Flavonoids | Alpinetin | Increased the macrophage cholesterol efflux by regulating the PPARγ/LXRα/ABCA1/ABCG1 pathway (Jiang et al., 2015). | N.A. |
| Cyanidin (Anthocyanins) | Cyanidin increased the macrophage cholesterol efflux from mouse peritoneal macrophages (MPMs) through PPARγ-LXRα-ABCA1 pathway (Xia et al., 2005), and activated PPARα-LXRα-ABCA1-dependent cholesterol efflux in human kidney 2 (HK-2) cells (Du et al., 2015). | The anthocyanin-rich diet reduced the levels of total cholesterol (TC) and low-density lipoprotein (LDL)-cholesterol, while upregulating high-density lipoprotein (HDL)-C in serum, and reduced atherosclerotic plaque formation in rats and ApoE−/− mice (Xia et al., 2006). Anthocyanin mixture reduced the inflammatory response in hypercholesterolemic patients by decreasing the levels of serum high sensitivity C-reactive protein (hs-CRP) (Zhu et al., 2013). |
| Baicalin | Promoted the cholesterol efflux through the PPARγ-LXRα-ABCA1/ABCG1/SR-BI pathway in THP-1 macrophages (He et al., 2016b; Yu et al., 2016). | Decreased atherosclerotic lesion sizes and lipid accumulation in the carotid arteries of atherosclerosis in vivo (He et al., 2016b). Baicalin reduced TC, TG, LDL-C, and hs-CRP in patients with rheumatoid arthritis that have an increased risk of coronary artery disease (Hang et al., 2018). |
| Chrysin | Increased the HDL-mediated macrophage cholesterol efflux by the upregulation of PPARγ, LXRα, ABCA1, and ABCG1 expression (Wang et al., 2015b), and prevented the cholesterol uptake by downregulating the expression of SR-A1 and SR-A2 (Wang et al., 2015b). | Decreased the mean levels of serum TC, triacylglycerol (TG), LDL-C, and very low-density lipoprotein (VLDL)-C significantly in a model of Wistar rats fed with a high-fat diet (HFD) (Anandhi et al., 2014). |
| Cyanidin-3-O-β–glucoside | Upregulated the expression of ABCG1 and ABCA1 in a dose-dependent manner and promoted the cholesterol efflux (Wang et al., 2012c). | Decreased body weight, visceral adiposity, TG, TC, free fatty acids, and atherosclerosis index in a high-fat-induced atherosclerosis rat model (Um et al., 2013). Decreased monocyte infiltration and atherosclerosis in ApoE−/− mice (Wang et al., 2011). A double-blind, randomized, placebo-controlled trial showed that anthocyanin consumption increased HDL-C, decreased LDL-C, and promoted cellular cholesterol efflux in hyperlipidemia patients. Cyanidin 3-O-β-glucosides revealed to inhibit CETP (Qin et al., 2009). |
| Daidzein | Induced paraoxonase-1 (PON-1) activity, which may regulate cholesterol efflux by stimulating the PPARγ/LXRα/ABCA1 pathway (Gao et al., 2008; Robb and Stuart, 2014). | Decreased the serum cholesterol, increased triglyceride (TG) level in the male middle-aged rats with HFD (Sosić-Jurjević et al., 2007), reduced plasma VLDL, LDL-C, and TG concentrations, while increased the HDL-C levels in a rheumatoid arthritis rat model (Ahmad et al., 2016). Daidzein was reported to be an inhibitor of HMG-CoA reductase, ACAT1, and ACAT2 (Borradaile et al., 2002; Sung et al., 2004). |
| Ellagic acid | Stimulated cholesterol efflux by promoting the expression of ABCA1 and SR-BI and up-regulating PPARγ and LXRα (Park et al., 2011), inhibited macrophage lipid accumulation by decreasing the expression of CD36 (Aviram et al., 2008). | Decreased the level of TC and TG and upregulated the expression of LXRα, PPARα, PPARγ, and their downstream gene ABCA1 in the high-fat-fed hamster model (Aviram et al., 2008). Reduced atherosclerotic lesions in ApoE−/− mice (Aviram et al., 2008). |
