Table 1.
Effects and mechanisms of MEPs in the treatment of dyslipidemia
| No | MEPs | Active ingredients | Lipid metabolism | Signaling pathway | Mechanism of action | References |
|---|---|---|---|---|---|---|
| 1 | Cinnamomi cortex | Polyphenol |
↓TC, TG, LDL; ↑HDL |
1) Inhibit the expressions of SREBP-1c, ACLY, and FAS; 2) Increase the expressions of PPAR-α and IRS |
1) Inhibit triglyceride synthesis; 2) Promote fatty acid oxidation; 3) Increase insulin sensitivity |
[40] |
| 2 | Chrysanthemi flos | Extract | ↓TC, TG, LDL |
1) Downregulate PPAR-γ, SREBP-1c, C/EBP-α, CD36, ACLY, ACC, FAS, SCD1, and DGAT2; 2) Upregulate PPARα and CPT1α; 3) Activate AMPK signaling pathway |
1) Inhibit triglyceride biosynthesis; 2) Increase fatty acid oxidation |
[50] |
| Flavonoids, luteolin, luteoloside |
↓TC, TG, LDL, Apo B; ↑Apo A1 |
1) Inhibit the enzymes activity of FAS, HMG-CoA and DGAT; 2) Increase the activity of FAβO, CYP7A1 and HL |
1) Inhibit lipid synthesis; 2) Promote bile acids biosynthesis; 3) Promote fatty acid oxidation |
[53] | ||
| 3 | Citri sarcodactylis fructus | Extract | ↓TC |
1) Activate AMPK phosphorylation; 2) Inhibit the activity of HMG-CoA, HMGCR and NPC1L1; |
1) Inhibit cholesterol biosynthesis; 2) Inhibit cholesterol absorption |
[60, 61] |
| Polyphenols |
↓TC, TG, LDL, Apo B; ↑HDL, Apo A1 |
1) Inhibit the activity of pCEH, ACAT and CETP; 2) Enhance the activity of LCAT |
1) Inhibit cholesterol esterification and absorption; 2) Improve lipid transport protein system |
[64, 65] | ||
| Naringin | ↓TC, LDL |
1) Upregulate p-AMPKα and LDLR; 2) Downregulate SREBP-1, SREBP-2, and PCSK9 |
1) Inhibit lipids biosynthesis; 2) Promote cholesterol metabolism |
[66] | ||
| 4 | Crataegi fructus | Extract; powder; juice |
↓TC, TG, LDL; ↑HDL |
1) Regulate the perturbed metabolism pathways; 2) Inhibit pancreatic lipase; 3) Increase the LCAT activity |
1) Improve gut microflora; 2) Inhibit lipid absorption; 3) Promote reverse cholesterol transport |
[71, 72, 75, 76, 80] |
| Pectin penta-oligogalacturonide | / |
1) Inhibit FXR-FGF15 axis; 2) Increase CYP7A1 and ASBT |
1) Promote bile acids biosynthesis; 2) Inhibit intestinal bile acid reabsorption |
[77] | ||
| Crude glycoprotein |
↓TC, TG; ↑HDL |
/ | / | [78] | ||
| Vitexin | ↓TC, TG |
1) Activate AMPKα; 2) Downregulate C/EBPα and FAS |
Inhibit de novo lipogenesis | [79] | ||
| 5 | Gardeniae fructus | Extract | ↓TC, TG, LDL |
1) Downregulate SREBP-1c, FAS, SCD1, and PPARγ; 2) Upregulate PPARα and CPT-1 |
Inhibit biosynthesis of triglyceride and cholesterol | [87] |
| Geniposide |
↓TC, TG, LDL, VLDL, ApoC3; ↑HDL |
1) Enhance the phosphorylation of ACC, AMPKα, and AMPKβ; 2) Upregulate PPARα, LDLR, SR-B1, ABCA1, ABCG1, CYP7A1, CYP27A1, CYP7B1, and CYP8B1; 3) Downregulate SREBP-1c, miR-101 and SR-A; 4) Inhibit FXR-mediated bile acids liver-gut crosstalk |
