Table 3.

Effects of Functional Berry Extracts on Liver and Other Tissues of NAFLD Animal Models

ReferenceExtract interventionAnimal modelIntervention and animal groupsEffects on liver of experimental groups that received berry extract vs NAFLDI group1Effects on other tissues of experimental groups that received berry extract vs NAFLDI group1
Al Zarzour et al, 20171Phyllanthus niruri, MeOH-W extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW)

  • 2. HFD (ND + 10% margarine (wt/wt), 10% ghee fat (wt/wt), 1% CHOL and 0.5% cholic acid) + DW (10 mL kg-1 BW), OG

  • 3. HFD + metformin 500 mg kg-1 BW (10 mL kg-1 BW), OG

  • 4. HFD + BE (W): 10 mL kg-1 BW, OG

  • 5. HFD + BE (50% MeOH, 50% W): 10 mL kg-1 BW, OG

  • 6. HFD + BE (MeOH): 10 mL kg-1 BW, OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Dose-response assay:

  • 1. ND + DW (10 mL kg-1 BW), OG

  • 2. HFD + DW (10 mL kg-1 BW), OG

  • 4. HFD + BE (50% MeOH -50% W) 1000 mg kg-1 (10 mL kg-1 BW), OG

  • 5. HFD + BE (50% MeOH-50% W) 500 mg kg-1 (10 mL kg-1 BW) OG

  • 6. HFD + BE (50% MeOH-50% W) 250 mg kg-1 (10 mL kg-1 BW) OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 4, 5, 6: ↓ steatosis, TC and MDA levels

  • Group 5: ↓ LW

  • Groups 5, 6: ↓ lobular inflammation, TG

  • Dose response assay: HFD + BE (50% MeOH-50% W)

  • ↓ LW, lobular inflammation and steatosis

  • Groups 4, 5, 6: ↓ visceral fat, Ins, HOMA-IR, TC, FFA, and LDL (serum)

  • Groups 5, 6: ↓ ALT (serum)

  • Group 5: ↓ ALP (serum)

  • Dose response assay:

  • Groups 4, 5, 6: ↓ TC, LDL, ALT and Ins, ↑AST to ALT ratio (serum)

  • Groups 4, 5: ↓ ALP, Glu (serum)

  • Group 4: ↓ visceral fat

Tavares et al, 20202Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V, IG

  • 3. HFD+ BE 300 mg kg-1 d-1, IG

  • NAFLDI: 8 wk

  • TP: 4 wk

  • ↓ LW and lipid accumulation

  • ↓ MDA and carbonyl levels

  • ↓ SOD, GPx, and CAT enzymatic activity

  • ↓ BW

  • ↓ TG, TC, LDL, VLDL, and ALT (serum)

De Oliveira et al,20153Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. ND + 300 mg kg-1 d-1 BE, IG

  • 3. HFD (60% fat)

  • 4. HFD + 300 mg kg-1 d-1 BE, IG

  • TP: 12 wk

  • ↓ LW and steatosis

  • ↓ TC, TG, MDA, and carbonyl protein levels

  • ↑ pAMPK, pACACA to ACACA ratio, ABCG5 and ABCG8 ↓ HMGCR, and SREBP-1c

  • ↑ SOD, CAT, and GPx enzymatic activity

  • ↓ BW, epididymal and retroperitoneal adipose tissues weights

  • ↓ TC, TG, LDL, VLDL (serum)

  • ↓ Leptin (plasma)

  • ↑ Adiponectin (plasma)

Morrison et al, 20154Vaccinium myrtillus L. extract
  • M: Female E3L mice

  • A/W: –

  • 1. WTD (15% CCB, 1% CO, 40.5% SUC, 20% acid casein, 10% CS, and 6.2% CEL) + 1% CHOL

  • 2. WTD

  • 3. WTD+ 1% CHOL+ 0.1% BE

  • NAFLDI: 4 wk

  • TP: 16 wk

  • ↓ Macro- and microvesicular steatosis

  • ↓ Hepatocellular damage (CK-18)

  • ↓ Inflammatory cell aggregates

  • ↓ Intrahepatic CHOL crystal formation

  • ↓ Collagen and TC, ↓ Col1a1 and Mpo, ↓ p65-NF-κB activity

Park et al, 20175Aronia melanocarpa ethanolic extract
  • M: Male C57BL/6N mice

  • A/W: 5 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + BE 50 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW

  • ↓ Lipid deposition, TG and FAS

  • Pparg2

  • Fabp4 and Lpl (mRNA and protein)

  • ↑ SOD and TEAC enzymatic activity

  • ↓ BW

  • ↓ AST, ALT, and leptin (serum)

Park et al, 201936Water extract of mulberry and silk amino acids
  • M: Male SD rats

  • A/W: 11 wk; 306 ± 20 g

  • 1. ND

  • 2. HFD (51% fat) + CEL 0.6%

  • 3. HFD + BE and SA (1:3) 200 mg kg-1 BW per day

  • 4. HFD + BE and SA (1:3) 600 mg kg-1 BW per day

  • 5. HFD + BE and SA (1:5) 200 mg kg-1 BW per day

  • 6. HFD + BE and SA (1:5) 600 mg kg-1 BW per day

  • TP: 12 wk

  • Groups 3, 4, 5, 6: ↓ LW, ballooning degeneration, macrophage infiltration, ↓ TNF-α, Tnfa,

  • Groups 4 & 6: ↓ Liver cellular damage, liver size and fat accumulation, ↑ pAKT/AKT, pACACA/ACACA and ACACA, ↓ Cyp2e1

  • Groups 4, 5, 6: ↓ TG and TC and MDA levels, Il1b, Fasn and Srebf1, ↑ glycogen levels, Cpt1a

  • Groups 3, 4, 6: ↑ GSH-peroxidase enzymatic activity and GSH levels

  • Group 4: ↑ SOD enzymatic activity

  • Groups 3, 4, 5, 6: ↓ AST and γ-GPT, HOMA-IR (serum), BW gain, ↓ AUC (Glu & Ins)

  • Groups 3, 4, 6: ↑ HDL

  • Groups 4, 5, 6: ↓ TNFa, ↓Glu and nonesterified FAs (serum)

  • Groups 4, 6: ↓ LDL and Ins (serum)

  • Groups 5, 6: ↓ BW, epididymal and retroperitoneal fat mass, TG

  • Group 6: ↓ ALT (serum)

  • Group 3, 4: ↑ Bacteroidales to Clostridiales ratio

  • Group 4: ↑ gut bacterial species

Xu et al, 201730Morus alba L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + β-glucan 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • 5. HFD  +  β-glucan 200 mg kg-1 d-1 + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • Groups 4, 5: ↓ LW

  • Group 5: ↓ TG and TC, ↑ GST, GSSG, Cu/Zn-SOD enzymatic activity, GSH/GSSG and ROS content

  • Groups 4, 5: ↓ BW, ↓ TG, FFA, CHOL, LDL-c, leptin, AST, ALT, IL1b, IL4, and TNF-α (serum), ↓ perineal fat mass

  • Group 5: ↓ AUC and fasting Glu and Ins

Ann et al, 201532Morus alba L. ethanolic extract
  • M: C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + DW

  • 2. HFD (45% kcal fat) + DW

  • 3. HFD + BE 133 mg kg-1 d-1 5 times/wk OG

  • 4. HFD + BE 666 mg kg-1 d-1 5 times/wk OG

  • TP: 12 wk

  • Groups 3, 4: ↓ fat accumulation, Lpl, Srebf1, Fabp4, Ucp2, Ppara, ↓ SREBP-1c and ACTA2

  • Group 4: ↓ Nr1h3, Fasn, Cebpa, Col1a1, ↓ LPL, 4-HNE, nuclear NRF2, HO-1, GPx enzymatic activity

  • Groups 3, 4: ↑ HDL, ↓TG, TC, LDL, AI, 4-HNE, ↓ GOT, GPT, GPx, and HO-1 plasma enzymatic activity

  • Group 3: ↓ epididymal and retroperitoneal fat

Hu et al, 202033Morus alba L. methanolic extract
  • M: Male SD rats

  • A/W: 100-120 g; 4 wk

  • 1. ND

  • 2. OAD (ND + 1% OA + 33% SUC)

  • 3. OAD + fenofibrate 50 mg kg-1 d-1 OG

  • 4. OAD + BE 50 mg kg-1 d-1 OG

  • 5. OAD + BE 100 mg kg-1 d-1 OG

  • 6. OAD + BE 200 mg kg-1 d-1 OG

  • TP: Unknown

  • Groups 4, 5, 6: ↓ TC and TG, ↓ no. of lipid droplets and histological lesion, ↓ Hmgcr and miR-33a

  • Groups 5, 6: ↓ Srebf2

  • Groups 4, 5: ↑ Cyp7a1

Lee et al, 202034Morus alba fermented extract
  • M: Male C57BL/6N mice

  • A/W: 8 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V 10 mg/kg (OO + 1% DMSO) 5 times wk-1, OG

  • 3. HFD+ orlistat 10 mg kg-1 5 times wk-1, OG

  • 4. HFD + BE 50 mg kg-1 5 times wk-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ no. and size of lipid droplets, and steatosis total score

  • Pparg, Fabp4, Fasn, Klf2, Nos2, Ptgs2, Il1b, Il6, Tnfa, Nfkb, Atg4b, Atg5, Atg7, and Atg12; ↓ p-JNK, p-p38, p-mTOR, beclin, and LC3 levels; ↑ p-PI3K, p-AKT, and p-ERK levels

↓ BW
Ma et al, 201835Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 8 wk; 275 ± 25 g

  • 1. ND

  • 2. ND + BE

  • 3. HFD (60% kcal from fat)

  • 4. HFD + BE prevention (10 g kg-1 d-1) 4 mo + BE therapeutic (10 g kg-1 d-1) 2 mo OG

  • 5. HFD + BE therapeutic (10 g kg-1 d-1) 3 mo OG

  • NAFLDI: 3 mo HFD. Immediately after STZ/citrate buffer (CT) IP (40 mg kg-1)

  • TP: 6 mo

Groups 4, 5: ↓ Srebf1 and Mlxipl Group 4: ↓ Fasn
  • Groups 4, 5: ↓ fasting Glu and HOMA-IR, ↑ Ins, ↓ TG, FFA, AST, ALT (serum)

  • Group 4: ↓ TC (serum)

Park et al, 20199Rubus fruticosus ethanolic extract
  • M: Male SD rats

  • A/W: 11 wk; 195 ± 11 g

  • 1. ND

  • 2. HFD (51% kcal fat) + dextrin (450 mg kg-1 BW per day)

  • 3. HFD + milk thistle extracts (150 mg kg-1 BW per day)

  • 4. HFD + 50% BE leaf (450 mg kg-1 BW per day)

  • 5. HFD + 50% BE fruit (450 mg kg-1 BW per day)

  • 6. HFD + BE leaf and fruit (2:1) (150 mg kg-1 BW per day)

  • TP: 12 wk

  • Groups 4, 5, 6: ↓ TG, MDA, and TNFa, Acaca, Fasn, TNFa; ↑glycogen levels, ↑ SOD enzymatic activity

  • Groups 4, 6: ↓ enlargement of the nucleus and the cell size, macrophage infiltration, CHOL, Srebf1 and Il1b, ↑ Cpt1a

  • Group 6: ↑ GSH enzymatic activity

  • Groups 4, 5 & 6: ↓ epididymal and retroperitoneal fat, ↓Serum levels of AST, ALT, TC, LDL, nonesterified FFAs, AUC (Glu & Ins)

  • Groups 4, 5: ↓ TG (serum)

  • Groups 4, 6: ↓ Ins serum levels, HOMA-IR, ↑ % goblet cells, ↑ Akkermansia and Lactobacillus population in feces

  • Group 6: ↑ intestinal surface area

Peng et al, 20176Morus alba aqueous extract
  • M: Male Wistar rats

  • A/W: 220 ± 10 g

  • 1. ND

  • 2. HFD (ND + 20% fat + 2% CHOL)

  • 3. HFD + BE 0.5%

  • 4. HFD + BE 1%

  • 5. HFD + BE 2%

  • NAFLDI: 4 wk

  • TP: 10 wk

  • Groups 3, 4, 5: ↓ FASN, HMGCR, and TBARS; ↑ CPT1

  • Groups 4, 5: ↓ TC, TG levels, and lipid accumulation; ↓ AGPAT; ↑ SOD enzymatic activity; ↑ PPARa

  • Groups 3, 4, 5: ↓ BW, ↓ total peripheral and total body fat, ↓ TNF-α and leptin serum levels

  • Groups 4, 5: ↓ ALT, TG, TC, and LDL (serum)

  • Group 5: ↓ perineal, mesenteric, subcutaneous, and groin fat; ↑ adiponectin (serum)

Song et al, 201631Morus nigra L. ethanolic extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. LFD + saline 100 mg kg-1 d-1 OG

  • 2. HFD (45% fat) + saline 100 mg kg-1 d-1 OG

  • 3. HFD + BE 100 mg kg-1 d-1 OG

  • TP: 14 wk

  • ↓ Steatosis grade

  • ↓ TG and TC levels, ↓ Gk and Fads2, ↑ Adipor2 and Insig1

  • ↓ BW, ↓ relative perineal and epididymal fat weight

  • ↓ TC, LDL, AST, ALT, Glu, Ins (serum), HOMA-IR, HOMA-IS, adiponectin (serum); ↑ leptin (serum)

Yang et al, 201837Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 240-260 g

  • 1. SD + DW, OG

  • 2. HFD + DW, OG

  • 3. HFD + BE 100 mg kg-1 BW, OG

  • 4. HFD + BE 200 mg kg-1 BW, OG

  • TP: 10 wk

  • ↓ LW, intracellular lipid accumulation, TG levels, Srebf1, Fasn, Acaca, and Scd1

  • ↓ Mitochondrial ROS production and NADPH oxidase activity

  • ↓ MDA, 4-HNE, and NOX4, ↑ SOD enzymatic activity, ↑ mitochondrial complex-I and complex-II activities, ↑ ATP content

↓ TG, TC, LDL, AST, and ALT, ↑ HDL (serum)
Fotschki et al, 202138Rubus idaeus L. acetone-water extract
  • M: Male Wistar rats

  • A/W: 8 wk; 165.3 ± 1.43 g

  • 1. HFD (23% fat)

  • 2. HFD + BE 0.64%

  • 3. HFD + BE 0.64% + fructo-oligosaccharides 3%

  • 4. HFD + BE 0.64% + pectins 3%

  • TP: 12 wk

  • Groups 2, 3, 4: ↓ ballooning and portal inflammation, ↓ Pparg

  • Groups 2, 3: ↓ lobular inflammation, ↓ MDA levels, ↓ Il6

  • Groups 3, 4: ↓ steatosis, ↓ fat content

  • Group 3: ↑ LW, ↓ TC and TG levels, ↓ Ppara and Angplt4

  • Groups 2, 3: ↓ AST (plasma)

  • Groups 3, 4: ↑ cecum mass

  • Group 3: ↓ TG (plasma)

