Natural products that are extracted from the source and from concentrated, fractionated, and purified yielding, which are generally defined as bioactive compounds, have the ability to modulate lipid metabolism, improve insulin signaling, and protect against cardiovascular damage.
Natural Products (Extracts) | Relevant miRNAs | Dose | Administration Methods |
Experimental Models | Targets | ||||||||||
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Natural Products (Compounds) | Relevant miRNAs | Dose | Observed Effects | References | |||||||||||
Administration Methods | Experimental Models | Targets | Observed Effects | References | |||||||||||
Averrhoa carambola free phenolic extract | miR-33↓ miR-34a↓ |
10, 20, 30 g/kg/d for 8 weeks | Gavage | db/db mice | / | ||||||||||
A-type ECG and EGCG dimers![]() |
miR-7a/b↑ | ECG dimer: 20 μg/mL for 1–8 days; ECGG dimer: 60 μg/mL for 1–8 days | ● Reduced liver TG; | Cell culture | ● Inhibited the signal transduction of hepatic lipogenesis; | 3T3-L1 pre-adipocyte cells | ● Exhibited a potent hepatic steatosis-relieving effect. |
PPARγ[20] | |||||||
● Inhibited pre-adipocyte differentiation; | ● Reduced intracellular lipid accumulation; | ● Blocked MCE process; | ● Decreased the fluidity and hydrophobicity and increased the permeability of membrane. | [40] | Cerasus humilis polyphenol extract | miR-7a/b↓ | 40 μg/mL for 48 h; 250 g/kg/day for 12 weeks |
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Curcumin![]() | Cell culture; | gavage | 3T3-L1 pre-adipocyte cells; obese mice | Sirt1, Prdm16 | ● Reduced body weight; ● Improved abnormal serum lipid and glucose levels; ● Inhibited adipocyte differentiation; ● Reduced fat accumulation by mitigating fat deposition, inflammation, and oxidation. |
miR-17↓[21] | |||||||||
2 μM or 10 μM for 6 h; | Cell culture | 3T3-L1 pre-adipocyte cells; | HFD-fed mice | TCF7L2 | ● Inhibited adipocyte differentiation and adipogenesis; ● Stimulated the Wnt signaling pathway. |
[41] | Citrus peel flavonoids | miR-33↓ miR-122↓ |
10 μg/mL for 0.5, 1, 3 and 6 h | Cell culture | Oleic acid-treated HepG2 cells | FAS, CPT1a | ● Attenuated intracellular lipid accumulation. | ||
Grape seed procyanidin B2![]() | [ | 22 | ] | ||||||||||||
miR-483↓ | 150 μg/mL for 48 h | Cell culture | 3T3-L1 pre-adipocyte cells | PPARγ | ● Inhibited pre-adipocyte differentiation; | ● Reduced intracellular lipid accumulation. |
[42] | Coffee polyphenols | miR-122↑ | 2.5 × 10−4%; diet containing 0.5% or 1.0% coffee polyphenols for 15 weeks |
Cell culture; diet |
Hepa 1-6 cells; HFD-fed mice |
SREBP1c | ● Activated AMPK; ● Enhanced energy metabolism; ● Reduced lipogenesis; ● Reduced body weight gain, abdominal and liver fat accumulation. |
[ |
EGCG![]() |
miR-143↑ | 50 μM for 24 h | Cell culture | 23 | ] | ||||||||||
3T3-L1 pre-adipocyte cells | MAPK7 | ● Inhibited 3T3-L1 cell growth. | [ | 43 | ] | Ginger extract | miR-21↓ miR-132↓ |
Diet containing 0.8% ginger extract for 10 weeks | Diet | HFD-fed rats | / | ||||
Lycopene![]() |
miR-21↑ | 50 μM for 24 h; diet containing 0.05% lycopene for 8 weeks |
Cell culture; gavage | ● Lowered body weight and white adipose tissue mass; | ● Reduced serum and hepatic lipid levels; ● Enhanced AMPK activity; ● Ameliorated obesity and inflammation. |
