Table 1.
Summarised anti-atherosclerotic and hypolipidemic effects of polyphenols included in the review through PPARs, LXRs, PCSK9, and inflammatory markers modulation.
| Polyphenols | |||
|---|---|---|---|
| Compound | Main natural source | Biological activity | References |
| Curcumin | Curcuma longa L. | Reduction of LDL oxidation and foam cell formation in patients with obesity. | [27,[45], [46], [47], [48], [49], [50], [51]] |
| Reduction of cholesterol, LDL-C, triglycerides in hypercholesterolemic mice. | |||
| Inhibition of Nrf/FXR/LXRα pathway in mice with metabolic syndrome. | |||
| Promotion of LXRα and ABCA1 stability in vitro and in vivo. | |||
| Reduction of HNF-1α and downregulation of PCSK9 in HepG2 cells. | |||
| Inhibition IL-6, IL-1β, TNF-α, TLR4, ERK, JNK, p38, NF-kB in THP-I cells. | |||
| Resveratrol | Veratrum grandiflorum O. Loes., Vitis vinifera L., Polygonum cuspidatum Siebold & Zucc. | Amelioration of atherosclerosis and lipid profile in humans. | [26,[52], [53], [54]] |
| Activation of PPARα/PPARγ, ABCA1 and ABCG1 in atherosclerotic mice model. | |||
| Decrease of PCSK9 and increase of LDLR-mediated cholesterol uptake in vitro. | |||
| Reduction of NF-kB and cytokines (IL-6, IL-1β, TNF-α) in clinical trials. | |||
| Epigallocatechin gallate | Camellia sinensis (L.) Kuntz | Reduction on LDL oxidation in healthy men. | [42,[55], [56], [57], [58]] |
| Reduction of TG, TC, LDL-C and increase in HDL-C in healthy smokers. | |||
| ERK-mediated increase in LDLR levels in hepatocytes models. | |||
| Upregulation of LDLR independent from 67 kDa laminin receptor in HepG2 cells. | |||
| Inhibition of HNF-1α, activation of FoxO3a and reduction of PCSK9 in HFD-mice. | |||
| Eugenol | Syzygium aromaticum (L.) Merr. & L.M.Perry, Origanum vulgare L. | Decrease of plasma and hepatic LDL-C in vivo. | [[59], [60], [61]] |
| Activation of PPARα pathway in diabetic rats. | |||
| In silico and in vitro reduction of PCSK9 and increase in LDLR. | |||
| Emodin | Rheum palmatum L., Rheum rhabarbarum L., Rheum officinale L., and Rheum rhaponticum L. | Beneficial effect in CVDs in preclinical studies. | [[62], [63], [64], [65]] |
| Regulation of TC, TG, TNFα and IL-1β through PPARα in vitro and in vivo. | |||
| Enhancement in AMPKα, LDLR, ABCA1, ABCG1 and downregulation of SREBP-2, PCSK9 and HMG-CoA reductase in hyperlipidemic zebrafish. | |||
| Decrease in LDL-C in HFD-rats and suppression of SREBP-2, HNF-1α and PCSK9 in vitro. | |||
| Chlorogenic acid | Coffea arabica L. and canephora Pierre ex A. Froehner | Reduction of hepatic LXRα expression in HFD-fed mice. | [27,66,67] |
| Reduction of NPC1L1 and HMG-CoA reductase expression in HepG2 cells. | |||
| Reduction of CRP, cytokines secretion and lipid peroxidation demonstrated in a meta-analysis. | |||
| Luteolin | Reseda luteola L. | Amelioration of atherosclerosis and inflammation in ApoE−/− HFD-mice. | [[68], [69], [70]] |
| Suppression of LXR-SREBP-1c in HepG2 cells. | |||
| Reduction of total cholesterol, LDL-C, TG via SREBP-2 inhibition in T2DM rats. | |||
| Naringin and Naringenin | Citrus L. | Reduction of plaque macrophages, plasma triglycerides and cholesterol in LDLR−/− and ApoE−/− mice. | [71,[72], [73], [74]] |
| Inhibition of cholesterol synthesis through HMG-CoA reductase, ACAT, PPARα and γ in ApoE−/− HFD-fed mice. | |||
| Increase in cholesterol efflux via LXRα activation in murine macrophages. | |||
| Reduction of hepatic SREBP-1 and -2, PCSK9 and enhancement of LDLR expression in obese mice. | |||
| Quercetin | Ginkgo biloba L., Hypericum perforatum L., Sambucus canadensis L. | Increase in ABCA1 and LXRα, reduction of PCSK9 and cytokines in ApoE−/− mice. | [[75], [76], [77], [78], [79]] |
| Activation of PPARγ-LXRα pathway with induction on ABCA1 in THP-I-derived foam cells and macrophages. | |||
| Enhancement of cholesterol efflux in THP-I. | |||
| Reduction of IL-1β, IL-6, IL-8 and TNFα, via suppression of NF-kB and JAK/STAT pathway in thymocytes and splenocytes. | |||
| Apigenin | Matricaria chamomilla L. | Reduction of total cholesterol, LDL-C and triglycerides in hyperlipidemic rats. | [[80], [81], [82]] |
| Activation of PPARα and γ pathway with a reduced hepatic lipid accumulation in HuH7 cells. | |||
| Inhibition of IL-1β, IL-6 and prostaglandin E2 release, ICAM-1 and VCAM-1 expression in endothelial cells. | |||
| Genistein | Glycine max (L.) Merr | Regulation of lipid metabolism and inflammation through PPARα, PPARγ, SREBP-1 in vivo. | [[83], [84], [85]] |
| Increase in LXRα in murine fibroblasts and human hepatocytes. | |||
| Decrease of CRP, MMP-9 via ER-p38/ERK1/2-PPARγ-NF-kB pathway and ERβ stimulation. | |||
Abbreviations: ABCA1, ATP-binding cassette transporter genes A1; ABCG1, ATP-binding cassette transporter genes G1; ACAT, acyl-coenzyme A (CoA):cholesterol acyltransferases; AMPK, Adenosine monophosphate-activated protein kinase; ApoE, apoliprotein ECOPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CVDs, cardiovascular diseases; ER, estrogen receptor; ERK, extracellular signal-regulated kinases; FXR, farnesoid X receptor; HFD, high-fat diet; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; HNF-1α, hepatocytes nuclear factor 1α; ICAM-1, intracellular adhesion molecule 1; IL-1β, interleukin 1β; IL-6, interleukin 6; IL-8, interleukin 8; JAK/STAT, Janus kinase/signal transducers and activators of transcription; JNK, c-Jun N-terminal kinases; LDL-C, low-density lipoprotein cholesterol; LXR, liver X receptor; MMP-9, metalloproteinase 9; NF-kB, nuclear factor kappa B; NPC1L1, Niemann-pick C1-like 1; Nrf, Nuclear factor erythroid 2-related factor 2; PCSK9, proprotein convertase subtilisin/kexin type 9; PPAR, peroxisome proliferator-activated receptor; SREBP, sterol regulatory element-binding protein; T2DM, type 2 diabetes mellitus; TLR4, toll-like receptor 4; TNF-α, tumour necrosis factor-α; VCAM-1, Vascular cell adhesion protein 1.