  • Group 4: ↓ cecum pH

Li et al, 201439Rubus aleaefolius Poir extract
  • M: Male Sprague-Dawley rats

  • A/W: 8 wk; 180-200 g

  • 1. ND + 10 mL kg-1 DW

  • 2. mHFD (10% lard + 2 % CHOL) + DW 10 mL kg-1 OG

  • 3. mHFD + BE 1.44 g kg-1 BW per day, OG

  • 4. mHFD + BE 0.72 g kg-1 BW per day, OG

  • NAFLDI: 8 wk

  • TP: 28 d

↓ Fat accumulation, hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci, ↓ Acaca, Fasn, Cpt1a↓ TG, TC, LDL; ↑ HDL (serum)
Nam et al, 201440Rubus coreanus
  • M: Male C57BL/6 mice

  • A/W: –

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD+ BE 100 mg kg-1

  • TP: 10 wk

↓ LW, TG, and TC, Nr1h3, Srebf1, Acaca, Cd36, Fasn, FASN, and HMGCR reductase activity; ↑CPT activity
  • ↓ BW, ↓ epididymal fat mass

  • ↓ AST, ALT, TC, TG, LDL, and leptin plasma levels

Zhao et al, 201341Rubus aleaefolius Poir. extract
  • M: Male SD

  • A/W: 8 wk; 180-200 g

  • 1. CT + DW, IG

  • 2. HFD (10% lard + 2% CHOL) + DW, IG

  • 3. HFD + polyene phosphatidylcholine 76 mg kg-1 BW per day IG

  • 4. HFD + BE 1.44 g kg-1 BW per day IG

  • 5. HFD + BE 0.72 g kg-1 BW per day IG

  • NAFLDI: 8 wk

  • TP: 7 d

  • Groups 4, 5: ↓ hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci

  • ↓ Nfkb, Tnfa, Ptgs2, and Il6 protein and mRNA expression

Groups 4, 5: ↓ BW ↓ ALT, AST, GGT, ALP, TC, TG, and LDL serum levels
Bae et al, 201742Lycium chinense aqueous extract
  • M: Male C57BLS/J-m mice

  • A/W: 7 wk

  • 1. ND

  • 2. MCD + PBS OG

  • 3. MCD + betaine 10 mg kg-1 d-1, OG

  • 4. MCD + BE 100 mg kg-1 d-1, OG

  • 5. MCD + BE 200 mg kg-1 d-1, OG

  • 6. MCD + BE 400 mg kg-1 d-1, OG

  • TP: 4 wk

  • Group 6: ↓ LW

  • Groups 5, 6: ↓ lipid accumulation, ↓ TG, GSH, and MDA levels, F4/80, Itgax, Ccl2, Icam1, Tnfa, Il6, Il1b, Tgfb, Col1a1, Acta2; ↑ SOD and CAT enzymatic activity, pERK; ↓ pJNK

↓ AST and ALT plasma levels
Glisan et al, 201643Vaccinium macrocarpon acetone:water:acetic acid (80:19.9:0.1, v:v:v) extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. HFD (60% kcal from fat)

  • 2. HFD + BE 0.8%

  • NAFLDI: 11 wk

  • TP: 10 wk

↓ Degree of lipidosis and lipid droplets area, ↓ TNF-α, CCL2, and IL1b; ↓ Tlr4, NFKB, Tnfa, Il1b, Ucp2, Ptgs2, Ccr2, Ccl3, Nlrp3, Casp1, Ppara, Txnip↓ FFA, IL-1b, ALT plasma levels
Huang et al, 201744Phyllantus emblica L. aqueous extract
  • M: Male SD rats

  • A/W: 160 ± 10 g

  • 1. ND

  • 2. HFD (40% fat)

  • 3. HFD + GA 100 mg kg-1, OG

  • 4. HFD + BE 125 mg kg-1 BW, OG

  • 5. HFD + BE 250 mg kg-1 BW, OG

  • 6. HFD + BE 500 mg kg-1 BW, OG

  • TP: 20 wk

  • Groups 4, 5, 6: ↓ Srebf1, ↑ CAT and GST enzymatic activity

  • Group 5: ↑ Ppara

  • Group 6: ↓ lipid droplets and fat deposition, ↓ Nr1h3, ↑ GRd enzymatic activity

  • Groups 4, 5, 6: ↓ BW, ↓ AST (serum), ↑ adiponectin (peritoneal fat)

  • Groups 5, 6: ↓ peritoneal and epididymal fat weight

  • Group 6: ↓ ALT and LDL (serum)

Tung et al, 201852Phyllanthus emblica L. reverse osmosis aqueous extract
  • M: Male C57BL/6JNarl mice with specific pathogen-free conditions

  • A/W: 5 wk; 20 ± 2 g

  • 1. ND

  • 2. MCD

  • 3. MCD + GA 100 mg kg-1 BW per day OG

  • 4. MCD + BE 125 mg kg-1 BW per day OG

  • 5. MCD + BE 250 mg kg-1 BW per day OG

  • 6. MCD + BE 500 mg kg-1 BW per day OG

  • TP: 4 or 8 wk

  • Groups 4, 5, 6: ↑ GST, SOD, ↓CAT activity (wk 8), ↓Cyp2e1, Tnfa (weeks 4 and 8), ↓Il1b (week 8)

  • Groups 4, 6: ↓ TBARs levels (week 4)

  • Group 5: ↓ TBAR levels (week 8)

  • Group 6: ↓ GPx enzymatic activity (weeks 4 and 8)

  • Group 4, 5, 6: ↓ AST and ALT (weeks 4 and 8), ↑ TG serum (week 8)

  • Group 6: ↑ TG serum levels (week 4)

Xiao et al, 201845Lycium barbarum Lynn aqueous extract
  • M: Male and female C57BL/6N mice

  • A/W: 20-25 g

  • 1. ND

  • 2. MCD

  • 3. ND + BE 1 mg/kg/ OG

  • 4. MCD + BE 1 mg kg-1 d-1 OG

  • NAFLDI: 3 wk

  • TP: 3 wk

  • ↓ NAS score and apoptotic cells number

  • ↓ ACTA2, SMAD2, TGFb1, p-SMAD2, MDA, TXNIP, TNF-α, IL10, NFKB p50, NFKBIA, BAX-1, cytochrome c, CYP2E1, cleaved CASP1, ASC, NLRP3, and NLRP6, ↑ CAT, GPx and BCL-2

  • ↑ BW

  • ↓ IL-18 and IL-1b

Pak et al,201223Vitis coignetiae Pulliat aqueous extract
  • M: Male Wistar rats

  • A/W: 6 wk

  • 1. ND

  • 2. CD HFD

  • 3. CD HFD + BE 100 mg kg-1 d-1 OG

  • 4. CD HFD + BE 300 mg kg-1 d-1 OG

  • NAFLDI: 13 wk (4 wk HFD+ 9 wk HFD and NaNO₂ 40 mg kg-1 d-1 IP)

  • TP: weeks 10 to 13

  • Groups 3, 4: ↑ relative LW, ↓ mitochondria ROS derivation, ↓ MPO activity, ↓ NFKB p65

  • Group 4: ↓ % of fibrosis area

  • Group 3, 4: ↓ ALT plasma levels

  • Group 4: ↑SOD enzymatic activity (serum)

Al Zarzour et al, 201847Phyllanthus niruri methanolic extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW) OG

  • 2. HFD (8.23% margarine (wt/wt), 8.23% ghee fat (wt/wt), 0.82% CHOL, and 0.41% cholic acid) + DW (10 mL kg-1 BW) OG

  • 3. HFD + metformin 500 mg kg-1 BW OG

  • 4. HFD + BE 1000 mg kg-1 BW OG

  • NAFLDI: 5 wk

  • TP: 3 wk

  • ↓ Micro- and macrovesicles and fibrosis

  • Pparg, Col1a1, and Slc10a2

  • ↑ Adiponectin serum levels

  • ↓ TNF-α, RBP4, vaspin, and IL-6 (serum)

Nanashima et al, 202050Ribes nigrum L. commercial extract
  • M: ovariectomized and sham surgery female SD rats

  • A/W: 12 wk; 249.7 ± 10.2 g

  • 1. ND ovariectomized rats (AIN-93M)

  • 2. ND sham surgery rats (AIN-93M)

  • 3. Ovariectomized rats: ND (AIN-93M) + BE 3%

  • TP: 12 wk

  • ↓ Adipocyte diameter

  • Tnfa, Il6, and Il1b

  • ↓ BW

  • ↓ Visceral fat weight

  • ↓ TG, TC, LDL, adiponectin, and leptin (serum)

Santos et al, 201748Vitis vinifera L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + W, OG

  • 2. HFD (60% fat) + W, OG

  • 3. ND + BE 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ liver fat density

  • ↓ TC, TG, and glycogen levels

  • ↓ MDA and carbonyl protein levels

  • ↑ p-IRS-1, pAKT, PI3-1K, SLC2A2, pLKB1, pACACA, HMGCR, and pAMPK/AMPK ratio, ABCG5 and ABCG8, ↓ SREBP-1c,↑ CAT, GPx, and SOD enzymatic activity

  • ↓ BW

  • ↓ Epididymal and retroperitoneal fat mass

  • ↓ Glu and Ins, HOMA-IR (serum)

Charradi et al, 201451Vitis vinifera ethanolic extract
  • M: Male Wistar rats

  • A/W: 210-230 g

  • 1. ND + 10% ethanol IP (daily)

  • 2. HFD (39% kcal fat) + ethanol 10% IP (daily)

  • 3. ND + BE 500 mg kg-1 d-1 BW IP

  • 4. HFD + BE 500 mg kg-1 d-1 BW IP

  • TP: 6 wk

  • ↓ Relative LW, macrovesicular steatosis, dilatation, and fat accumulation within hepatocytes and sinusoids, ↓ TG, TC, LDL/HDL ratio, TPL, (LDL+VLDL) to HDL ratio, Apo B to Apo AI ratio, MDA, carbonyl protein, and GSSG levels; ↑ levels of ApoAI, GSH, and GSH to GSSG ratio, ↑ GPx and total-, Cu/Zn-, Mn-, and Fe-SOD enzymatic activity

  • ↓ ALAT, ASAT, and lipase activity

  • ↑ Liver alcohol dehydrogenase activity, ↓ Zn depletion

De Bem et al, 201846Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male Wistar rats

  • A/W: 180-200 g

  • 1. ND

  • 2. ND + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 3. ND + BE 200 mg kg-1 d-1 IG

  • 4. ND + EXE + BE 200 mg kg-1 d-1 IG

  • 5. HFD (45% kcal fat)

  • 6. HFD + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 7. HFD + BE 200 mg kg-1 d-1 IG

  • 8. HFD + EXE + BE 200 mg kg-1 d-1 IG

  • NAFLDI: 5 wk (streptozotocin/citrate buffer [CT] IP [35 mg kg-1] once in wk 3)

  • TP: 4 wk

  • Groups 7, 8: ↓ LW and steatosis, TC, TG, MDA, protein carbonyl and 8-isoprostane levels; ↑ ABCG5, pAMPK, pLKB1 to LKB1 ratio, pAMPK/AMPK, pACC/ACC; ↓ SREBP-1c, ACACA, HMGCR; ↑ SOD and GPx enzymatic activity

  • Group 7: ↑ pACC

  • Group 8: ↓ glycogen levels, AMPK

  • Groups 7, 8: ↓ TC, TG, VLDL, ALT, MDA, and protein carbonyl (serum)

  • Group 8: ↓ AST (serum)

Freitas et al, 201649Euterpe edulis oil extract or defatted extract
  • M: Male Wistar rats

  • A/W: 4 wk; 85 ± 5 g

  • 1. ND

  • 2. HFD (50% fat)

  • 3. HFD + BE oil 4%

  • 4. HFD + BE pulp 5%

  • 5. HFD + BE pulp 10%

  • 6. HFD + defatted BE 5%

  • 7. HFD + defatted BE 10%

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 3, 4, 5, 6: ↓ CAT, SOD enzymatic activity

  • Groups 3, 4, 6: ↓ TBARs

  • Groups 4, 6: ↓ inflammatory infiltration and hepatocytes nucleus, GST enzymatic activity

Group 6: ↑ TC serum levels
ReferenceExtract interventionAnimal modelIntervention and animal groupsEffects on liver of experimental groups that received berry extract vs NAFLDI group1Effects on other tissues of experimental groups that received berry extract vs NAFLDI group1
Al Zarzour et al, 20171Phyllanthus niruri, MeOH-W extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW)

  • 2. HFD (ND + 10% margarine (wt/wt), 10% ghee fat (wt/wt), 1% CHOL and 0.5% cholic acid) + DW (10 mL kg-1 BW), OG

  • 3. HFD + metformin 500 mg kg-1 BW (10 mL kg-1 BW), OG

  • 4. HFD + BE (W): 10 mL kg-1 BW, OG

  • 5. HFD + BE (50% MeOH, 50% W): 10 mL kg-1 BW, OG

  • 6. HFD + BE (MeOH): 10 mL kg-1 BW, OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Dose-response assay:

  • 1. ND + DW (10 mL kg-1 BW), OG

  • 2. HFD + DW (10 mL kg-1 BW), OG

  • 4. HFD + BE (50% MeOH -50% W) 1000 mg kg-1 (10 mL kg-1 BW), OG

  • 5. HFD + BE (50% MeOH-50% W) 500 mg kg-1 (10 mL kg-1 BW) OG

  • 6. HFD + BE (50% MeOH-50% W) 250 mg kg-1 (10 mL kg-1 BW) OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 4, 5, 6: ↓ steatosis, TC and MDA levels

  • Group 5: ↓ LW

  • Groups 5, 6: ↓ lobular inflammation, TG

  • Dose response assay: HFD + BE (50% MeOH-50% W)

  • ↓ LW, lobular inflammation and steatosis

  • Groups 4, 5, 6: ↓ visceral fat, Ins, HOMA-IR, TC, FFA, and LDL (serum)

  • Groups 5, 6: ↓ ALT (serum)

  • Group 5: ↓ ALP (serum)

  • Dose response assay:

  • Groups 4, 5, 6: ↓ TC, LDL, ALT and Ins, ↑AST to ALT ratio (serum)

  • Groups 4, 5: ↓ ALP, Glu (serum)

  • Group 4: ↓ visceral fat

Tavares et al, 20202Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V, IG

  • 3. HFD+ BE 300 mg kg-1 d-1, IG

  • NAFLDI: 8 wk

  • TP: 4 wk

  • ↓ LW and lipid accumulation

  • ↓ MDA and carbonyl levels

  • ↓ SOD, GPx, and CAT enzymatic activity

  • ↓ BW

  • ↓ TG, TC, LDL, VLDL, and ALT (serum)

De Oliveira et al,20153Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. ND + 300 mg kg-1 d-1 BE, IG

  • 3. HFD (60% fat)

  • 4. HFD + 300 mg kg-1 d-1 BE, IG

  • TP: 12 wk

  • ↓ LW and steatosis

  • ↓ TC, TG, MDA, and carbonyl protein levels

  • ↑ pAMPK, pACACA to ACACA ratio, ABCG5 and ABCG8 ↓ HMGCR, and SREBP-1c

  • ↑ SOD, CAT, and GPx enzymatic activity

  • ↓ BW, epididymal and retroperitoneal adipose tissues weights

  • ↓ TC, TG, LDL, VLDL (serum)

