TABLE 2.
Phytochemical enhances mitophagy to treat metabolic disorders.
| Phytochemical | Disease | Type of mitophagy | Molecular mechanism | References |
| Akebia saponin D | Non-alcoholic fatty liver disease | BNIP3-mediated mitophagy | • Enhancing autophagy: p-AMPK ↑, p-mTOR ↓ and LC3-II ↑; • Enhancing mitophagy: BNIP3 ↑. |
Gong et al., 2018 |
| Quercetin | Non-alcoholic fatty liver disease | PINK1/Parkin-mediated mitophagy | • Suppressing hyperlipidemia: triglyceride↓ and cholesterol ↓; • Suppressing lipogenic gene expression: fatty acid synthase (FAS) ↓; • Enhancing β-oxidation enzyme: carnitine palmitoyltransferase I (CPT1) ↑; • Enhancing mitochondrial function: respiratory control ratio ↑ and mitochondrial membrane potential ↑; • Enhancing mitophagy: Frataxin ↑, Parkin ↑;PINK1 ↑, Beclin1 ↑, LC3-II ↑, p62 ↓, CISD1 ↓, VDAC1 ↑, TOM20 ↓ and HIF-1α↓. |
Liu et al., 2018 |
| Cyanidin-3-O-glucoside | Non-alcoholic fatty liver disease | PINK1-mediated mitophagy | • Suppressing hyperlipidemia: cholesterol synthesis-related genes (HMGCR) ↓, fatty acid uptake related genes (FABP1 ↓, FATB1 ↓ and CD36 ↓), fatty acid synthesis related genes (FAS ↓, ACCα↓, SREBF1 ↓ and PPAR-γ↓), cholesterol efflux-related genes (CYP7A1 ↑) and fatty acid β-oxidation-related genes (PPARA ↑, CPT1A ↑, ACOX1 ↑ and MCAD ↑); • Suppressing inflammation: IL-1β↓, IL-18 ↓, NLRP3 ↓, Caspase-1 ↓, Pro-Caspase-1 ↓ and IL-1β↓; • Suppressing oxidative stress: H2O2 ↓, MDA ↓, SOD ↑, CAT ↑, GSH-PX ↑ and ROS ↓; • Enhancing mitochondrial function: peroxisome proliferative activated receptor- γ (NR1C3) ↑, nuclear respiratory factor 1 (NRF1) ↑, nuclear factor erythroid derived 2 like 2 (NRF2) ↑ and mitochondrial transcription factor A (TFAM) ↑; • Enhancing mitophagy: PINK1 ↑, Parkin ↑;LC3-II ↑, p62 ↓, TOM20 ↓, PIK3C3 ↑, Beclin1 ↑, ATG5 ↑, ATG12 ↑, ATG7 ↑ and TFEB ↑. |
Li X. et al., 2020 |
| Corilagin | Non-alcoholic fatty liver disease | Parkin-mediated mitophagy | • Suppressing hyperlipidemia: triglyceride ↓, cholesterol ↓, low-density lipoprotein cholesterol ↓, high-density lipoprotein cholesterol ↑; fatty acid synthesis genes (FASN ↓, ACC1 ↓, and SREBP-1c ↓) and fatty acid oxidation genes (PPARA ↑, CPT1A ↑, and ACOX1 ↑); • Suppressing inflammation: MCP1 ↓, F4/80 ↓, TNF-α↓ and IL-6 ↓; • Enhancing mitophagy: LC3-II ↑, p62 ↓, Parkin ↑ and VDAC1 ↑; • Suppressing oxidative stress: ROS ↓, SOD ↑, GSH-PX ↑, CAT ↑, and MDA ↓; • Enhancing mitochondrial function: mitochondrial membrane potential ↑ and mitochondrial biogenesis related gene (NRF1 ↑, NRF2 ↑, and TFAM ↑). |
Zhang R. et al., 2019 |
| Melatonin | Non-alcoholic fatty liver disease | BNIP3-mediated mitophagy | • Suppressing hyperlipidemia: triglycerides ↓ and cholesterol ↓; • Suppressing inflammation: IL-6 ↓, TNF-α↓ and TGF-β↓; • Suppressing oxidative stress: ROS ↓, SOD ↑, GSH-PX ↑ and MDA ↓; • Enhancing mitochondrial function: ATP generation ↑ and mitochondrial respiratory function ↑; • Enhancing mitophagy: DRP ↓, BNIP3 ↑, LC3-II ↑, Beclin1 ↑, Atg5 ↑, DNA-PKcs ↓, p53 ↓ and NR4A1 ↑. |
Zhou et al., 2018 |
