Cytoprotective Effects of Oleanolic Acid in Human Umbilical Vascular Endothelial Cells is Mediated Via UCP2/ROS/Cytochrome C/AIF Pathway

Kong, Dexin; Han, Yantao; Wang, Chunbo; Chen, Xuehong; Jiang, Qixiao; Wang, Qiaoyun; Han, Ze‐Guang

doi:10.1097/fjc.0000000000000360

Cited by 3 publications

(5 citation statements)

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“…The prevention of VSMC proliferation is among the most promising atherosclerosis prevention strategies, in which oxidative stress and inflammatory cytokines are crucial factors to consider (Li et al, ). On the other hand, OA was known for its antioxidant and anti‐inflammation effects (Tsai and Yin, ; Kong et al, ). In vivo studies also revealed that OA exerted anti‐atherosclerotic effects (Jiang et al, ); however, the role of OA in VSMC proliferation had yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…OA has been reported to exert various benefits, including hypolipidemic, hepatoprotective, and anti-tumor effects (Kim et al, 2005;Jiang et al, 2015;Guo et al, 2017). In vitro studies had revealed its antioxidative and anti-inflammatory effects (Tsai and Yin, 2008;Jiang et al, 2015;Kong et al, 2016). However, previous studies had not investigated its potential effects on VSMCs.…”

Section: Introductionmentioning

confidence: 99%

“…The current study observed the effects of OA against ox‐LDL‐induced effects in A7r5 cells. In addition, according to the previous reports that OA could affect UCP2 in endothelial cells (Kong et al, ), FGF‐2 in hepatic cancer cells (Lin et al, ), and p53 in cancer cells (Li et al, ), the role of UCP2, FGF‐2, p53, and TSP‐1 was investigated as potential molecular mechanisms of OA. Our study provided information regarding the vascular protective effects of OA and could potentially facilitate further development of new cardioprotective agents.…”

Section: Introductionmentioning

confidence: 99%

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The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

Han

Jiang

Wang

et al. 2017

Cell Biology International

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Vascular smooth muscle cell (VSMC) proliferation is a major contributor to atherosclerosis. This study investigated the inhibitory effects of oleanolic acid (OA) against oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation in A7r5 cells and explored underlying molecular mechanism. The cell proliferation was quantified with cell counting kit-8 (CCK-8), in which ox-LDL significantly increased A7r5 cells proliferation, while OA pretreatment effectively alleviated such changes without inducing overt cytotoxicity, as indicated by lactate dehydrogenase (LDH) assay. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting revealed increased UCP2 and FGF-2 expression levels as well as decreased p53 and TSP-1 expression levels in A7r5 cells following ox-LDL exposure, while OA pretreatment reversed such changes. Furthermore, inhibiting UCP2 with genipin remarkably reversed the changes in the expression levels of FGF-2, p53, and TSP-1 induced by ox-LDL exposure; silencing FGF-2 with siRNA did not significantly change the expression levels of UCP2 but effectively reversed the changes in the expression levels of p53 and TSP-1, and activation of p53 with PRIMA-1 only significantly affected the changes in the expression levels of TSP-1, but not in UCP2 or FGF-2, suggesting a UCP-2/FGF-2/p53/TSP-1 signaling in A7r5 cells response to ox-LDL exposure. Additionally, co-treatment of OA and genipin exhibited similar effects to the expression levels of UCP2, FGF-2, p53, and TSP-1 as OA or genipin solo treatment in ox-LDL-exposed A7r5 cells, suggesting the involvement of UCP-2/FGF-2/p53/TSP-1 in the mechanism of OA. In conclusion, OA inhibits ox-LDL-induced VSMC proliferation in A7r5 cells, the mechanism involves the changes in UCP-2/FGF-2/p53/TSP-1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

Han

Jiang

Wang

et al. 2017

Cell Biology International

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“…Finally, ow cytometry was utilized to quantitatively evaluate the apoptosis rate of DA neurons. The intracellular ROS production in primary DA neurons was detected utilizing ow cytometry with uorescent DCFH-DA as probe (Enzo Life Sciences) [17] .The mPTP opening of primary DA neurons was evaluated with a ow cytometer after CoCl 2 -calcein uorescence quenching assay [18]. The data of aforementioned three assay were processed with CellQuest Pro software (BD Bioscience).…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