1) Inhibit triglyceride and cholesterol biosynthesis; 2) Decrease free cholesterol esterification and cholesterol uptake; 3) Promote cholesterol efflux; 4) Facilitate reverse cholesterol transport; 5) Motivate bile acid biosynthesis and excretion |
[88–91] | ||
| Genipin |
↓TC, TG ↑HDL |
1) Upregulate the gene expressions of HSL, ATGL, CPT‐1α and PPARα; 2) Downregulate SREBP-1c, FAS, and SCD1 |
1) Promote triglyceride decomposition; 2) Inhibit triglyceride synthesis |
[93, 94] | ||
| 6 | Hippophae fructus | Flavonoids; isorhamnetin | ↓TG |
1) Upregulate PPARα, LXRα, LDLR, CYP7A1, ABCA1 and CPT1A; 2) Downregulate SREBP-2 |
1) Promote cholesterol metabolism; 2) Inhibit cholesterol de novo synthesis; 3) Accelerate fatty acid oxidation |
[101, 102] |
| Kaempferol and kaempferide | ↓TG | Downregulate SREBP-1, FAS, SCD1, PPARγ and C/EBPβ | Inhibit fatty acid synthesis and adipogenesis | [103] | ||
| Sterols |
↓TC, TG, LDL; ↑HDL |
1) Increase Apo-A, HL and LPL; 2) Reduce Apo-B |
Promote lipids transport and decomposition | [104] | ||
| 7 | Mori fructus | Extract |
↓TC, TG, LDL; ↑HDL |
1) Downregulate miR-33, miR-21, miR-143, FXR, SHP, SREBP-2, PPARγ, and C/EBPα; 2) Upregulate LXR-α, ABCG5, CYP7A1, ABCA1, ApoA-1 and LCAT; 3) Inhibit GPDH activity; 4) Increase AMPK activity |
1) Inhibit de novo cholesterol biosynthesis; 2) Increase bile acids synthesis; 3) Promote cholesterol reversal transport; 4) Inhibit adipogenesis and adipocyte differentiation |
[110, 111] |
| Polysaccharides |
↓TC, TG, LDL; ↑HDL |
Selective enrich bacteria and reduce intestinal microbial diversity | Regulate gut microbiota | [113] | ||
| 8 | Mori folium | Powder |
↓TC, LDL; ↑HDL |
1) Inhibit FXR expression; 2) Promote CYP7A1 expression; 3) Maintain the ratio of ABCG5/ABCG8 |
1) Promote cholesterol efflux; 2) Promote bile acids biosynthesis and excretion |
[121] |
| Extract |
↓TC, TG, LDL; ↑HDL |
1) Increase CYP7A1, LXRα, ABCG5/ABCG8, CPT1 and PPARα expression; 2) Decrease SREBP-1, FAS, AGPAT and miR-33 expression; 3) Increase the AMPK activity |
1) Increase hepatic bile acid biosynthesis; 2) Inhibit lipid biosynthesis; 3) Promote lipid degradation; 4) Promote fecal cholesterol excretion |
[116, 122, 123] | ||
| Flavonoids; quercetin |
↓TC, TG, LDL; ↑HDL |
1) Activate AMPK-PGC-1α signaling pathway; 2) Downregulate SREBP-2, HMGCR, LXRβ and miR-33a; 3) Increase the expressions of CPT-1 and CYP7A1 |
1) Promote mitochondrial fatty acid oxidation; 2) Improve insulin resistance; 3) Inhibit cholesterol biosynthesis; 4) Promote cholesterol convert to bile acid; |
[124, 125] | ||
| Polyphenols and fiber |
↓TC, TG, LDL; ↑HDL |
1) Downregulate FAS, C/EBP-α and PPARγ; 2) Improve intestinal flora diversity |
