Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through STAT3-mediated pathway

Zhao, Qiuping; Gao, Chuanyu; Cui, Zhifeng

doi:10.1016/j.intimp.2015.02.001

Cited by 39 publications

(27 citation statements)

References 29 publications

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“…Our results indicate that GA could potently restrain macrophage-mediated inflammation stimulated by LPS. Taken together with recent reports showing that GA reduced inflammatory responses in CCl 4 -induced liver [13] and high-glucose-stimulated human umbilical vein endothelial cells [12], all of these findings corroborate the global anti-inflammatory potential of GA targeting versatile phlogogenous factors.…”

Section: Discussionsupporting

confidence: 86%

“…Although other types of ginkgolides have shown anti-inflammatory activity, which of GA has not been widely reported. Only two studies recently showed that GA could mediate protection against liver inflammation in CCl 4 -induced mice [12] and reduce inflammatory responses in high-glucose-stimulated human umbilical vein endothelial cells [13]. However, the exact anti-inflammatory activity of GA and the underlying mechanisms have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

Yao

et al. 2017

IJMS

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Ginkgolide A (GA) is a natural compound isolated from Ginkgo biloba and has been used to treat cardiovascular diseases and diabetic vascular complications. However, only a few studies have been conducted on the anti-inflammatory effects of GA. In particular, no related reports have been published in a common inflammation model of lipopolysaccharide (LPS)-stimulated macrophages, and the anti-inflammatory mechanisms of GA have not been fully elucidated. In the present study, we extensively investigated the anti-inflammatory potential of GA in vitro and in vivo. We showed that GA could suppress the expression of pro-inflammatory mediators (cyclooxygenase-2 (COX-2) and nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β) in LPS-treated mouse peritoneal macrophages, mouse macrophage RAW264.7 cells, and differentiated human monocytes (dTHP-1) in vitro. These effects were partially carried out via downregulating Nuclear factor kappa-B (NF-κB), Mitogen-activated protein kinases (MAPKs) (p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinase (JNK), and activating the AMP-activated protein kinase (AMPK) signaling pathway also seems to be important. Consistently, GA was also shown to inhibit the LPS-stimulated release of TNF-α and IL-6 in mice. Taken together, these findings suggest that GA can serve as an effective inflammatory inhibitor in vitro and in vivo.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

Yao

et al. 2017

IJMS

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“…dose of YinXing-TongZhi tablet at 3 tablets/person, the label daily dose of the tablet. Serial blood samples (around 2.5 mL) were collected, from an antecubital vein catheter into heparinized vacuum tubes, before and 1, 2, 3,5,7,8,10,12,13,15,24,29,34,48,58, and 72 h after dosing, while serial urine samples were collected before and at 0-3, 3-7, 7-24, 24-48, and 48-72 h after dosing. Subjects in the other group received a 2-h i.v.…”

Section: Materials and Chemicalsmentioning

confidence: 99%

“…Bilobalide has four five-membered rings (three lactones and a carbocycle) and a tert-butyl group. Many terpene lactones are reported to have anti-inflammatory [6,7], endothelial protective [8,9], cardioprotective [10], antiplatelet [11], and antioxidant properties in cell-based and animal-based studies [12,13]. Ginkgolides A, B, and C are also platelet-activating factor (PAF) receptor antagonists [14,15].…”

