From Diabetes Care to Heart Failure Management: A Potential Therapeutic Approach Combining SGLT2 Inhibitors and Plant Extracts

Gliozzi, Micaela; Macrì, Roberta; Coppoletta, Anna Rita; Musolino, Vincenzo; Carresi, Cristina; Scicchitano, Miriam; Bosco, Francesca; Guarnieri, Lorenza; Cardamone, Antonio; Ruga, Stefano; Scarano, Federica; Nucera, Saverio; Mollace, Rocco; Bava, Irene; Caminiti, Rosamaria; Serra, Maria; Maiuolo, Jessica; Palma, Ernesto; Mollace, Vincenzo

doi:10.3390/nu14183737

Cited by 10 publications

(6 citation statements)

References 110 publications

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“…Moreover, in an in vivo study on mice fed a high-fat diet, it has been demonstrated that luteolin shows anti-obesity properties, decreases the body and epididymal fat weight and improves vascular dysfunction, by inhibiting the ROS and TNF-α action [ 109 ]. This is in also in accordance with our previous studies showing that, polyphenols improve dyslipidaemia in NAFLD [ 26 , 110 , 111 , 112 , 113 ].…”

Section: Discussionsupporting

confidence: 94%

Nocellara Del Belice (Olea europaea L. Cultivar): Leaf Extract Concentrated in Phenolic Compounds and Its Anti-Inflammatory and Radical Scavenging Activity

Musolino

Macrì

Cardamone

et al. 2022

Plants

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Olea europaea L. is a plant belonging to the Oleaceae family, widely grown around the Mediterranean Basin and its leaves are a source of phenolic compounds with antioxidant and anti-inflammatory capacity. Among these, oleuropein and luteolin-7-O-glucoside represent two major polyphenolic compounds in olive-leaf extract. Herein, a polystyrene resin was used to recover the polyphenolic fraction from the acetone-water leaf extract from Nocellara del Belice cultivar, which showed the higher level of analysed bioactive compounds, compared to Carolea cultivar. The antioxidant activity of the extract concentrated in phenolic compounds (OLECp) was evaluated through a classical assay and electron paramagnetic resonance (EPR) for DPPH and hydroxyl radicals scavenging. Thus, the anti-inflammatory activity and the potential beneficial effects in reducing lipid accumulation in an in vitro model of NAFLD using McA-RH7777 cells exposed to oleic acid (OA) were evaluated. Nile Red and Oil Red O have been used to stain the lipid accumulation, while the inflammatory status was assessed by Cytokines Bioplex Assay. OLECp (TPC: 92.93 ± 9.35 mg GAE/g, TFC: 728.12 ± 16.04 mg RE/g; 1 g of extract contains 315.250 mg of oleuropein and 17.44 mg of luteolin-7-O-glucoside) exerted a good radical scavenging capability (IC50: 2.30 ± 0.18 mg/mL) with a neutralizing power against DPPH and hydroxyl radicals, as confirmed by the decreased signal area of the EPR spectra. Moreover, OLECp at concentration of 25, 50 and 100 μg/mL counteracted the intracellular inflammatory status, as result of decreased intracellular lipid content. Our results highlighted the multiple properties and applications of an O. europaea extract concentrated in polyphenols, and the possibility to formulate novel nutraceuticals with antioxidant properties, destined to ameliorate human health.

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Section: Discussionsupporting

confidence: 94%

Nocellara Del Belice (Olea europaea L. Cultivar): Leaf Extract Concentrated in Phenolic Compounds and Its Anti-Inflammatory and Radical Scavenging Activity

Musolino

Macrì

Cardamone

et al. 2022

Plants

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“…Likewise, it cannot provide significant protection against CAD, MI, LAS, and CES, which are triggered by insufficient perfusion due to vascular occlusion. Another potential reason for the difference in results could be that one of the main contributors of dried fruits to reduce CVD risk is to improve glucose tolerance and insulin sensitivity and then to regulate lipid and glucose metabolism, which requires a long-term process ( 41 ). Thus dried fruit was more protective against chronic diseases with less severe lesions.…”

Section: Discussionmentioning

confidence: 99%

Causal associations between dried fruit intake and cardiovascular disease: A Mendelian randomization study

Zeng

Cao²,

Yang³

2023

Front. Cardiovasc. Med.