| Hesperetin | Increased activities of ABCA1 promoter and LXR enhancer, the expression of ABCA1, and consequently upregulated the ApoA-1-mediated cholesterol efflux (Iio et al., 2012). | Reduced foam cell formation in plaques by enhancing the expression of ABCA1 (Iio et al., 2012). Reduced plasma TC level, endothelial dysfunction, macrophage infiltration, and atherosclerotic lesion in ApoE−/− mice (Sugasawa et al., 2019). |
| Icariin | Inhibited cholesterol intake and foam cell formation by the reduced expression of CD36 and upregulated SR-BI expression through p38 MAPK pathway (Yang et al., 2015). | Decreased the concentrations of TC, TG, and LDL-C in models of normal rats (Hu et al., 2016b) and ApoE−/− mice with HFD (Xiao et al., 2017). |
| Iristectorigenin B | Acted as a novel LXR modulator that increases ABCA1 and ABCG1 expression in RAW 264.7 macrophage (Jun et al., 2012). | N.A. |
| Pratensein | Upregulated the CLA-1 expression, a human homolog of SR-BI, may play a potential role in cholesterol efflux to HDL in vitro (Yang et al., 2007, 2009). | One clinical trial showed that red clover isoflavones significantly reduced the incidence of arteriosclerosis (Gordon, 2003). |
| Puerarin | Promoted ABCA1-mediated cholesterol efflux through the pathways involving miRNA-7, STK11, and the AMPK/PPARγ/LXRα/ABCA1 cascade (Li et al., 2017a) suppressed lipid deposition by downregulating the expression of CD36 (Zhang et al., 2015). | Decreased the level of blood sugar, TC, TG, LDL-C, and increased HDL-C level in diabetic animal model (Smith et al., 2006). |
| Quercetin | Enhanced ApoA-1-mediated cholesterol efflux, induced ABCA1 expression, and increased the expression of PPARγ in THP-1-derived foam cells (Sun et al., 2015) and LXRα activity (Lee et al., 2013). | Quercetin inhibits atherosclerosis by promoting ABCA1- and ABCG1-dependent reverse cholesterol transport in ApoE−/− mice (Cui et al., 2017). |
| Isosilybin A (Silymarin) | Isosilybin A promoted cholesterol efflux from THP-1 macrophages by activating PPARγ (Wang et al., 2015a). | Supplementation of silybin in food decreased serum level of TC, TG, VLDL-C, LDL-C and increased HDL-C in model of hypercholesterolemic rats (Wang et al., 2005). Furthermore, silybin reduced the formation of atherosclerotic plaque (Gobalakrishnan et al., 2016). |
| Wogonin | Enhanced cholesterol efflux through increasing the ABCA1 protein expression (Chen et al., 2011) and decreasing phosphorylated level of ABCA1 protein. | Wogonin ameliorated hyperglycemia and dyslipidemia in db/db mice via PPARα activation (Bak et al., 2014). |
Terpenoids | Astaxanthin | Downregulated the expression of SR-A and CD36, which is relevant to uptake of cholesterol in THP-1 macrophages (Yoshida et al., 2010). Promoted ABCA1/G1 expression, resulting in increased ApoA-1/HDL-mediated cholesterol efflux from RAW264.7 cells via an LXR-independent manner (Ramírez-Tortosa et al., 1999; Iizuka et al., 2012). | A randomized, placebo-controlled clinical study in humans with mild hyperlipidemia displayed that astaxanthin administration significantly increased HDL-C (Yoshida et al., 2010). Astaxanthin also decreases macrophage infiltration, and plaque vulnerability in hyperlipidemic rabbits (Li et al., 2004c). |
| Capsanthin | N.A. | An in vivo study showed that male Wistar rats fed with capsanthin exhibited an increase in plasma HDL-C, an upregulation of ApoA-5 and LCAT mRNA expression (Aizawa and Inakuma, 2009). |
