A novel CB2 agonist, COR167, potently protects rat brain cortical slices against OGD and reperfusion injury

Contartese, Antonella; Valoti, Massimo; Corelli, Federico; Pasquini, Serena; Mugnaini, Claudia; Pessina, Federica; Aldinucci, Carlo; Sgaragli, Giampietro; Frosini, Maria

doi:10.1016/j.phrs.2012.08.003

Cited by 32 publications

(38 citation statements)

References 52 publications

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“…Moreover, we also investigated the intracellular levels of IL-10, which has been shown to be increased by CB2 activation through the ERK 1/2 pathway [35]. Indeed, while the effects of JWH-133 on pro-inflammatory cytokines replicated results obtained in previous studies with other cell types [13], [36], i.e. the compound inhibited their LPS-stimulated levels and, in some cases also their basal levels, we obtained some unexpected results when examining extracellular IL-10 levels.…”

Section: Discussionmentioning

confidence: 58%

The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties

et al. 2013

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Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive properties of human mesenchymal stromal cells have attracted much attention from immunologists, stem cell biologists and clinicians.Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated. Endocannabinoids, mainly acting through the cannabinoid receptor subtype 2, are able to modulate cytokine release and to act as immunosuppressant when added to activated T lymphocytes.In the present study, we have investigated, through a multidisciplinary approach, the involvement of the endocannabinoids in migration, viability and cytokine release of human mesenchymal stromal cells.We show, for the first time, that cultures of human mesenchymal stromal cells express all of the components of the endocannabinoid system, suggesting a potential role for the cannabinoid CB2 receptor as a mediator of anti-inflammatory properties of human mesenchymal stromal cells, as well as of their survival pathways and their capability to home and migrate towards endocannabinoid sources.

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Section: Discussionmentioning

confidence: 58%

The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties

et al. 2013

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“…OGD/R-induced Neuro-2a cell injury acts as a model to mimic cerebral I/R injury in vitro and results in neuronal insult [18,19]. This model could mimic extracellular condition in cerebral ischemia and subsequently reperfusion, which is used as a common model for research in vitro .…”

Section: Resultsmentioning

confidence: 99%

DRAM1 Protects Neuroblastoma Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Injury via Autophagy

Jiang

Feng

et al. 2014

IJMS

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DNA damage-regulated autophagy modulator protein 1 (DRAM1), a multi-pass membrane lysosomal protein, is reportedly a tumor protein p53 (TP53) target gene involved in autophagy. During cerebral ischemia/reperfusion (I/R) injury, DRAM1 protein expression is increased, and autophagy is activated. However, the functional significance of DRAM1 and the relationship between DRAM1 and autophagy in brain I/R remains uncertain. The aim of this study is to investigate whether DRAM1 mediates autophagy activation in cerebral I/R injury and to explore its possible effects and mechanisms. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) Neuro-2a cell model to mimic cerebral I/R conditions in vitro, and RNA interference is used to knock down DRAM1 expression in this model. Cell viability assay is performed using the LIVE/DEAD viability/cytotoxicity kit. Cell phenotypic changes are analyzed through Western blot assays. Autophagy flux is monitored through the tandem red fluorescent protein–Green fluorescent protein–microtubule associated protein 1 light chain 3 (RFP–GFP–LC3) construct. The expression levels of DRAM1 and microtubule associated protein 1 light chain 3II/I (LC3II/I) are strongly up-regulated in Neuro-2a cells after OGD/R treatment and peaked at the 12 h reperfusion time point. The autophagy-specific inhibitor 3-Methyladenine (3-MA) inhibits the expression of DRAM1 and LC3II/I and exacerbates OGD/R-induced cell injury. Furthermore, DRAM1 knockdown aggravates OGD/R-induced cell injury and significantly blocks autophagy through decreasing autophagosome-lysosome fusion. In conclusion, our data demonstrate that DRAM1 knockdown in Neuro-2a cells inhibits autophagy by blocking autophagosome-lysosome fusion and exacerbated OGD/R-induced cell injury. Thus, DRAM1 might constitute a new therapeutic target for I/R diseases.

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“…Viability of tissue was also assessed by using MTT assay [69]. Rings were placed in 24 multiwell, one ring/well, and incubated for one hour at 37 • C with 800 µl of MTT solution (0.5 mg/mL).…”

Section: Rat Ileum or Colon Ringsmentioning

confidence: 99%

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

Chiaino

Micucci

Budriesi

et al. 2020

IJMS

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The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at the gastrointestinal level. This study characterized AC for its catechins content and investigated the apoptosis-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. MTT assay was used to describe the time course, concentration dependence and reversibility of AC-mediated cytotoxicity. Cell cycle analysis and AV-PI and DAPI-staining were performed to evaluate apoptosis, together with ROS formation, mitochondrial membrane potential (MMP) changes and caspase activities. Rat ileum and colon rings were tested for their viability and functionality to explore AC effects on healthy tissue. Quantitative analysis highlighted that AC was rich in (±)-catechin (31.5 ± 0.82 mg/g) and (−)-epicatechin (12.5 ± 0.42 mg/g). AC irreversibly decreased cell viability in a concentration-dependent, but not time-dependent fashion. Cytotoxicity was accompanied by increases in apoptotic cells and ROS, a reduction in MMP and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings' viability and functionality, suggesting a safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment.3 of 17 at approximately the same content level was observed (Figure 1b). The latter was assumed as a marker of the epimerization as the consequence of the process applied in decoction preparation (thermal treatment). Analysis of decoction preparations stored during very long-term period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation. Int. J. Mol. Sci. 2020, 21, x FOR PEER REVIEW 3 of 17 period (at least two years) at room temperature in the dark, did not show loss of (−)-EC and (+)-C, nor epimerization progression, thus suggesting very high chemical stability of the preparation.

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A novel CB2 agonist, COR167, potently protects rat brain cortical slices against OGD and reperfusion injury

Cited by 32 publications

References 52 publications

The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties

The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties

DRAM1 Protects Neuroblastoma Cells from Oxygen-Glucose Deprivation/Reperfusion-Induced Injury via Autophagy

Apoptotic-Induced Effects of Acacia Catechu Willd. Extract in Human Colon Cancer Cells

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