Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

Yang, Shuai; Hu, Bin; Wang, Zongming; Zhang, Changming; Jiao, Haosen; Mao, Zhi-gang; Wei, Liguang; Jia, Ji-dong; Zhao, Jingling

doi:10.1038/s41420-020-00338-3

Cited by 22 publications

(15 citation statements)

References 35 publications

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“…In addition, we found that ACEA treatment did not impact the expression of CB2 in both SW480 and SW620 cells, excluding the possibility that the changes observed with ACEA might be caused by CB2. In line with our study, similar observations have been reported by other teams [ 28 – 31 ], and related mechanisms included enhancing promoter activity via Akt and NF-kB or inducing Human antigen R nucleoplasmic transport. Our results also showed that CB1 activation inhibited the proliferation, migration and invasion of colorectal cancer cells.…”

Section: Discussionsupporting

confidence: 93%

Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

Deng

Zhao

et al. 2022

Cell Death Discov.

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Cannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.

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Section: Discussionsupporting

confidence: 93%

Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

Deng

Zhao

et al. 2022

Cell Death Discov.

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“…Finally, ACEA is a well described synthetic CB 1 agonist and analogue of AEA [ 164 ]. ACEA has the proclivity to protect ischemic neurons from oxygen-glucose deprivation/reoxygenation and middle cerebral artery occlusion [ 165 ].…”

Section: Synthetic Cannabinoidsmentioning

confidence: 99%

Cannabidiol modulation of oxidative stress and signalling

et al. 2021

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Cannabidiol (CBD), one of the primary non-euphoric components in the Cannabis sativa L. plant, has undergone clinical development over the last number of years as a therapeutic for patients with Lennox-Gastaut syndrome and Dravet syndromes. This phytocannabinoid demonstrates functional and pharmacological diversity, and research data indicate that CBD is a comparable antioxidant to common antioxidants. This review gathers the latest knowledge regarding the impact of CBD on oxidative signalling, with focus on the proclivity of CBD to regulate antioxidants and control the production of reactive oxygen species. CBD is considered an attractive therapeutic agent for neuroimmune disorders, and a body of literature indicates that CBD can regulate redox function at multiple levels, with a range of downstream effects on cells and tissues. However, pro-oxidant capacity of CBD has also been reported, and hence caution must be applied when considering CBD from a therapeutic standpoint. Such pro- and antioxidant functions of CBD may be cell- and model-dependent, and may also be influenced by CBD dose, the duration of CBD treatment and the underlying pathology.

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“…First, it is difficult to mimic the pathological process of SAH in vitro, so we only verified our hypothetical mechanism in vivo. Second, a previous study showed that ACEA alleviated cerebral ischemia/reperfusion injury through the CB1R-Drp1 pathway [ 48 ], so we cannot exclude other signaling pathways that improve the prognosis of SAH. These deficiencies would be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

ACEA Attenuates Oxidative Stress by Promoting Mitophagy via CB1R/Nrf1/PINK1 Pathway after Subarachnoid Hemorrhage in Rats

Liu

Tian

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background and Purpose. Oxidative stress plays a pivotal role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). The CB1R agonist ACEA has been reported to have a neuroprotective effect in many central nervous system diseases. Our study was aimed at exploring the effect and mechanism of ACEA in an experimental SAH model. Method. Endovascular perforation was performed to establish a SAH model of rats. ACEA was administered intraperitoneally 1 h after SAH. The CB1R antagonist AM251 was injected intraperitoneally 1 h before SAH induction. Adenoassociated virus- (AAV-) Nrf1 shRNA was infused into the lateral ventricle 3 weeks before SAH induction. Neurological tests, immunofluorescence, DHE, TUNEL, Nissl staining, transmission electron microscopy (TEM), and Western blot were performed. Results. The expression of CB1R, Nrf1, PINK1, Parkin, and LC3II increased and peaked at 24 h after SAH. ACEA treatment exhibited the antioxidative stress and antiapoptosis effects after SAH. In addition, ACEA treatment increased the expression of Nrf1, PINK1, Parkin, LC3II, and Bcl-xl but repressed the expression of Romo-1, Bax, and cleaved caspase-3. Moreover, the TEM results demonstrated that ACEA promoted the formation of mitophagosome and maintained the normal mitochondrial morphology of neurons. The protective effect of ACEA was reversed by AM251 and Nrf1 shRNA, respectively. Conclusions. This study demonstrated that ACEA alleviated oxidative stress and neurological dysfunction by promoting mitophagy after SAH, at least in part via the CB1R/Nrf1/PINK1 signaling pathway.

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Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

Cited by 22 publications

References 35 publications

Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

Cannabidiol modulation of oxidative stress and signalling

ACEA Attenuates Oxidative Stress by Promoting Mitophagy via CB1R/Nrf1/PINK1 Pathway after Subarachnoid Hemorrhage in Rats

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