Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production

Wu, Hsin-Ying; Huang, Chung-Hsiung; Lin, Yuan-Chih; Wang, Chia-Chi; TongRong, Jan

doi:10.1016/j.freeradbiomed.2018.06.023

Cited by 81 publications

(77 citation statements)

References 43 publications

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“…150,151 CBD-induced apoptosis (1-16 lM CBD) in human monocytes was due to a cascade of intracellular events, including opening of the mitochondrial permeability transition pore, depolarization of the mitochondrial membrane potential, oxidation of a lipid in the mitochondrial inner membrane, and mitochondrial ROS generation, leading to cytochrome C release. 115 Thus, this latest study demonstrates a critical role of the mitochondria in CBD-induced apoptosis.…”

Section: Cbd Effects and Mechanisms Of Immune Suppression In Lymphocytesmentioning

confidence: 68%

“…118,120 Interestingly, the reports of CBD on oxidative stress are different across studies, with some articles identifying CBD as an antioxidant, 59,118,184,185 and others reporting that CBD induces oxidative stress. 114,115,150,151 CBD-mediated effects on IL-10 pro-duction also revealed opposing effects when compared across several studies. 95,123,124,127,148,[186][187][188][189] Effects of CBD on IL-10 could be tied to regulatory cell production (i.e., Tregs or MDSCs) or changes in T cell subpopulations.…”

Section: Nichols and Kaplanmentioning

confidence: 98%

“…Later studies focused on human monocytic cells revealed that CBD can induce apoptosis in either HL-60 (1-8 lg/mL CBD or 3.2-26 lM CBD) 113 or primary human monocytic cells (1-16 lM CBD). 114,115 Macrophages are also targets, although they have been studied more commonly in animal models. Peritoneal macrophages were used early on to demonstrate that CBD (3 lg/mL or 10 lM) targets nitric oxide, 116 and this has also been a well-studied target of suppression by CBD in many tissues and cell types.…”

Section: Cbd Effects and Mechanisms Of Immune Suppression In Innate Cmentioning

confidence: 99%

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Immune Responses Regulated by Cannabidiol

Nichols

Kaplan

2020

Cannabis and Cannabinoid Research

209

176

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Introduction: Cannabidiol (CBD) as Epidiolex Ò (GW Pharmaceuticals) was recently approved by the U.S. Food and Drug Administration (FDA) to treat rare forms of epilepsy in patients 2 years of age and older. Together with the increased societal acceptance of recreational cannabis and CBD oil for putative medical use in many states, the exposure to CBD is increasing, even though all of its biological effects are not understood. Once such example is the ability of CBD to be anti-inflammatory and immune suppressive, so the purpose of this review is to summarize effects and mechanisms of CBD in the immune system. It includes a consideration of reports identifying receptors through which CBD acts, since the ' 'CBD receptor,' ' if a single one exists, has not been definitively identified for the myriad immune system effects. The review then provides a summary of in vivo and in vitro effects in the immune system, in autoimmune models, with a focus on experimental autoimmune encephalomyelitis, and ends with identification of knowledge gaps. Conclusion: Overall, the data overwhelmingly support the notion that CBD is immune suppressive and that the mechanisms involve direct suppression of activation of various immune cell types, induction of apoptosis, and promotion of regulatory cells, which, in turn, control other immune cell targets.

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Section: Cbd Effects and Mechanisms Of Immune Suppression In Lymphocytesmentioning

confidence: 68%

Section: Nichols and Kaplanmentioning

confidence: 98%

Section: Cbd Effects and Mechanisms Of Immune Suppression In Innate Cmentioning

confidence: 99%

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Immune Responses Regulated by Cannabidiol

Nichols

Kaplan

2020

Cannabis and Cannabinoid Research

209

176

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“…Once released into the cytosol, it forms a complex known as the apoptosome. These events allow for the catalytic maturation of caspase-3, which eventually mediates apoptosis (Morciano et al, 2017;SileikyteandForte, 2019;Wu et al, 2018). To identify the mechanism underlying the antiapoptotic effects of PGE1, we detected the protein levels of (cytosolic) cytochrome c and cleaved caspase-3.…”

Section: Pge1 Regulates Cytochrome C Caspase 3 and Gsk3βmentioning

confidence: 99%

“…Although PAMD is temporary after resuscitation, approximately two-thirds of the patients that achieve ROSC die from PAMD within the rst 72 h (Dragancea et Mitochondria-mediated cardiomyocyte apoptosis is one of the primary mechanisms underlying PAMD due to CA (Heusch et al, 2010;Jentzer et al, 2015;Liu et al, 2018). Global myocardial ischemia due to CA induces mitochondrial permeability transition pore (mPTP) opening, which results in cytochrome c leaking from the mitochondrial matrix to the cytoplasm, leading to caspase-3 activation and apoptosis (Morciano et al, 2017;SileikyteandForte, 2019;Wu et al, 2018). Inhibiting mPTP opening and apoptosis is a potential therapeutic target for PAMD (Cour et al, 2011;Huang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E1 Attenuates Post-Cardiac Arrest Myocardial Dysfunction via Inhibiting Mitochondria-Mediated Cardiomyocyte Apoptosis

Fan

et al. 2020

Preprint

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Background: Post-cardiac arrest myocardial dysfunction (PAMD) is a leading cause of death in resuscitated patients after cardiac arrest (CA). Prostaglandin E1 (PGE1) is a clinical drug used to mitigate ischemia injury. However, its effect on PAMD remains unknown. Methods: We investigated the protective effects of PGE1 on PAMD in a rat model of cardiac arrest and a hypoxia-reoxygenation (H/R) H9c2 cell model. Forty-two male Wistar rats were randomly assigned to CA, CA+PGE1, and sham groups. Asphyxia for 8 min followed by cardiopulmonary resuscitation was performed in the CA and CA+PGE1 groups. PGE1 (1 μg/kg) was intravenously administered at the onset of return of spontaneous circulation (ROSC). Ejection fraction (EF) and cardiac output (CO) were measured at baseline, 1, 2, 3, and 4 h after ROSC; survival was monitored for 72 h. Cardiomyocyte apoptosis, mitochondrial permeability transition pore (mPTP) opening, and protein levels of glycogen synthase kinase 3β (GSK3β), cytochrome c, and cleaved caspase-3 were measured 4 h after ROSC. H9c2 cells were treated with PGE1(0.5 μM) at the start of reoxygenation. Apoptosis, mPTP opening, and protein levels of GSK3β, cytochrome c, and cleaved caspase-3 of H9c2 cells were detected. Results: Compared to the CA group, PGE1 treatment significantly increased the EF and CO within 4 h after ROSC and improved the survival rate. It activated GSK3β, prevented mPTP opening, suppressed cytochrome c and cleaved caspase-3 expression, and reduced cardiomyocyte apoptosis in the rat model. In vitro, Changes in GSK3β, mPTP opening, cytochrome c and cleaved caspase-3 expression, and apoptosis in H9c2 cells were consistent with those in the rat model. Conclusions: Our results indicate that PGE1 attenuates PAMD via inhibiting mitochondria-mediated cardiomyocyte apoptosis.

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