Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice

Cheng, Shi; Zhou, Fenghua; Xu, Yongqiang; Liu, Xiaoyu; Zhang, Yu; Gu, Minhua; Su, Zhijie; Zhao, Dandan; Zhang, Lei; Jia, Yuhua

doi:10.1016/j.imbio.2018.12.005

Cited by 51 publications

(40 citation statements)

References 26 publications

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“…Geniposide exhibits a broad spectrum of pharmacological actions involving anti-apoptosis (12), anti-inflammatory injury (13), anti-oxidative stress (14), anti-cancer (15) and anti-angiogenesis effects (16). Previous in vitro and in vivo studies have focused on the potential cardioprotective effects of geniposide, particularly in atherosclerosis (17)(18)(19). cheng et al (17) demonstrated that geniposide can decrease plaque size and mitigate atherosclerosis-associated inflammatory damage by regulating the miR-101-associated signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Previous in vitro and in vivo studies have focused on the potential cardioprotective effects of geniposide, particularly in atherosclerosis (17)(18)(19). cheng et al (17) demonstrated that geniposide can decrease plaque size and mitigate atherosclerosis-associated inflammatory damage by regulating the miR-101-associated signaling pathway. Another study also demonstrated that the combination of Scutellaria baicalensis georgi with geniposide exerts inflammation-regulatory effects and inhibits atherosclerotic lesions (19).…”

Section: Introductionmentioning

confidence: 99%

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miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

et al. 2020

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Oxidized low-density lipoprotein (ox-LdL)-induced vascular endothelial damage, oxidative stress and inflammation play a vital role in the pathophysiology of atherosclerosis. Geniposide is the primary active ingredient from Gardenia jasminoides Ellis associated with anti-oxidative properties and cardioprotective action. However, the therapeutic mechanism of geniposide in atherosclerosis remains unclear. Hence, the present study aimed to elucidate the underlying mechanisms of geniposide in oxidative stress and inflammatory response during ox-LdL injury in human umbilical vein endothelial cells (HUVEcs), focusing particularly on the microRNA (miR)-21/PTEN pathway. The results demonstrated that geniposide pretreatment significantly increased cell viability, decreased lactate dehydrogenase release, increased miR-21 level and decreased PTEN expression under ox-LdL condition. Subsequently, transfection with miR-21 mimic enhanced the protection of geniposide on ox-LdL-induced cytotoxicity and apoptosis (mediated by the upregulation of apoptotic rate and caspase-3 activity), whereas miR-21 inhibitor reversed these effects of geniposide. In addition, geniposide resulted in an anti-oxidant effect as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NAdPH oxidase 2 expression, and the increase in superoxide dismutase, glutathione peroxidase and catalase activities in ox-LdL-treated HUVEcs, which were exacerbated by miR-21 mimic and reversed by miR-21 inhibitor. Furthermore, geniposide mitigated the ox-LdL-induced inflammatory response, demonstrated by a downregulation of pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels and an upregulation of anti-inflammatory cytokine (IL-10) level. However, miR-21 mimic enhanced, whereas miR-21 inhibitor attenuated, these effects of geniposide. In conclusion, the present results indicated that geniposide protects HUVEcs from ox-LdL injury by inhibiting oxidative stress and inflammation, and that these effects are partly due to the enhancement of the miR-21/PTEN pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

et al. 2020

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“…Geniposide is an active ingredient of traditional Chinese herbal medicine Gardenia jasminoides Ellis, which is extensively applied in clinic to treat stroke in China. Geniposide has various pharmacological properties, such as anti-inflammatory, antidiabetic, anti-fibrotic, antioxidative, anti-apoptotic and antitumour activities [5][6][7][8][9]. Besides this, geniposide was revealed to be beneficial in suppressing Helicobacter pylori infections [10].…”

Section: Introductionmentioning

confidence: 99%

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 lg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1b, IL-6, IL-8 and TNF-a evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-jB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-jB and JNK pathways. HIGHLIGHTS 1. Geniposide prevents LPS-induced injury in PC12 cells; 2. Geniposide up-regulates miR-145-5p; 3. Geniposide protects PC12 cells via up-regulation of miR-145-5p; 4. Geniposide inhibits NF-jB and JNK pathways via up-regulation of miR-145-5p.

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“…In the kingdom of natural products, terpenoids have emerged as one of the most important families because of their distinct biological activities and drug‐like properties . In China and other countries, many kinds of terpenoids have been found with good anti‐inflammatory activities and some of which were used clinically for treating inflammation ( Figure ) . Finding new anti‐inflammatory drugs from terpenoids is therefore a good strategy …”

Section: Introductionmentioning

confidence: 99%

“…[5,6] In China and other countries, many kinds of terpenoids have been found with good anti-inflammatory activities and some of which were used clinically for treating inflammation (Figure 1). [7][8][9][10][11][12] Finding new anti-inflammatory drugs from terpenoids is therefore a good strategy. [13] The seeds of Euphorbia lathyris are utilized as traditional Chinese medicine for treating terminal schistosomiasis, ascites, hydropsy, and snakebites.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New Lathyrane Diterpenoid Derivatives from Euphorbia lathyris and Evaluation of Their Anti‐Inflammatory Activities

Wang

et al. 2020

Chemistry & Biodiversity

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Euphorbia factor L3, a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti‐inflammatory activity with very low cytotoxicity. To find more potent anti‐inflammatory drugs, two series of Euphorbia factor L3 derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS‐induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L3 derivatives that contribute to anti‐inflammatory activity, we conducted a structure‐activity relationship study of these compounds.

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Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice

Cited by 51 publications

References 26 publications

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Synthesis of New Lathyrane Diterpenoid Derivatives from Euphorbia lathyris and Evaluation of Their Anti‐Inflammatory Activities

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