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BackgroundPrevious studies have shown controversy about whether dried fruit intake is associated with cardiovascular disease. This study aimed to examine the potential causal effect of dried fruit intake on cardiovascular disease by conducting a two-sample Mendelian randomization study.MethodsWe used genome-wide association study (GWAS) summary statistics for MR analysis to explore the causal association of dried fruit intake with CVD. The inverse-variance weighted (IVW) method was used as the main analytical method for MR analysis. In addition, the MR-Egger method and the weighted median method were applied to supplement the IVW method. Furthermore, Cochrane’s Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were used to perform sensitivity analysis.ResultsThe results from the IVW analysis indicated that dried fruit intake could reduce the risk of heart failure [odds ratio (OR) = 0.6014, 95% confidence interval (CI): 0.4243–0.8522, p-value = 0.0043], total ischemic stroke (OR = 0.4547, 95% CI: 0.2950–0.7010, p-value = 0.0004), and small vessel stroke (OR = 0.3499, 95% CI: 0.1466–0.8349, p-value = 0.0180). In addition, the results of two additional methods (MR Egger and Weighted median) were parallel to the effects estimated by IVW. Furthermore, the sensitivity analysis illustrates that our MR analysis was unaffected by heterogeneity and horizontal pleiotropy. Finally, the results of the leave-one-out method showed the robustness of our MR results.ConclusionOur study provides evidence for the benefits of dried fruit intake on CVD. Therefore a reasonable consumption of dried fruit may provide primary prevention.

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“…However, if supplementation with ketone supplements, for example, leads to an acute elevation of β-OHB in the blood, it can significantly increase activation of caspase-1 and increase secretion of the proinflammatory cytokine IL-1β in whole blood ( 161 – 163 ). Multiple studies ( 120 , 164 ) have shown that in patients with T2D combined with CVD, SGLT2 inhibitors significantly inhibit NLRP3 inflammasome activation and IL-1β secretion in human macrophages by increasing serum β-OHB levels and decreasing serum insulin, glucose, and uric acid levels.…”

Section: The Role Of An Sglt2 Inhibitor On the Nlrp3 Inflammasome: Po...mentioning

confidence: 99%

Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis

Yang

Zhang²,

Wang³

2022

Front. Endocrinol.

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Atherosclerosis is a lipid-driven chronic inflammatory disease that is widespread in the walls of large and medium-sized arteries. Its pathogenesis is not fully understood. The currently known pathogenesis includes activation of pro-inflammatory signaling pathways in the body, increased oxidative stress, and increased expression of cytokines/chemokines. In the innate immune response, inflammatory vesicles are an important component with the ability to promote the expression and maturation of inflammatory factors, release large amounts of inflammatory cytokines, trigger a cascade of inflammatory responses, and clear pathogens and damaged cells. Studies in the last few years have demonstrated that NLRP3 inflammatory vesicles play a crucial role in the development of atherosclerosis as well as its complications. Several studies have shown that NLRP3 binding to ligands promotes inflammasome formation, activates caspase-1, and ultimately promotes its maturation and the maturation and production of IL-1β and IL-18. IL-1β and IL-18 are considered to be the two most prominent inflammatory cytokines in the inflammasome that promote the development of atherosclerosis. SGLT2 inhibitors are novel hypoglycemic agents that also have significant antiatherosclerotic effects. However, their exact mechanism is not yet clear. This article is a review of the literature on the effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, focusing on their role in antiatherosclerosis.

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From Diabetes Care to Heart Failure Management: A Potential Therapeutic Approach Combining SGLT2 Inhibitors and Plant Extracts

Cited by 10 publications

References 110 publications

Nocellara Del Belice (Olea europaea L. Cultivar): Leaf Extract Concentrated in Phenolic Compounds and Its Anti-Inflammatory and Radical Scavenging Activity

Nocellara Del Belice (Olea europaea L. Cultivar): Leaf Extract Concentrated in Phenolic Compounds and Its Anti-Inflammatory and Radical Scavenging Activity

Causal associations between dried fruit intake and cardiovascular disease: A Mendelian randomization study

Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis

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