| β-Carotene (β-carotene isomers all-trans-β-carotene (all-trans-βc), and 9-cis-β-carotene (9-cis-βc)) | Suppressed cellular cholesterol synthesis by inhibiting cellular HMG-CoA reductase activity in J774 macrophages (Fuhrman et al., 1997; Relevy et al., 2015). | β-Carotene comprises several isomers (all-trans-βc and 9-cis-βc), which increased plasma HDL-C and attenuated atherosclerosis in LDLR–/– mice (Harari et al., 2008), ApoE–/– mice (Harari et al., 2013), and even in fibrate-treated patients (Shaish et al., 2006), which is related with transcriptional induction of ABCA1, ABCG1, and ApoE (Bechor et al., 2016). |
| 9-cis retinoic acid (9-cis-RA, Retinoids) | 9-cis-RA and ATRA acted as inducers of ABCA1, ABCG1, and ApoE expression in J774 macrophages and THP-1 macrophages (Kiss et al., 2005) and RAW264.7 macrophages (Schwartz et al., 2000), as well as inducers of cholesterol efflux to ApoA-1 in RAW264.7 macrophages (Langmann et al., 2005). | 9-cis-RA inhibited foam cell formation and atherosclerosis by activation of LXRα and upregulation of ABCA1 and ABCG1 expression in ApoE−/− mice fed with HFD (Zhou et al., 2015). |
| Lycopene | Decreased cholesterol accumulation through downregulation of SR-A mRNA expression and lipid synthesis in human monocyte-derived macrophages (HMDMs) and THP-1 macrophages (Napolitano et al., 2007). Increased cholesterol efflux possibly through HMG-CoA reductase/RhoA/PPARγ/LXRα/ABCA1 and caveolin 1 pathway (Palozza et al., 2011). | Clinical investigation reported that dietary supplementation of lycopene reduced plasma LDL-C level (Fuhrman et al., 1997; Sesso et al., 2005; Palozza et al., 2012). Lycopene displays potent hypolipidemic effects via inhibiting PCSK9 and HMG-CoA reductase, thus increasing hepatic LDLR (Sultan Alvi et al., 2017). |
| Ursolic acid | Promoted ApoA-1-mediated cholesterol efflux from LDL-loaded macrophages through autophagy (Leng et al., 2016). | Reduced atherosclerotic lesion size, along with an increase of macrophage autophagy in LDLR−/− mice (Leng et al., 2016). Ursolic acid is a pharmacological inhibitor of ACAT1 and ACAT2 (Lee et al., 2006). |
| Betulinic acid | Induced cholesterol efflux through blocking NF-κB/miRNA-33s/ABCA1 signaling pathway in LPS-treated macrophages (Zhao et al., 2013a) and increased ABCA1/ABCG1-mediated cholesterol efflux in both RAW264.7 and THP-1 cells (Zhao et al., 2013a). | Increased ABCA1 expression and enhanced fecal cholesterol excretion, along with suppressed macrophage positive areas in the aorta of ApoE−/− mice (Gui et al., 2016). Betulinic acid is a potent pharmacological inhibitor of ACAT1 and ACAT2 (Lee et al., 2006). |
| Erythrodiol | Increased ApoA-1-mediated cholesterol efflux by inhibiting ABCA1 degradation in THP-1 macrophages (Wang et al., 2017f). | N.A. |
| Ginsenoside Rb1 (Ginsenosides) | Ginsenoside Rb1 increased ABCA1 protein expression in macrophage foam cells (Liu et al., 2016c; Qiao et al., 2017). Ginsenoside Rd inhibited SR-A protein expression and oxLDL uptake, thus decreasing intracellular cholesterol content (Li et al., 2011). | Ginsenoside Rb1 treatment reduced lipid metabolism and enhanced atherosclerotic plaque stability via enhancing macrophage autophagy and polarization (Liu et al., 2016c; Qiao et al., 2017). Ginsenoside Rd treatment reduced the oxLDL uptake and atherosclerotic plaque areas in ApoE–/– mice (Li et al., 2011). |
| Saikosaponin A | Suppressed lipoprotein uptake by diminishing LOX-1 and CD36 expression, as well as stimulated cholesterol efflux through upregulating of ABCA1 and PPARγ expression (He et al., 2016a). | N.A. |