Section: Introductionmentioning

confidence: 99%

Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity

Yang

Niu

et al. 2018

Acta Pharmacol Sin

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Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of their carboxylation in blood. Human subjects received oral YinXing-TongZhi tablet or intravenous ShuXueNing, two standardized ginkgo preparations. Their plasma protein-binding and platelet-activating factor antagonistic activity were assessed in vitro. Their carboxylation was assessed in phosphate-buffered saline (pH 7.4) and in human plasma. After dosing YinXing-TongZhi tablet, ginkgolides A and B and bilobalide exhibited significantly higher systemic exposure levels than ginkgolides C and J; after dosing ShuXueNing, ginkgolides A, B, C, and J exhibited high exposure levels. The compounds' unbound fractions in plasma were 45-92%. Apparent oral bioavailability of ginkgolides A and B was mostly >100%, while that of ginkgolides C and J was 6-15%. Bilobalide's bioavailability was probably high but lower than that of ginkgolides A/B. Terminal half-lives of ginkgolides A, B, and C (4-7 h) after dosing ShuXueNing were shorter than their respective values (6-13 h) after dosing YinXing-TongZhi tablet. Half-life of bilobalide after dosing the tablet was around 5 h. Terpene lactones were roughly evenly distributed in various body fluids and tissues; glomerular-filtration-based renal excretion was the predominant elimination route for the ginkgolides and a major route for bilobalide. Terpene lactones circulated as trilactones and monocarboxylates. Carboxylation reduced platelet-activating factor antagonistic activity of ginkgolides A, B, and C. Ginkgolide J, bilobalide, and ginkgo flavonoids exhibited no such bioactivity. Collectively, differences in terpene lactones' exposure between the two preparations and influence of their carboxylation in blood should be considered in investigating the relative contributions of terpene lactones to ginkgo preparations' therapeutic effects. The results here will inform rational clinical use of ginkgo preparations.

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“…Diabetes is a greater risk for cardiovascular morbidity and mortality. Research showed that improving endothelial function and decreasing inflammation could lower cardiovascular disease risk of diabetes patients [19][20][21] . In the present study, we found that high glucose could increase the secretion of IL-1b, IL-6 and TNF-a in TAECs.…”

Section: Discussionmentioning

confidence: 99%

Curcumin attenuates high glucose‐induced inflammatory injury through the reactive oxygen species–phosphoinositide 3‐kinase/protein kinase B–nuclear factor‐κB signaling pathway in rat thoracic aorta endothelial cells

Zhang

2017

J of Diabetes Invest

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Aims/IntroductionEndothelial cell inflammatory injury is likely required for barrier dysfunction under hyperglycemic conditions. Curcumin (CUR) is well known for its anti‐inflammatory effect. However, there have been few reports about the anti‐inflammatory effect of CUR induced by high glucose in endothelial cells. The aim of the present study was to investigate the inflammatory effect of high glucose and the anti‐inflammatory effect of CUR induced by high glucose in rat thoracic aorta endothelial cells (TAECs).Materials and MethodsWell characterized TAECs were established and cell viability was assayed by the cell counting kit‐8 method, messenger ribonucleic acid and protein expression were identified by real‐time polymerase chain reaction, western blot or enzyme‐linked immunosorbent assay, respectively. The production of reactive oxygen species was observed by a fluorescence microscope.ResultsHigh glucose (30 mmol/L) significantly decreased the cell viability of TAECs after being co‐cultivated for 12 h and showed a time‐dependent manner, and increased interleukin (IL)‐1β, IL‐6 and tumor necrosis factor‐α secretion in TAECs. The injury effect of high glucose was involved in the reactive oxygen species–phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)–nuclear factor (NF)‐κB signaling pathway. Anti‐oxidant N‐acetylcysteine, PI3K and NF‐κB‐specific pathway inhibitors can abolish the secretion of these inflammatory factors; pretreatment with anti‐oxidant N‐acetylcysteine significantly decreased PI3K expression, the level of phosphorylated AKT and nuclear NF‐κB; pretreatment of LY294002 can significantly decrease the NF‐κB level in nuclei. After treatment with CUR for 12 h, IL‐1β, IL‐6 and tumor necrosis factor‐α secretion were markedly decreased, and PI3K expression, the phosphorylation of AKT and nuclear NF‐κB level were also decreased.ConclusionCurcumin attenuates high glucose‐induced inflammatory injury through the reactive oxygen species–PI3K/AKT–NF‐κB signaling pathway in rat thoracic aorta endothelial cells.

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Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through STAT3-mediated pathway

Cited by 39 publications

References 29 publications

Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

Ginkgolide A Ameliorates LPS-Induced Inflammatory Responses In Vitro and In Vivo

Human pharmacokinetics of ginkgo terpene lactones and impact of carboxylation in blood on their platelet-activating factor antagonistic activity

Curcumin attenuates high glucose‐induced inflammatory injury through the reactive oxygen species–phosphoinositide 3‐kinase/protein kinase B–nuclear factor‐κB signaling pathway in rat thoracic aorta endothelial cells

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