| Cyanidin-3-O-glucoside | Obesity | PINK1-mediated mitophagy | • Suppressing cholesterol synthesis-related genes (HMGCR ↓), fatty acid uptake related genes (FABP1 ↓, FATB1 ↓ and CD36 ↓) and fatty acid synthesis related genes (FAS ↓, ACCα↓, SREBF1 ↓ and PPAR-γ↓); • Enhancing cholesterol efflux-related genes (CYP7A1 ↑) and fatty acid β-oxidation-related genes (PPARA ↑, CPT1A ↑, ACOX1 ↑ and MCAD ↑); • Suppressing inflammation response: IL-1β↓, IL-18 ↓, NLRP3 ↓, Caspase-1 ↓, Pro-Caspase-1 ↓ and IL-1β↓; • Suppressing oxidative stress: H2O2 ↓, MDA ↓, SOD ↑, l-cysteine:2-oxoglutarate aminotransferase (CAT) ↑ and glutathione peroxidase (GSH-PX) ↑ and ROS ↓; • Enhancing mitochondrial function: peroxisome proliferative activated receptor- γ (NR1C3) ↑, nuclear respiratory factor 1 (NRF1) ↑, nuclear factor erythroid derived 2 like 2 (NRF2) ↑ and mitochondrial transcription factor A (TFAM) ↑; • Enhancing mitophagy: PINK1 ↑, Parkin ↑;LC3-II ↑, p62 ↓, TOM20 ↓, PIK3C3 ↑, Beclin 1 ↑, ATG5 ↑, ATG12 ↑, ATG7 ↑ and TFEB ↑. |
Li X. et al., 2020 |
| Quercetin | Obesity | PINK1/Parkin-mediated mitophagy | • Suppressing hyperlipidemia: triglyceride ↓ and cholesterol ↓; • Suppressing lipogenic gene expression: fatty acid synthase (FAS) ↓; • Enhancing β-oxidation enzyme: carnitine palmitoyltransferase I (CPT1) ↑; • Enhancing mitochondrial function: respiratory control ratio and mitochondrial membrane potential ↑; • Enhancing mitophagy: Frataxin ↑, Parkin ↑, PINK1 ↑, Beclin1 ↑, LC3-II ↑, p62 ↓, CISD1 ↓, VDAC1 ↑, TOM20 ↓ and HIF-1α↓. |
Liu et al., 2018 |
| Notoginsenoside R1 | Diabetic retinopathy | PINK1-mediated mitophagy | • Suppressing oxidative stress: ROS ↓, 4-HNE ↓, protein carbonyl ↓ and 8-OHdG ↓; • Suppressing inflammation: MCP-1 ↓, TNF-α↓, IL-6 ↓ and ICAM-1 ↓; • Enhancing mitophagy: Parkin ↑, PINK1 ↑, LC3 ↑ and p62 ↓. |
Zhou et al., 2019a |
| Scutellarin | Diabetes-related vascular disease | PINK1/Parkin-mediated mitophagy | • Suppressing oxidative stress: ROS ↓, SOD ↑ and SOD2 ↑; • Enhancing mitophagy: LC3-II ↑, p62 ↓, Beclin1 ↑, Atg5 ↑, Parkin ↑, PINK1 ↑ and MFN2 ↑; • Suppressing vascular endothelial cell apoptosis: Bcl-2 ↑, Bax ↓, Cytochrome C ↓ and cleaved caspase-3 ↓. |
Xi et al., 2021 |
| Delphinidin-3-O-β-glucoside | Atherosclerosis | AMPK/SIRT1-dependent mitophagy | • Enhancing mitophagy: SIRT1 ↑, Phospho-AMPKα↑, LC3-II ↑ and p62 ↓. | Jin et al., 2014 |
| Salvianolic acid B | Atherosclerosis | SIRT1-mediated mitophagy | • Suppressing inflammation: NLRP3 ↓, IL-1β↓, apoptosis-associated speck-like protein (ASC) ↓ and caspase-1 ↓; • Enhancing mitophagy: SIRT1 ↑, Parkin ↑, Beclin1 ↑, PINK1 ↓, LC3-II ↑ and p62 ↓; • Enhancing mitochondrial function: ROS ↓ and mitochondrial membrane potential ↑. |
Hu et al., 2020 |
| Melatonin | Atherosclerosis | Sirt3/FOXO3/Parkin-mediated mitophagy | • Suppressing inflammation: NLRP3 ↓, caspase-1 ↓ and IL-1β↓; • Enhancing mitophagy: Sirt3 ↑, FOXO3a ↓, LC3-II ↑, TOM20 ↓, Parkin ↑ and Beclin1 ↑; • Enhancing mitochondrial function: ROS ↓ and mitochondrial membrane potential ↑. |
Ma et al., 2018 |
| Resveratrol | Atherosclerosis | BNIP3-related mitophagy | • Suppressing oxidative stress: SOD ↑, GSH ↑ and GSH-PX ↑; • Enhancing mitochondrial function: Mitochondrial respiration complex I and III ↑; • Enhancing mitophagy: BNIP3 ↑, Beclin1 ↑, Atg5 ↑, HIF1 ↑ and AMPK ↑. |
Li C. et al., 2020 |