TABLE 2.
Potential approaches to target podocyte mitochondrial dysfunction in preclinical developments.
| Agent | Classification | Mechanism of action | DKD model | References |
|---|---|---|---|---|
| Mitochondria-targeted antioxidant | Salvianolate | Modulates NOX4 activity and ameliorates oxidative injury | Db/db mice and human podocyte cell line | Liang et al. (2021) |
| MCC950 | Inhibits NLRP3 inflammasome and suppresses lipid accumulation, ROS generation and NF-κB p65 activation | Db/db mice and mouse podocyte cell line | Wu et al. (2021) | |
| Berberine | Activates the PGC-1α signalling pathway and promotes mitochondrial fatty acid oxidation | Db/db mice and mouse podocyte cell line | Qin et al. (2020) | |
| Resveratrol | Activates SIRT1 and suppresses oxidative stress | Db/db mice and human podocyte cell line | Wang et al. (2020a), Zhang et al. (2019) | |
| GKT137831 | Inhibits Nox1/4 activity and suppresses ROS generation | Streptozotocin-induced diabetic mice and human podocyte cell line | Jha et al. (2014) | |
| INO-1001 and PJ-34 | Inhibits poly (ADP-ribose) polymerase activity and blocks the ROS generation | Db/db mice and mouse podocyte cell line | Szabo et al. (2006) | |
| Grape seed proanthocyanidin extracts | Activates the AMPK-SIRT1-PGC-1a signaling pathway and inhibits oxidative stress | Streptozotocin-induced diabetic mice | Bao et al. (2014) | |
| Inhibits mitochondrial fission | Mdivi-1 | Inhibits DRP1 activity and suppresses mitochondrial fission | Db/db mice and primary mouse podocyte | Ayanga et al. (2016) |
| Berberine | Inhibits palmitic acid-induced activation of DRP1 activity and suppresses mitochondrial fission | Db/db mice and mouse podocyte cell line | Qin et al. (2019) | |
| Promotes mitochondrial biogenesis | LJ-2698 | Inhibits adenosine receptor activity and promotes mitochondrial biogenesis | Db/db mice | Dorotea et al. (2018) |
| Salidroside | Stimulates the Sirt1/PGC-1 axis and promotes mitochondrial biogenesis | Streptozotocin-induced diabetic mice | Xue et al. (2019) | |
| TEPP-46 | Activates pyruvate kinase M2 and induces mitochondrial biogenesis | Streptozotocin-induced diabetic mice, mouse and human podocyte cell lines | Qi et al. (2017) | |
| INT-777 | Activates G protein-coupled receptor TGR5 and induces mitochondrial biogenesis | Db/db mice and human podocyte cell line | Wang et al. (2016) |