. 2022 Jul 15;13:925993. doi: 10.3389/fphar.2022.925993

TABLE 2.

Kidney protective effects are provided by phytochemicals targeting the mitochondrial fitness in cellular models.

Disease model	Phytochemical	Dosage	Experimental model	Pathobiology	Alteration in molecular markers in response to treatment	References
DN	Berberine	0.4 μM/L, 12 h	Podocytes cells treated with PA	Mitochondrial dysfunction, oxidative stress, apoptosis	↓MMP-9, ↓Drp1, ↓MFF, ↓Fis1, ↓Mid49, ↓Mid51	Qin et al. (2019)
					↓ROS, ↓MDA
					↑PGC-1α, ↑TFAM↑, ↑Nrf-1, ↑Nrf-2
					↓caspase-3, ↓Bax, ↓cytochrome C
					↑Bcl-2
		0.4 μM/L, 12 h	Podocytes cells treated with PA	Oxidative stress, mitochondrial dysfunction, lipid accumulation	↓ROS, ↓MDA, ↑SOD	Qin et al. (2020)
					↑AMPK, ↑PGC-1α, ↑OXPHOS, ↑FAO
					↓FFA, ↓TG
	Polydatin	25 mM, 24, 48, 72 h	HG-induced MPC5 cells	Apoptosis, mitochondrial fragmentation, dysfunction, oxidative stress	↓Caspase 3, 9, ↓cytochrome-C	Ni et al. (2017)
					↓Drp1
					↓ROS
	Resveratrol	10 μM, 6 h	Rat mesangial cells treated with high glucose	Oxidative stress, mitochondrial dysfunction	↑MnSOD, ↓ROS	Xu et al. (2012)
					↑mt complex III, ↑mtDNA
					↑ATP
		10 μM/L, 48 h	Podocytes exposed to high glucose	Oxidative stress, mitochondrial dysfunction	↓mtROS	Zhang et al. (2019)
		10 μM/L, 48 h	Podocytes exposed to high glucose	Oxidative stress, mitochondrial dysfunction	↑mt respiratory chain complex I/III	Zhang et al. (2019)
Obstructed nephropathy	Resveratrol	5–20 μM, 72 h	HK-2 cells treated with TGF-β	Fibrosis	↓FN, ↓α-SMA, ↓TGF-β1	Liu et al. (2019)
Obstructed nephropathy	Resveratrol	5–20 μM, 72 h	HK-2 cells treated with TGF-β	Fibrosis	↓p-Smad3	Liu et al. (2019)
Aged kidney	Resveratrol	50µM, 24 h	H₂O₂-induced HK2 cells	Oxidative Stress	↑HO-1, ↑NQO-1, ↑SOD1, ↑SOD2	Kim et al. (2018)
Sepsis-induced AKI	Curcumin	0.3684 g, 12 d	LPS-induced HK-2 cells	Oxidative stress	↓ROS	Wang et al. (2021a)
Drug-induced AKI	Celastrol	10–100 μM, 24 h	Cisplatin-induced HK-2 and RTECs	Mitochondrial dysfunction, inflammation, apoptosis	↓KIM-1, ↑mtDNA, ↑MMP	Yu et al. (2018)
					↓IL-1β, ↓IL-6, ↓COX-2, ↓NF-κB, ↓ROS
					↑Bcl -2, ↓Bax, ↓Caspase-3
Chemical-induced AKI	Resveratrol	50 μM/L, 30 min	Aldosterone induced podocytes	Mitochondrial dysfunction	↑mtDNA, ↑PGC-1α, ↑TFAM, ↑SIRT3	Yuan et al. (2012)
Chemical-induced AKI	Resveratrol	50 μM/L, 30 min	Aldosterone induced podocytes	Apoptosis	↓caspase-9, ↓caspase-3	Yuan et al. (2012)

AMPK, AMP-activated protein kinase; BCL-2, B-cell lymphoma 2; Drp1, dynamin-related protein 1; FAO, fatty acid oxidation; FN, fibronectin; FFA, free fatty acids; Fis1, mitochondrial fission protein 1; HO-1, Heme oxygenase-1; HK-2, human renal proximal tubule epithelial cell line; HG, hyperglycemia; Mid51 and Mid49, mitochondrial dynamics proteins of 51 and 49 kDa; MMP, mitochondrial membrane potential; mtDNA, mitochondrial DNA; MFF, mitochondrial fission protein; MnSOD, manganese superoxide dismutase; MMP-9, matrix metalloproteinase-9; MDA, malondialdehyde; NQO-1, Quinone Oxidoreductase 1; Nrf-1 and Nrf-2, nuclear respiratory factors 1 and 2; OXPHOS, oxidative phosphorylation; PA, palmitic acid; PGC-1α, peroxisome proliferator-activated receptor-γ co-activator 1α; ROS, reactive oxygen species; SIRT3, silent mating type information regulation 2 homolog 3; SOD1 and SOD2, superoxide dismutase 1 and 2; TFAM, transcription factor A; TG, triglyceride.