Oleanolic acid attenuates MK-801-induced schizophrenia-like behaviors in mice

Park, Se Jin; Lee, Younghwa; Oh, Hee Kyong; Lee, Hyung Eun; Lee, Younghwan; Ko, Sang Yoon; Kim, Boseong; Cheong, Jae Hoon; Shin, Chan Young; Ryu, Jong Hoon

doi:10.1016/j.neuropharm.2014.06.025

Cited by 58 publications

(31 citation statements)

References 38 publications

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“…Oleanolic acid (OA) is a plant‐derived pentacyclic terpenoid that is widely distributed in various medicinal plants, fruits and herbs (Park et al, ). In China, OA has been used clinically as an anti‐hepatitis drug for more than 20 years.…”

Section: Introductionmentioning

confidence: 99%

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

Nie

Wang

Qin

et al. 2016

Cell Biology International

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Oleanolic acid (OA), a plant-derived pentacyclic terpenoid, is known to have hepatoprotective effects. In this study, we found that OA induced autophagic cell death in multiple human gastric cancer cell lines. Moreover, OA-induced autophagy was shown for the first time in human gastric cancer cells, evidenced by the formation of GFP-RFP-LC3 puncta and autophagosomes. OA suppressed phospho-mTOR through inhibition of the PI3 K/AKT and ERK/p38 MAPK signalling pathways and through activation of the AMPK signalling pathway. Furthermore, we found that OA-induced cytotoxicity and autophagy could be blocked by the autophagy inhibitor 3-methyladenine or via siRNA targeting Beclin-1. Our in vivo research showed that OA delayed the formation of MGC-803 tumours in an autophagy-dependent manner. These results reveal a novel mechanism for OA in gastric cancer cells and suggest that OA could be a novel agent in the treatment of gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

Nie

Wang

Qin

et al. 2016

Cell Biology International

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“…However, a derivative of BM, CDDO-MA, improved spatial memory and reduced hippocampal amyloid plaques in a mouse model of Alzheimer's disease (Dumont et al , 2009). It has been demonstrated that administration of oleanolic acid has been found to reverse recognition memory impairments in mice (Park et al , 2014). Furthermore, synthetically modifying side chains on oleanolic acid to a derivative form, such as BM, significantly increases its potency (Zhang et al , 2008).…”

Section: Introductionmentioning

confidence: 99%

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Camer

Szabo

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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X. (2015). Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 59 68-75. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory AbstractHigh fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood-brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. Recognition memory was assessed by performing a novel object recognition test on the treated mice. Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were examined in the prefrontal cortex (PFC) and hippocampus of mice via Western blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented HF dietinduced impairment in recognition memory (p < 0.001). In HF diet fed mice, BM administration attenuated alterations in the NMDA receptor binding density in the PFC (p < 0.05), however, no changes were seen in the hippocampus (p > 0.05). In the PFC and hippocampus of the HF diet fed mice, BM administration improved downstream BDNF signalling as indicated by increased protein levels of BDNF, phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p < 0.05). BM administration also prevented the HF diet-induced increase in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet-induced impairments in recognition memory by improving downstream BDNF signal transduction, increasing pAMPK, and reducing inflammation in the PFC and hippocampus. AbstractHigh-fat (HF) diets are known to induce changes in synaptic plasticity in the forebrain leading to learning and memory impairments. Previous studies of oleanolic acid derivatives have found that these compounds can cross the blood brain barrier to prevent neuronal cell death. We examined the hypothesis that the oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow (LC) (5% of energy as fat), HF (40% of energy as fat), or HF diet supplemented with 10 mg/kg/day BM orally for 21 weeks. and phosphorylated protein kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase (pAMPK) (p<0.05). BM a...

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“…ASR test and PPI test were performed in SR‐LAB startle chambers (San Diego Instruments, San Diego, CA), as previously described (Park et al, ). Each chamber contained plexiglas cylinder inside a ventilated box.…”

Section: Methodsmentioning

confidence: 99%

Vaccinia‐related kinase 2 plays a critical role in microglia‐mediated synapse elimination during neurodevelopment

Lee

Ryu

et al. 2019

Glia

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During postnatal neurodevelopment, excessive synapses must be eliminated by microglia to complete the establishment of neural circuits in the brain. The lack of synaptic regulation by microglia has been implicated in neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Here we suggest that vaccinia‐related kinase 2 (VRK2), which is expressed in microglia, may stimulate synaptic elimination by microglia. In VRK2‐deficient mice (VRK2KO), reduced numbers of presynaptic puncta within microglia were observed. Moreover, the numbers of presynaptic puncta and synapses were abnormally increased in VRK2KO mice by the second postnatal week. These differences did not persist into adulthood. Even though an increase in the number of synapses was normalized, adult VRK2KO mice showed behavioral defects in social behaviors, contextual fear memory, and spatial memory.

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Oleanolic acid attenuates MK-801-induced schizophrenia-like behaviors in mice

Cited by 58 publications

References 38 publications

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory

Vaccinia‐related kinase 2 plays a critical role in microglia‐mediated synapse elimination during neurodevelopment

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