Table 1.
Effect and mechanism of the candidate drugs in human diseases.
| Drugs | Disease | Model | Effect and Mechanism |
|---|---|---|---|
| Urolithin A | Alzheimer’s disease | human neuronal SH-SY5Y cells; AD mice | Urolithin A induces neuronal mitophagy by increasing key mitophagy-related proteins. It can also enhance the phagocytic efficiency of microglia, and mitigate NLRP3/caspase-1-dependent neuroinflammation [124] |
| Rapamycin | Parkinson’s disease | SH-SY5Y cells treated with rotenone | Rapamycin enhances mitophagy through inhibition of mTOR to clear the Cytochrome c, thereby inhibiting the occurrence of apoptosis caused by rotenone [125] |
| Pifithrin-α | Diabetes | streptozotocin-treated and db/db mice | Pifithrin-α induces mitophagy by promoting Parkin activity through p53 downregulation, then ameliorates mitochondrial dysfunction and glucose intolerance [126] |
| Resveratrol | Diabetic cardiomyopathy | rats by a high-fat diet combined with STZ injection | Resveratrol alleviates cardiac dysfunction in diabetes by improving mitochondrial function via SIRT1-mediated PGC-1α deacetylation [127] |
| Rapamycin | Leigh syndrome | Ndufs4−/− mice | Rapamycin delays the onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions [128] |
| Ginsenoside Rg3 | Hepatitis C Virus | HCV-infected Huh7 and Huh7.5.1 cells | Ginsenoside Rg3 restores the HCV-induced dynamin-related protein 1-mediated aberrant mitochondrial fission process, thereby resulting in the suppression of persistent HCV infection [129] |
| Panax notoginseng saponins | Hypoxia/reoxygenation | H9c2 cells with H/R injury | Panax notoginseng saponins reduce H/R injury in cardiomyocytes by activating HIF-1α/BNIP3 mitochondrial autophagy signaling pathways [130] |
| Empagliflozin | Cardiac microvascular ischemia/reperfusion | myocardial ischemia (45 min)/reperfusion (2 h) injury mice | Empagliflozin normalizes mitochondrial fission and fusion, neutralizes supraphysiologic ROS concentrations, and suppresses mitochondrial apoptosis by activating FUNDC1-dependent mitophagy through the AMPKα1/ULK1 pathway [131] |
| Spermidine | Aging | yeast, flies, nematodes, and human immune cells | Spermidine plays an important role in mitophagy-mediated cytoprotective and anti-aging effects through energy metabolism restoration [132] |