1) Inhibit triglyceride biosynthesis and adipocyte differentiation; 2) Regulate gut microbiota |
[126] | ||
| Polysaccharides |
↓TC, TG, LDL; ↑HDL |
Inhibit pancreatic lipase activity | Inhibit lipids absorption | [128] | ||
| 9 | Nelumbinis folium | Powder | ↓TC, TG |
1) Downregulate SREBP-1c mRNA; 2) Inhibit HMG-CoA activity; 3) Enhance LPL activity |
1) Inhibit synthesis of triglycerides and cholesterol; 2) Promote triglyceride decomposition |
[131] |
| Nuciferine | ↓TC, TG, LDL |
1) Downregulate SREBP-1, ACLY, ACC, FAS, PPARγ, C/EBPα and C/EBPβ; 2) Upregulate LCAT activity and PPARγ/LXRα/ABCA1 pathways; 3) Inhibit PI3K/AKT/mTOR pathways; 4) Alter the diversity and composition of gut microbiota |
1) Inhibit lipids biosynthesis; 2) Increase cholesterol efflux; 3) Promote autophagy and reduce macrophage foaming; 4) Regulate gut microbiota |
[133, 134, 136–140] | ||
| 10 | Citri reticulatae pericarpium | Ethanol extract |
↓TC, TG, LDL, ApoB; ↑ApoA1 |
1) Inhibit the activity of HMGCR; 2) Regulate apolipoprotein; 3) Regulate PPARγ-LPL/ATGL/HSL and FXR-HL pathway |
1) Decrease cholesterol synthesis; 2) Regulate cholesterol transport; 3) promote triglyceride metabolism |
[148, 149] |
| Water extract |
↓TC, TG, LDL; ↑HDL |
Alter the diversity and composition of gut microbiota | Improve gut microflora | [150] | ||
| 11 | Zanthoxyli pericarpium | Hydroxy-α-sanshool |
↓TC, TG, LDL; ↑HDL |
Increase mRNA and protein expression of PPARγ and ApoE | Promote lipid metabolism and lipoprotein transformation | [157] |
| 12 | Dioscoreae rhizoma | Diosgenin |
↓TC, TG; ↑HDL |
Activate the catabolic pathway via AMPK | Inhibit cholesterol absorption and facilitate cholesterol excretion | [162] |
| Resistant starch |
↓TC, TG, LDL; ↑HDL |
Increase the relative abundance of probiotics | Regulate gut microbiota | [164] | ||
| 13 | Polygonati rhizoma | Extract |
↓TC, LDL; ↑HDL |
1) Upregulate CPT-1 mRNA expression; 2) Regulate the composition and concentration of amino acids, carbohydrates and esters |
1) Promote fatty acid β-oxidation; 2) Regulate endogenous metabolites |
[165, 170] |
| Polysaccharides |
↓TC, TG, LDL; ↑HDL |
1) Upregulate PPAR-α and PPAR-β; 2) Downregulate PPAR-γ and SREBP-1c; 3) Regulate gut microbiota and restore the intestinal permeability barrier; |
1) Inhibit lipid synthesis; 2) Promote fatty acid oxidation and lipolysis; 3) Regulate gut microbiota |
[171, 172] | ||
| Saponin |
↓TC, TG, LDL; ↑HDL |
Modulate the composition, abundance and diversity of gut microbiota | Regulate gut microbiota | [173] | ||
| Syringaresinol‑di‑O‑β‑D‑glucoside | ↓TC, TG, LDL‑C, VLDL‑C, FFA | Promote insulin secretion | Improve insulin sensitivity | [174] | ||
| 14 | Astragali radix | Total flavonoids |