| Tanshinone IIA | Decreased oxLDL uptake, as well as CD36 expression in mouse macrophages (Tang et al., 2011), increased ABCA1/G1-mediated cholesterol efflux via the ERK/Nrf2/HO-1 loop in THP-1-derived foam cells (Liu et al., 2014c). | Downregulated SR-A expression and ameliorated atherosclerotic lesions in aortas of ApoE−/− mice (Liu et al., 2014c). Tanshinone IIA promoted ABCA1-dependent cholesterol efflux (Liu et al., 2014c) and upregulated LDLR in hyperlipidemic rats (Jia et al., 2016). A clinical trial has shown that tanshinone IIA reduced hs-CRP in patients with coronary artery disease (Li et al., 2017b). |
| Tanshindiol C | Inhibited oxLDL-induced foam cell formation via activation of Prdx1/ABCA1 signaling pathway (Yang et al., 2018b). | N.A. |
| Zerumbone | Suppressed the SR-A and CD36 expression via regulating AP-1 and NK-κB repression, leading to a blockade of acLDL uptake in THP-1 macrophages (Eguchi et al., 2007). Reduced cholesterol level via upregulation of ABCA1, coupled with the enhanced phosphorylation of ERK1/2 in THP-1 macrophages (Zhu and Liu, 2015). | Prevented the development of atherosclerotic lesions in the cholesterol-fed rabbit model by reducing lipid level and oxidative stress (Hemn et al., 2013, 2015). |
Phenols | Gallotannin | Induced cholesterol efflux in oxLDL-stimulated macrophages by increasing SR-BI/ABCA1 expression (Zhao et al., 2015). | N.A. |
| Curcumin | Ameliorated lipid accumulation in macrophages by both decreasing SR-A-dependent oxLDL uptake via ubiquitin/proteasome pathway-reduced SR-A expression, and increasing ABCA1-dependent cholesterol efflux via LXRα-induced ABCA1 protein expression (Kou et al., 2013; Min et al., 2013; Lin et al., 2015c; Soltani et al., 2017). Activation of AMPK/SIRT1/LXRα pathway (Lin et al., 2015c) and Nrf2/HO-1 pathway (Kou et al., 2013), and as well as inhibition of p38 MAPK pathway (Min et al., 2013) may be involved in its effects. | Protected against atherosclerosis in ApoE−/− mice (Zhao et al., 2012), and LDLR−/− mice (Hasan et al., 2014). Curcumin lowers LDL-C, and TG in patients at risk for CVD (Qin et al., 2017). Curcumin functions as an inhibitor of PCSK9 and upregulates hepatic LDLR expression (Tai et al., 2014). |
| Danshensu | Prevented cholesterol accumulation in mouse macrophages by inhibiting CD36-mediated lipid uptake, while enhancing ABCA1/G1-mediated cholesterol efflux (Wang et al., 2010b; Gao et al., 2016). | Attenuated high methionine-rich diet-induced accumulation of foam cells in rat aortic endothelium by attenuating TNF-α and ICAM1 expression (Yang et al., 2010). Danshensu improved dyslipidemia by decreasing LDL-C and fatty acid by inhibiting HMG-CoA reductase and fatty acid synthase expression (Yang et al., 2011). |
| 6-Dihydroparadol | Promoted cholesterol efflux from THP-1 macrophages by increasing the expression of ABCA1 and ABCG1 via preventing the proteasome-dependent protein degradation (Wang et al., 2018a). | N.A. |
| Paeonol | Promoted cholesterol efflux via activating LXRα/ABCA1 pathway in macrophages (Zhao et al., 2013b; Li et al., 2015c), inhibited cholesterol uptake through CD36 inhibition (Li et al., 2015c). | Reduced atherosclerotic lesion formation and attenuated systemic inflammation as well as increased ABCA1 expression in ApoE−/− mice (Zhao et al., 2013b). Paeonol reduced the levels of malondialdehyde and oxidzed LDL in hyperlipidemia rats (Dai et al., 2000). |
| Polydatin | Activation of PPARγ-dependent ABCA1 upregulation and decrease of CD36 expression (Wu et al., 2015b). | Reduced TC, FC, CE, together with reduction of secretion of TNF-α and IL-1β in oxLDL-stimulated ApoE−/− mouse macrophages (Wu et al., 2015b). Polydatin improved dyslipidemia via suppressing PCSK9 and upregulation of hepatic LDLR expression (Li et al., 2018a). |
