TABLE 1.
Mechanisms of natural products and active components in the treatment of NAFLD.
| Classification | Natural Product | Animal model | Cell model | Function | Mechanism/Target | Reference |
|---|---|---|---|---|---|---|
| Phenolics | Resveratrol (RSV) | C57BL/6 mice (RSV 20 mg/kg) | HepG2 cells (RSV 1 μM) AML-12 cells | Mitochondrial biogenesis promotion, ROS reduction | eNOS/NO/cGMP pathway, Akt/Nrf2 pathway | Kim et al. (2014) |
| — | HepG2 cells (RSV 10, 20 μM) | Mitochondrial dynamic and β-oxidation promotion | FAS, p-AMPK, CPT1α, Sirt1, PPARγ, SREBP-1c | Izdebska et al. (2018); Rafiei et al. (2019) | ||
| C57BL/6J mice | — | Mitophagy promotion | PINK1/Parkin pathway, CoQs | Meza-Torres et al. (2020) | ||
| Wistar rats (RSV 100 mg) | — | Mitochondrial number elevation | UCP2 | Poulsen et al. (2012) | ||
| Punicalagin (PU) | SD rats (PE 50, 150 mg/kg) | HepG2 cells (4 μg/ml PU and 10 μg/ml PE) | ROS reduction, increase ATP production | Nrf2/HO-1/NQO1 pathway, UCP2, PGC-1α, ACADL, ACADM (MRC complex) | Zou et al. (2014) | |
| C57BL/6J mice (PU 50, 200 mg/kg) | HepG2 cells (PU 10, 20 μg/ml) | Mitochondrial biogenesis promotion, MMP recovery | Nrf2, PGC-1α, FAS, ACC1 | Cao et al. (2020) | ||
| — | HepG2 cells (PU 10, 20 μg/ml) | ROS reduction; mitochondrial translocation reduction | Keap1-Nrf2 pathway | Zou et al. (2014) | ||
| Litchi pulp phenol (LPPs) | Kunming mice (LPP 50, 100 and 200 mg/kg) | — | ROS reduction; MMP recovery | MRC complex, Na+ K+ ATPase | Su et al. (2016) | |
| Procyanidins | ICR mice (procyanidins 50, 200 mg/kg) | 3T3-L1 cells (flavan-3-ols 0–100 μM) | Mitochondrial biogenesis promotion | PGC-1α, NRF1, TFAM, Mfn1, Mfn2, Drp1 | Tie et al. (2020) | |
| C57BL/6 mice (procyanidins 50, 150 mg/kg)) | HepG2 cells (procyanidin B2 10 μg/ml) | ROS reduction | C/EBPα, SREBP-1c, TNFα, TFEB | Su et al. (2018) | ||
| 6-gingerol, 6-shogaol | Balb/c mice (GE 1,2 g/kg) | HepG2 cells (6-gingerol 25, 50, 100, 200 μM) | ATP production, OXPHOS and mitochondrial biogenesis promotion | AMPK/PGC1α pathway, MRC complex | Deng et al. (2019b) | |
| Helenalin (HCM) | C57BL/6 mice (HCM 0.75, 1.5 and 3 mg/kg) | — | ROS reduction; MMP recovery | Nrf2 pathway, NQO1, HO-1, NF-κB | Li et al. (2019b) | |
| Alkaloids | Benzoyl aconitine (BAC) | Balb/c mice (BAC 10 mg/kg) | HepG2 cells (BAC 25, 50, 75 μM) | OXPHOS, mitochondrial biogenesis, and mitophagy promotion | AMPK pathway, NDUFS1, SDHA, UQCRC1, COX4, ATP5A1 | Deng et al. (2019a) |
| Matrine (Mat) | C57BL/6J mice (Mat 0.5, 2.5, 10 mg/kg) | L02 cells (Mat 200 and 400 μM) | Maintain cytosolic calcium homeostasis, mitophagy protection | SERCA pump, SREBP1c, FAS, ACC | Gao et al. (2018) | |
| Dendrobium nobile Lindl. (DNLA) | Wild-type and Nrf2−/−mice (DNLA 10 mg/kg) | — | ROS reduction; increase ATP production | Nrf2 pathway | Li et al. (2019a); Zhou et al. (2020) | |
| Berberine (BBR) | C57BL/6J mice (BBR 0.075, 1.4 g/kg) | — | Mitochondrial swelling improvement; mitochondrial fusion promotion | SCD1, FABP1, CD36, CPT1α | Yu et al. (2021) | |
| C57BL/6 and Sirt3−/− mice | — | Mitochondrial β-oxidation promotion | Sirt3, LCAD | Teodoro et al. (2013) | ||
| SD rats (BBR 100 mg/kg) | — | Increase ATP production; MMP recovery | Sirt3 | Xu et al. (2019b) | ||
