Compounds-Targets-Disease (D-C-T-D)" network to analyze the active compounds of JTW, and the protein-protein interaction (PPI) network was constructed by the STRING database to screen and analyze the key target proteins. Finally, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the intersection targets were carried out by the database for annotation, visualization and integrated discovery (DAVID). Results: 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the above databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include insulin (INS), protein kinase B1 (AKT1), interleukin-6 (IL-6), vascular endothelial growth factor A (VEGF-A), tumor necrosis factor (TNF) and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc.Conclusion: In this paper, the possible mechanism of JTW on DM and depression was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.

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Section: Discussionmentioning

confidence: 86%

Potential Molecular Mechanisms of JTW in the Treatment of Diabetes Mellitus and Depression Based on Network Pharmacology

Tang

et al. 2021

Preprint

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“…It has been found that saffron suppresses the secretion of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFNγ, among others, decreasing inflammation in different organs or systems (such as the nervous system [ 59 , 60 , 61 , 62 , 63 ], respiratory system [ 64 , 65 ], gastrointestinal system [ 66 , 67 ], cardiovascular system [ 68 , 69 ], and urogenital system [ 70 , 71 ]), as observed in various experimental models and in vitro experiments. In the present study, the oral administration of saffron seems to prevent and/or revert the release of these cytokines, possibly as a result of the previously reported decrease in microglial activation [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?

Fernández‐Albarral

Martínez‐López

Marco

et al. 2021

JCM

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Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

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“…Crocin reduces liver toxicity by protecting mitochondria and lysosomes [22]. Researchers have found that crocin can play a significant role in regulating the PI3K/Akt-mediated inflammatory pathway [23]. Crocetin liver protection may be related to down-regulation of p-p38 MAPK and anti-inflammatory effects [24].…”

Section: Discussionmentioning

confidence: 99%

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells

Lan

et al. 2019

Molecules

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Fructus Gardeniae (FG) is a common Chinese medicine and food. However, the toxicity of FG has drawn increasing concern, especially its hepatotoxicity. The purpose of this study was to screen the hepatotoxic components of FG and evaluate their effects on rat liver BRL-3A cells. The chemical composition of FG was determined by HPLC-ESI-MS. CCK-8 assay was used to evaluate the cytotoxicity of ten chemical components from FG, and then the toxic components with significant inhibitory activity were selected for further study. The results showed that geniposide, genipin, genipin-1-gentiobioside, gardenoside, and shanzhiside all suppress cells viability. Apoptosis assays further indicated that geniposide and its metabolite genipin are the main hepatotoxic components of FG. Pretreatment of cells with geniposide or genipin increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The activities of superoxide dismutase (SOD) and glutathione (GSH) were decreased, while the malondialdehyde (MDA) level was increased. The cell contents of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were also increased. Molecular docking simulations were used to investigate the mechanism of FG-induced hepatotoxicity, revealing that geniposide and genipin bind strongly to the pro-inflammatory factor TNFR1 receptor of the NF-κB and MAPK signaling pathways. The obtained results strongly indicate that the hepatotoxicity of FG is caused by iridoids compounds. Genipin had the most significant hepatotoxic effect. These toxic substances destroy the cell antioxidant defense system, increasing inflammatory injury to the liver cells and leading to apoptosis and even necrosis. Thus, this study lays a foundation for toxicology research into FG and its rational application.

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Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation

Cited by 68 publications

References 34 publications

Potential Molecular Mechanisms of JTW in the Treatment of Diabetes Mellitus and Depression Based on Network Pharmacology

Potential Molecular Mechanisms of JTW in the Treatment of Diabetes Mellitus and Depression Based on Network Pharmacology

Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells

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