  • ↓ Leptin (plasma)

  • ↑ Adiponectin (plasma)

Morrison et al, 20154Vaccinium myrtillus L. extract
  • M: Female E3L mice

  • A/W: –

  • 1. WTD (15% CCB, 1% CO, 40.5% SUC, 20% acid casein, 10% CS, and 6.2% CEL) + 1% CHOL

  • 2. WTD

  • 3. WTD+ 1% CHOL+ 0.1% BE

  • NAFLDI: 4 wk

  • TP: 16 wk

  • ↓ Macro- and microvesicular steatosis

  • ↓ Hepatocellular damage (CK-18)

  • ↓ Inflammatory cell aggregates

  • ↓ Intrahepatic CHOL crystal formation

  • ↓ Collagen and TC, ↓ Col1a1 and Mpo, ↓ p65-NF-κB activity

Park et al, 20175Aronia melanocarpa ethanolic extract
  • M: Male C57BL/6N mice

  • A/W: 5 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + BE 50 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW

  • ↓ Lipid deposition, TG and FAS

  • Pparg2

  • Fabp4 and Lpl (mRNA and protein)

  • ↑ SOD and TEAC enzymatic activity

  • ↓ BW

  • ↓ AST, ALT, and leptin (serum)

Park et al, 201936Water extract of mulberry and silk amino acids
  • M: Male SD rats

  • A/W: 11 wk; 306 ± 20 g

  • 1. ND

  • 2. HFD (51% fat) + CEL 0.6%

  • 3. HFD + BE and SA (1:3) 200 mg kg-1 BW per day

  • 4. HFD + BE and SA (1:3) 600 mg kg-1 BW per day

  • 5. HFD + BE and SA (1:5) 200 mg kg-1 BW per day

  • 6. HFD + BE and SA (1:5) 600 mg kg-1 BW per day

  • TP: 12 wk

  • Groups 3, 4, 5, 6: ↓ LW, ballooning degeneration, macrophage infiltration, ↓ TNF-α, Tnfa,

  • Groups 4 & 6: ↓ Liver cellular damage, liver size and fat accumulation, ↑ pAKT/AKT, pACACA/ACACA and ACACA, ↓ Cyp2e1

  • Groups 4, 5, 6: ↓ TG and TC and MDA levels, Il1b, Fasn and Srebf1, ↑ glycogen levels, Cpt1a

  • Groups 3, 4, 6: ↑ GSH-peroxidase enzymatic activity and GSH levels

  • Group 4: ↑ SOD enzymatic activity

  • Groups 3, 4, 5, 6: ↓ AST and γ-GPT, HOMA-IR (serum), BW gain, ↓ AUC (Glu & Ins)

  • Groups 3, 4, 6: ↑ HDL

  • Groups 4, 5, 6: ↓ TNFa, ↓Glu and nonesterified FAs (serum)

  • Groups 4, 6: ↓ LDL and Ins (serum)

  • Groups 5, 6: ↓ BW, epididymal and retroperitoneal fat mass, TG

  • Group 6: ↓ ALT (serum)

  • Group 3, 4: ↑ Bacteroidales to Clostridiales ratio

  • Group 4: ↑ gut bacterial species

Xu et al, 201730Morus alba L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + β-glucan 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • 5. HFD  +  β-glucan 200 mg kg-1 d-1 + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • Groups 4, 5: ↓ LW

  • Group 5: ↓ TG and TC, ↑ GST, GSSG, Cu/Zn-SOD enzymatic activity, GSH/GSSG and ROS content

  • Groups 4, 5: ↓ BW, ↓ TG, FFA, CHOL, LDL-c, leptin, AST, ALT, IL1b, IL4, and TNF-α (serum), ↓ perineal fat mass

  • Group 5: ↓ AUC and fasting Glu and Ins

Ann et al, 201532Morus alba L. ethanolic extract
  • M: C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + DW

  • 2. HFD (45% kcal fat) + DW

  • 3. HFD + BE 133 mg kg-1 d-1 5 times/wk OG

  • 4. HFD + BE 666 mg kg-1 d-1 5 times/wk OG

  • TP: 12 wk

  • Groups 3, 4: ↓ fat accumulation, Lpl, Srebf1, Fabp4, Ucp2, Ppara, ↓ SREBP-1c and ACTA2

  • Group 4: ↓ Nr1h3, Fasn, Cebpa, Col1a1, ↓ LPL, 4-HNE, nuclear NRF2, HO-1, GPx enzymatic activity

  • Groups 3, 4: ↑ HDL, ↓TG, TC, LDL, AI, 4-HNE, ↓ GOT, GPT, GPx, and HO-1 plasma enzymatic activity

  • Group 3: ↓ epididymal and retroperitoneal fat

Hu et al, 202033Morus alba L. methanolic extract
  • M: Male SD rats

  • A/W: 100-120 g; 4 wk

  • 1. ND

  • 2. OAD (ND + 1% OA + 33% SUC)

  • 3. OAD + fenofibrate 50 mg kg-1 d-1 OG

  • 4. OAD + BE 50 mg kg-1 d-1 OG

  • 5. OAD + BE 100 mg kg-1 d-1 OG

  • 6. OAD + BE 200 mg kg-1 d-1 OG

  • TP: Unknown

  • Groups 4, 5, 6: ↓ TC and TG, ↓ no. of lipid droplets and histological lesion, ↓ Hmgcr and miR-33a

  • Groups 5, 6: ↓ Srebf2

  • Groups 4, 5: ↑ Cyp7a1

Lee et al, 202034Morus alba fermented extract
  • M: Male C57BL/6N mice

  • A/W: 8 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V 10 mg/kg (OO + 1% DMSO) 5 times wk-1, OG

  • 3. HFD+ orlistat 10 mg kg-1 5 times wk-1, OG

  • 4. HFD + BE 50 mg kg-1 5 times wk-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ no. and size of lipid droplets, and steatosis total score

  • Pparg, Fabp4, Fasn, Klf2, Nos2, Ptgs2, Il1b, Il6, Tnfa, Nfkb, Atg4b, Atg5, Atg7, and Atg12; ↓ p-JNK, p-p38, p-mTOR, beclin, and LC3 levels; ↑ p-PI3K, p-AKT, and p-ERK levels

↓ BW
Ma et al, 201835Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 8 wk; 275 ± 25 g

  • 1. ND

  • 2. ND + BE

  • 3. HFD (60% kcal from fat)

  • 4. HFD + BE prevention (10 g kg-1 d-1) 4 mo + BE therapeutic (10 g kg-1 d-1) 2 mo OG

  • 5. HFD + BE therapeutic (10 g kg-1 d-1) 3 mo OG

  • NAFLDI: 3 mo HFD. Immediately after STZ/citrate buffer (CT) IP (40 mg kg-1)

  • TP: 6 mo

Groups 4, 5: ↓ Srebf1 and Mlxipl Group 4: ↓ Fasn
  • Groups 4, 5: ↓ fasting Glu and HOMA-IR, ↑ Ins, ↓ TG, FFA, AST, ALT (serum)

  • Group 4: ↓ TC (serum)

Park et al, 20199Rubus fruticosus ethanolic extract
  • M: Male SD rats

  • A/W: 11 wk; 195 ± 11 g

  • 1. ND

  • 2. HFD (51% kcal fat) + dextrin (450 mg kg-1 BW per day)

  • 3. HFD + milk thistle extracts (150 mg kg-1 BW per day)

  • 4. HFD + 50% BE leaf (450 mg kg-1 BW per day)

  • 5. HFD + 50% BE fruit (450 mg kg-1 BW per day)

  • 6. HFD + BE leaf and fruit (2:1) (150 mg kg-1 BW per day)

  • TP: 12 wk

  • Groups 4, 5, 6: ↓ TG, MDA, and TNFa, Acaca, Fasn, TNFa; ↑glycogen levels, ↑ SOD enzymatic activity

  • Groups 4, 6: ↓ enlargement of the nucleus and the cell size, macrophage infiltration, CHOL, Srebf1 and Il1b, ↑ Cpt1a

  • Group 6: ↑ GSH enzymatic activity

  • Groups 4, 5 & 6: ↓ epididymal and retroperitoneal fat, ↓Serum levels of AST, ALT, TC, LDL, nonesterified FFAs, AUC (Glu & Ins)

  • Groups 4, 5: ↓ TG (serum)

  • Groups 4, 6: ↓ Ins serum levels, HOMA-IR, ↑ % goblet cells, ↑ Akkermansia and Lactobacillus population in feces

  • Group 6: ↑ intestinal surface area

Peng et al, 20176Morus alba aqueous extract
  • M: Male Wistar rats

  • A/W: 220 ± 10 g

  • 1. ND

  • 2. HFD (ND + 20% fat + 2% CHOL)

  • 3. HFD + BE 0.5%

  • 4. HFD + BE 1%

  • 5. HFD + BE 2%

  • NAFLDI: 4 wk

  • TP: 10 wk

  • Groups 3, 4, 5: ↓ FASN, HMGCR, and TBARS; ↑ CPT1

  • Groups 4, 5: ↓ TC, TG levels, and lipid accumulation; ↓ AGPAT; ↑ SOD enzymatic activity; ↑ PPARa

  • Groups 3, 4, 5: ↓ BW, ↓ total peripheral and total body fat, ↓ TNF-α and leptin serum levels

  • Groups 4, 5: ↓ ALT, TG, TC, and LDL (serum)

  • Group 5: ↓ perineal, mesenteric, subcutaneous, and groin fat; ↑ adiponectin (serum)

Song et al, 201631Morus nigra L. ethanolic extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. LFD + saline 100 mg kg-1 d-1 OG

  • 2. HFD (45% fat) + saline 100 mg kg-1 d-1 OG

  • 3. HFD + BE 100 mg kg-1 d-1 OG

  • TP: 14 wk

  • ↓ Steatosis grade

  • ↓ TG and TC levels, ↓ Gk and Fads2, ↑ Adipor2 and Insig1

  • ↓ BW, ↓ relative perineal and epididymal fat weight

  • ↓ TC, LDL, AST, ALT, Glu, Ins (serum), HOMA-IR, HOMA-IS, adiponectin (serum); ↑ leptin (serum)

Yang et al, 201837Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 240-260 g

  • 1. SD + DW, OG

  • 2. HFD + DW, OG

  • 3. HFD + BE 100 mg kg-1 BW, OG

  • 4. HFD + BE 200 mg kg-1 BW, OG

  • TP: 10 wk

  • ↓ LW, intracellular lipid accumulation, TG levels, Srebf1, Fasn, Acaca, and Scd1

  • ↓ Mitochondrial ROS production and NADPH oxidase activity

  • ↓ MDA, 4-HNE, and NOX4, ↑ SOD enzymatic activity, ↑ mitochondrial complex-I and complex-II activities, ↑ ATP content

↓ TG, TC, LDL, AST, and ALT, ↑ HDL (serum)
Fotschki et al, 202138Rubus idaeus L. acetone-water extract
  • M: Male Wistar rats

  • A/W: 8 wk; 165.3 ± 1.43 g

  • 1. HFD (23% fat)

  • 2. HFD + BE 0.64%

  • 3. HFD + BE 0.64% + fructo-oligosaccharides 3%

  • 4. HFD + BE 0.64% + pectins 3%

  • TP: 12 wk

  • Groups 2, 3, 4: ↓ ballooning and portal inflammation, ↓ Pparg

  • Groups 2, 3: ↓ lobular inflammation, ↓ MDA levels, ↓ Il6

  • Groups 3, 4: ↓ steatosis, ↓ fat content

  • Group 3: ↑ LW, ↓ TC and TG levels, ↓ Ppara and Angplt4

  • Groups 2, 3: ↓ AST (plasma)

  • Groups 3, 4: ↑ cecum mass

  • Group 3: ↓ TG (plasma)

  • Group 4: ↓ cecum pH

Li et al, 201439Rubus aleaefolius Poir extract
  • M: Male Sprague-Dawley rats

  • A/W: 8 wk; 180-200 g

  • 1. ND + 10 mL kg-1 DW

  • 2. mHFD (10% lard + 2 % CHOL) + DW 10 mL kg-1 OG

  • 3. mHFD + BE 1.44 g kg-1 BW per day, OG

  • 4. mHFD + BE 0.72 g kg-1 BW per day, OG

  • NAFLDI: 8 wk

  • TP: 28 d

↓ Fat accumulation, hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci, ↓ Acaca, Fasn, Cpt1a↓ TG, TC, LDL; ↑ HDL (serum)
Nam et al, 201440Rubus coreanus
  • M: Male C57BL/6 mice

  • A/W: –

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD+ BE 100 mg kg-1

  • TP: 10 wk

↓ LW, TG, and TC, Nr1h3, Srebf1, Acaca, Cd36, Fasn, FASN, and HMGCR reductase activity; ↑CPT activity
  • ↓ BW, ↓ epididymal fat mass

  • ↓ AST, ALT, TC, TG, LDL, and leptin plasma levels

Zhao et al, 201341Rubus aleaefolius Poir. extract
  • M: Male SD

  • A/W: 8 wk; 180-200 g

  • 1. CT + DW, IG

  • 2. HFD (10% lard + 2% CHOL) + DW, IG

  • 3. HFD + polyene phosphatidylcholine 76 mg kg-1 BW per day IG

  • 4. HFD + BE 1.44 g kg-1 BW per day IG

  • 5. HFD + BE 0.72 g kg-1 BW per day IG

  • NAFLDI: 8 wk

  • TP: 7 d

  • Groups 4, 5: ↓ hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci

  • ↓ Nfkb, Tnfa, Ptgs2, and Il6 protein and mRNA expression

Groups 4, 5: ↓ BW ↓ ALT, AST, GGT, ALP, TC, TG, and LDL serum levels
Bae et al, 201742Lycium chinense aqueous extract
  • M: Male C57BLS/J-m mice

  • A/W: 7 wk

  • 1. ND

  • 2. MCD + PBS OG

  • 3. MCD + betaine 10 mg kg-1 d-1, OG

  • 4. MCD + BE 100 mg kg-1 d-1, OG

  • 5. MCD + BE 200 mg kg-1 d-1, OG

  • 6. MCD + BE 400 mg kg-1 d-1, OG

  • TP: 4 wk

  • Group 6: ↓ LW

  • Groups 5, 6: ↓ lipid accumulation, ↓ TG, GSH, and MDA levels, F4/80, Itgax, Ccl2, Icam1, Tnfa, Il6, Il1b, Tgfb, Col1a1, Acta2; ↑ SOD and CAT enzymatic activity, pERK; ↓ pJNK

↓ AST and ALT plasma levels
Glisan et al, 201643Vaccinium macrocarpon acetone:water:acetic acid (80:19.9:0.1, v:v:v) extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. HFD (60% kcal from fat)

  • 2. HFD + BE 0.8%

  • NAFLDI: 11 wk

  • TP: 10 wk

↓ Degree of lipidosis and lipid droplets area, ↓ TNF-α, CCL2, and IL1b; ↓ Tlr4, NFKB, Tnfa, Il1b, Ucp2, Ptgs2, Ccr2, Ccl3, Nlrp3, Casp1, Ppara, Txnip↓ FFA, IL-1b, ALT plasma levels
Huang et al, 201744Phyllantus emblica L. aqueous extract
  • M: Male SD rats

