Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions
Abstract
:1. Introduction
1.1. The Hits in NAFLD?
1.2. Biomarkers and Criteria Used in the Diagnosis of NAFLD
1.3. Phytotherapy
1.4. Rationale and Objectives
2. Methods
2.1. Eligibility Criteria
- (a)
- Articles that were published in English,
- (b)
- Animal studies,
- (c)
- NAFLD model induced by diet
- (d)
- Studies assessing the effectiveness of plant-derived extracts or fractions or polyherbal mixtures in the treatment of NAFLD
- (e)
- Studies evaluating at least disordered lipid metabolism, insulin resistance/T2DM, and histologically confirmed steatosis
- (f)
- Studies with one or more of the following: oxidative stress, inflammation, hepatocyte injury, obesity, fibrosis, and cardiometabolic risks (in addition to the pathological conditions in (e)).
- (a)
- Studies conducted in vitro,
- (b)
- Human studies
- (c)
- Reviews,
- (d)
- NAFLD not induced by diet
- (e)
- Studies involving the use of isolated or single phyto-compound to treat NAFLD
- (f)
- Studies not meeting the inclusion criteria stated above.
2.2. Information Sources
2.3. Search Strategy
2.4. Study Selection
- (a)
- Animal models,
- (b)
- Assessments of the effectiveness of plant extracts in NAFLD model
- (c)
- Full-text articles in English
- (d)
- Evaluation of disordered lipid metabolism, steatosis, insulin resistance (HOMA-IR), with one or more of the following: oxidative stress, inflammation, hepatocyte injury, obesity, fibrosis, and cardiometabolic risks.
2.5. Data Collection
3. Results
3.1. Study Selection
3.2. Study Characteristics
4. Discussion
4.1. Trapa quadrispinosa Pericarp Extract (TQPE) Exerts Multiple Therapeutic Hits on NAFLD
4.2. Leonurus japonicus Ethanol Extract (LJE) and Its Multiple Hit Effects on NAFLD
4.3. Multiple Effects of Phyllanthus niruri 50% Methanol in Water Extract (PN50ME) on NAFLD
4.4. Multiple Therapeutic Actions of Combinations of Salvia miltiorrhiza Root and Fruit of Gardenia jasminoides Extracts (SGE)
4.5. Multiple Therapeutic Effects of Methanol Extract from Erica multiflora Leaf (M-EML) on NAFLD
4.6. Alisma orientalis Methanolic Extract (AOME) Alleviate Hyperlipidemia, Hepatic Steatosis, Insulin Resistance, Oxidative Stress, Hepatocyte Injury, and Obesity Associated with NAFLD
4.7. Cissus quadrangularis Stem Extract (CQEt)
4.8. Ethanol Extract of Zingiber zerumbet Rhizome (EEZZR) Attenuates NAFLD by Multiple Mechanism
4.9. Angelica gigas Nakai Extract (AGNE) Alleviate Dyslipidemia, Hepatic Steatosis, Insulin Resistance and Inflammation Related to NAFLD
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Metabolic Risk Abnormalities | Values |
---|---|
Waist circumference | ≥102/88 cm in Caucasian men and women (or ≥90/80 cm in Asian men and women) |
Blood pressure | ≥130/85 mmHg or specific drug treatment |
Plasma triglycerides | ≥150 mg/dL (≥1.70 mmol/L) or specific drug treatment |
Plasma HDL-cholesterol | <40 mg/dL (<1.0 mmol/L) for men and <50 mg/dL (<1.3 mmol/L) for women or specific drug treatment |
(a) Fasting glucose levels or (b) 2-h post-load glucose levels or (c) HbA1c | 100 to 125 mg/dL (5.6 to 6.9 mmol/L) 140 to 199 mg/dL (7.8 to 11.0 mmol) 5.7% to 6.4% (39 to 47 mmol/mol) |
HOMA-IR score | ≥2.5 |
Plasma hs-CRP level | >2 mg/L |
Phytomedicine | Dosage | NAFLD Model | Study Duration | Effect on Lipometabolism | Effect on Glycometabolism/ Insulin Resistance | Effect on Hepatic Steatosis | Effect on Oxidative Stress | Effect on Hepatocyte Injury | Effect on Inflammation | Effect on Obesity | Effect on Fibrosis | Effect on Cardiometabolic Risk | Reference |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Trapa quadrispinosa pericarp extract (TQPE) | 30 mg/kg/d TQPE (p.o.) | HFD/ICR mice | 12 weeks (therapy from week 5) | ↓P-TG ↓P-TC ↓P-LDL-c ↑P-HDL-c ↑p-AMPK/AMPK ↓SREBP/β-Actin ↑p-ACC/ACC | ↓S-INS ↓HOMA-IR ↑p-IRS1/IRS1 ↑p-Akt/Akt | ↓Steatosis (HE) | ↓MDA ↑SOD | ↓P-ALT ↓P-AST | n/a | ↓BW gain | n/a | n/a | [32] |