| Protocatechuic acid | Promoted cholesterol efflux from macrophages by increasing ABCA1 and ABCG1 expression via reduction of miRNA-10b expression (Wang et al., 2012a). | Reduced the development of atherosclerosis in ApoE−/− mice (Wang et al., 2010a, 2011; Stumpf et al., 2013). Protocatechuic acid could possibly regulate lipid metabolism via suppressing the expression of HMG-CoA reductase (Liu et al., 2010b). |
| Salicylic acid | Upregulated the expression of ABCA1 and SR-BI by AMPK activation or PPARα pathway, thereby stimulating cholesterol efflux from macrophages (Viñals et al., 2005; Lu et al., 2010). | Aspirin attenuated atherosclerosis in ApoE−/− mice by suppressing systemic inflammation and promoting inflammation resolution (Petri et al., 2017). |
| Salvianolic acid B | Acted as an effective CD36 antagonist that blocks oxLDL uptake in mouse macrophages (Wang et al., 2010b) and THP-1 macrophages (Bao et al., 2012), promoted cholesterol efflux via a PPARγ/LXRα/ABCA1-depen-dent pathway in THP-1 macrophages (Bao et al., 2012). | Exhibited antiatherosclerotic effects in neointimal hyperplasia in rabbits (Yang et al., 2011) and in ApoE−/− mice (Chen et al., 2006; Lin et al., 2007). Salvianolic acid B ameliorated hyperlipidemia via AMPK activation (Cho et al., 2008) and inhibition of LDL oxidation (Yang et al., 2011). |
| Sesamol | Decreased the expression of CD36, CD68, SR-A, and LOX-1 (Narasimhulu et al., 2018), and increased the expression/activity of PPARγ and LXRα in macrophages via a MAPK-dependent mechanism (Wu et al., 2015d). | Sesamol derivative (INV-403) and sesame oil prevent or regress atherosclerosis in LDLR−/− mice (Narasimhulu et al., 2018) and hyperlipidemic rabbits fed with an atherogenic diet by suppressing NF-κB dependent vascular inflammation (Ying et al., 2011). |
| Resveratrol | Reduced oxLDL uptake (Voloshyna et al., 2013), promoted ApoA-1- and HDL-mediated cholesterol efflux in both mouse and human macrophages by increasing the expression of ABCA1 and ABCG1 via PPARv/LXRα (Berrougui et al., 2009; Allen and Graham, 2012) and adenosine 2A receptor pathway (Voloshyna et al., 2013). | Exhibited antiatherosclerotic effects in several animal models, including ApoE−/− mice (Do et al., 2008; Chang et al., 2015), APOE*3-Leiden.CETP mice (Berbée et al., 2013), and ApoE−/−/LDLR−/− mice (Fukao et al., 2004). Resveratrol lowered the level of TC and TG in patients with dyslipidemia (Simental-Mendia and Guerrero-Romero, 2019) and regulated lipid metabolism via inhibiting cholesterol-ester-transport protein and HMG-CoA expression/level (Cho et al., 2008). |
| Epigallocatechin gallate (EGCG) | Reduced cholesterol efflux from macrophages by increasing ABCA1 expression via activating Nrf2-dependent NF-κB inhibitory effects (Jiang et al., 2012) and blocked oxLDL-induced upregulation of SR-A, thus reducing oxLDL uptake (Chen et al., 2017). | Displayed potential antiatherosclerotic and plaque-stabilizing effects in rats, rabbits, and ApoE−/− mice (Chyu et al., 2004; Xu et al., 2014a; Wang et al., 2018e,f). EGCG prevented hyperlipidemia by increasing the expression and activity of LDLR (Lee et al., 2008). |
Phenylpropanoids | (–)-Arctigenin | Upregulated the expression of ABCA1, ABCG1, and ApoE, resulting in promoting cholesterol efflux in oxLDL-loaded THP-1 macrophages (Xu et al., 2013d). | Decreased cholesterol levels in mice (Huang et al., 2012a) and suppressed lipid accumulation and body weight gain in HFD-induced obese mice (Han et al., 2016). |