  • A/W: 160 ± 10 g

  • 1. ND

  • 2. HFD (40% fat)

  • 3. HFD + GA 100 mg kg-1, OG

  • 4. HFD + BE 125 mg kg-1 BW, OG

  • 5. HFD + BE 250 mg kg-1 BW, OG

  • 6. HFD + BE 500 mg kg-1 BW, OG

  • TP: 20 wk

  • Groups 4, 5, 6: ↓ Srebf1, ↑ CAT and GST enzymatic activity

  • Group 5: ↑ Ppara

  • Group 6: ↓ lipid droplets and fat deposition, ↓ Nr1h3, ↑ GRd enzymatic activity

  • Groups 4, 5, 6: ↓ BW, ↓ AST (serum), ↑ adiponectin (peritoneal fat)

  • Groups 5, 6: ↓ peritoneal and epididymal fat weight

  • Group 6: ↓ ALT and LDL (serum)

Tung et al, 201852Phyllanthus emblica L. reverse osmosis aqueous extract
  • M: Male C57BL/6JNarl mice with specific pathogen-free conditions

  • A/W: 5 wk; 20 ± 2 g

  • 1. ND

  • 2. MCD

  • 3. MCD + GA 100 mg kg-1 BW per day OG

  • 4. MCD + BE 125 mg kg-1 BW per day OG

  • 5. MCD + BE 250 mg kg-1 BW per day OG

  • 6. MCD + BE 500 mg kg-1 BW per day OG

  • TP: 4 or 8 wk

  • Groups 4, 5, 6: ↑ GST, SOD, ↓CAT activity (wk 8), ↓Cyp2e1, Tnfa (weeks 4 and 8), ↓Il1b (week 8)

  • Groups 4, 6: ↓ TBARs levels (week 4)

  • Group 5: ↓ TBAR levels (week 8)

  • Group 6: ↓ GPx enzymatic activity (weeks 4 and 8)

  • Group 4, 5, 6: ↓ AST and ALT (weeks 4 and 8), ↑ TG serum (week 8)

  • Group 6: ↑ TG serum levels (week 4)

Xiao et al, 201845Lycium barbarum Lynn aqueous extract
  • M: Male and female C57BL/6N mice

  • A/W: 20-25 g

  • 1. ND

  • 2. MCD

  • 3. ND + BE 1 mg/kg/ OG

  • 4. MCD + BE 1 mg kg-1 d-1 OG

  • NAFLDI: 3 wk

  • TP: 3 wk

  • ↓ NAS score and apoptotic cells number

  • ↓ ACTA2, SMAD2, TGFb1, p-SMAD2, MDA, TXNIP, TNF-α, IL10, NFKB p50, NFKBIA, BAX-1, cytochrome c, CYP2E1, cleaved CASP1, ASC, NLRP3, and NLRP6, ↑ CAT, GPx and BCL-2

  • ↑ BW

  • ↓ IL-18 and IL-1b

Pak et al,201223Vitis coignetiae Pulliat aqueous extract
  • M: Male Wistar rats

  • A/W: 6 wk

  • 1. ND

  • 2. CD HFD

  • 3. CD HFD + BE 100 mg kg-1 d-1 OG

  • 4. CD HFD + BE 300 mg kg-1 d-1 OG

  • NAFLDI: 13 wk (4 wk HFD+ 9 wk HFD and NaNO₂ 40 mg kg-1 d-1 IP)

  • TP: weeks 10 to 13

  • Groups 3, 4: ↑ relative LW, ↓ mitochondria ROS derivation, ↓ MPO activity, ↓ NFKB p65

  • Group 4: ↓ % of fibrosis area

  • Group 3, 4: ↓ ALT plasma levels

  • Group 4: ↑SOD enzymatic activity (serum)

Al Zarzour et al, 201847Phyllanthus niruri methanolic extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW) OG

  • 2. HFD (8.23% margarine (wt/wt), 8.23% ghee fat (wt/wt), 0.82% CHOL, and 0.41% cholic acid) + DW (10 mL kg-1 BW) OG

  • 3. HFD + metformin 500 mg kg-1 BW OG

  • 4. HFD + BE 1000 mg kg-1 BW OG

  • NAFLDI: 5 wk

  • TP: 3 wk

  • ↓ Micro- and macrovesicles and fibrosis

  • Pparg, Col1a1, and Slc10a2

  • ↑ Adiponectin serum levels

  • ↓ TNF-α, RBP4, vaspin, and IL-6 (serum)

Nanashima et al, 202050Ribes nigrum L. commercial extract
  • M: ovariectomized and sham surgery female SD rats

  • A/W: 12 wk; 249.7 ± 10.2 g

  • 1. ND ovariectomized rats (AIN-93M)

  • 2. ND sham surgery rats (AIN-93M)

  • 3. Ovariectomized rats: ND (AIN-93M) + BE 3%

  • TP: 12 wk

  • ↓ Adipocyte diameter

  • Tnfa, Il6, and Il1b

  • ↓ BW

  • ↓ Visceral fat weight

  • ↓ TG, TC, LDL, adiponectin, and leptin (serum)

Santos et al, 201748Vitis vinifera L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + W, OG

  • 2. HFD (60% fat) + W, OG

  • 3. ND + BE 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ liver fat density

  • ↓ TC, TG, and glycogen levels

  • ↓ MDA and carbonyl protein levels

  • ↑ p-IRS-1, pAKT, PI3-1K, SLC2A2, pLKB1, pACACA, HMGCR, and pAMPK/AMPK ratio, ABCG5 and ABCG8, ↓ SREBP-1c,↑ CAT, GPx, and SOD enzymatic activity

  • ↓ BW

  • ↓ Epididymal and retroperitoneal fat mass

  • ↓ Glu and Ins, HOMA-IR (serum)

Charradi et al, 201451Vitis vinifera ethanolic extract
  • M: Male Wistar rats

  • A/W: 210-230 g

  • 1. ND + 10% ethanol IP (daily)

  • 2. HFD (39% kcal fat) + ethanol 10% IP (daily)

  • 3. ND + BE 500 mg kg-1 d-1 BW IP

  • 4. HFD + BE 500 mg kg-1 d-1 BW IP

  • TP: 6 wk

  • ↓ Relative LW, macrovesicular steatosis, dilatation, and fat accumulation within hepatocytes and sinusoids, ↓ TG, TC, LDL/HDL ratio, TPL, (LDL+VLDL) to HDL ratio, Apo B to Apo AI ratio, MDA, carbonyl protein, and GSSG levels; ↑ levels of ApoAI, GSH, and GSH to GSSG ratio, ↑ GPx and total-, Cu/Zn-, Mn-, and Fe-SOD enzymatic activity

  • ↓ ALAT, ASAT, and lipase activity

  • ↑ Liver alcohol dehydrogenase activity, ↓ Zn depletion

De Bem et al, 201846Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male Wistar rats

  • A/W: 180-200 g

  • 1. ND

  • 2. ND + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 3. ND + BE 200 mg kg-1 d-1 IG

  • 4. ND + EXE + BE 200 mg kg-1 d-1 IG

  • 5. HFD (45% kcal fat)

  • 6. HFD + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 7. HFD + BE 200 mg kg-1 d-1 IG

  • 8. HFD + EXE + BE 200 mg kg-1 d-1 IG

  • NAFLDI: 5 wk (streptozotocin/citrate buffer [CT] IP [35 mg kg-1] once in wk 3)

  • TP: 4 wk

  • Groups 7, 8: ↓ LW and steatosis, TC, TG, MDA, protein carbonyl and 8-isoprostane levels; ↑ ABCG5, pAMPK, pLKB1 to LKB1 ratio, pAMPK/AMPK, pACC/ACC; ↓ SREBP-1c, ACACA, HMGCR; ↑ SOD and GPx enzymatic activity

  • Group 7: ↑ pACC

  • Group 8: ↓ glycogen levels, AMPK

  • Groups 7, 8: ↓ TC, TG, VLDL, ALT, MDA, and protein carbonyl (serum)

  • Group 8: ↓ AST (serum)

Freitas et al, 201649Euterpe edulis oil extract or defatted extract
  • M: Male Wistar rats

  • A/W: 4 wk; 85 ± 5 g

  • 1. ND

  • 2. HFD (50% fat)

  • 3. HFD + BE oil 4%

  • 4. HFD + BE pulp 5%

  • 5. HFD + BE pulp 10%

  • 6. HFD + defatted BE 5%

  • 7. HFD + defatted BE 10%

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 3, 4, 5, 6: ↓ CAT, SOD enzymatic activity

  • Groups 3, 4, 6: ↓ TBARs

  • Groups 4, 6: ↓ inflammatory infiltration and hepatocytes nucleus, GST enzymatic activity

Group 6: ↑ TC serum levels
1

Outcomes refer to groups with berry extract administration vs groups after NAFLD induction, unless otherwise specified.

Abbreviations: A/W, age/weight; AI, atherogenic index (AI); AUC ROC, area under the receiver operating characteristic curve; BE, berry extract; BW, body weight; CCB, cocoa butter; CEL, cellulose; CHOL, cholesterol; CO, corn oil; CS, corn starch; DW, distilled water; FA, fatty acid; FFA, free fatty acid; Glu, glucose; HFD, high-fat diet; IG, intragastric; Ins, insulin; IP, intraperitoneal; LFD, low-fat diet; LW, liver weight; M, animal model; MCD, methionine-choline–deficient diet; MeOH, methanol; mHFD, modified high-fat diet; NAFLDI, nonalcoholic fatty liver disease induction; ND, normal diet; OA, orotic acid; OAD, orotic acid diet; OG, oral gavage; OO, olive oil; SA, silk amino acid; SD, Sprague-Dawley rats; STZ, streptozotocin; SUC, sucrose; TG, triglyceride; TEAC, trolox equivalent antioxidant capacity; TP, treatment period; V, vehicle; W, water; WTD, Western-type diet.

Biomarker abbreviations (genes and proteins): ABCG5, ABCG8: ATP binding cassette subfamily G member 5 and 8; ACC or ACACA: acetyl-CoA carboxylase; AdipoR2: adiponectin Receptor 2; AGPAT: 1-acylglycerol-3-phosphate-O-acyltransferase enzyme; ALAT: alanine transaminase; ALP, alkaline phosphatase; ANGPTL4: angiopoietin-like 4 gene; Apo: apolipoprotein; aP2 or FABP4: fatty acid binding protein 4; ASAT: aspartate aminotransferase; ASC or PYCARD: apoptosis-associated speck-like protein containing a CARD; α-SMA or Acta2: α smooth muscle actin; AST: aspartate aminotransferase; Atg4b, Atg5, Atg7, Atg12: autophagy-related cysteine peptidase 4, 5, 7, and 12; Bax-1: apoptosis regulator BAX; Bcl-2: B-cell lymphoma 2; CAT: catalase; CASP1: Casparian strip membrane protein 1; CCR2: C-C chemokine receptor type 2; CCL2 or 3: C-C motif chemokine ligand 2 or 3 protein; CD11c or Itgax: integrin α-X; CD36: platelet glycoprotein 4; C/EBPα or Cebpa: CCAAT-enhancer-binding proteins; CK-18: cytokeratin 18; CYP7A1: cholesterol 7-α-monooxygenase; CYP2E1: cytochrome P450 2E1; CPT1: carnitine palmitoyltransferase; Col1a1: collagen type I α 1 chain; COX2 or Ptgs2: cyclooxygenase-2; Mlxipl; ChREBP: carbohydrate-responsive element-binding protein; CYP2E1: N-nitrosodimethyl-amine demethylase; ERK: extracellular-signal-regulated kinase; Fabp4: fatty acid-binding protein 4; FASN: fatty acid synthase enzyme; Fads2: acyl-CoA 6-desaturase; F4/80: rat anti–mouse F4/80 antibody; GSH: glutathione reductase; GSSG: glutathione disulfide; GST: glutathione S-transferase; GPx: glutathione peroxide; GRd: glutathione reductase; Gk or GYK: glycerol kinase; SLC2A2 or Glut 2: glucose transporter 2; 4-HNE: 4-hydroxynonenal; HMGCR: 3-hydroxy-3-methy-glutaril-CoA reductase enzyme; HO-1: heme oxygenase-1; ICAM-1: intercellular adhesion molecule; IκB-α or Nfkbia: nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α; IL-6: interleukin 6 cytokine featuring pleiotropic activity; IL-1β: interleukin -1 β pro-inflammatory cytokine produced by cells of the innate immune system; Nos2 or iNOS: inducible nitric oxide synthase; INSIG1: insulin induced gene 1; JNK: Jun N-terminal kinase; Klf2: Krüppel-like factor 2; LC3: microtubule-associated protein light chain 3; LPL: lipoprotein lipase; LXRa or Nr1h3: liver X receptor α; MDA: malondialdehyde; MPO: myeloperoxidase; miR-33a: microRNA 33a; NADPH: nicotinamide adenine dinucleotide phosphate; NAS: NAFLD Activity Score; NF-κB: nuclear factor κ B; NLRP3: NACHT, LRR, and PYD domains-containing protein 3; NLRP6: NOD‐like receptor family pyrin domain containing 6; Nrf2: nuclear factor erythroid 2-related factor 2; NOX4: NADPH oxidase 4; PPAR-γ: peroxisome proliferator-activated receptor γ; pAMPK: phosphorylated AMP-activated protein kinase; pAKT: phospho-AKT; p-ERK: extracellular signal-related kinase; p-IRS-1: phosphorylated insulin receptor substrate; PI3-1K: phosphatidylinositol 3-kinase 1; p-mTOR: phosphorylated serine/threonine-protein kinase mTOR; p-JNK: phosphorylated Jun N-terminal kinase; LKB1: serine/threonine protein kinase liver kinase B1; p-PI3K: phosphorylated phosphatidylinositol-3 kinase; PPARα: peroxisome proliferator-activated receptor α; ROS: reactive oxygen species; SCD-1: stearoyl-coenzyme A desaturase 1; SOD: superoxide dismutase; SLC10A2: ileal sodium/bile acid cotransporter; Smad2: Mothers Against Decantaplegic homolog 2; SREBP: sterol regulatory element-binding protein; Srebf1: sterol regulatory element binding transcription factor 1; TGF-β: transforming growth factor β; TXNIP: thioredoxin-interacting protein; TBARS: thiobarbituric acid reactive substances; TPL: protein TOPLESS; TNF-α: tumor necrosis factor α; Tlr4: Toll-like receptor 4; UCP2: mitochondrial uncoupling protein 2.

Table 3.

