Biology subjects

Periandavan, K.

Publications and source records attributed to Periandavan, K..

5 recordsLinked to original sources

bioRxiv2026

Aegeline and Atorvastatin Synergistically Attenuate oxLDL-Induced Inflammation and Intracellular Cholesterol Accumulation in THP-1 Macrophages

BackgroundAtherosclerosis is driven by macrophage foam cell formation resulting from excessive oxidized low-density lipoprotein (oxLDL) accumulation and chronic vascular inflammation. This study evaluated the therapeutic potential of Aegeline, Atorvastatin, and their combined in mitigating oxLDL-induced inflammatory responses, cholesterol accumulation, and oxLDL uptake in human THP-1 macrophages. MethodsTHP-1 monocytes were differentiated into macrophages using a 72-hour differentiation protocol followed by a 48-hour resting period, confirmed via CD14 surface marker characterization. Macrophages were exposed to DiI-oxLDL and treated with Aegeline, Atorvastatin, or their combination. Key inflammatory cytokines and chemokines (CRP, TNF-, IL-6, and IL-8) were measured using ELISA. Cholesterol efflux capacity and cellular oxLDL uptake were quantitatively assessed using fluorescence retention assays and immunofluorescence imaging. ResultsDifferentiation of THP-1 monocytes to macrophages resulted in marked down-regulation of CD14 expression. DiI-oxLDL exposure triggered significant pro-inflammatory mediator secretion (p<0.001) and excessive intracellular cholesterol accumulation. Single-agent treatment with Aegeline or Atorvastatin significantly attenuated oxLDL-induced elevations of CRP, TNF-, IL-6, and IL-8. Atorvastatin alone strongly suppressed CRP expression back to physiological baseline levels (p=ns vs. control). Notably, the combination of Aegeline and Atorvastatin demonstrated enhanced, broad-spectrum anti-inflammatory efficacy, achieving superior suppression of TNF- (p=ns vs. control), IL-6, and IL-8 compared to monotherapies. Furthermore, both agents promoted cholesterol efflux and suppressed oxLDL uptake, with the combination treatment producing the lowest residual intracellular cholesterol levels (p<0.001). ConclusionAegeline and Atorvastatin effectively suppress oxLDL-induced macrophage inflammatory cascades and intracellular lipid overload. While Atorvastatin monotherapy exerts robust control over CRP and oxLDL loading, combining Aegeline with Atorvastatin provides synergistic efficacy, enhancing cholesterol efflux and restoring pro-inflammatory cytokine expression toward physiological levels. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/744794v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1d90d88org.highwire.dtl.DTLVardef@1079202org.highwire.dtl.DTLVardef@2d659org.highwire.dtl.DTLVardef@4685af_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

Temporal changes in miR-23a-5p levels in subclinical atherosclerosis: A Potential biomarker.

A high-cholesterol diet (HCD) is a well-established contributor to oxidative stress, inflammation, and atherogenesis, yet the temporal progression of these pathological changes and the regulatory role of circulating microRNAs (miRNAs) remain incompletely understood. In this study, we investigated the effects of prolonged HCD exposure to rats on lipid metabolism, oxidative stress, inflammation, endothelial dysfunction, and miRNA expression in a rat model. Male Wistar rats were fed either a standard diet or HCD for 30, 60, 90, or 120 days. Biochemical analyses revealed a progressive dyslipidemic profile characterized by elevated total cholesterol, triglycerides, LDL, VLDL, and atherogenic index, alongside a significant reduction in HDL. Lipid peroxidation levels increased markedly with HCD duration, while antioxidant markers PON1 and ApoA1 were significantly reduced and oxLDL levels were elevated. Inflammatory cytokines (CRP, TNF-, IL-6, IL-8) and VCAM-1 were significantly increased, indicating systemic inflammation and endothelial activation. Notably, miR-23a-5p and miR-15b-5p were elevated in the serum of HCD-fed rats, with miR-23a-5p peaking at day 120. Correlation analyses revealed that miR-23a-5p expression positively correlated with oxLDL and inversely with ApoA1 and PON1 levels, suggesting its involvement in oxidative and lipoprotein dysregulation. These findings demonstrate that prolonged HCD induces a coordinated cascade of oxidative, inflammatory, and lipoprotein alterations, with miR-23a-5p emerging as promising biomarkers and potential regulators of redox and lipid homeostasis in atherogenesis.

molecular biology↗

bioRxiv2024

Ironing out the role of Nrf2 in cardiac iron metabolism during myocardial infarction

