Table 1 Effects and mechanisms of MEPs in the treatment of dyslipidemia

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

[88,89,90,91]

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, 136,137,138,139,140]

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]