Effects of Functional Berry Extracts on Liver and Other Tissues of NAFLD Animal Models

ReferenceExtract interventionAnimal modelIntervention and animal groupsEffects on liver of experimental groups that received berry extract vs NAFLDI group1Effects on other tissues of experimental groups that received berry extract vs NAFLDI group1
Al Zarzour et al, 20171Phyllanthus niruri, MeOH-W extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW)

  • 2. HFD (ND + 10% margarine (wt/wt), 10% ghee fat (wt/wt), 1% CHOL and 0.5% cholic acid) + DW (10 mL kg-1 BW), OG

  • 3. HFD + metformin 500 mg kg-1 BW (10 mL kg-1 BW), OG

  • 4. HFD + BE (W): 10 mL kg-1 BW, OG

  • 5. HFD + BE (50% MeOH, 50% W): 10 mL kg-1 BW, OG

  • 6. HFD + BE (MeOH): 10 mL kg-1 BW, OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Dose-response assay:

  • 1. ND + DW (10 mL kg-1 BW), OG

  • 2. HFD + DW (10 mL kg-1 BW), OG

  • 4. HFD + BE (50% MeOH -50% W) 1000 mg kg-1 (10 mL kg-1 BW), OG

  • 5. HFD + BE (50% MeOH-50% W) 500 mg kg-1 (10 mL kg-1 BW) OG

  • 6. HFD + BE (50% MeOH-50% W) 250 mg kg-1 (10 mL kg-1 BW) OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 4, 5, 6: ↓ steatosis, TC and MDA levels

  • Group 5: ↓ LW

  • Groups 5, 6: ↓ lobular inflammation, TG

  • Dose response assay: HFD + BE (50% MeOH-50% W)

  • ↓ LW, lobular inflammation and steatosis

  • Groups 4, 5, 6: ↓ visceral fat, Ins, HOMA-IR, TC, FFA, and LDL (serum)

  • Groups 5, 6: ↓ ALT (serum)

  • Group 5: ↓ ALP (serum)

  • Dose response assay:

  • Groups 4, 5, 6: ↓ TC, LDL, ALT and Ins, ↑AST to ALT ratio (serum)

  • Groups 4, 5: ↓ ALP, Glu (serum)

  • Group 4: ↓ visceral fat

Tavares et al, 20202Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V, IG

  • 3. HFD+ BE 300 mg kg-1 d-1, IG

  • NAFLDI: 8 wk

  • TP: 4 wk

  • ↓ LW and lipid accumulation

  • ↓ MDA and carbonyl levels

  • ↓ SOD, GPx, and CAT enzymatic activity

  • ↓ BW

  • ↓ TG, TC, LDL, VLDL, and ALT (serum)

De Oliveira et al,20153Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. ND + 300 mg kg-1 d-1 BE, IG

  • 3. HFD (60% fat)

  • 4. HFD + 300 mg kg-1 d-1 BE, IG

  • TP: 12 wk

  • ↓ LW and steatosis

  • ↓ TC, TG, MDA, and carbonyl protein levels

  • ↑ pAMPK, pACACA to ACACA ratio, ABCG5 and ABCG8 ↓ HMGCR, and SREBP-1c

  • ↑ SOD, CAT, and GPx enzymatic activity

  • ↓ BW, epididymal and retroperitoneal adipose tissues weights

  • ↓ TC, TG, LDL, VLDL (serum)

  • ↓ Leptin (plasma)

  • ↑ Adiponectin (plasma)

Morrison et al, 20154Vaccinium myrtillus L. extract
  • M: Female E3L mice

  • A/W: –

  • 1. WTD (15% CCB, 1% CO, 40.5% SUC, 20% acid casein, 10% CS, and 6.2% CEL) + 1% CHOL

  • 2. WTD

  • 3. WTD+ 1% CHOL+ 0.1% BE

  • NAFLDI: 4 wk

  • TP: 16 wk

  • ↓ Macro- and microvesicular steatosis

  • ↓ Hepatocellular damage (CK-18)

  • ↓ Inflammatory cell aggregates

  • ↓ Intrahepatic CHOL crystal formation

  • ↓ Collagen and TC, ↓ Col1a1 and Mpo, ↓ p65-NF-κB activity

Park et al, 20175Aronia melanocarpa ethanolic extract
  • M: Male C57BL/6N mice

  • A/W: 5 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + BE 50 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW

  • ↓ Lipid deposition, TG and FAS

  • Pparg2

  • Fabp4 and Lpl (mRNA and protein)

  • ↑ SOD and TEAC enzymatic activity

  • ↓ BW

  • ↓ AST, ALT, and leptin (serum)

Park et al, 201936Water extract of mulberry and silk amino acids
  • M: Male SD rats

  • A/W: 11 wk; 306 ± 20 g

  • 1. ND

  • 2. HFD (51% fat) + CEL 0.6%

  • 3. HFD + BE and SA (1:3) 200 mg kg-1 BW per day

  • 4. HFD + BE and SA (1:3) 600 mg kg-1 BW per day

  • 5. HFD + BE and SA (1:5) 200 mg kg-1 BW per day

  • 6. HFD + BE and SA (1:5) 600 mg kg-1 BW per day

  • TP: 12 wk

  • Groups 3, 4, 5, 6: ↓ LW, ballooning degeneration, macrophage infiltration, ↓ TNF-α, Tnfa,

  • Groups 4 & 6: ↓ Liver cellular damage, liver size and fat accumulation, ↑ pAKT/AKT, pACACA/ACACA and ACACA, ↓ Cyp2e1

  • Groups 4, 5, 6: ↓ TG and TC and MDA levels, Il1b, Fasn and Srebf1, ↑ glycogen levels, Cpt1a

  • Groups 3, 4, 6: ↑ GSH-peroxidase enzymatic activity and GSH levels

  • Group 4: ↑ SOD enzymatic activity

  • Groups 3, 4, 5, 6: ↓ AST and γ-GPT, HOMA-IR (serum), BW gain, ↓ AUC (Glu & Ins)

  • Groups 3, 4, 6: ↑ HDL

  • Groups 4, 5, 6: ↓ TNFa, ↓Glu and nonesterified FAs (serum)

  • Groups 4, 6: ↓ LDL and Ins (serum)

  • Groups 5, 6: ↓ BW, epididymal and retroperitoneal fat mass, TG

  • Group 6: ↓ ALT (serum)

  • Group 3, 4: ↑ Bacteroidales to Clostridiales ratio

  • Group 4: ↑ gut bacterial species

Xu et al, 201730Morus alba L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + β-glucan 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • 5. HFD  +  β-glucan 200 mg kg-1 d-1 + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • Groups 4, 5: ↓ LW

  • Group 5: ↓ TG and TC, ↑ GST, GSSG, Cu/Zn-SOD enzymatic activity, GSH/GSSG and ROS content

  • Groups 4, 5: ↓ BW, ↓ TG, FFA, CHOL, LDL-c, leptin, AST, ALT, IL1b, IL4, and TNF-α (serum), ↓ perineal fat mass

  • Group 5: ↓ AUC and fasting Glu and Ins

Ann et al, 201532Morus alba L. ethanolic extract
  • M: C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + DW

  • 2. HFD (45% kcal fat) + DW

  • 3. HFD + BE 133 mg kg-1 d-1 5 times/wk OG

  • 4. HFD + BE 666 mg kg-1 d-1 5 times/wk OG

  • TP: 12 wk

  • Groups 3, 4: ↓ fat accumulation, Lpl, Srebf1, Fabp4, Ucp2, Ppara, ↓ SREBP-1c and ACTA2

  • Group 4: ↓ Nr1h3, Fasn, Cebpa, Col1a1, ↓ LPL, 4-HNE, nuclear NRF2, HO-1, GPx enzymatic activity

  • Groups 3, 4: ↑ HDL, ↓TG, TC, LDL, AI, 4-HNE, ↓ GOT, GPT, GPx, and HO-1 plasma enzymatic activity

  • Group 3: ↓ epididymal and retroperitoneal fat

Hu et al, 202033Morus alba L. methanolic extract
  • M: Male SD rats

  • A/W: 100-120 g; 4 wk

  • 1. ND

  • 2. OAD (ND + 1% OA + 33% SUC)

  • 3. OAD + fenofibrate 50 mg kg-1 d-1 OG

  • 4. OAD + BE 50 mg kg-1 d-1 OG

  • 5. OAD + BE 100 mg kg-1 d-1 OG

  • 6. OAD + BE 200 mg kg-1 d-1 OG

  • TP: Unknown

  • Groups 4, 5, 6: ↓ TC and TG, ↓ no. of lipid droplets and histological lesion, ↓ Hmgcr and miR-33a

  • Groups 5, 6: ↓ Srebf2

  • Groups 4, 5: ↑ Cyp7a1

Lee et al, 202034Morus alba fermented extract
  • M: Male C57BL/6N mice

  • A/W: 8 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V 10 mg/kg (OO + 1% DMSO) 5 times wk-1, OG

  • 3. HFD+ orlistat 10 mg kg-1 5 times wk-1, OG

  • 4. HFD + BE 50 mg kg-1 5 times wk-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ no. and size of lipid droplets, and steatosis total score

  • Pparg, Fabp4, Fasn, Klf2, Nos2, Ptgs2, Il1b, Il6, Tnfa, Nfkb, Atg4b, Atg5, Atg7, and Atg12; ↓ p-JNK, p-p38, p-mTOR, beclin, and LC3 levels; ↑ p-PI3K, p-AKT, and p-ERK levels

↓ BW
Ma et al, 201835Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 8 wk; 275 ± 25 g

  • 1. ND

  • 2. ND + BE

  • 3. HFD (60% kcal from fat)

  • 4. HFD + BE prevention (10 g kg-1 d-1) 4 mo + BE therapeutic (10 g kg-1 d-1) 2 mo OG

  • 5. HFD + BE therapeutic (10 g kg-1 d-1) 3 mo OG

  • NAFLDI: 3 mo HFD. Immediately after STZ/citrate buffer (CT) IP (40 mg kg-1)

  • TP: 6 mo

Groups 4, 5: ↓ Srebf1 and Mlxipl Group 4: ↓ Fasn
  • Groups 4, 5: ↓ fasting Glu and HOMA-IR, ↑ Ins, ↓ TG, FFA, AST, ALT (serum)

  • Group 4: ↓ TC (serum)

Park et al, 20199Rubus fruticosus ethanolic extract
  • M: Male SD rats

  • A/W: 11 wk; 195 ± 11 g

  • 1. ND

  • 2. HFD (51% kcal fat) + dextrin (450 mg kg-1 BW per day)

  • 3. HFD + milk thistle extracts (150 mg kg-1 BW per day)

  • 4. HFD + 50% BE leaf (450 mg kg-1 BW per day)

  • 5. HFD + 50% BE fruit (450 mg kg-1 BW per day)

  • 6. HFD + BE leaf and fruit (2:1) (150 mg kg-1 BW per day)

  • TP: 12 wk

  • Groups 4, 5, 6: ↓ TG, MDA, and TNFa, Acaca, Fasn, TNFa; ↑glycogen levels, ↑ SOD enzymatic activity

  • Groups 4, 6: ↓ enlargement of the nucleus and the cell size, macrophage infiltration, CHOL, Srebf1 and Il1b, ↑ Cpt1a

  • Group 6: ↑ GSH enzymatic activity

  • Groups 4, 5 & 6: ↓ epididymal and retroperitoneal fat, ↓Serum levels of AST, ALT, TC, LDL, nonesterified FFAs, AUC (Glu & Ins)

  • Groups 4, 5: ↓ TG (serum)

  • Groups 4, 6: ↓ Ins serum levels, HOMA-IR, ↑ % goblet cells, ↑ Akkermansia and Lactobacillus population in feces

  • Group 6: ↑ intestinal surface area

Peng et al, 20176Morus alba aqueous extract
  • M: Male Wistar rats

  • A/W: 220 ± 10 g

  • 1. ND

  • 2. HFD (ND + 20% fat + 2% CHOL)

  • 3. HFD + BE 0.5%

  • 4. HFD + BE 1%

  • 5. HFD + BE 2%

  • NAFLDI: 4 wk

  • TP: 10 wk

  • Groups 3, 4, 5: ↓ FASN, HMGCR, and TBARS; ↑ CPT1

  • Groups 4, 5: ↓ TC, TG levels, and lipid accumulation; ↓ AGPAT; ↑ SOD enzymatic activity; ↑ PPARa

  • Groups 3, 4, 5: ↓ BW, ↓ total peripheral and total body fat, ↓ TNF-α and leptin serum levels

  • Groups 4, 5: ↓ ALT, TG, TC, and LDL (serum)

  • Group 5: ↓ perineal, mesenteric, subcutaneous, and groin fat; ↑ adiponectin (serum)

Song et al, 201631Morus nigra L. ethanolic extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. LFD + saline 100 mg kg-1 d-1 OG

  • 2. HFD (45% fat) + saline 100 mg kg-1 d-1 OG

  • 3. HFD + BE 100 mg kg-1 d-1 OG

  • TP: 14 wk

  • ↓ Steatosis grade

  • ↓ TG and TC levels, ↓ Gk and Fads2, ↑ Adipor2 and Insig1

  • ↓ BW, ↓ relative perineal and epididymal fat weight

  • ↓ TC, LDL, AST, ALT, Glu, Ins (serum), HOMA-IR, HOMA-IS, adiponectin (serum); ↑ leptin (serum)

Yang et al, 201837Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 240-260 g

  • 1. SD + DW, OG

  • 2. HFD + DW, OG

  • 3. HFD + BE 100 mg kg-1 BW, OG

  • 4. HFD + BE 200 mg kg-1 BW, OG

  • TP: 10 wk

  • ↓ LW, intracellular lipid accumulation, TG levels, Srebf1, Fasn, Acaca, and Scd1

  • ↓ Mitochondrial ROS production and NADPH oxidase activity

  • ↓ MDA, 4-HNE, and NOX4, ↑ SOD enzymatic activity, ↑ mitochondrial complex-I and complex-II activities, ↑ ATP content

↓ TG, TC, LDL, AST, and ALT, ↑ HDL (serum)
Fotschki et al, 202138Rubus idaeus L. acetone-water extract
  • M: Male Wistar rats

  • A/W: 8 wk; 165.3 ± 1.43 g

  • 1. HFD (23% fat)

  • 2. HFD + BE 0.64%

  • 3. HFD + BE 0.64% + fructo-oligosaccharides 3%

  • 4. HFD + BE 0.64% + pectins 3%

  • TP: 12 wk

  • Groups 2, 3, 4: ↓ ballooning and portal inflammation, ↓ Pparg

  • Groups 2, 3: ↓ lobular inflammation, ↓ MDA levels, ↓ Il6

  • Groups 3, 4: ↓ steatosis, ↓ fat content

  • Group 3: ↑ LW, ↓ TC and TG levels, ↓ Ppara and Angplt4

  • Groups 2, 3: ↓ AST (plasma)

  • Groups 3, 4: ↑ cecum mass

  • Group 3: ↓ TG (plasma)

  • Group 4: ↓ cecum pH

Li et al, 201439Rubus aleaefolius Poir extract
  • M: Male Sprague-Dawley rats

  • A/W: 8 wk; 180-200 g

  • 1. ND + 10 mL kg-1 DW

  • 2. mHFD (10% lard + 2 % CHOL) + DW 10 mL kg-1 OG

  • 3. mHFD + BE 1.44 g kg-1 BW per day, OG

  • 4. mHFD + BE 0.72 g kg-1 BW per day, OG

  • NAFLDI: 8 wk

  • TP: 28 d

↓ Fat accumulation, hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci, ↓ Acaca, Fasn, Cpt1a↓ TG, TC, LDL; ↑ HDL (serum)
Nam et al, 201440Rubus coreanus
  • M: Male C57BL/6 mice

