Antioxidative Property and Molecular Mechanisms Underlying Geniposide-Mediated Therapeutic Effects in Diabetes Mellitus and Cardiovascular Disease

Li, Ning; Li, Ling; Wu, Haiming; Zhou, Haoming

doi:10.1155/2019/7480512

Cited by 34 publications

(25 citation statements)

References 136 publications

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“…Endotoxin-induced multi-organ failure is common in ICU patients and related to the increased risk of death ( Hurley et al, 2012 ; Huang et al, 2016 ; Li et al, 2019 ). LPS is an indispensable content for the pathogenicity of endotoxemia, and the LPS-induced mice model is a frequently used animal model for endotoxemia ( Pils et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms

Zhang

Liao

Liu

et al. 2020

Front. Mol. Biosci.

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BackgroundTo this day, the molecular mechanism of endotoxin-induced multi-organ failure has not been completely clarified. This study aimed to construct an miRNA-mRNA regulatory network and identify main pathways and key genes in multi-organ of LPS-mediated endotoxemic mice.MethodsPublic datasets from six mRNA and three miRNA microarray datasets were downloaded from the GEO website to screen final differentially expressed genes (FDEGs) and hub genes in the heart, lung, liver, and kidney of LPS-mediated endotoxemic mice. Functional and pathway enrichment analysis of FDEGs was used to identify the main pathways in multi-organ damage of LPS-treated mice. Finally, hub genes of each organ were intersected to obtain the key genes of multi-organ.ResultsFirstly, 158, 358, 299, and 91 FDEGs were identified in the heart, lung, liver, and kidney, respectively. The pathway enrichment analysis of the FDEGs then showed that the TNF signaling pathway, Toll-like receptor signaling pathway, and some viral-infection-related pathways (influenza A, measles, and herpes simplex) were the main pathways in multi-organ damage of LPS-mediated endotoxemic mice. Moreover, miRNA-mRNA or PPI regulatory networks were constructed based on FDEGs. According to these networks, 31, 34, 34, and 31 hub genes were identified in the heart, lung, liver, and kidney, respectively. Among them, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) were enriched in Toll-like receptor signaling pathway and chemokine signaling pathway. Finally, seven potential drugs were predicted based on these key genes.ConclusionThe shared underlying molecular pathways in endotoxin-induced multi-organ damage that have been identified include Toll-like receptor signaling pathway and TNF signaling pathway. Besides, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) and seven potential drugs were identified. Our data provide a new sight and potential target for future therapy in endotoxemia-induced multi-organ failure.

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Section: Discussionmentioning

confidence: 99%

Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms

Zhang

Liao

Liu

et al. 2020

Front. Mol. Biosci.

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“…The antioxidative properties of geniposide eventuates from either the inhibition of numerous pathological processes (e.g., production of some inflammatory cytokines, LPS-induction of nitric oxide, and blocking upstream of TLR4, NF-κB, and MAPK pathways) or the activation of various proteins associated with cell survival, e.g., heme oxygenase-1 (HO-1) and B-cell lymphoma-2 (Bcl-2) or a combination of both. It was proven that geniposide may be useful in the prophylaxis or treatment of not only diabetes mellitus but also cardiac fibrosis, cardiac hypertrophy, myocardium I/R, obesity-related cardiac injury, atherosclerosis, ischemic stroke, and diabetic nephropathy [65].…”

Section: Iridoids In Fatty Liver Diseasementioning

confidence: 99%

The Effects of Natural Iridoids and Anthocyanins on Selected Parameters of Liver and Cardiovascular System Functions

