Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-κB, MAPK and AP-1 signaling pathways in macrophages

Shi, Qinghai; Jinjun, Cao; Li, Fang; Zhao, Hongyan; Liu, Zhengxiang; Ran, Juntao; Zheng, Xinchuan; Li, Xiaoling; Zhou, Yu; Ge, Di; Zhang, Hongming; Wang, Li; Ran, Ying; Fu, Jianfeng

doi:10.1016/j.intimp.2014.04.004

Cited by 122 publications

(77 citation statements)

References 29 publications

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“…Icariin inhibited TNF‐α/IFN‐γ induced inflammatory response via inhibition of p38‐MAPK signalling pathway in human keratinocytes 34. Geniposide suppressed LPS‐induced nitric oxide, PGE2 and inflammatory cytokine by downregulating MAPK and AP‐1 signalling pathways in macrophages 35. In this study, our results showed that TV suppressed the phosphorylation of MAPKs and AP‐1 complex in UVB irradiated NHDFs, indicating that TV inhibited MMP‐1 production via MAPK and AP‐1 signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP‐1 and activation of Nrf2‐ARE antioxidant system

Sun

Park

Hwang

et al. 2016

J Cellular Molecular Medi

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Solar ultraviolet (UV) radiation‐induced reactive oxidative species is mainly responsible for the development of photoageing. Rosmarinic acid was one of the main bioactive components detected in Thymus vulgaris (TV) we extracted. In this study, UVB‐induced skin damages have been shown to be ameliorated by treatment with TV in hairless mice (HR‐1) skin, demonstrated by decreased matrix metalloproteinases (MMPs) and increased collagen production. However, the underlying molecular mechanism on which TV acted was unclear. We examined the photoprotective effects of TV against UVB and elucidated the molecular mechanism in normal human dermal fibroblasts. Thymus vulgaris remarkably prevented the UVB‐induced reactive oxygen species and lactate dehydrogenase. Dose‐dependent increase in glutathione, NAD(P)H: quinone oxidoreductase1 and heme oxygenase‐1, by TV was confirmed by increased nuclear accumulation of Nrf2. Furthermore, 5‐Methoxyindole‐2‐carboxylic acid was introduced as a specific inhibitor of dihydrolipoyl dehydrogenase (DLD). We demonstrated that Nrf2 expression was regulated by DLD, which was a tricarboxylic acid cycle‐associated protein that decreased after UVB exposure. Besides, TV significantly diminished UVB induced phosphorylation of mitogen activated protein kinases pathway, containing extracellular signal‐regulated kinase, Jun N‐terminal kinase and p38, which consequently reduced phosphorylated c‐fos and c‐jun. Our results suggest that TV is a potential botanical agent for use against UV radiation‐induced oxidative stress mediated skin damages.

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Section: Discussionmentioning

confidence: 99%

Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP‐1 and activation of Nrf2‐ARE antioxidant system

Sun

Park

Hwang

et al. 2016

J Cellular Molecular Medi

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“…4) Geniposide, a major iridoid glycoside found in Gardenia jasminoides ELLIS fruits, is widely used in Asian countries. 9) It has been reported to have a wide spectrum of biological and pharmacological activities, including hepatoprotection, 10) neuroprotection, 11,12) anti-inflammation, 13) anti-nociception, 14) anti-diabetes, 15,16) anti-apoptosis 17) and anti-allergic. 18) The first report of geniposide hypoglycemic activity in high sugar diet-induced diabetic mice was made in 1982.…”

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confidence: 99%

Geniposide Suppresses Hepatic Glucose Production <i>via</i> AMPK in HepG2 Cells

Guo

Zheng

Liu

et al. 2016

Biological & Pharmaceutical Bulletin

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Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPKα expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK-FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis.Key words geniposide; hepatic glucose production; AMP-activated protein kinase; HepG2 cell Type 2 diabetes mellitus (T2DM) comprises heterogeneous disorders that result in chronic hyperglycemia and lifethreatening complications. The pathological change in hepatic glucose production is a central characteristic in diabetic patients.1) Hyperglycemia in both types 1 and 2 diabetes mellitus is associated with high hepatic glucose production.2) Suppression of hepatic glucose production has been shown to improve overall glycemic control in both human patients and type 2 diabetes animal models.3) The control of hepatic glucose production depends on many factors, including the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), insulin levels, and the concentration of gluconeogenic substrates (lactate, gluconeogenic amino acids, and glycerol). A variety of molecular signaling pathways were demonstrated to regulate hepatic glucose production, such as AMP-activated protein kinase (AMPK) activation, 4) protein kinase B (AKT or PKB) phosphorylation and mitogen-activated protein kinase (MAPK) inhibition. Among them, AMPK, the evolutionarily conserved serine/threonine kinase, is considered as the major signaling molecule responsible for this process. AMPK acts as an intracellular sensor to maintain the glucose homeostasis in the hypothalamus, skeletal muscle and liver [5][6][7] by the phosphorylation of several downstream metabolic enzymes and certain transcription factors. In the liver, the acute activation of AMPK, achieved by adenovirus-mediated gene transfer of a co...

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“…The results of the current study indicated that geniposide reduces AP-1 protein expression in mouse epilepsy. Shi et al demonstrated that geniposide suppresses the LPS-induced inflammatory cytokine, prostaglandin E2, and NO through inhibition of AP-1 signaling pathways in macrophages (28).…”

Section: Discussionmentioning

confidence: 99%

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway

Wei¹,

Duan²,

He³

et al. 2017

Exp Ther Med

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Abstract. Previous reports on the pharmacological actions of geniposide have indicated that it has anti-asthmatic, anti-inflammatory and analgesic effects in the liver and gallbladder, and therapeutic effects in neurological, cardiovascular and cerebrovascular diseases. The results of the current study demonstrate that geniposide attenuates epilepsy in a mouse model through the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A mouse model of epilepsy was induced by maximal electric shock (50 mA, 50 Hz, 1 sec). Epilepsy mice were intragastrically administered with 0, 5, 10 or 20 mg/kg geniposide. Geniposide significantly reduced the incidence and significantly increased the latency of clonic seizures in epileptic mice compared with non-treated epileptic mice (both P<0.01). Geniposide treatment significantly inhibited cyclooxygenase-2 mRNA expression in epilepsy mice (P<0.01). Furthermore, geniposide significantly suppressed the protein expression of activator protein 1, increased the activation of Akt and increased the protein expression of GSK-3β and PI3K in epilepsy mice (all P<0.01). These results suggest that geniposide attenuates epilepsy in mice through the PI3K/Akt/GSK-3β signaling pathway.

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Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-κB, MAPK and AP-1 signaling pathways in macrophages

Cited by 122 publications

References 29 publications

Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP‐1 and activation of Nrf2‐ARE antioxidant system

Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP‐1 and activation of Nrf2‐ARE antioxidant system

Geniposide Suppresses Hepatic Glucose Production <i>via</i> AMPK in HepG2 Cells

Geniposide attenuates epilepsy symptoms in a mouse model through the PI3K/Akt/GSK‑3β signaling pathway

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