  • A/W: –

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD+ BE 100 mg kg-1

  • TP: 10 wk

↓ LW, TG, and TC, Nr1h3, Srebf1, Acaca, Cd36, Fasn, FASN, and HMGCR reductase activity; ↑CPT activity
  • ↓ BW, ↓ epididymal fat mass

  • ↓ AST, ALT, TC, TG, LDL, and leptin plasma levels

Zhao et al, 201341Rubus aleaefolius Poir. extract
  • M: Male SD

  • A/W: 8 wk; 180-200 g

  • 1. CT + DW, IG

  • 2. HFD (10% lard + 2% CHOL) + DW, IG

  • 3. HFD + polyene phosphatidylcholine 76 mg kg-1 BW per day IG

  • 4. HFD + BE 1.44 g kg-1 BW per day IG

  • 5. HFD + BE 0.72 g kg-1 BW per day IG

  • NAFLDI: 8 wk

  • TP: 7 d

  • Groups 4, 5: ↓ hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci

  • ↓ Nfkb, Tnfa, Ptgs2, and Il6 protein and mRNA expression

Groups 4, 5: ↓ BW ↓ ALT, AST, GGT, ALP, TC, TG, and LDL serum levels
Bae et al, 201742Lycium chinense aqueous extract
  • M: Male C57BLS/J-m mice

  • A/W: 7 wk

  • 1. ND

  • 2. MCD + PBS OG

  • 3. MCD + betaine 10 mg kg-1 d-1, OG

  • 4. MCD + BE 100 mg kg-1 d-1, OG

  • 5. MCD + BE 200 mg kg-1 d-1, OG

  • 6. MCD + BE 400 mg kg-1 d-1, OG

  • TP: 4 wk

  • Group 6: ↓ LW

  • Groups 5, 6: ↓ lipid accumulation, ↓ TG, GSH, and MDA levels, F4/80, Itgax, Ccl2, Icam1, Tnfa, Il6, Il1b, Tgfb, Col1a1, Acta2; ↑ SOD and CAT enzymatic activity, pERK; ↓ pJNK

↓ AST and ALT plasma levels
Glisan et al, 201643Vaccinium macrocarpon acetone:water:acetic acid (80:19.9:0.1, v:v:v) extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. HFD (60% kcal from fat)

  • 2. HFD + BE 0.8%

  • NAFLDI: 11 wk

  • TP: 10 wk

↓ Degree of lipidosis and lipid droplets area, ↓ TNF-α, CCL2, and IL1b; ↓ Tlr4, NFKB, Tnfa, Il1b, Ucp2, Ptgs2, Ccr2, Ccl3, Nlrp3, Casp1, Ppara, Txnip↓ FFA, IL-1b, ALT plasma levels
Huang et al, 201744Phyllantus emblica L. aqueous extract
  • M: Male SD rats

  • A/W: 160 ± 10 g

  • 1. ND

  • 2. HFD (40% fat)

  • 3. HFD + GA 100 mg kg-1, OG

  • 4. HFD + BE 125 mg kg-1 BW, OG

  • 5. HFD + BE 250 mg kg-1 BW, OG

  • 6. HFD + BE 500 mg kg-1 BW, OG

  • TP: 20 wk

  • Groups 4, 5, 6: ↓ Srebf1, ↑ CAT and GST enzymatic activity

  • Group 5: ↑ Ppara

  • Group 6: ↓ lipid droplets and fat deposition, ↓ Nr1h3, ↑ GRd enzymatic activity

  • Groups 4, 5, 6: ↓ BW, ↓ AST (serum), ↑ adiponectin (peritoneal fat)

  • Groups 5, 6: ↓ peritoneal and epididymal fat weight

  • Group 6: ↓ ALT and LDL (serum)

Tung et al, 201852Phyllanthus emblica L. reverse osmosis aqueous extract
  • M: Male C57BL/6JNarl mice with specific pathogen-free conditions

  • A/W: 5 wk; 20 ± 2 g

  • 1. ND

  • 2. MCD

  • 3. MCD + GA 100 mg kg-1 BW per day OG

  • 4. MCD + BE 125 mg kg-1 BW per day OG

  • 5. MCD + BE 250 mg kg-1 BW per day OG

  • 6. MCD + BE 500 mg kg-1 BW per day OG

  • TP: 4 or 8 wk

  • Groups 4, 5, 6: ↑ GST, SOD, ↓CAT activity (wk 8), ↓Cyp2e1, Tnfa (weeks 4 and 8), ↓Il1b (week 8)

  • Groups 4, 6: ↓ TBARs levels (week 4)

  • Group 5: ↓ TBAR levels (week 8)

  • Group 6: ↓ GPx enzymatic activity (weeks 4 and 8)

  • Group 4, 5, 6: ↓ AST and ALT (weeks 4 and 8), ↑ TG serum (week 8)

  • Group 6: ↑ TG serum levels (week 4)

Xiao et al, 201845Lycium barbarum Lynn aqueous extract
  • M: Male and female C57BL/6N mice

  • A/W: 20-25 g

  • 1. ND

  • 2. MCD

  • 3. ND + BE 1 mg/kg/ OG

  • 4. MCD + BE 1 mg kg-1 d-1 OG

  • NAFLDI: 3 wk

  • TP: 3 wk

  • ↓ NAS score and apoptotic cells number

  • ↓ ACTA2, SMAD2, TGFb1, p-SMAD2, MDA, TXNIP, TNF-α, IL10, NFKB p50, NFKBIA, BAX-1, cytochrome c, CYP2E1, cleaved CASP1, ASC, NLRP3, and NLRP6, ↑ CAT, GPx and BCL-2

  • ↑ BW

  • ↓ IL-18 and IL-1b

Pak et al,201223Vitis coignetiae Pulliat aqueous extract
  • M: Male Wistar rats

  • A/W: 6 wk

  • 1. ND

  • 2. CD HFD

  • 3. CD HFD + BE 100 mg kg-1 d-1 OG

  • 4. CD HFD + BE 300 mg kg-1 d-1 OG

  • NAFLDI: 13 wk (4 wk HFD+ 9 wk HFD and NaNO₂ 40 mg kg-1 d-1 IP)

  • TP: weeks 10 to 13

  • Groups 3, 4: ↑ relative LW, ↓ mitochondria ROS derivation, ↓ MPO activity, ↓ NFKB p65

  • Group 4: ↓ % of fibrosis area

  • Group 3, 4: ↓ ALT plasma levels

  • Group 4: ↑SOD enzymatic activity (serum)

Al Zarzour et al, 201847Phyllanthus niruri methanolic extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW) OG

  • 2. HFD (8.23% margarine (wt/wt), 8.23% ghee fat (wt/wt), 0.82% CHOL, and 0.41% cholic acid) + DW (10 mL kg-1 BW) OG

  • 3. HFD + metformin 500 mg kg-1 BW OG

  • 4. HFD + BE 1000 mg kg-1 BW OG

  • NAFLDI: 5 wk

  • TP: 3 wk

  • ↓ Micro- and macrovesicles and fibrosis

  • Pparg, Col1a1, and Slc10a2

  • ↑ Adiponectin serum levels

  • ↓ TNF-α, RBP4, vaspin, and IL-6 (serum)

Nanashima et al, 202050Ribes nigrum L. commercial extract
  • M: ovariectomized and sham surgery female SD rats

  • A/W: 12 wk; 249.7 ± 10.2 g

  • 1. ND ovariectomized rats (AIN-93M)

  • 2. ND sham surgery rats (AIN-93M)

  • 3. Ovariectomized rats: ND (AIN-93M) + BE 3%

  • TP: 12 wk

  • ↓ Adipocyte diameter

  • Tnfa, Il6, and Il1b

  • ↓ BW

  • ↓ Visceral fat weight

  • ↓ TG, TC, LDL, adiponectin, and leptin (serum)

Santos et al, 201748Vitis vinifera L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + W, OG

  • 2. HFD (60% fat) + W, OG

  • 3. ND + BE 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ liver fat density

  • ↓ TC, TG, and glycogen levels

  • ↓ MDA and carbonyl protein levels

  • ↑ p-IRS-1, pAKT, PI3-1K, SLC2A2, pLKB1, pACACA, HMGCR, and pAMPK/AMPK ratio, ABCG5 and ABCG8, ↓ SREBP-1c,↑ CAT, GPx, and SOD enzymatic activity

  • ↓ BW

  • ↓ Epididymal and retroperitoneal fat mass

  • ↓ Glu and Ins, HOMA-IR (serum)

Charradi et al, 201451Vitis vinifera ethanolic extract
  • M: Male Wistar rats

  • A/W: 210-230 g

  • 1. ND + 10% ethanol IP (daily)

  • 2. HFD (39% kcal fat) + ethanol 10% IP (daily)

  • 3. ND + BE 500 mg kg-1 d-1 BW IP

  • 4. HFD + BE 500 mg kg-1 d-1 BW IP

  • TP: 6 wk

  • ↓ Relative LW, macrovesicular steatosis, dilatation, and fat accumulation within hepatocytes and sinusoids, ↓ TG, TC, LDL/HDL ratio, TPL, (LDL+VLDL) to HDL ratio, Apo B to Apo AI ratio, MDA, carbonyl protein, and GSSG levels; ↑ levels of ApoAI, GSH, and GSH to GSSG ratio, ↑ GPx and total-, Cu/Zn-, Mn-, and Fe-SOD enzymatic activity

  • ↓ ALAT, ASAT, and lipase activity

  • ↑ Liver alcohol dehydrogenase activity, ↓ Zn depletion

De Bem et al, 201846Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male Wistar rats

  • A/W: 180-200 g

  • 1. ND

  • 2. ND + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 3. ND + BE 200 mg kg-1 d-1 IG

  • 4. ND + EXE + BE 200 mg kg-1 d-1 IG

  • 5. HFD (45% kcal fat)

  • 6. HFD + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 7. HFD + BE 200 mg kg-1 d-1 IG

  • 8. HFD + EXE + BE 200 mg kg-1 d-1 IG

  • NAFLDI: 5 wk (streptozotocin/citrate buffer [CT] IP [35 mg kg-1] once in wk 3)

  • TP: 4 wk

  • Groups 7, 8: ↓ LW and steatosis, TC, TG, MDA, protein carbonyl and 8-isoprostane levels; ↑ ABCG5, pAMPK, pLKB1 to LKB1 ratio, pAMPK/AMPK, pACC/ACC; ↓ SREBP-1c, ACACA, HMGCR; ↑ SOD and GPx enzymatic activity

  • Group 7: ↑ pACC

  • Group 8: ↓ glycogen levels, AMPK

  • Groups 7, 8: ↓ TC, TG, VLDL, ALT, MDA, and protein carbonyl (serum)

  • Group 8: ↓ AST (serum)

Freitas et al, 201649Euterpe edulis oil extract or defatted extract
  • M: Male Wistar rats

  • A/W: 4 wk; 85 ± 5 g

  • 1. ND

  • 2. HFD (50% fat)

  • 3. HFD + BE oil 4%

  • 4. HFD + BE pulp 5%

  • 5. HFD + BE pulp 10%

  • 6. HFD + defatted BE 5%

  • 7. HFD + defatted BE 10%

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 3, 4, 5, 6: ↓ CAT, SOD enzymatic activity

  • Groups 3, 4, 6: ↓ TBARs

  • Groups 4, 6: ↓ inflammatory infiltration and hepatocytes nucleus, GST enzymatic activity

Group 6: ↑ TC serum levels
ReferenceExtract interventionAnimal modelIntervention and animal groupsEffects on liver of experimental groups that received berry extract vs NAFLDI group1Effects on other tissues of experimental groups that received berry extract vs NAFLDI group1
Al Zarzour et al, 20171Phyllanthus niruri, MeOH-W extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW)

  • 2. HFD (ND + 10% margarine (wt/wt), 10% ghee fat (wt/wt), 1% CHOL and 0.5% cholic acid) + DW (10 mL kg-1 BW), OG

  • 3. HFD + metformin 500 mg kg-1 BW (10 mL kg-1 BW), OG

  • 4. HFD + BE (W): 10 mL kg-1 BW, OG

  • 5. HFD + BE (50% MeOH, 50% W): 10 mL kg-1 BW, OG

  • 6. HFD + BE (MeOH): 10 mL kg-1 BW, OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Dose-response assay:

  • 1. ND + DW (10 mL kg-1 BW), OG

  • 2. HFD + DW (10 mL kg-1 BW), OG

  • 4. HFD + BE (50% MeOH -50% W) 1000 mg kg-1 (10 mL kg-1 BW), OG

  • 5. HFD + BE (50% MeOH-50% W) 500 mg kg-1 (10 mL kg-1 BW) OG

  • 6. HFD + BE (50% MeOH-50% W) 250 mg kg-1 (10 mL kg-1 BW) OG

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 4, 5, 6: ↓ steatosis, TC and MDA levels

  • Group 5: ↓ LW

  • Groups 5, 6: ↓ lobular inflammation, TG

  • Dose response assay: HFD + BE (50% MeOH-50% W)

  • ↓ LW, lobular inflammation and steatosis

  • Groups 4, 5, 6: ↓ visceral fat, Ins, HOMA-IR, TC, FFA, and LDL (serum)

  • Groups 5, 6: ↓ ALT (serum)

  • Group 5: ↓ ALP (serum)

  • Dose response assay:

  • Groups 4, 5, 6: ↓ TC, LDL, ALT and Ins, ↑AST to ALT ratio (serum)

  • Groups 4, 5: ↓ ALP, Glu (serum)

  • Group 4: ↓ visceral fat

Tavares et al, 20202Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V, IG

  • 3. HFD+ BE 300 mg kg-1 d-1, IG

  • NAFLDI: 8 wk

  • TP: 4 wk

  • ↓ LW and lipid accumulation

  • ↓ MDA and carbonyl levels

  • ↓ SOD, GPx, and CAT enzymatic activity

  • ↓ BW

  • ↓ TG, TC, LDL, VLDL, and ALT (serum)

De Oliveira et al,20153Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. ND + 300 mg kg-1 d-1 BE, IG

  • 3. HFD (60% fat)

  • 4. HFD + 300 mg kg-1 d-1 BE, IG

  • TP: 12 wk

  • ↓ LW and steatosis

  • ↓ TC, TG, MDA, and carbonyl protein levels

  • ↑ pAMPK, pACACA to ACACA ratio, ABCG5 and ABCG8 ↓ HMGCR, and SREBP-1c

  • ↑ SOD, CAT, and GPx enzymatic activity

  • ↓ BW, epididymal and retroperitoneal adipose tissues weights

  • ↓ TC, TG, LDL, VLDL (serum)

  • ↓ Leptin (plasma)

  • ↑ Adiponectin (plasma)

Morrison et al, 20154Vaccinium myrtillus L. extract
  • M: Female E3L mice

  • A/W: –

  • 1. WTD (15% CCB, 1% CO, 40.5% SUC, 20% acid casein, 10% CS, and 6.2% CEL) + 1% CHOL

