Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Almowallad, Sanaa; Huwait, Etimad; Almassabi, Rehab; Saddeek, Salma; Gauthaman, Kalamegam; Prola, Alexandre

doi:10.3390/ph13110372

Cited by 14 publications

(6 citation statements)

References 43 publications

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“…Punicalagin is a water-soluble polyphenolic compound with a high degree of hydroxylation and a high molecular weight, equal to 1084.7 Da. This compound is naturally found in the forms of two α and β reversible anomers [10,[45][46][47].…”

Section: Bioactive Polyphenolic Compounds Of Pomegranate and Their Bi...mentioning

confidence: 99%

Healthy Effects of Pomegranate (Punica granatum L.) in Internal Medicine and Dentistry

Marrone,

Basilicata,

Di Lauro

et al. 2024

Applied Sciences

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Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, the Middle East and the USA. While in ancient times pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, making it a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs), and its consumption appears to exert numerous healthy effects, in particular, in several pathological conditions as metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies have pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and dentistry represents a promising field, as it could enable the development of innovative natural adjuvant therapies and empower standard pharmaceutical therapies.

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Section: Bioactive Polyphenolic Compounds Of Pomegranate and Their Bi...mentioning

confidence: 99%

Healthy Effects of Pomegranate (Punica granatum L.) in Internal Medicine and Dentistry

Marrone,

Basilicata,

Di Lauro

et al. 2024

Applied Sciences

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“…UroA also inhibited TNF-α-induced expression of both MCP-1 and IL-8 in human aortic ECs together with their migration and adhesion to monocytes [94]. In addition, an in vitro study in THP-1 macrophages, in which IFN-γ was used to induce the expression of several pro-inflammatory genes, in particular ICAM-1 and MCP-1, PC significantly inhibited their expression together with MCP-1-induced monocytic migration [139]. UroA also reduced the expression of various inflammatory factors in response to the oxLDL stimulation of human artery ECs, such as MCP-1, ICAM-1, TNF-α, and IL-6.…”

Section: Effects Of Pc and Its Metabolites On Inflammation And Expres...mentioning

confidence: 99%

The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease

Alalawi,

Albalawi,

Ramji

2023

IJMS

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Atherosclerotic cardiovascular disease (ACVD) is the leading cause of death worldwide. Although current therapies, such as statins, have led to a marked reduction in morbidity and mortality from ACVD, they are associated with considerable residual risk for the disease together with various adverse side effects. Natural compounds are generally well-tolerated; a major recent goal has been to harness their full potential in the prevention and treatment of ACVD, either alone or together with existing pharmacotherapies. Punicalagin (PC) is the main polyphenol present in pomegranates and pomegranate juice and demonstrates many beneficial actions, including anti-inflammatory, antioxidant, and anti-atherogenic properties. The objective of this review is to inform on our current understanding of the pathogenesis of ACVD and the potential mechanisms underlying the beneficial actions of PC and its metabolites in the disease, including the attenuation of dyslipidemia, oxidative stress, endothelial cell dysfunction, foam cell formation, and inflammation mediated by cytokines and immune cells together with the regulation of proliferation and migration of vascular smooth muscle cells. Some of the anti-inflammatory and antioxidant properties of PC and its metabolites are due to their strong radical-scavenging activities. PC and its metabolites also inhibit the risk factors of atherosclerosis, including hyperlipidemia, diabetes mellitus, inflammation, hypertension, obesity, and non-alcoholic fatty liver disease. Despite the promising findings that have emerged from numerous in vitro, in vivo, and clinical studies, deeper mechanistic insights and large clinical trials are required to harness the full potential of PC and its metabolites in the prevention and treatment of ACVD.

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“…Cholesterol efflux assay was performed using the commercial Cholesterol Efflux Assay kit as previously described (Almowallad et al, 2020;Almassabi et al, 2021) to analyze the impact of quercetin on AS progression in our cellular model. THP-1 monocytes were seeded at a density of 1 × 10 5 cells/well in the culture medium (100 μl media/well) in a 96well black plate with a clear bottom (kit content) and incubated for 1 h to settle down.…”

Section: Cholesterol Efflux Assaymentioning

confidence: 99%

Antiatherogenic Effects of Quercetin in the THP-1 Macrophage Model In Vitro, With Insights Into Its Signaling Mechanisms Using In Silico Analysis

et al. 2021

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Background: Atherosclerosis (AS), a major risk factor for stroke and brain tissue destruction, is an inflammatory disease of the blood vessels, and the underlying pathology is inflammation mediated by various chemokines and cytokines. Quercetin, a natural flavonol, is reported to have both anti-inflammatory and antioxidant properties. As such, in the present study, we evaluated the antiatherogenic effects of quercetin in a human THP-1 cell line in vitro and also the signaling mechanisms using in silico analysis.Materials and Methods: THP-1 macrophages exposed to different concentrations of quercetin (5–100 μM for 24 h) were tested for cytotoxicity. Real-time gene expression assay for intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) was carried out following treatment with quercetin at 15 and 30 μM for 24 h either in the absence or presence of interferon (IFN-γ) for 3 h to induce inflammation. Monocyte migration and cholesterol efflux were also assessed.Results: Quercetin did not exert any cytotoxic effects on THP-1 cells at the various concentrations tested. The gene expression assay showed a significant decrease in ICAM-1 (by 3.05 and 2.70) and MCP-1 (by 22.71 and 27.03), respectively. Quercetin at 15 µM decreased THP-1 monocyte migration by 33% compared to the MCP-1-treated cells. It also increased cholesterol efflux significantly by1.64-fold and 1.60-fold either alone or in combination with IFN-γ, respectively. Ingenuity Pathway Analysis of the molecular interactions of quercetin identified canonical pathways directly related to lipid uptake and cholesterol efflux. Furthermore, CD36, SR-A, and LXR-α also demonstrated significant increases by 72.16-, 149.10-, and 29.68-fold, respectively.Conclusion: Our results from both in vitro and in silico studies identified that quercetin inhibited the THP-1 monocyte migration, MCP-1, and ICAM-1 and increased cholesterol efflux probably mediated via the LXR/RXR signaling pathway. Therefore, quercetin will help prevent cell infiltration in atherosclerotic plaques and reduce the risk of stroke or brain destruction.

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Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Cited by 14 publications

References 43 publications

Healthy Effects of Pomegranate (Punica granatum L.) in Internal Medicine and Dentistry

Healthy Effects of Pomegranate (Punica granatum L.) in Internal Medicine and Dentistry

The Role of Punicalagin and Its Metabolites in Atherosclerosis and Risk Factors Associated with the Disease

Antiatherogenic Effects of Quercetin in the THP-1 Macrophage Model In Vitro, With Insights Into Its Signaling Mechanisms Using In Silico Analysis

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