| Leoligin | Increased cholesterol efflux from THP-1 macrophages by upregulating the expression of ABCA1 and ABCG1 (Wang et al., 2016a). | Reduced LDL-C level and postprandial serum glucose peaks due to the direct inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) and moderate PPARγ agonistic activity; however, no obvious effect on atherosclerotic plaque size was observed (Scharinger et al., 2016). |
| Sesamin | Inhibited oxLDL-induced cholesterol accumulation and enhanced cholesterol efflux from RAW264.7 macrophages via up-regulation of PPARγ, LXRα, and ABCG1 (Liu et al., 2014a). | Prevented fat storage, decreased cholesterol level in serum (Lee et al., 2009c; Rogi et al., 2011). Attenuated atherosclerosis in ApoE−/− mice by suppressing vascular inflammation (Wu et al., 2010). The lipid-lowering effect of sesamin was exerted through promoting the fecal excretion of sterols and inhibiting HMG-CoA reductase (Liang et al., 2015). |
| Honokiol | Activated the RXR/LXR heterodimer in RAW264.7 cells, resulting in the induction of ABCA1 expression and enhancement of cholesterol efflux from MPMs (Kotani et al., 2010), and increased ABCG1 and ApoE expression in THP-1 macrophages (Jung et al., 2010). | N.A. |
| α-Asarone | Promoted macrophage cholesterol efflux through the PPARγ-LXRα-ABC transporters pathway (Park et al., 2015). | Decreased level of serum cholesterol in hypercholesterolemic rats by inhibition of HMG-CoA reductase (Rodriguez-Paez et al., 2003). |
| Chlorogenic acid | Enhanced HDL-mediated cholesterol efflux from macrophages through increasing the expression of ABCG1 and SR-BI (Uto-Kondo et al., 2010) and enhancement of PPARα ligand binding capacity in vitro (Kim et al., 2014). | Chlorogenic acid prevented atherosclerosis in ApoE−/− mice by inhibiting lipid accumulation and promoting cholesterol efflux via PPARγ/LXRα/ABCA1(G1) pathway (Wu et al., 2014). |
| Caffeic acid | Decreased oxLDL-elicited neutral lipid and cholesterol accumulation in RAW264.7 macrophages via increasing the transcription of PPARγ, LXRα, ABCA1, and ABCG1 (Wu et al., 2014). | Reduced the percentage and the total atherosclerotic lesion area as well as promoted vasodilatation in cholesterol-rich diet-fed ApoE−/− mice, and decreased levels of TC, LDL-C and TG in the serum (Wu et al., 2014). Caffeic acid reversed insulin resistance, dyslipidemia, hyperglycemia, inflammation, and oxidative stress in high-fructose diet-induced metabolic syndrome in rats (Ibitoye and Ajiboye, 2018). |
| Ferulic acid | Increased the expression of ABCA1 and ABCG1 in macrophage form cells and further promoted cholesterol efflux (Chen and Wang, 2015). | Ferulic acid suppressed atherosclerosis in ApoE−/− mice by inhibiting the activities of hepatic ACAT and HMG-CoA reductase (Kwon et al., 2010). Ferulic acid also lowered TC, LDL-C, oxLDL, TG, and increased HDL-C in patients with dyslipidemia (Bumrungpert et al., 2018). |
Alkaloids | Arecoline | Promoted cholesterol efflux by increasing ABCA1 expression (Ouyang et al., 2012). | Arecoline suppressed atherosclerosis in ApoE−/− mice by inhibiting NF-κB activation (Zhou et al., 2014). |
| Berberine | Inhibited macrophage foam cell formation by promoting LXRα/ABCA1-dependent cholesterol efflux (Lee et al., 2010). Prevented oxLDL-induced upregulation of LOX-1 and downregulation of SR-BI in THP-1 macrophages (Guan et al., 2010; Chi et al., 2014a). It was reported to increase foam cell formation in human and mouse macrophages (Li et al., 2009b). | Suppressed atherosclerosis development in mice (Feng et al., 2017; Shi et al., 2018; Zhu et al., 2018). One report suggests that berberine promoted atherosclerosis in mice by enhancing SR-A-mediated oxLDL uptake and foam cell formation (demonstrated in human and mouse macrophages) through suppressing phosphatase and tensin homolog expression, thus promoting the activation of Akt (Li et al., 2009b). In patients with dyslipidemia, berberine reduced TC, LDL-C, TG, and increased HDL-C, partially through inhibiting PCSK9 and increasing LDLR expression/activity (Kong et al., 2004; Cameron et al., 2008; Ju et al., 2018). |