↓TC, TG, LDL, VLDL; ↑HDL |
1) Upregulate FXR, TGR5, CYP7A1, ASBT, AMPKα and CPT1α; 2) Downregulate FAS and SREBP-1c; |
1) Promote bile acids synthesis and excretion; 2) Enhance fatty acid oxidation; 3) Inhibit lipid synthesis |
[182, 183] |
| Astragaloside IV |
↓TC, TG, FFA; ↑HDL |
1) Activate AMPK, ACC and SREBP-1 phosphorylation; 2) Downregulate SREBP-1, ACC1, FAS and SCD1 |
Inhibit lipid biosynthesis | [185, 186] | ||
| 15 | Puerariae radix | Extract |
↓TC; ↑HDL |
Activate AMPK and PGC-1α proteins | Promote mitochondrial biogenesis and energy metabolism | [193] |
| Puerarin | ↓TC, TG, LDL |
1) Downregulate SREBP-1c, FAS, SCD1 and HMGCR; 2) Upregulate CPT1, ACOX and HL; 3) Increase the phosphorylation of AMPK and ACC |
1) Inhibit triglycerides and cholesterol synthesis; 2) Promote fatty acid oxidation and lipolysis |
[194, 195] | ||
| Polysaccharides |
↓TC, TG, LDL, FFA; ↑HDL |
1) Downregulate SREBP-1 and ACC; 2) Upregulate PPARα and LDLR; 3) Upregulate FXR, FGFR4, CYP7A1, BSEP, MRP2, and LXR |
1) Inhibit lipid synthesis; 2) Promote β-oxidation; 3) Promote LDL-C degradation; 4) Promote bile acids synthesis and excretion |
[187, 196] | ||
| 16 | Cassiae semen | Extract | ↓TC, TG, LDL, |
1) Improve intestinal microbiota composition and barrier damage; 2) Upregulate LDLR mRNA |
1) Regulate gut microbiota; 2) Promote LDL-C degradation |
[203, 204] |
| Anthraquinone glycoside |
↓ LDL; ↑HDL |
1) Increase the PPARα expression; 2) Inhibit the SREBP-1c expression |
1) Inhibit triglyceride synthesis; 2) Promote fatty acid oxidation |
[206] | ||
| 1,8-Dihydroxyanthraquinone |
↓TC, TG, LDL; ↑HDL |
1) Upregulate CYP7A1; 2) Downregulate HMGCR |
1) Inhibit cholesterol synthesis; 2) Promote cholesterol conversion into bile acids |
[207] | ||
| 17 | Canavaliae semen | Bacillus subtilis-fermented extract | ↓TG |
1) Downregulate aP2, adiponectin, C/EBPα, PPARγ and FAS; 2) Upregulate PPARα, ACOX, LCAD, pHSL and ATG |
1) Inhibit lipid biosynthesis; 2) Promote triglyceride hydrolysis and β-oxidation |
[212] |
| Total terpenoids; total flavonoids |
↓TC, TG, LDL; ↑HDL |
/ | / | [213] | ||
| 18 | Lablab semen album | Extract | ↓TC, TG, LDL, FFA |
1) Downregulate Fsp27/Cidec, VLDLR, CD36, DGAT1 and DGAT2; 2) Increase adiponectin levels; 3) Regulate GL/FFA cycle and bile acid metabolism |
1) Inhibit TG synthesis and fatty acid up-take; 2) Increase FFA oxidation; 3) Improve endogenous metabolites |
[220, 221] |
| 19 | Persicae semen | Amygdalin |
↓TC, TG, LDL; ↑HDL |
/ | / | [225, 226] |
| Peach kernel oil |
↓TC, TG, LDL; ↑HDL |
/ | / | [228] | ||
| 20 | Portulacae herba | Extract/powder |
↓TC, TG, LDL, VLDL; ↑HDL |
Upregulate the protein expression of PPAR-α and PPAR-γ | Promote lipolysis and fatty acid oxidation | [236, 239] |