Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation

Wei, Tzu-Tang; Chandy, Mark; Nishiga, Masataka; Zhang, Angela; Kumar, Kaavya Krishna; Thomas, Dilip; Manhas, Amit; Rhee, Siyeon; Justesen, Johanne Marie; Chen, Ian Y.; Wo, Hung‐Ta; Khanamiri, Saereh; Yang, Johnson Y.; Seidl, Frederick J.; Burns, Noah Z.; Li, Chun; Sayed, Nazish; Shie, Jiun‐Jie; Yeh, Chih Ching; Yang, Kai‐Chien; Lau, Edward; Lynch, Kara L.; Rivas, Manuel A.; Kobilka, Brian K.; Wu, Joseph C.

doi:10.1016/j.cell.2022.04.005

Cited by 73 publications

(58 citation statements)

References 85 publications

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“…In a recent study published in Cell , Wei and colleagues describe the role of canabis in mediating inflammation and oxidative stress induced endothelial dysfunction and thereby contributing to the pathogenesis of atherosclerosis. 1 …”

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confidence: 99%

“… 4 The major psychoactive constituent in cannabis is ∆ 9 -tetrahydrocannabinol (∆ 9 -THC), which has shown selectively binding to cannabinoid receptor 1 (CB1/CNR1) in the endothelial cells (ECs) and is involved in the pathogenesis of CVDs. 1 The underlying molecular mechanisms involved in the ∆ 9 -THC induced vascular events are yet to be fully understood.…”

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confidence: 99%

“…Further assessment found that inflammatory cytokines associated with the pathogenesis of atherosclerosis were significantly elevated after smoking a marijuana cigarette. 1 In order to explore the molecular mechanisms, the authors aptly used ligand-based high-throughput virtual screening with the SWEETLEAD chemical database to identify novel selective CB1 antagonists. They found that genistein, a nature soybean flavonoid, is a neutral ligand for CB1 and can selectively bind to CB1.…”

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confidence: 99%

“…Human induced pluripotent stem cells (hiPSC-ECs) is an ideal platform for ex vivo models of vascular disease and screen toxicity and bioactive compounds. 1 In addition, hiPSC-ECs are without environmental exposures, which can avoid the environmental effect on ∆ 9 -THC induced phenotype in endothelial cells exposure to cannabis use. Interestingly, hiPSC-ECs only express the CB1 receptor.…”

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confidence: 99%

“…Genistein treatment significantly reversed ∆ 9 -THC-induced inflammation-related genes and oxidative stress protective-related gene expression, which is consistent with the protective effect mediated by siRNA CB1 and CRISPR interference (CRISPRi). 1 Vascular inflammation and oxidative stress are major triggers of endothelial dysfunctions contributing to the atherosclerosis initiation and progression. Genistein may serve as a potential therapeutic drug for treating ∆ 9 -THC related atherosclerosis by reducing inflammation and oxidative stress.…”

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confidence: 99%

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Prostate cancer is the most common malignancy among men worldwide, and androgen‐deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer‐related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk‐mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

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Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

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Obesity is a major risk factor for morbidity and mortality because it has a close relationship to metabolic illnesses, such as diabetes, cardiovascular diseases, and some types of cancer. With no drugs available, the mainstay of obesity management remains lifestyle changes with exercise and dietary modifications. In light of the tremendous disease burden and unmet therapeutics, fresh perspectives on pathophysiology and drug discovery are needed. The development of epigenetics provides a compelling justification for how environmental, lifestyle, and other risk factors contribute to the pathogenesis of obesity. Furthermore, epigenetic dysregulations can be restored, and it has been reported that certain natural products obtained from plants, such as tea polyphenols, ellagic acid, urolithins, curcumin, genistein, isothiocyanates, and citrus isoflavonoids, were shown to inhibit weight gain. These substances have great antioxidant potential and are of great interest because they can also modify epigenetic mechanisms. Therefore, understanding epigenetic modifications to target the primary cause of obesity and the epigenetic mechanisms of anti‐obesity effects with certain phytochemicals can prove rational strategies to prevent the disease and develop novel therapeutic interventions. Thus, the current review aimed to summarize the epigenetic mechanisms and advances in therapies for obesity based on natural products to provide evidence for the development of several potential anti‐obesity drug targets.

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Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation

Cited by 73 publications

References 85 publications

The cannabis paradox: contrasting role for marijuana in cardiovascular disease

The cannabis paradox: contrasting role for marijuana in cardiovascular disease

A practical guide for assessing and managing cardiovascular risk during androgen‐deprivation therapy in patients with prostate cancer

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products

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