Danielewski

Matuszewska

Nowak

et al. 2020

Oxidative Medicine and Cellular Longevity

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The old adage says, “you are what you eat.” And although it is a banality repeated by many with a grain of salt, it also has quite a bit of truth in it, as the products we eat have a considerable impact on our health. Unfortunately, humanity is eating worse from one year to another, both in terms of product quality and eating habits. At the same time, it is brought up frequently that plant products should form the basis of our diet. This issue was also reflected in the new version of the food pyramid. Iridoids and anthocyanins are groups of plant compounds with proven beneficial effects on health. Both groups affect the cardiovascular system and the liver functions. Although many mechanisms of action and the therapeutic effects of these compounds have already been learned, intensive animal and clinical research is still underway to explore their new curative mechanisms and effects or to broaden our knowledge of those previously described. In this article, we review the effects of natural iridoids and anthocyanins on selected parameters of liver and cardiovascular system functions.

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“…The apparent permeability coe cient (Papp) was calculated by formula (1), and the e ux ratio (ER) was calculated by formula (2). Papp = (dQ/dt) / (A × C0) (1), where dQ/dt is the transmission rate of GE per unit time, A is the surface area of Caco-2 monolayer (0.03 cm 2 ), and C0 is the initial drug concentration on the donor side.…”

Section: Bidirectional Transport Experimentsmentioning

confidence: 99%

“…Geniposide (GE), an iridoid glycoside compound, is the major active component of Gardenia jasminoides Ellis fruit, which is traditionally used for its antiphlogistic and antipyretic effects in many Asian countries [1] . In recent years, the pharmacological effects of geniposide on antioxidation and angiogenesis have been gradually studied [2,3] . The development of new drugs and the wide application of drugs and herbs resulted in the potential of drug-drug interaction (DDI) have been noticed [4] .…”

Section: Introductionmentioning

confidence: 99%

Intestinal Absorption of Geniposide and Inhibition of Transporter-P-GP Across the Caco-2 Monolayer

Bu¹,

Wu²,

Sun³

et al. 2020

Preprint

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Background: Geniposide (GE) is the main bioactive component of Gardenia jasminoides Ellis, which has many pharmacological effects, such as anti-inflammatory, anti-oxidation, and anti-angiogenesis. GE has low absolute bioavailability after oral administration, and speculated that GE might have an effect on P-glycoprotein (P-gp) described in our previous study. However, intestinal absorption characteristics involved in the Caco-2 cells of GE are still unknown. Therefore, we aimed to investigate absorption mechanisms of GE and the effects on P-gp. Methods: By establishing the Caco-2 cells model and HPLC method, bidirectional transport of GE in the different conditions and the presence of P-gp inhibitors－verapamil were conducted to observe its absorption mechanisms. Transport assays of digoxin, a P-gp substrate, were also performed in the presence of GE or verapamil. The effects of GE on the function and expression of P-gp were analyzed by flow cytometry and Western blot using rhodamine-123 (rho-123) and the antibody, respectively. Results: Both absorption and secretion of GE were positively correlated with concentration and time at Caco-2 cell monolayer. The Papp of bidirectional transport was decreased in low temperature and the Papp(BL-AP) of GE decreased significantly in the presence of verapamil. Meanwhile, the ER value was higher than 1.5. In addition, in the bidirectional transport of digoxin, the values of Papp(BL-AP) and ER decreased significantly in the presence of GE, just like verapamil. GE increased the intracellular accumulation of rho-123 and also have a significant decrease on P-gp expression. Conclusion: Transepithelial transport mechanism of GE in Caco-2 cell monolayer is mainly passive diffusion and P-gp mediated active transportation. GE was a potential inhibitor of P-gp, can inhibit transport of digoxin and the function and expression of P-gp.

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Antioxidative Property and Molecular Mechanisms Underlying Geniposide-Mediated Therapeutic Effects in Diabetes Mellitus and Cardiovascular Disease

Cited by 34 publications

References 136 publications

Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms

Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms

The Effects of Natural Iridoids and Anthocyanins on Selected Parameters of Liver and Cardiovascular System Functions

Intestinal Absorption of Geniposide and Inhibition of Transporter-P-GP Across the Caco-2 Monolayer

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