AVE0991 Promotes Neuroprotection via Mas/ERK/mPTP Pathway in α-Synuclein A53T Transgenic Mice

Xue

et al. 2021

Preprint

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Parkinson’s disease (PD) is the most prevalent neurodegenerative movement diseases featured by selective loss of dopaminergic (DA) neurons within the striatum and substantia nigra (SN). Accumulating evidence have indicated that angiotensin-(1-7) (Ang-(1-7)) prevents neuronal damage by binding to its specific receptor Mas in PD. To date, the underlying mechanisms is not known thus far. In the present study, by using α-synuclein A53T transgenic mice (A53T mice), we showed that the neuronal apoptosis in the SN of A53T mice may be attributed to a decrease in Ang-(1-7) levels. Additionally, we revealed that AVE0991, a recently found non-peptide analogue of Ang-(1−7), ameliorated neuronal apoptosis via Mas/ERK pathway in primary DA neurons. More importantly, we provided novel evidence that this beneficial impact was dependent on the suppression of mitochondrial permeability transition pore opening. In conclusion, these findings disclose the neuroprotective impact of Ang-(1−7) in the etiology of PD, and support the application of its nonpeptide analogue AVE0991 in the therapies of this neurodegenerative disease.

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“…Oleanolic acid (OLA) is a natural pentacyclic triterpenoid compound mainly extracted from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum ), which is an important Chinese herbal medicine for protecting against inflammation, osteoporosis and endocrine metabolic disorders . Numerous studies reveal that OLA has the ability to block stimuli‐induced cell apoptosis, including podocyte, lung epithelial cell and human umbilical vascular endothelial cells . Several studies suggest that OLA has a beneficial effect on injury‐induced metabolic disorders of articular cartilage .…”

Section: Introductionmentioning

confidence: 99%

Oleanolic acid mitigates interleukin‐1β‐induced chondrocyte dysfunction by regulating miR‐148‐3p‐modulated FGF2 expression

Nie

Ping

2020

The Journal of Gene Medicine

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Background: microRNA (miR)-mediated post-transcriptional repression has been reported in the process of chondrocyte dysfunction. The present study aimed to investigate the molecular mechanisms underlying in oleanolic acid (OLA)-prevented interleukin (IL)-1β-induced chondrocyte dysfunction via the miR-148-3p/fibroblast growth factor-2 (FGF-2) signaling pathway.Methods: Candidate miRs were filtrated using miR microarray assays in chondrocytes with or without IL-1β stimulation. Gene expression of candidate miRs and protein expression of FGF2 were analyzed using a quantitative reverse transcriptasepolymerase chain reaction and western blotting, respectively. Cell growth was evaluated using cell counting kit-8 assays. Cell apoptosis was detected using Annexin V-fluorescein isothiocyanate double staining.Results: Treatment with OLA counteracted IL-1β-evoked chondrocyte growth inhibition, apoptosis, caspase3 production, and release of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine. Additionally, FGF2 protein expression levels elevated by IL-1β were down-regulated by OLA and transfection with miR-148-3p mimics. IL-1β-induced down-regulation of miR-148-3p in chondrocytes was evaluated by OLA administration. Bioinformatics algorithms and experimental measurements indicated that FGF2 might be a direct target of miR-148-3p. miR-148-3p mimics exhibited equal authenticity of OLA to protect against IL-1β-induced chondrocyte dysfunction. Conclusions:Our present findings highlight a protective effect of OLA on IL-1βinduced chondrocyte dysfunction, and a novel signal cascade comprising the miR-148-3p/FGF2 signaling pathway might be a potential therapeutic target of OLA with respect to preventing the progression of osteoarthritis.

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Cytoprotective Effects of Oleanolic Acid in Human Umbilical Vascular Endothelial Cells is Mediated Via UCP2/ROS/Cytochrome C/AIF Pathway

Cited by 3 publications

References 41 publications

The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

The anti‐proliferative effects of oleanolic acid on A7r5 cells—Role of UCP2 and downstream FGF‐2/p53/TSP‐1

AVE0991 Promotes Neuroprotection via Mas/ERK/mPTP Pathway in α-Synuclein A53T Transgenic Mice

Oleanolic acid mitigates interleukin‐1β‐induced chondrocyte dysfunction by regulating miR‐148‐3p‐modulated FGF2 expression

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