  • 2. WTD

  • 3. WTD+ 1% CHOL+ 0.1% BE

  • NAFLDI: 4 wk

  • TP: 16 wk

  • ↓ Macro- and microvesicular steatosis

  • ↓ Hepatocellular damage (CK-18)

  • ↓ Inflammatory cell aggregates

  • ↓ Intrahepatic CHOL crystal formation

  • ↓ Collagen and TC, ↓ Col1a1 and Mpo, ↓ p65-NF-κB activity

Park et al, 20175Aronia melanocarpa ethanolic extract
  • M: Male C57BL/6N mice

  • A/W: 5 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + BE 50 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW

  • ↓ Lipid deposition, TG and FAS

  • Pparg2

  • Fabp4 and Lpl (mRNA and protein)

  • ↑ SOD and TEAC enzymatic activity

  • ↓ BW

  • ↓ AST, ALT, and leptin (serum)

Park et al, 201936Water extract of mulberry and silk amino acids
  • M: Male SD rats

  • A/W: 11 wk; 306 ± 20 g

  • 1. ND

  • 2. HFD (51% fat) + CEL 0.6%

  • 3. HFD + BE and SA (1:3) 200 mg kg-1 BW per day

  • 4. HFD + BE and SA (1:3) 600 mg kg-1 BW per day

  • 5. HFD + BE and SA (1:5) 200 mg kg-1 BW per day

  • 6. HFD + BE and SA (1:5) 600 mg kg-1 BW per day

  • TP: 12 wk

  • Groups 3, 4, 5, 6: ↓ LW, ballooning degeneration, macrophage infiltration, ↓ TNF-α, Tnfa,

  • Groups 4 & 6: ↓ Liver cellular damage, liver size and fat accumulation, ↑ pAKT/AKT, pACACA/ACACA and ACACA, ↓ Cyp2e1

  • Groups 4, 5, 6: ↓ TG and TC and MDA levels, Il1b, Fasn and Srebf1, ↑ glycogen levels, Cpt1a

  • Groups 3, 4, 6: ↑ GSH-peroxidase enzymatic activity and GSH levels

  • Group 4: ↑ SOD enzymatic activity

  • Groups 3, 4, 5, 6: ↓ AST and γ-GPT, HOMA-IR (serum), BW gain, ↓ AUC (Glu & Ins)

  • Groups 3, 4, 6: ↑ HDL

  • Groups 4, 5, 6: ↓ TNFa, ↓Glu and nonesterified FAs (serum)

  • Groups 4, 6: ↓ LDL and Ins (serum)

  • Groups 5, 6: ↓ BW, epididymal and retroperitoneal fat mass, TG

  • Group 6: ↓ ALT (serum)

  • Group 3, 4: ↑ Bacteroidales to Clostridiales ratio

  • Group 4: ↑ gut bacterial species

Xu et al, 201730Morus alba L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD + β-glucan 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • 5. HFD  +  β-glucan 200 mg kg-1 d-1 + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • Groups 4, 5: ↓ LW

  • Group 5: ↓ TG and TC, ↑ GST, GSSG, Cu/Zn-SOD enzymatic activity, GSH/GSSG and ROS content

  • Groups 4, 5: ↓ BW, ↓ TG, FFA, CHOL, LDL-c, leptin, AST, ALT, IL1b, IL4, and TNF-α (serum), ↓ perineal fat mass

  • Group 5: ↓ AUC and fasting Glu and Ins

Ann et al, 201532Morus alba L. ethanolic extract
  • M: C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + DW

  • 2. HFD (45% kcal fat) + DW

  • 3. HFD + BE 133 mg kg-1 d-1 5 times/wk OG

  • 4. HFD + BE 666 mg kg-1 d-1 5 times/wk OG

  • TP: 12 wk

  • Groups 3, 4: ↓ fat accumulation, Lpl, Srebf1, Fabp4, Ucp2, Ppara, ↓ SREBP-1c and ACTA2

  • Group 4: ↓ Nr1h3, Fasn, Cebpa, Col1a1, ↓ LPL, 4-HNE, nuclear NRF2, HO-1, GPx enzymatic activity

  • Groups 3, 4: ↑ HDL, ↓TG, TC, LDL, AI, 4-HNE, ↓ GOT, GPT, GPx, and HO-1 plasma enzymatic activity

  • Group 3: ↓ epididymal and retroperitoneal fat

Hu et al, 202033Morus alba L. methanolic extract
  • M: Male SD rats

  • A/W: 100-120 g; 4 wk

  • 1. ND

  • 2. OAD (ND + 1% OA + 33% SUC)

  • 3. OAD + fenofibrate 50 mg kg-1 d-1 OG

  • 4. OAD + BE 50 mg kg-1 d-1 OG

  • 5. OAD + BE 100 mg kg-1 d-1 OG

  • 6. OAD + BE 200 mg kg-1 d-1 OG

  • TP: Unknown

  • Groups 4, 5, 6: ↓ TC and TG, ↓ no. of lipid droplets and histological lesion, ↓ Hmgcr and miR-33a

  • Groups 5, 6: ↓ Srebf2

  • Groups 4, 5: ↑ Cyp7a1

Lee et al, 202034Morus alba fermented extract
  • M: Male C57BL/6N mice

  • A/W: 8 wk

  • 1. ND

  • 2. HFD (60% kcal fat) + V 10 mg/kg (OO + 1% DMSO) 5 times wk-1, OG

  • 3. HFD+ orlistat 10 mg kg-1 5 times wk-1, OG

  • 4. HFD + BE 50 mg kg-1 5 times wk-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ no. and size of lipid droplets, and steatosis total score

  • Pparg, Fabp4, Fasn, Klf2, Nos2, Ptgs2, Il1b, Il6, Tnfa, Nfkb, Atg4b, Atg5, Atg7, and Atg12; ↓ p-JNK, p-p38, p-mTOR, beclin, and LC3 levels; ↑ p-PI3K, p-AKT, and p-ERK levels

↓ BW
Ma et al, 201835Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 8 wk; 275 ± 25 g

  • 1. ND

  • 2. ND + BE

  • 3. HFD (60% kcal from fat)

  • 4. HFD + BE prevention (10 g kg-1 d-1) 4 mo + BE therapeutic (10 g kg-1 d-1) 2 mo OG

  • 5. HFD + BE therapeutic (10 g kg-1 d-1) 3 mo OG

  • NAFLDI: 3 mo HFD. Immediately after STZ/citrate buffer (CT) IP (40 mg kg-1)

  • TP: 6 mo

Groups 4, 5: ↓ Srebf1 and Mlxipl Group 4: ↓ Fasn
  • Groups 4, 5: ↓ fasting Glu and HOMA-IR, ↑ Ins, ↓ TG, FFA, AST, ALT (serum)

  • Group 4: ↓ TC (serum)

Park et al, 20199Rubus fruticosus ethanolic extract
  • M: Male SD rats

  • A/W: 11 wk; 195 ± 11 g

  • 1. ND

  • 2. HFD (51% kcal fat) + dextrin (450 mg kg-1 BW per day)

  • 3. HFD + milk thistle extracts (150 mg kg-1 BW per day)

  • 4. HFD + 50% BE leaf (450 mg kg-1 BW per day)

  • 5. HFD + 50% BE fruit (450 mg kg-1 BW per day)

  • 6. HFD + BE leaf and fruit (2:1) (150 mg kg-1 BW per day)

  • TP: 12 wk

  • Groups 4, 5, 6: ↓ TG, MDA, and TNFa, Acaca, Fasn, TNFa; ↑glycogen levels, ↑ SOD enzymatic activity

  • Groups 4, 6: ↓ enlargement of the nucleus and the cell size, macrophage infiltration, CHOL, Srebf1 and Il1b, ↑ Cpt1a

  • Group 6: ↑ GSH enzymatic activity

  • Groups 4, 5 & 6: ↓ epididymal and retroperitoneal fat, ↓Serum levels of AST, ALT, TC, LDL, nonesterified FFAs, AUC (Glu & Ins)

  • Groups 4, 5: ↓ TG (serum)

  • Groups 4, 6: ↓ Ins serum levels, HOMA-IR, ↑ % goblet cells, ↑ Akkermansia and Lactobacillus population in feces

  • Group 6: ↑ intestinal surface area

Peng et al, 20176Morus alba aqueous extract
  • M: Male Wistar rats

  • A/W: 220 ± 10 g

  • 1. ND

  • 2. HFD (ND + 20% fat + 2% CHOL)

  • 3. HFD + BE 0.5%

  • 4. HFD + BE 1%

  • 5. HFD + BE 2%

  • NAFLDI: 4 wk

  • TP: 10 wk

  • Groups 3, 4, 5: ↓ FASN, HMGCR, and TBARS; ↑ CPT1

  • Groups 4, 5: ↓ TC, TG levels, and lipid accumulation; ↓ AGPAT; ↑ SOD enzymatic activity; ↑ PPARa

  • Groups 3, 4, 5: ↓ BW, ↓ total peripheral and total body fat, ↓ TNF-α and leptin serum levels

  • Groups 4, 5: ↓ ALT, TG, TC, and LDL (serum)

  • Group 5: ↓ perineal, mesenteric, subcutaneous, and groin fat; ↑ adiponectin (serum)

Song et al, 201631Morus nigra L. ethanolic extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. LFD + saline 100 mg kg-1 d-1 OG

  • 2. HFD (45% fat) + saline 100 mg kg-1 d-1 OG

  • 3. HFD + BE 100 mg kg-1 d-1 OG

  • TP: 14 wk

  • ↓ Steatosis grade

  • ↓ TG and TC levels, ↓ Gk and Fads2, ↑ Adipor2 and Insig1

  • ↓ BW, ↓ relative perineal and epididymal fat weight

  • ↓ TC, LDL, AST, ALT, Glu, Ins (serum), HOMA-IR, HOMA-IS, adiponectin (serum); ↑ leptin (serum)

Yang et al, 201837Morus alba ethanolic extract
  • M: Male SD rats

  • A/W: 240-260 g

  • 1. SD + DW, OG

  • 2. HFD + DW, OG

  • 3. HFD + BE 100 mg kg-1 BW, OG

  • 4. HFD + BE 200 mg kg-1 BW, OG

  • TP: 10 wk

  • ↓ LW, intracellular lipid accumulation, TG levels, Srebf1, Fasn, Acaca, and Scd1

  • ↓ Mitochondrial ROS production and NADPH oxidase activity

  • ↓ MDA, 4-HNE, and NOX4, ↑ SOD enzymatic activity, ↑ mitochondrial complex-I and complex-II activities, ↑ ATP content

↓ TG, TC, LDL, AST, and ALT, ↑ HDL (serum)
Fotschki et al, 202138Rubus idaeus L. acetone-water extract
  • M: Male Wistar rats

  • A/W: 8 wk; 165.3 ± 1.43 g

  • 1. HFD (23% fat)

  • 2. HFD + BE 0.64%

  • 3. HFD + BE 0.64% + fructo-oligosaccharides 3%

  • 4. HFD + BE 0.64% + pectins 3%

  • TP: 12 wk

  • Groups 2, 3, 4: ↓ ballooning and portal inflammation, ↓ Pparg

  • Groups 2, 3: ↓ lobular inflammation, ↓ MDA levels, ↓ Il6

  • Groups 3, 4: ↓ steatosis, ↓ fat content

  • Group 3: ↑ LW, ↓ TC and TG levels, ↓ Ppara and Angplt4

  • Groups 2, 3: ↓ AST (plasma)

  • Groups 3, 4: ↑ cecum mass

  • Group 3: ↓ TG (plasma)

  • Group 4: ↓ cecum pH

Li et al, 201439Rubus aleaefolius Poir extract
  • M: Male Sprague-Dawley rats

  • A/W: 8 wk; 180-200 g

  • 1. ND + 10 mL kg-1 DW

  • 2. mHFD (10% lard + 2 % CHOL) + DW 10 mL kg-1 OG

  • 3. mHFD + BE 1.44 g kg-1 BW per day, OG

  • 4. mHFD + BE 0.72 g kg-1 BW per day, OG

  • NAFLDI: 8 wk

  • TP: 28 d

↓ Fat accumulation, hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci, ↓ Acaca, Fasn, Cpt1a↓ TG, TC, LDL; ↑ HDL (serum)
Nam et al, 201440Rubus coreanus
  • M: Male C57BL/6 mice

  • A/W: –

  • 1. ND

  • 2. HFD (60% kcal fat)

  • 3. HFD+ BE 100 mg kg-1

  • TP: 10 wk

↓ LW, TG, and TC, Nr1h3, Srebf1, Acaca, Cd36, Fasn, FASN, and HMGCR reductase activity; ↑CPT activity
  • ↓ BW, ↓ epididymal fat mass

  • ↓ AST, ALT, TC, TG, LDL, and leptin plasma levels

Zhao et al, 201341Rubus aleaefolius Poir. extract
  • M: Male SD

  • A/W: 8 wk; 180-200 g

  • 1. CT + DW, IG

  • 2. HFD (10% lard + 2% CHOL) + DW, IG

  • 3. HFD + polyene phosphatidylcholine 76 mg kg-1 BW per day IG

  • 4. HFD + BE 1.44 g kg-1 BW per day IG

  • 5. HFD + BE 0.72 g kg-1 BW per day IG

  • NAFLDI: 8 wk

  • TP: 7 d

  • Groups 4, 5: ↓ hepatocyte ballooning, scattered lobular inflammatory cell infiltration, and inflammatory foci

  • ↓ Nfkb, Tnfa, Ptgs2, and Il6 protein and mRNA expression

Groups 4, 5: ↓ BW ↓ ALT, AST, GGT, ALP, TC, TG, and LDL serum levels
Bae et al, 201742Lycium chinense aqueous extract
  • M: Male C57BLS/J-m mice

  • A/W: 7 wk

  • 1. ND

  • 2. MCD + PBS OG

  • 3. MCD + betaine 10 mg kg-1 d-1, OG

  • 4. MCD + BE 100 mg kg-1 d-1, OG

  • 5. MCD + BE 200 mg kg-1 d-1, OG

  • 6. MCD + BE 400 mg kg-1 d-1, OG

  • TP: 4 wk

  • Group 6: ↓ LW

  • Groups 5, 6: ↓ lipid accumulation, ↓ TG, GSH, and MDA levels, F4/80, Itgax, Ccl2, Icam1, Tnfa, Il6, Il1b, Tgfb, Col1a1, Acta2; ↑ SOD and CAT enzymatic activity, pERK; ↓ pJNK

↓ AST and ALT plasma levels
Glisan et al, 201643Vaccinium macrocarpon acetone:water:acetic acid (80:19.9:0.1, v:v:v) extract
  • M: Male C57BL/6J mice

  • A/W: 4 wk

  • 1. HFD (60% kcal from fat)

  • 2. HFD + BE 0.8%

  • NAFLDI: 11 wk

  • TP: 10 wk

↓ Degree of lipidosis and lipid droplets area, ↓ TNF-α, CCL2, and IL1b; ↓ Tlr4, NFKB, Tnfa, Il1b, Ucp2, Ptgs2, Ccr2, Ccl3, Nlrp3, Casp1, Ppara, Txnip↓ FFA, IL-1b, ALT plasma levels
Huang et al, 201744Phyllantus emblica L. aqueous extract
  • M: Male SD rats