| Piperine | Promoted ABCA1 protein expression in THP-1-differentiated macrophages by increasing ABCA1 protein stability by preventing calpain-mediated ABCA1 protein degradation (Wang et al., 2017d). | Regulated lipid metabolism via increasing hepatic LDLR expression through proteolytic activation of SREBPs (Ochiai et al., 2015). |
| Rutaecarpine | Upregulated expression of ABCA1 and SR-BI via LXRα and LXRβ, thereby promoting cholesterol efflux (Xu et al., 2014b). | Reduced atherosclerotic plaque development, as well as macrophage and lipid content in atherosclerotic plaques in ApoE−/− mice (Xu et al., 2014b). Lowered the level of TC, TG, and LDL-C, and hs-CRP in hyperlipidemic and hyperglycemic rats via AMPK activation and NF-κB inhibition (Nie et al., 2016; Tian et al., 2019b). |
| Evodiamine | Increased cholesterol efflux from THP-1-derived macrophages by directly binding to ABCA1 and thereby increasing ABCA1 stability (Wang et al., 2018c). | Decreased the size of atherosclerotic lesions and alleviated the hyperlipidemia, as well as hepatic macrovesicular steatosis in ApoE−/− mice, probably via transient receptor potential vanilloid type 1 (TRPV1) pathway (Su et al., 2014). |
| Leonurine | Promoted ApoA-1- and HDL-mediated cholesterol efflux via the PPARγ/LXRα/ABCA1 and ABCG1 pathway (Jiang et al., 2017a). | Reduced atherosclerotic development in ApoE−/− mice fed with atherogenic diet (Jiang et al., 2017a). |
Steroids | Diosgenin | Inhibited oxLDL uptake by blocking systemic inflammation and LOX-1/NF-κB pathway (Wang et al., 2017g). Promoted cholesterol efflux by increasing the ABCA1 expression independent of LXRα (Lv et al., 2015). | Inhibited atherosclerosis in ApoE−/− mice by reducing TC and CE via promoting ABCA1-dependent cholesterol efflux (Lv et al., 2015). |
| Fucosterol | Promoted cholesterol efflux by increasing the efflux transporters ABCA1, ABCG1, and ApoE (Hoang et al., 2012). | Reduced LDL-C, and increased HDL-C (Hoang et al., 2012). |
| Ginsenoside Rd (Panax notoginseng saponins (PNS)) | Decreased the accumulation of cholesterol esters via increasing ABCA1 expression (Jia et al., 2010). | Inhibited foam cell formation in zymosan A-induced atherosclerosis in rats (Yuan et al., 2011). Prevented atherosclerosis in ApoE−/− mice by decreasing SR-A-mediated oxLDL uptake and cholesterol accumulation (Li et al., 2011). |
| Vitamin D3 (Vitamin D) | Vitamin D inhibited CD36 and SR-A-mediated lipid (oxLDL and ac-LDL) uptake (Oh et al., 2009; Yin et al., 2015). | Deficiency of vitamin D receptor (VDR) promoted modified LDL-induced foam cell formation of macrophages from diabetic patients (Oh et al., 2015). Deficiency of macrophage VDR aggravated CD36 and SR-A-mediated lipid uptake (via JNK activation) to increase atherosclerosis in mice (Oh et al., 2015). Vitamin D supplementation improved glycemic control, increased HDL-C and decreased hs-CRP levels in patients with CVD (Ostadmohammadi et al., 2019). |
Fatty acids | Docosahexaenoic acid (DHA) | Inhibited the uptake of modified LDL in human macrophages partially through reduction of the expression of CD36 and SR-A (Pietsch et al., 1995), as well as of macropinocytosis and expression of syndecan-4 (McLaren et al., 2011b). | Reduced atherosclerosis in ApoE−/− mice by reducing proinflammatory cytokine IL-1β (Alfaidi et al., 2018). Lowered TG in dyslipidemic patients (Weintraub, 2013). |
