TABLE 1.

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

Disease model	Phytochemical	Dosage	Experimental model	Pathobiology	Alteration in molecular markers in response to treatment	References
DN	Berberine	300 mg/kg/d, 8 w	db/db diabetic mice	Mesangial matrix accumulation	↓TG, ↓ACR, ↓FBG, ↓FFA, ↓Drp1	Qin et al. (2019)
		200, 300 mg/kg/d, 8 w	db/db mice model	Lipid accumulation	↓FFA, ↓TG	Qin et al. (2020)
	Curcumin	100 mg/kg, 12 w	Streptozotocin (STZ)-injected rats	Fibrosis, inflammation, oxidative stress, mitochondrial dysfunction	↓Collagen I/III, ↓TGF-β1, ↓NF-κB, ↓ROS, ↓MDA ↑GSH↑, ↑MnSOD, ↓cytochrome-C, ↓caspase-3, ↑Bcl-2↑, ↑Nrf-2, ↓p66Shc	ALTamimi et al. (2021)
	Polydatin	100 mg/kg, 8 w	KKAy mice	Mitochondrial dysfunction	↓Drp1	Ni et al. (2017)
	Resveratrol	30 mg/kg/d, 12 w	STZ-injected CD-1 mouse	Oxidative stress, apoptosis, mitochondrial dysfunction	↑MnSOD, ↓MDA, ↓caspase 3 ↑SIRT1, ↑PGC-1α, ↑Nrf-1↑, ↑TFAM	Zhang et al. (2019)
	Salidroside	50, 100 mg/kg/d, 10 w	High-fat diet (HFD)/STZ-induced diabetic rats	Extracellular matrix (ECM) deposition, mitochondrial dysfunction	↓collagen I, ↓FN, ↓α-SMA ↑SIRT1, ↑PGC-1α	Xue et al. (2019)
Obstructed nephropathy	Resveratrol	12.5 or 25 mg/kg, 14 d	UUO-operated C57BL/6 mice	Fibrosis	↓Collagen, ↓TGF-β/Smad, ↓FN, ↓α-SMA, SIRT1↑	Liu et al. (2019)
Aged kidney	Resveratrol	40 mg/kg, 6 m	18-month-old C57BL/6 mice	ECM accumulation, Apoptosis, Oxidative stress, mitochondrial dysfunction	↓Col IV, ↓TGF-β1, ↑COX IV, ↑BCL-2, ↓Bax, ↑Nrf-2, ↑HO-1, ↑NQO-1, ↓ROS, ↑SOD, ↑SOD2, ↑SIRT1, ↑AMPK, ↑PGC-1α	Kim et al. (2018)
Sepsis-induced AKI	Curcumin	4 mg/kg, 1, 6, 12 and 24 h	Sepsis-induced AKI mice model	Inflammation, Oxidative stress	↓IL-6, ↓ TNF-α ↓ROS, ↓MDA, ↑GSH, ↑SOD	Wang et al. (2021a)
	Polydatin	30 mg/kg, 6, 12, 18 h	Rats with caecal ligation and puncture (CLP)-induced sepsis	Mitochondrial dysfunction, inflammation	↑Mt membrane potential, ↑Mt-ATP levels ↓IL-6, ↓LPO	Gao et al. (2015)
		30 mg/kg, 12 h	C57BL/6 mice with CLP-induced sepsis	Mitochondrial dysfunction, inflammation, apoptosis	↓KIM-1, ↓NLRP3, ↓IL-6, ↓TNF-α, ↓IL-1β, ↓caspase-1, ↓Bax, ↓caspase-3 ↑ SIRT1, ↑Bcl-1	Gao et al. (2020)
	Resveratrol	0.3 ml; 50 mg/kg, 30 min	Rats with CLP-induced sepsis	Mitochondrial dysfunction	↑SIRT1/3, ↑ATP, ↓cytochrome-C, ↑SOD2	Xu et al. (2016)
Ischemia-reperfusion-induced AKI	Berberine	20 and 40 mg/kg, 4 w	Renal ischemia/reperfusion (RIR)-induced Wistar rats	Oxidative stress	↑SOD, ↑GSH, ↓MDA	Kaur et al. (2016)
				Mitochondrial dysfunction apoptosis	↓KIM-1
				Inflammation	↑Bcl-2, ↓caspase-3, ↓Bax
					↓TNF-α
Drug-induced AKI	Berberine	10, 20, and 40 mg/kg; p.o., 7 d	Gentamycin–induced nephrotoxicity Sprague-Dawley rats	Oxidative stress, inflammation, apoptosis, mitochondrial dysfunction	↓MDA, ↑SOD, ↑GSH	Adil et al. (2016)
					↓NF-κB
					↑Bcl-2
					↑mt complex (I – IV), ↓NO, ↓KIM-1
	Celastrol	1, 2 mg/kg/d	Cisplatin-induced C57BL/6 mice	Oxidative stress, apoptosis, inflammation, mitochondrial dysfunction	↓MDA	Yu et al. (2018)
					↓Bax, ↑Bcl-2
					↓IL-1β, ↓IL-6, ↓TNF-α, ↓ NF-κB p65
					↓KIM -1, ↓NGAL
	Curcumin	200 mg/kg/d, 3 d	Cisplatin-induced male Wister rats	mitochondrial dysfunction and dynamics	↑SIRT3, ↑mt complex I, ↑OXPHOS	Ortega-Domínguez et al. (2017)
					↓Fis1
					↑OPA1, ↑MFN1
Chemical-induced AKI	Curcumin	400 mg/kg, 5 d	Maleate-induced Wistar rats	Oxidative stress	↓MDA, ↓ROS, ↑GSSG, ↑GSH	Molina-Jijón et al. (2016)
				Mitochondrial fragmentation	↓Drp1, ↓Fis1
		400 mg/kg, 10 d	Chromium-induced Wistar rats	Oxidative stress	↑CAT, ↑GR, ↑GPx, ↑SOD, ↑GSH, ↑GST	Molina-Jijón et al. (2011)
				Mitochondrial dysfunction	↑mt complex (I – IV)
	Resveratrol	400 mg/kg, 90 d	Cadmium (Cd)-induced white chickens	Oxidative stress, mitochondrial dysfunction	↑T-SOD, ↑Cu-Zn SOD, ↑CAT, ↑GST, ↑GSH-Px, ↓MDA, ↑Nrf-2	Zhang et al. (2020)
					↑SIRT3, ↑SIRT1, ↑PGC-1α, ↑Nrf-1, ↑TFAM
		400 mg/kg, 14 d	Aldosterone-induced C57BL/6J mice	Mitochondrial dysfunction	↑PGC-1α, ↑TFAM, ↑SIRT-3	Yuan et al. (2012)
Other AKI-related diseases	Curcumin	60 mg/kg/day, 7 d	Nephrectomy-induced Wistar rats	Oxidative stress, mitochondrial dysfunction	↑CAT, ↑SOD, ↑GR, ↑GPx, ↑GST, ↑Nrf-2	Ortega-Domínguez et al. (2017)
					↓Drp1, ↓Fis1, ↑mt complex I/V
	Resveratrol	30 mg/kg, 1 h	Hemorrhagic shock-induced Evans rats	Oxidative stress, mitochondrial dysfunction	↑SOD2, ↑CAT, ↑Nrf-2, ↓ROS ↓NGAL, ↓LP, ↓NADH, ↑SIRT1, ↑PGC1-α	Wang et al. (2015)