Leonurus japonicus ethanol extract (LJE) | 100 or 200 mg/kg/d LJE p.o. | HFD/male C57BL/6 mice | 14 weeks | ↓S-TG; ↓L-TG ↓S-TC; ↓L-TC ↓S-LDL-c ↓SREBP (ns) ↑p-AMPK/AMPK ↑PPAR-α | ↓S-INS ↓S-GLU ↓HOMA-IR | ↓Steatosis (HE) | ↓MDA | ↓S-ALT ↓S-AST ↓S-LDH | n/a | ↓BW gain | n/a | n/a | [33] |
Phyllanthus niruri 50% methanol in water extract (PN50ME) | 1000 mg/kg bw/d PN50ME p.o. | HFD/male Sprague–Dawley rats | 8 weeks (therapy from week 5) | ↓S-FFA ↓S-TC; ↓L-TC ↓L-TG ↓S-LDL | ↓S-INS ↓S-GLU ↓HOMA-IR | ↓Steatosis (HE) ↓Hepatocyte Ballooning | ↓MDA | ↓S-ALT ↓AST/ALT | ↓inflammation score (HE) | ↓BW gain | n/a | ↓CRI-I ↓CRI-II ↓AC | [34] |
Salvia miltiorrhiza root and fruit of Gardenia jasminoides extracts (SGE) | 2 g/kg bw/d SGE p.o. | HFD/Male Sprague-Dawley | 10 weeks; therapy from week 7–10 | ↓S-FFA ↓S-TG; ↓L-TG ↓S-TC ↓S-LDL-c ↑S-HDL-c ↑AT-Leptin | ↓S-INS ↓S-GLU ↓HOMA-IR | ↓Steatosis (HE & ORO) | n/a | ↓S-ALT ↓S-AST | ↓AT-TNF-α ↓AT-IL-6 | ↓BW gain ↓Visceral fat mass | ↓Fibrosis (M3T) | n/a | [35] |
Methanol extract from Erica multiflora leaf (M-EML) | 250 mg/kg bw/d p.o. | HFHFD/male Wistar rats | 8 weeks (therapy from week 5) | ↓P-TG ↓P-TC ↓P-LDL-c ↓P-VLDL-c ↓P-Lipase ↑P-HDL-c | ↓P-INS ↓P-GLU ↓HOMA-IR | ↓Steatosis (HE & ORO) | ↓MDA ↑SOD ↑CAT ↑GPx | ↓B-ALT ↓B-AST ↓B-ALP ↓P-TB ↓P-DB | ↓NO ↓Lysosomal activity ↓P-TNF-α ↓P-IL-6 | ↓BW gain | n/a | ↓CRI ↓AIP ↓AI | [36] |
Alisma orientalis methanolic extract (AOME) | 150,300 and 600 mg kg−1) | HFD/Male Sprague-Dawley rats | 12 weeks, therapy from week 7 | ↓S-TG; ↓L-TG ↓S-TC; ↓L-TC | ↓FSG ↓FSI ↑ISI ↓IRI | ↓Steatosis (HE) | ↓S-MDA ↑S-SOD | ↓S-ALT ↓S-AST | n/a | BW gain (ns) | ↓Fibrosis (M3T) | n/a | [37] |
Cissus quadrangularis stem extract (CQEt) | CQEt (10 g/100 g diet | HFFD/male Wistar albino rats | 60 days, therapy from day 16 | ↓L-FFAs ↑L-PL ↓L-TG ↓L-TC | ↓P-INS ↓P-GLU ↓HOMA-IR ↓QUICKI ↓FIRI | ↓Steatosis (HE & ORO | ↓L-TBARS ↓L-LHP ↓L-Protein carbonyls ↑SOD ↑CAT ↑GPx | ↓P-ALT ↓P-AST ↓P-GGT ↓P-ALP | n/a | ↓BW gain | n/a | n/a | [38] |
Ethanol extract of Zingiber zerumbet rhizome (EEZZR) | 200, and 300 mg/kg | HFD/Male Golden Syrian hamsters | 10 weeks, therapy from week 3 | ↓L-TC; ↓P-TC ↓P-TG; ↓L-TG ↓P-LDL-c ↓P-FFAs ↑P-HDL-c ↓L-SREBP-1c ↓L-ACC1 ↓L-FAS ↓L-SCD-1 ↑L-PPARα ↑L-CPT-1 ↑L-ACO ↑L-ACOX1 | ↓P-INS ↓P-GLU ↓HOMA-IR | ↓Steatosis (HE | n/a | n/a | ↓L-TNF-α ↓L-IL-6 ↓L-MCP1 ↓F4/80 | ↓BW gain | ↓A-SMA | n/a | [39] |
Angelica gigas Nakai extract (AGNE) | 40 mg/kg) | HFD/c57BL6/J mice | 16 weeks. | ↓S-Leptin ↓L-TG ↓S-TG ↓S-TC ↓S-LDL S-HDL (ns) ↓L-FAS/β-actin ↓SREBP1/LaminB ↓L-CD36/β-actin ↓L-SCD-1/β-actin ↑Sirt1/β-actin ↑p-AMPK/AMPK ↑L-p-ACC/ACC | ↓S-INS ↓S-GLU ↓HOMA-IR ↓B-GLU (GTT) ↓B-GLU (ITT) ↑S-Adiponectin ↑p-Akt/Akt | ↓Steatosis (HE, ORO) | n/a | n/a | ↓S-TNF-α ↓S-IL-6 ↓S-MCP1 ↓L-F4/80 | n/a | n/a | n/a | [40] |
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Ore, A.; Akinloye, O.A. Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions. Medicina 2021, 57, 822. https://doi.org/10.3390/medicina57080822
Ore A, Akinloye OA. Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions. Medicina. 2021; 57(8):822. https://doi.org/10.3390/medicina57080822
Chicago/Turabian StyleOre, Ayokanmi, and Oluseyi Adeboye Akinloye. 2021. "Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions" Medicina 57, no. 8: 822. https://doi.org/10.3390/medicina57080822