| Eicosapentaenoic acid (EPA) | Inhibited the uptake of modified LDL in human macrophages partially through reduction of the expression of CD36 and SR-A (Pietsch et al., 1995), as well as of macropinocytosis and expression of syndecan-4 (McLaren et al., 2011b). | Reduced and stabilized atherosclerotic plaques in ApoE−/− and LDLR−/− mice through its anti-inflammatory effects (Ringseis et al., 2006; Laguna-Fernandez et al., 2018). Lowered TG in dyslipidemic patients. EPA served as a substrate for resolvin E1 (RvE1), which promotes inflammation resolution i (Bäck and Hansson, 2019). |
| 13-Hydroxyoctadecadienoic acid (13-HODE) | Promoted cholesterol efflux by activating PPAR/LXRα/ABCA1 and ABCG1 pathway (Kämmerer et al., 2011). | N.A. |
| Linoleic acid | Functioned as an endogenous activator of PPARα, PPARγ, and PGC1α, thus stimulating cholesterol efflux (Ringseis et al., 2008). | Induced the regression of pre-established atherosclerotic plaques in ApoE−/− mice by promoting macrophage polarization toward a M2 anti-inflammatory phenotype (McCarthy et al., 2013). Possibly reduced TC via increasing hepatic LDLR expression and activity (Ringseis et al., 2006). |
Amino acids | L-(+)-citrulline | Promoted cholesterol efflux by increasing ABCA1 and ABCG1 expression in differentiated THP-1 macrophages (Tsuboi et al., 2018). | Citrulline consumption promoted HDL- and ApoA-1-mediated cholesterol efflux by increasing the expression of both ABCA1 and ABCG1 (Uto-Kondo et al., 2014). |
| S-allyl cysteine | Increased ABCA1 expression, thus promoting cholesterol efflux in differentiated THP-1 macrophages (Malekpour-Dehkordi et al., 2013). | N.A. |
Carbohydrates | Polysaccharide isolated from Phellinus linteus N.A. | Promoted ApoA-1-mediated cholesterol efflux by activating PPARγ/ABCA1 and ABCG1 pathway (Li et al., 2015d). | N.A. |
| Astragalus polysaccharides | Promoted ABCA1 expression in foam cells, thus increasing cholesterol efflux (Wang et al., 2010d). | N.A. |
Others | Organosulfur compounds: Allicin | Upregulated ABCA1-dependent cholesterol efflux via PPARγ/LXRα signaling pathway in THP-1 macrophage-derived foam cells (Lin et al., 2017). | Decreased carotid intima/media thickness, decreased homocysteine, TC, and TG in CAD patients with hyperhomocysteinemia (Liu et al., 2017a). |
| Pyranone derivatives: Asperlin | Promoted cholesterol efflux from mouse macrophages (Zhou et al., 2017). | Reduced the secretion of proinflammatory cytokines (IL-6, TNFα. MCP-1) and atherosclerosis in ApoE−/− mice (Zhou et al., 2017). |
| Anthraquinone derivatives: Emodin | Promoted ApoA-1-mediated cholesterol efflux from macrophages via PPARγ/LXRα/ABCA1 and ABCG1 pathway (Zhou et al., 2008; Fu et al., 2014) | Reduced atherosclerosis in ApoE−/− mice (Zhou et al., 2008) and rabbits (Hei et al., 2006). Lowered blood glucose, TC, TG, in diabetic and hyperlipidemic rats (Zhao et al., 2009) by inhibiting SREBP-1 and SREBP-2 (Li et al., 2016). |
| Polyacetylene derivatives: Falcarindiol | Promoted ApoA-1-mediated cholesterol efflux in macrophages not only by increasing ABCA1 gene expression, but also via preventing cathepsins-dependent ABCA1 protein degradation (Wang et al., 2017e). | N.A. |
| Spiromastixones: Spiromastixone A | Inhibited lipid uptake by reducing the expression of CD36. Promoted cholesterol efflux by upregulation of PPARγ/ABCA1 and ABCG1 (Wu et al., 2015a). | N.A. |