[24] | |||||||||
Hepa 1–6 cells; | HFD-fed mice | FABP7 | ● Lowered body weight; | ● Inhibited intracellular lipid accumulation; ● Protected against HFD-induced hepatic steatosis. |
[44] | Grape seed proanthocyanidins extract | miR-33a↓ miR-122↓ |
5, 25, 50 mg/kg for 3 weeks | Gavage | HFD–induced obese rats | ABCA1; FAS, PPARβ/δ |
● Hypolipidemic; ● Decreased total liver fat. |
[16] | ||
Nonivamide![]() |
miR let-7d↑ | 1 μM for 12 days | Cell culture | 3T3-L1 pre-adipocyte cells | PPARγ | ● Impaired adipogenesis; ● Reduced mean lipid accumulation; ● Activated TRPV1. |
[45] | miR-33a↓ miR-122↓ |
5, 15, 25, 50 mg/kg for 3 weeks | Gavage | Healthy Wistar rats | ABCA1; FAS |
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Oleanolic acid![]() | ● Improved postprandial hyperlipemia; | ● Increased liver cholesterol efflux to HDL formation; | ● Reduced fatty acid synthesis. | [25] | |||||||||||
miR-98↑ | 10 mM for 6, 12, 24 h; | 20 mg/kg for 4 weeks |
Cell culture | HFD-fed mice; db/db mice |
PGC1β | ● Hypolipidemic. | [46] | miR-33↓ miR-122↓ |
10, 25, 50, or 100 mg/L for 0.5, 1, 3, or 5 h; 250 mg/kg for 1 or 3 h |
Cell culture; gavage |
FAO cells; Wistar rats |
ABCA1; FAS |
● Hypolipidemic; ● Reduced lipogenesis; ● Increased liver cholesterol efflux to HDL formation. |
[26] | |
Persimmon tannin![]() |
miR-27↑ | 20, 40, or 60 μg/mL for 1–8 days | Cell culture | 3T3-L1 pre-adipocyte cells | PPARγ, C/EBPα | ● Inhibited pre-adipocyte differentiation; ● Reduced intracellular lipid accumulation; ● Delayed MCE process. |
[47] | miR-33a↓ miR-122↓ |
25 mg/kg for 3 weeks | Gavage | Dyslipidemic obese rats | ABCA1, CPT1a; FAS, PPARβ/δ |
● Improved dyslipidemia; ● Decreased total liver fat. |
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Pseudoprotodioscin![]() | [ | miR-33a/b↓ | 27 | ] | |||||||||||
25 μM for 24 h | Cell culture | Human HepG2 cells and THP-1 monocytic cells | SREBP1c, SREBP2 | ● Promoted the cholesterol effluxion. | [ | 48 | ] | miR-96↓ | 200 mg/kg/day for 180 days | Diet | HFD-fed mice | mTOR, FOXO1 | ● Decreased the weight gain, serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol but increased high-density lipoprotein cholesterol; ● Clearance of lipid accumulation. |
[28] | |
Resveratrol![]() |
miR-103↓ miR-107↓ miR-122↓ |
30 mg/kg for 6 weeks | Diet | Obesogenic diet-fed rats | SREBP1; SREBP1, CPT1a; FAS |
● Reduced obesogenic diet-induced hepatic steatosis; ● Activated AMPK. |
[49] | miR-33↓ miR-122↓ |
250 mg/kg once | Gavage | HFD-fed grass carp | / | ● Decreased TG accumulation by reducing de novo lipogenesis and enhancing lipolysis and β-oxidation. | ||
miR-539↑ | 30 mg/kg for 6 weeks | Diet | [ | Obesogenic diet-fed rats | 29 | ] | |||||||||
SP1 | ● Inhibited de novo lipogenesis. | [ | 50 | ] | Green tea extract | miR-34a↓ miR-194↑ |
500 mg/kg for 12 weeks (5 days/week) | Gavage | HFD-fed mice | Sirt1, PPARα, INSIG2; HMGCS, APOA5 | ● Protected against NAFLD development by altering lipid metabolism, increasing gene expression involved in triglycerides and fatty acid catabolism, and decreasing uptake and lipid accumulation. | ||||