| SD rats (BBR 300 mg/kg) | Huh7 cells (BBR 5,10 μM) | ROS reduction | Nrf2, MRC complex | Shi et al. (2018) | ||
| Holstein cows | Bovine hepatocyte (BBR 10, 20 μM) | Increase ATP production | AMPK pathway, PGC1α | Sun et al. (2017) | ||
| Flavonoids | Silybin (Sil) | — | Rat hepatoma FaO cells (Sil 50 μM) | Mitophagy promotion | miR-122, AQP9, UCP2, NF-κB | Baldini et al. (2020) |
| Silybin-phospholipid complex (SILIPHOS) | Wistar rats (Sil or SILIPHOS 0.4 g/kg) | — | ROS reduction | MRC complex, H2O2 | Serviddio et al. (2010); Grattagliano (2013) | |
| Increase ATP production | ||||||
| MMP recovery | ||||||
| Cyanidin-3-O-glucoside (C3G) | Over expression and knockdown of PINK1 mice (C3G 0.2%) | AML-12 cells HepG2 cells (C3G 100 μM) | Mitophagy promotion | PINK1/Parkin pathway, NLRP3 | Li et al. (2020) | |
| Neohesperidin (NHP) | C57BL/6 mice (NHP 50 mg/kg) | HepG2 cells (NHP 100 μM) | Mitochondrial biogenesis promotion | AMPK/PGC-1α pathway | Wang et al. (2020) | |
| Eriocitrin | Zebrafish (32 mg/day) | HepG2 cells (Erio 1, 3, 10 μM) | Mitochondrial β-oxidation and biogenesis, ATP production promotion | MRC complex, ACOX1, ACADM | Hiramitsu et al. (2015) | |
| Kaempferol-3-O-glucuronide (K3O) | Zebrafish (10, 20, 40 μM) | HepG2 cells (K3O 10, 15, 20 μM) | ROS reduction ATP production promotion | Nrf2/Keap1 pathway | Deng et al. (2021) | |
| Aspalasin | — | C3A liver cells (Aspalasin 10 μM) | Mitophagy promotion | PI3K/Akt signaling pathway | Mazibuko-Mbeje et al. (2019) | |
| Isoflavone | Puerarin | C57BL/6 mice (100, 200, 400 mg/kg) | HepG2 cells (0.1, 1, 10 μM) | ROS reduction | PINK1/Parkin signaling pathway, PI3K/Akt signaling pathway, AMPK, OPA1, Mfn2 | HOU et al. (2020); Wang et al. (2019b); Chen et al. (2018) |
| MMP recovery | ||||||
| ATP and mitochondrial autophagy production | ||||||
| Terpenoids | Celastrol | SD rats (Celastrol 1, 3 mg/kg) | C3A human cells (30, 100 nM) | Mitochondrial biogenesis promotion | AMPK and SIRT1 signaling pathways, PPARγ, PGC-1α, NRF1 | Abu et al. (2017); Abu et al. (2020) |
| C57BL/6 and Nur77−/− mice (Celastrol 0.1 mg/kg) | HepG2, SMMC-7721, QGY-7703 cells (Celastrol 2, 4 μM) | Increase mitochondrial antioxidant activity and biogenesis | Nur77, p62 | Hu et al. (2017) | ||
| Sweroside | C57BL/6 mice (Sweroside 5, 30, 60, 120, 240 mg/kg) | Bone marrow-derived macrophages (BMDMs) | ROS reduction | PPARα, CD36, NLRP3 inflammasome, IL-1β | Yang et al. (2020b); Mridha et al. (2017); Yang et al. (2020a) | |
| Sweroside (25, 50,10 μM) | ||||||
| Amarogentin | — | HepG2 cells (Amarogentin 12.5, 25, 50 μM) | ROS reduction | CYP450 system | Dai et al. (2018) | |
| Mitochondrial biogenesis promotion | ||||||
| Reverse mtDNA damage | ||||||
| Other compounds | Polygonatum kingianum (PK) | SD rats (PK 1, 2, 4 g/kg) | — | Mitochondrial biogenesis promotion | CPT-1α, UCP-2, MRC complex | Yang et al. (2019) |
| Sulforaphane | Rats | — | Increase mitochondrial antioxidant defenses and inhibits redox-sensitive PTP opening | Keap1-Nrf2 pathway | Kubo et al. (2017); Nagata et al. (2017); Greco et al. (2011) | |
| C57BL/6JSlc mice | ||||||
| Wistar Rats (SFN 20 mg/kg) | HHL-5 cells (SFN 1, 5, 10 μM) | Mitochondrial biogenesis promotion | Nrf1, TFAM, PGC-1α, ATGL, HSL | Lei et al. (2019) | ||
| Mitochondrial swelling improvement |