Background And Purpose: Our previous study reported that fructose intake increased systemic blood pressure and reduced nitric oxide (NO) in the nucleus tractus solitarius (NTS) due to oxidative stress and neuroinflammation. However, it remains unclear how reactive oxygen species (ROS) reduce NO and how this process impacts neuroinflammation in the NTS. This study aimed at investigating the effect of ROS on acetylation of high mobility group box 1 protein (HMGB1) in the NTS of fructose-induced hypertensive rats.
Experimental Approach: Male Wistar-Kyoto (WKY) rats were fed with 10% fructose water to elevate blood pressure. Thereafter, CLI-095 and glycyrrhizic acid (GA) treatments were delivered for up to 2 weeks (1 mg·12 μL·day, by intracerebroventricular injection) to reduce the negative effects of toll-like receptor 4 (TLR4) and HMGB1 activation.
Key Results: Two weeks of CLI-095 and GA treatment reduced systemic blood pressure and significantly preserved neuronal and endothelial nitric oxide synthase (nNOS and eNOS) availability against the inflammatory insults of fructose consumption. Both CLI-095 and GA halted the interaction of acetylated HMGB1 and TLR4. Two weeks of CLI-095 and GA treatment markedly reduced NTS inflammation (pro-inflammatory cytokines and microglial activation) and lowered serum norepinephrine levels.
Conclusion And Implications: Our data reveal novel pharmacological properties for CLI-095 and GA, which improved blood pressure and inflammatory conditions by decreasing the interaction of acetylated HMGB1 with TLR4. These findings challenge the commonly accepted dogma that essential hypertension is specifically mediated by neuroinflammation due to acetylated HMGB1 coupling to TLR4.
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http://dx.doi.org/10.1111/bph.17402 | DOI Listing |
Gut Microbes
December 2025
Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash, Clayton, Australia.
The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance.
View Article and Find Full Text PDFGut Pathog
December 2024
Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
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View Article and Find Full Text PDFBMC Geriatr
December 2024
Department of Chemical Pathology, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria.
Background: The number of people reaching old age is rising, bringing an increase in age-related diseases like cardiovascular conditions and cognitive dysfunction. Cognitive impairment (CI) impacts various brain functions, affecting daily activities and quality of life. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, has been implicated in CI.
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View Article and Find Full Text PDFNeurotherapeutics
December 2024
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, Essex, UK; MTRC, Anglia Ruskin School of Medicine, Chelmsford, Essex, UK.
This article aims to highlight high-quality observational and intervention studies focused on promoting psychological well-being among cardiac arrest (CA) survivors and their families. Following CA, many patients experience significant psychological distress, including depression, generalized anxiety, and post-traumatic stress. Recent studies indicate that this distress can narrow patients' focus, resulting in heightened awareness of cardiac signals-such as fluctuations in heart rate or blood pressure-that lead to constant monitoring and increased anxiety.
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