Background and PurposeIron plays a crucial role in maintaining cardiac health. However, existing research has focused on understanding how cardiac cells regulates intercellular iron levels through their own cell-autonomous cardiac hepcidin/ferroportin axis. In Addition, several studies have explored the mechanisms linking cardiac dysfunction with iron imbalance. Recent insights also emphasize the importance of Nrf2, a key transcriptional regulator that not only counteracts iron-mediated oxidative stress, but also governs several genes involved in iron metabolism. Consequently, the Nrf2/hepcidin/ferroportin axis is emerging as a central hub connecting cardiac iron metabolism with redox alterations. However, the precise mechanisms linking these components remain elusive. This study aims to elucidate how disruptions in the Nrf2/hepcidin/ferroportin axis contribute to the altered iron metabolism in Myocardial infarction (MI). Experimental ApproachMI was induced in adult Wistar rats by subcutaneous administration of isoproterenol (ISO; 85 mg/kg body weight) for two days. H9c2 cardiomyoblasts were differentiated into cardiomyocytes using all-trans-retinoic acid (ATRA, 2.5M for 5-days) and subjected to hypoxic stress using CoCl2 (100M). In vitro pharmacological suppression of Nrf2 was performed using brusatol (50nM). Key ResultsMorphological examination revealed maladaptive remodeling, and histopathological analysis demonstrated disoriented myofibrils with intense neutrophil infiltration and necrotic impressions in MI-affected animals. Furthermore, elevated levels of labile redox-active iron and inflammatory markers were observed in serum of ISO induced animals. qPCR & Western blot analysis indicated an increase in HIF-1 and hepcidin levels, and downregulation of FTH levels in MI-induced animals, with no significant changes observed in FPN-1. The transcriptional activity of Nrf2 is enhanced in the MI-heart. Moreover, increased levels of NCOA4, beclin-1, and LC3-II/LC3-I, along with decreased p62, suggest enhanced ferritinophagy in MI-induced hearts. Nrf2 was pharmacologically suppressed in differentiated H9c2 cardiomyocytes to explore its potential role in MI pathophysiology. Remarkably, this inhibition rescued CoCl2-induced hypoxic stress, as evidenced by the decreased ferritinophagy and apoptotic cell death. Conclusion and ImplicationsAugmented Nrf2-transcriptional activity disrupts iron metabolism through the hepcidin/ferroportin axis, leading to iron sequestration and promoting ferritinophagy within cardiomyocytes, thereby exacerbating MI.

biochemistry↗

bioRxiv2019

CHOLESTEROL MYTH AND THE IMPERATIVE ROLE OF FUNCTIONAL EVALUATION OF LIPOPROTEINS IN ATHEROSCLEROTIC RISK PREDICTION STRATEGIES

ObjectiveTo arrive at apposite risk prediction strategies in identifying markers that could delineate patients susceptible for atherosclerotic progression from other diabetic patient population thus circumventing undesirable drug exposure or conversely inadequate treatment. Research Design and MethodsThe study was designed to assess and compare the biochemical parameters along with lipoprotein ratios assessed in structural and functional aspects between the probable risk factor groups for CAD(diabetics with no symptoms for CAD) and untreated CAD patients (on admission for CAD) in a total of 593 participants. Anthropometric measurements were made and serum fasting glucose, lipid peroxide levels, lipid and lipoprotein ratio assessments were carried out. In addition to these basic parameters, oxidized LDL (Ox-LDL) and serum paraoxonase (PON) activity were also measured in this study. To ascertain the diagnostic accuracy of the individual markers, receiver operating characteristic curve analysis was carried out. ResultsSerum levels of blood lipids, lipid peroxides were higher in the diabetic and the cardiovascular patients with a concomitant decrease in the levels of HDL. Increased median levels of Ox-LDL and decreased PON activity was observed in the cardiovascular patients both with and without diabetes. ConclusionThis study proposes Ox-LDL/PON assessment would be more functional than the traditional LDL-c/HDL-c to categorize the risk group of patients into prospective atherosclerotic predisposed and non-predisposed population, thus enabling the former to get treated with appropriate medication.

biochemistry↗

bioRxiv2018

Scopoletin Augments DJ1/Nrf2 Signalling and Prevents Protein Aggregation in Parkinson’s disease

Given the role of oxidative stress in PD pathogenesis and off-target side effects of currently available drugs, several natural phytochemicals seems to be promising in the management of PD. Here, we tested the hypothesis that scopoletin, an active principle obtained from Morinda citrifolia (MC), efficiently quenches oxidative stress through DJ-1/Nrf2 signalling and ameliorates rotenone-induced PD. Despite reducing the oxidative stress, administration of MC extract (MCE) has lessened the protein aggregation as evident from decreased levels of nitrotyrosine and -Synuclein. In vitro studies revealed that scopoletin lessened rotenone-induced apoptosis in SH-SY5Y cells through preventing oxidative injury. Particularly, scopoletin markedly up-regulated DJ-1, which then promoted the nuclear translocation of Nrf2 and transactivation of antioxidant genes. Furthermore, we found that scopoletin prevent the nuclear exportation of Nrf2 by reducing the levels of Keap1 and thereby enhancing the neuronal defence system. Overall, our findings suggest that scopoletin acts through DJ-1 mediated Nrf2 signalling to protect the brain from rotenone-induced oxidative stress and PD. Thus, we postulate that scopoletin could be a potential drug to treat PD.

biochemistry↗