miR-155↑ | 25 μM for 1–8 days | Cell culture | [ | 3T3-L1 pre-adipocyte cells | 30 | ] | |||||||||
CEBP/α | ● Inhibited adipogenesis. | [ | 51 | ] | miR-335↓ | 500 mg/kg for 12 weeks (5 days/week) | Gavage | HFD-fed mice | |||||||
Zerumbone | FOXO1, GSK3β | ![]() | ● Reduced weight gain, adiposity and inflammation; | miR-46b↓ | 25 μM for 48 h; diet containing 0.025% zerumbone for 8 weeks |
Cell culture; diet | ● Increased energy expenditure; ● Improved insulin sensitivity. |
[31] | |||||||
3T3-L1 fibroblasts; | HFD-fed mice | Sirt1 | ● Induced AMPK activation and phosphorylation of acetyl-CoA carboxylase; | ● Ameliorated diet-induced obesity and inhibited adipogenesis. | Guarana extract | miR-27b↓ miR-34b↓ miR-760↓ |
150 µg/mL for 48 h | Cell culture | 3T3-L1 pre-adipocyte cells | Wnt3a, Wnt1, Wnt10b | ● Anti-adipogenic effect. | [32] | |||
Lychee pulp phenolics | miR-33↓ miR-122↓ |
500 mg/kg for 10 weeks | Gavage | HFD-fed mice | ABCA1, ABCG1, NPC1; FAS, ACC1, ACC2, SCD1, ACLY |
● Hypolipidemic; ● Repressed fatty acid synthesis and promoting fatty acid β-oxidation and cholesterol efflux in the liver; ● Decreased body fat accumulation; ● Ameliorated lipid metabolism. |
[33] | ||||||||
Mulberry fruit extract | miR-33↓ | Diet containing 0.4% mulberry fruit extract for 4 weeks | Diet | High cholesterol/cholic acid diet-fed rats | / | ● Promoted serum high-density lipoprotein cholesterol levels; ● Decreased serum and hepatic cholesterol, serum low-density lipoprotein cholesterol, and fecal bile acid levels. |
[34] | ||||||||
Mulberry leaf extract | miR-34a↓ | 3 mg/mL for 24 h | Cell culture | Glucolipotoxicity-induced HepG2 cells | Sirt1 | ● Reduced liver fat accumulation; ● Decreased inflammatory responses and steatohepatitis; ● Exerted anti-glucolipotoxicity effects. |
[35] | ||||||||
Moringa oleifera leaf extract | miR-21a↓ miR-103↓ miR-122↓ miR-34a↓ |
9.375 mg/d for 8 weeks | Gavage | HFD-fed mice | / | ● Improved ITT and decreased SREBP1c hepatic protein, while Sirt1 increased; ● Reduced insulin resistance, de novo lipogenesis, hepatic inflammation, and ER stress; ● Prevented progression of liver damage in a model of NASH. |
[36] | ||||||||
Portulaca oleracea extract | miR-122↓ | 25, 50, 100 mg/kg/d for 7 days | Gavage | Acute alcoholic liver injury rats | / | ● Decreased content of NO and MDA; ● Increased antioxidant capacity; ● Relieved the inflammatory injury; ● Improved the lipid metabolism disorder. |
[37] | ||||||||
[ | 52 | ] | ● Reduced the ethanol-elevated serum level of ALT, AST, ALP, and TG; | ● Enhanced activities of SOD and GSH-Px; | miR-33↓ miR-34a↓ |
Diet containing 0.8% portulaca oleracea L. extract for 4 weeks | Diet | High-cholesterol diet-fed rats | / | ● Improved serum, liver, and fecal lipid profiles; ● Promoted cholesterol efflux and bile acid synthesis; ● Enhanced hepatic AMPK activity. |
[38] | ||||
Rosmarinus officinalis extract | miR let-7f-1↑ | 30 μg/mL for 35 days | Cell culture | Human primary omental pre-adipocytes and adipocytes | / | ● Decreased triglyceride accumulation; ● Increased glycerol release; ● Stimulated lipolytic activity in differentiating pre-adipocytes and mature adipocytes; ● Modulated the adipocyte life cycle at different levels. |
[39] |