ATP, adenosine triphosphate; AMPK, AMP-activated protein kinase; ACR, microalbumin-to-creatinine ratios; BCL-2, B-cell lymphoma 2; CAT, catalase; Col IV, Collagen IV; Cr, Chromium; Cd, cadmium; COX IV, Cytochrome Oxidase IV; Drp1, dynamin-related protein 1; ECM, Extracellular matrix; ERRAα, Estrogen-related receptor alpha; FBG, fasting blood glucose; FAO, fatty acid oxidation; FN, fibronectin; FFA, free fatty acids; Fis1, mitochondrial fission protein 1; GSSG, glutathione disulfide; GPx, glutathione peroxidase; GSH, glutathione; HO-1, Heme oxygenase-1; ICAM-1, intercellular adhesion molecule-1; IL-6, interleukin 6; IL-1β, interleukin 1 β; KIM-1, kidney injury molecule-1; 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; NGAL, neutrophil gelatinase associated lipocalin; NQO-1, Quinone Oxidoreductase 1; NADH, nicotinamide adenine dinucleotide plus hydrogen; Nrf-1 and Nrf-2, nuclear respiratory factors 1 and 2; NF-κB, nuclear factor-kappa B; OXPHOS, oxidative phosphorylation; PPAR, peroxisome proliferator-activated receptor; PA, palmitic acid; PGC-1α, peroxisome proliferator-activated receptor-γ co-activator 1α; RIR, renal ischemia reperfusion; ROS, reactive oxygen species; STZ, streptozotocin; SIRT1, silent mating type information regulation 2 homolog 1; SOD1 and SOD2, superoxide dismutase 1 and 2; TBARS, thiobarbituric acid reactive substances; TFAM, transcription factor A; TG, triglyceride; TNF-α, tumor necrosis factor α; TGF-β1, transforming growth factor- β-1; UUO, unilateral ureteral obstruction; α-SMA, α-smooth muscle actin.