  • A/W: 160 ± 10 g

  • 1. ND

  • 2. HFD (40% fat)

  • 3. HFD + GA 100 mg kg-1, OG

  • 4. HFD + BE 125 mg kg-1 BW, OG

  • 5. HFD + BE 250 mg kg-1 BW, OG

  • 6. HFD + BE 500 mg kg-1 BW, OG

  • TP: 20 wk

  • Groups 4, 5, 6: ↓ Srebf1, ↑ CAT and GST enzymatic activity

  • Group 5: ↑ Ppara

  • Group 6: ↓ lipid droplets and fat deposition, ↓ Nr1h3, ↑ GRd enzymatic activity

  • Groups 4, 5, 6: ↓ BW, ↓ AST (serum), ↑ adiponectin (peritoneal fat)

  • Groups 5, 6: ↓ peritoneal and epididymal fat weight

  • Group 6: ↓ ALT and LDL (serum)

Tung et al, 201852Phyllanthus emblica L. reverse osmosis aqueous extract
  • M: Male C57BL/6JNarl mice with specific pathogen-free conditions

  • A/W: 5 wk; 20 ± 2 g

  • 1. ND

  • 2. MCD

  • 3. MCD + GA 100 mg kg-1 BW per day OG

  • 4. MCD + BE 125 mg kg-1 BW per day OG

  • 5. MCD + BE 250 mg kg-1 BW per day OG

  • 6. MCD + BE 500 mg kg-1 BW per day OG

  • TP: 4 or 8 wk

  • Groups 4, 5, 6: ↑ GST, SOD, ↓CAT activity (wk 8), ↓Cyp2e1, Tnfa (weeks 4 and 8), ↓Il1b (week 8)

  • Groups 4, 6: ↓ TBARs levels (week 4)

  • Group 5: ↓ TBAR levels (week 8)

  • Group 6: ↓ GPx enzymatic activity (weeks 4 and 8)

  • Group 4, 5, 6: ↓ AST and ALT (weeks 4 and 8), ↑ TG serum (week 8)

  • Group 6: ↑ TG serum levels (week 4)

Xiao et al, 201845Lycium barbarum Lynn aqueous extract
  • M: Male and female C57BL/6N mice

  • A/W: 20-25 g

  • 1. ND

  • 2. MCD

  • 3. ND + BE 1 mg/kg/ OG

  • 4. MCD + BE 1 mg kg-1 d-1 OG

  • NAFLDI: 3 wk

  • TP: 3 wk

  • ↓ NAS score and apoptotic cells number

  • ↓ ACTA2, SMAD2, TGFb1, p-SMAD2, MDA, TXNIP, TNF-α, IL10, NFKB p50, NFKBIA, BAX-1, cytochrome c, CYP2E1, cleaved CASP1, ASC, NLRP3, and NLRP6, ↑ CAT, GPx and BCL-2

  • ↑ BW

  • ↓ IL-18 and IL-1b

Pak et al,201223Vitis coignetiae Pulliat aqueous extract
  • M: Male Wistar rats

  • A/W: 6 wk

  • 1. ND

  • 2. CD HFD

  • 3. CD HFD + BE 100 mg kg-1 d-1 OG

  • 4. CD HFD + BE 300 mg kg-1 d-1 OG

  • NAFLDI: 13 wk (4 wk HFD+ 9 wk HFD and NaNO₂ 40 mg kg-1 d-1 IP)

  • TP: weeks 10 to 13

  • Groups 3, 4: ↑ relative LW, ↓ mitochondria ROS derivation, ↓ MPO activity, ↓ NFKB p65

  • Group 4: ↓ % of fibrosis area

  • Group 3, 4: ↓ ALT plasma levels

  • Group 4: ↑SOD enzymatic activity (serum)

Al Zarzour et al, 201847Phyllanthus niruri methanolic extract
  • M: Male SD rats

  • A/W: 10 wk

  • 1. ND + DW (10 mL kg-1 BW) OG

  • 2. HFD (8.23% margarine (wt/wt), 8.23% ghee fat (wt/wt), 0.82% CHOL, and 0.41% cholic acid) + DW (10 mL kg-1 BW) OG

  • 3. HFD + metformin 500 mg kg-1 BW OG

  • 4. HFD + BE 1000 mg kg-1 BW OG

  • NAFLDI: 5 wk

  • TP: 3 wk

  • ↓ Micro- and macrovesicles and fibrosis

  • Pparg, Col1a1, and Slc10a2

  • ↑ Adiponectin serum levels

  • ↓ TNF-α, RBP4, vaspin, and IL-6 (serum)

Nanashima et al, 202050Ribes nigrum L. commercial extract
  • M: ovariectomized and sham surgery female SD rats

  • A/W: 12 wk; 249.7 ± 10.2 g

  • 1. ND ovariectomized rats (AIN-93M)

  • 2. ND sham surgery rats (AIN-93M)

  • 3. Ovariectomized rats: ND (AIN-93M) + BE 3%

  • TP: 12 wk

  • ↓ Adipocyte diameter

  • Tnfa, Il6, and Il1b

  • ↓ BW

  • ↓ Visceral fat weight

  • ↓ TG, TC, LDL, adiponectin, and leptin (serum)

Santos et al, 201748Vitis vinifera L. hydroalcoholic extract
  • M: Male C57BL/6 mice

  • A/W: 4 wk

  • 1. ND + W, OG

  • 2. HFD (60% fat) + W, OG

  • 3. ND + BE 200 mg kg-1 d-1, OG

  • 4. HFD + BE 200 mg kg-1 d-1, OG

  • TP: 12 wk

  • ↓ LW, ↓ liver fat density

  • ↓ TC, TG, and glycogen levels

  • ↓ MDA and carbonyl protein levels

  • ↑ p-IRS-1, pAKT, PI3-1K, SLC2A2, pLKB1, pACACA, HMGCR, and pAMPK/AMPK ratio, ABCG5 and ABCG8, ↓ SREBP-1c,↑ CAT, GPx, and SOD enzymatic activity

  • ↓ BW

  • ↓ Epididymal and retroperitoneal fat mass

  • ↓ Glu and Ins, HOMA-IR (serum)

Charradi et al, 201451Vitis vinifera ethanolic extract
  • M: Male Wistar rats

  • A/W: 210-230 g

  • 1. ND + 10% ethanol IP (daily)

  • 2. HFD (39% kcal fat) + ethanol 10% IP (daily)

  • 3. ND + BE 500 mg kg-1 d-1 BW IP

  • 4. HFD + BE 500 mg kg-1 d-1 BW IP

  • TP: 6 wk

  • ↓ Relative LW, macrovesicular steatosis, dilatation, and fat accumulation within hepatocytes and sinusoids, ↓ TG, TC, LDL/HDL ratio, TPL, (LDL+VLDL) to HDL ratio, Apo B to Apo AI ratio, MDA, carbonyl protein, and GSSG levels; ↑ levels of ApoAI, GSH, and GSH to GSSG ratio, ↑ GPx and total-, Cu/Zn-, Mn-, and Fe-SOD enzymatic activity

  • ↓ ALAT, ASAT, and lipase activity

  • ↑ Liver alcohol dehydrogenase activity, ↓ Zn depletion

De Bem et al, 201846Euterpe oleracea Mart. hydroalcoholic extract
  • M: Male Wistar rats

  • A/W: 180-200 g

  • 1. ND

  • 2. ND + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 3. ND + BE 200 mg kg-1 d-1 IG

  • 4. ND + EXE + BE 200 mg kg-1 d-1 IG

  • 5. HFD (45% kcal fat)

  • 6. HFD + EXE (treadmill 30 min d-1; 5 d wk-1)

  • 7. HFD + BE 200 mg kg-1 d-1 IG

  • 8. HFD + EXE + BE 200 mg kg-1 d-1 IG

  • NAFLDI: 5 wk (streptozotocin/citrate buffer [CT] IP [35 mg kg-1] once in wk 3)

  • TP: 4 wk

  • Groups 7, 8: ↓ LW and steatosis, TC, TG, MDA, protein carbonyl and 8-isoprostane levels; ↑ ABCG5, pAMPK, pLKB1 to LKB1 ratio, pAMPK/AMPK, pACC/ACC; ↓ SREBP-1c, ACACA, HMGCR; ↑ SOD and GPx enzymatic activity

  • Group 7: ↑ pACC

  • Group 8: ↓ glycogen levels, AMPK

  • Groups 7, 8: ↓ TC, TG, VLDL, ALT, MDA, and protein carbonyl (serum)

  • Group 8: ↓ AST (serum)

Freitas et al, 201649Euterpe edulis oil extract or defatted extract
  • M: Male Wistar rats

  • A/W: 4 wk; 85 ± 5 g

  • 1. ND

  • 2. HFD (50% fat)

  • 3. HFD + BE oil 4%

  • 4. HFD + BE pulp 5%

  • 5. HFD + BE pulp 10%

  • 6. HFD + defatted BE 5%

  • 7. HFD + defatted BE 10%

  • NAFLDI: 4 wk

  • TP: 4 wk

  • Groups 3, 4, 5, 6: ↓ CAT, SOD enzymatic activity

  • Groups 3, 4, 6: ↓ TBARs

  • Groups 4, 6: ↓ inflammatory infiltration and hepatocytes nucleus, GST enzymatic activity

Group 6: ↑ TC serum levels
1

Outcomes refer to groups with berry extract administration vs groups after NAFLD induction, unless otherwise specified.

Abbreviations: A/W, age/weight; AI, atherogenic index (AI); AUC ROC, area under the receiver operating characteristic curve; BE, berry extract; BW, body weight; CCB, cocoa butter; CEL, cellulose; CHOL, cholesterol; CO, corn oil; CS, corn starch; DW, distilled water; FA, fatty acid; FFA, free fatty acid; Glu, glucose; HFD, high-fat diet; IG, intragastric; Ins, insulin; IP, intraperitoneal; LFD, low-fat diet; LW, liver weight; M, animal model; MCD, methionine-choline–deficient diet; MeOH, methanol; mHFD, modified high-fat diet; NAFLDI, nonalcoholic fatty liver disease induction; ND, normal diet; OA, orotic acid; OAD, orotic acid diet; OG, oral gavage; OO, olive oil; SA, silk amino acid; SD, Sprague-Dawley rats; STZ, streptozotocin; SUC, sucrose; TG, triglyceride; TEAC, trolox equivalent antioxidant capacity; TP, treatment period; V, vehicle; W, water; WTD, Western-type diet.

Biomarker abbreviations (genes and proteins): ABCG5, ABCG8: ATP binding cassette subfamily G member 5 and 8; ACC or ACACA: acetyl-CoA carboxylase; AdipoR2: adiponectin Receptor 2; AGPAT: 1-acylglycerol-3-phosphate-O-acyltransferase enzyme; ALAT: alanine transaminase; ALP, alkaline phosphatase; ANGPTL4: angiopoietin-like 4 gene; Apo: apolipoprotein; aP2 or FABP4: fatty acid binding protein 4; ASAT: aspartate aminotransferase; ASC or PYCARD: apoptosis-associated speck-like protein containing a CARD; α-SMA or Acta2: α smooth muscle actin; AST: aspartate aminotransferase; Atg4b, Atg5, Atg7, Atg12: autophagy-related cysteine peptidase 4, 5, 7, and 12; Bax-1: apoptosis regulator BAX; Bcl-2: B-cell lymphoma 2; CAT: catalase; CASP1: Casparian strip membrane protein 1; CCR2: C-C chemokine receptor type 2; CCL2 or 3: C-C motif chemokine ligand 2 or 3 protein; CD11c or Itgax: integrin α-X; CD36: platelet glycoprotein 4; C/EBPα or Cebpa: CCAAT-enhancer-binding proteins; CK-18: cytokeratin 18; CYP7A1: cholesterol 7-α-monooxygenase; CYP2E1: cytochrome P450 2E1; CPT1: carnitine palmitoyltransferase; Col1a1: collagen type I α 1 chain; COX2 or Ptgs2: cyclooxygenase-2; Mlxipl; ChREBP: carbohydrate-responsive element-binding protein; CYP2E1: N-nitrosodimethyl-amine demethylase; ERK: extracellular-signal-regulated kinase; Fabp4: fatty acid-binding protein 4; FASN: fatty acid synthase enzyme; Fads2: acyl-CoA 6-desaturase; F4/80: rat anti–mouse F4/80 antibody; GSH: glutathione reductase; GSSG: glutathione disulfide; GST: glutathione S-transferase; GPx: glutathione peroxide; GRd: glutathione reductase; Gk or GYK: glycerol kinase; SLC2A2 or Glut 2: glucose transporter 2; 4-HNE: 4-hydroxynonenal; HMGCR: 3-hydroxy-3-methy-glutaril-CoA reductase enzyme; HO-1: heme oxygenase-1; ICAM-1: intercellular adhesion molecule; IκB-α or Nfkbia: nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α; IL-6: interleukin 6 cytokine featuring pleiotropic activity; IL-1β: interleukin -1 β pro-inflammatory cytokine produced by cells of the innate immune system; Nos2 or iNOS: inducible nitric oxide synthase; INSIG1: insulin induced gene 1; JNK: Jun N-terminal kinase; Klf2: Krüppel-like factor 2; LC3: microtubule-associated protein light chain 3; LPL: lipoprotein lipase; LXRa or Nr1h3: liver X receptor α; MDA: malondialdehyde; MPO: myeloperoxidase; miR-33a: microRNA 33a; NADPH: nicotinamide adenine dinucleotide phosphate; NAS: NAFLD Activity Score; NF-κB: nuclear factor κ B; NLRP3: NACHT, LRR, and PYD domains-containing protein 3; NLRP6: NOD‐like receptor family pyrin domain containing 6; Nrf2: nuclear factor erythroid 2-related factor 2; NOX4: NADPH oxidase 4; PPAR-γ: peroxisome proliferator-activated receptor γ; pAMPK: phosphorylated AMP-activated protein kinase; pAKT: phospho-AKT; p-ERK: extracellular signal-related kinase; p-IRS-1: phosphorylated insulin receptor substrate; PI3-1K: phosphatidylinositol 3-kinase 1; p-mTOR: phosphorylated serine/threonine-protein kinase mTOR; p-JNK: phosphorylated Jun N-terminal kinase; LKB1: serine/threonine protein kinase liver kinase B1; p-PI3K: phosphorylated phosphatidylinositol-3 kinase; PPARα: peroxisome proliferator-activated receptor α; ROS: reactive oxygen species; SCD-1: stearoyl-coenzyme A desaturase 1; SOD: superoxide dismutase; SLC10A2: ileal sodium/bile acid cotransporter; Smad2: Mothers Against Decantaplegic homolog 2; SREBP: sterol regulatory element-binding protein; Srebf1: sterol regulatory element binding transcription factor 1; TGF-β: transforming growth factor β; TXNIP: thioredoxin-interacting protein; TBARS: thiobarbituric acid reactive substances; TPL: protein TOPLESS; TNF-α: tumor necrosis factor α; Tlr4: Toll-like receptor 4; UCP2: mitochondrial uncoupling protein 2.

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