A transcriptomics and molecular biology based investigation reveals the protective effect and mechanism of carnosol on t-BHP induced HRMECs via Nrf2 signaling pathway

Ren, Yue; Liu, Yanan; Liu, Kaiyang; Shu, Zhan; Lv, Tianyi; Chen, Zijun; Feng, Wenqing; Zhang, Yanling

doi:10.1016/j.ejphar.2022.174933

Cited by 5 publications

(5 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In response to external stimuli, NRF2 activates endogenous protective genes, including HO‐1, thereby regulating antioxidant stress. Recent studies have highlighted the regulatory effects of carnosol on NRF2‐mediated antioxidant properties in various diseases, such as polycystic ovary syndrome (Ji et al, 2023), diabetic microvascular complications (Li et al, 2019), and diabetic retinopathy (Ren, Liu, et al, 2022). Our study reveals a decline in NRF2 and HO‐1 expression in cardiac remodeling, consistent with previous research.…”

Section: Discussionmentioning

confidence: 99%

Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload‐induced heart failure mice

Fang,

Lu,

Huang

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

Cardiac remodeling is a commonly observed pathophysiological phenomenon associated with the progression of heart failure in various cardiovascular disorders. Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti‐inflammatory, antioxidant, and anti‐apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC‐induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II‐induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti‐inflammatory, anti‐oxidative, and anti‐apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1/PI3K/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti‐inflammatory, anti‐oxidative, and anti‐apoptotic effects mediated by Sirt1/PI3K/AKT signaling pathways, thereby alleviating heart failure and VF.

show abstract

Section: Discussionmentioning

confidence: 99%

Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload‐induced heart failure mice

Fang,

Lu,

Huang

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…The cells were exposed to 1 μg/mL LPS, carnosol (10 μM), Nrf2 siRNA(100 nM, sc-37030, Santa Cruz), or SIRT3 siRNA (100 nM, sc-61555, Santa Cruz). The carnosol dosage accepted in vitro experiment was referred to a previous study (Ren et al, 2022). After 24 h of treatment, HPMECs were harvested for subsequent experiments.…”

Section: Cell Culturementioning

confidence: 99%

Carnosol alleviates sepsis‐induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2‐related factor 2/sirtuin‐3 signaling pathway to attenuate oxidative damage

Li,

Wang,

Luo

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

Excessive reactive oxygen species production during acute lung injury (ALI) will aggravate the inflammatory process and endothelial barrier dysfunction. Carnosol is a natural phenolic diterpene with antioxidant and anti‐inflammatory properties, but its role in treating sepsis‐induced ALI remains unclear. This study aims to explore the protective effects and underlying mechanisms of carnosol in sepsis‐induced ALI. C57BL/6 mouse were preconditioned with carnosol for 1 h, then the model of lipopolysaccharide (LPS)‐induced sepsis was established. The degree of pulmonary edema, oxidative stress, and inflammation were detected. Endothelial barrier function was evaluated by apoptosis and cell junctions. In vitro, Mito Tracker Green probe, JC‐1 staining, and MitoSOX staining were conducted to investigate the effect of carnosol on mitochondria. Finally, we investigated the role of nuclear factor‐erythroid 2‐related factor (Nrf2)/sirtuin‐3 (SIRT3) in carnosol against ALI. Carnosol alleviated LPS‐induced pulmonary oxidative stress and inflammation by inhibiting excess mitochondrial reactive oxygen species production and maintaining mitochondrial homeostasis. Furthermore, carnosol also attenuated LPS‐induced endothelial cell barrier damage by reducing vascular endothelial cell apoptosis and restoring occludin, ZO‐1, and vascular endothelial‐Cadherin expression in vitro and in vivo. In addition, carnosol increased Nrf2 nuclear translocation to promote SIRT3 expression. The protective effects of carnosol on ALI were largely abolished by inhibition of Nrf2/SIRT3. Our study has provided the first evidence that the Nrf2/SIRT3 pathway is a protective target of the endothelial barrier in ALI, and carnosol can serve as a potential therapeutic candidate for ALI by utilizing its ability to target this pathway.

show abstract

“…Ameliorates the inhibitory effect of high glucose on migration and angiogenesis of HUVECs in vitro [84] Carnosol Nrf2/t-BHP Protects against t-BHP-induced human retinal microvascular endothelial cells (HRMECs) injury [112] β-Buyang Huanwu Decoction AKT/GSK3/Nrf2 Enhances revascularization in a mouse model of diabetic hindlimb ischemia (HLI) [113] Antrodin C Nrf2/HO-1 Prevents hyperglycemia-induced senescence and apoptosis in human ECs in vitro [114] Allicin Nrf2…”

Section: Metformin Nrf2mentioning

confidence: 99%

Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective

Hendrix

Nair

et al. 2022

Cells

View full text Add to dashboard Cite

Nuclear factor-erythroid 2-related factor 2 (Nrf2), a transcription factor, controls the expression of more than 1000 genes that can be clustered into different categories with distinct functions ranging from redox balance and metabolism to protein quality control in the cell. The biological consequence of Nrf2 activation can be either protective or detrimental in a context-dependent manner. In the cardiovascular system, most studies have focused on the protective properties of Nrf2, mainly as a key transcription factor of antioxidant defense. However, emerging evidence revealed an unexpected role of Nrf2 in mediating cardiovascular maladaptive remodeling and dysfunction in certain disease settings. Herein we review the role of Nrf2 in cardiovascular diseases with a focus on vascular disease. We discuss the negative effect of Nrf2 on the vasculature as well as the potential underlying mechanisms. We also discuss the clinical relevance of targeting Nrf2 pathways for the treatment of cardiovascular and other diseases.

show abstract

A transcriptomics and molecular biology based investigation reveals the protective effect and mechanism of carnosol on t-BHP induced HRMECs via Nrf2 signaling pathway

Cited by 5 publications

References 36 publications

Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload‐induced heart failure mice

Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload‐induced heart failure mice

Carnosol alleviates sepsis‐induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2‐related factor 2/sirtuin‐3 signaling pathway to attenuate oxidative damage

Nrf2-Mediated Dichotomy in the Vascular System: Mechanistic and Therapeutic Perspective

Contact Info

Product

Resources

About