Mitochondrial Dysfunction and Diabetic Nephropathy: Nontraditional Therapeutic Opportunities

Table 1

Mitochondria-targeted herb medicine in DN.

Herb medicine	The form of herb medicine	Experimental model	Target	Pathway	Observed effect	Ref.
			Mitochondrial biogenesis
Berberine	Pure chemical	Patients with DN, db/db diabetic mice	PCG-1α↑, FAO↑, AMPK↑	PGC-1α signaling pathway	Restoration of PGC-1α activity and the energy homeostasis	[10]
Tangshen formula	Extract	db/db diabetic mice, mTECs	PGC-1α↑, LXR↑, ABCA1↑	PGC-1α-LXR-ABCA1 pathway	Improving cholesterol efflux	[11]
Salidroside	Pure chemical	db/db diabetic mice	SIRT1↑, PGC-1α↑	SIRT1/PGC-1α axis	Improving mitochondrial biogenesis	[12]
Resveratrol	Pure chemical	db/db diabetic mice, HGECs	AdipoR1↑, AdipoR2↑, AMPK↑, SIRT1↑, PGC-1α↑, PPARα↑	AMPK–SIRT1–PGC–1α axis	Ameliorating lipotoxicity, oxidative stress, apoptosis, and endothelial dysfunction	[13]
Resveratrol	Pure chemical	db/db diabetic mice	AMPK↑, SIRT1↑, PGC-1α↑, PPARα↑	AMPK–SIRT1–PGC–1α axis	Prevention of lipotoxicity-related apoptosis and oxidative stress	[14]
Resveratrol	Pure chemical	STZ-induced diabetic rats, podocytes	SIRT1↑, PGC-1α↑, ROS↓	SIRT1/PGC-1α axis	Inhibition of mitochondrial oxidative stress and apoptosis	[15]
Resveratrol	Pure chemical	DN rabbits with AKI, HK-2 cells	SIRT1↑, PGC-1α↑, HIF-1α↓	SIRT1–PGC–1α–HIF-1α signaling pathways	Reducing renal hypoxia, mitochondrial dysfunction and renal tubular cell apoptosis	[16]
Marein	Extract	db/db diabetic mice, HK-2 cells	SGLT2↓, SREBP-1↓, AMPK↑, PGC-1α↑	AMPK/ACC/PGC-1α pathway	Amelioration of fibrosis and inflammation	[17]
			Mitochondrial dynamics
Berberine	Pure chemical	db/db diabetic mice, podocytes	DRP1↓, MFF↓, FIS1↓, MID49↓, MID51↓, PGC-1α↑	DRP1 modulator	Inhibiting mitochondrial fission and cell apoptosis	[18]
Astragaloside IV	Pure chemical	db/db diabetic mice	Drp1↓, MFF↓, Fis1↓	Mitochondrial quality control network	Amelioration of renal injury	[19]
Polydatin	Pure chemical	KKAy mice, hyperglycemia-induced MPC5 cells	DRP1↓, ROS↓, caspase-3↓, caspase-9↓	ROS/DRP1/mitochondrial fission/apoptosis pathway	Impairing mitochondria fitness and ameliorating podocyte injury	[20]
			Mitophagy
Astragaloside II	Pure chemical	STZ-induced diabetic rats	NRF2↑, Keap1↓, PINK1↑, Parkin↑	NRF2 and PINK1 pathway	Amelioration of podocyte injury and mitochondrial dysfunction	[21]
Huangqi-Danshen decoction	Extract	db/db diabetic mice	DRP-1↓, PINK1↑, Parkin↑	PINK1/Parkin pathway	Protection kidney injury by inhibiting PINK1/Parkin-mediated mitophagy	[22]
			Mitochondria ROS
Nepeta angustifolia C. Y. Wu	Extract	HFD/STZ-induced diabetic rats, mesangial cells	SOD↑, ROS↓, MDA↓	Mitochondrial-caspase apoptosis pathway	Antioxidative stress, inflammation and inhibiting mesangial cell apoptosis	[23]
Resveratrol	Pure chemical	db/db diabetic mice	ROS↓, AMPK↑, SIRT1	AMPK/SIRT1-independent pathway	Antioxidative stress and enhanced mitochondrial biogenesis	[24]
Betulinic acid	Pure chemical	STZ-induced diabetic rats	SOD↑, CAT ↑, MDA↓, AMPK, NF-κB↓, NRF2↑	AMPK/NF-κB/NRF2 signaling pathway	Attenuating the oxidative stress and inflammatory condition	[25]
Obacunone	Pure chemical	NRK-52E cells	SOD↑, GSK-3β↓, NRF2↑	GSK-3β/Fyn pathway	Inhibiting oxidative stress and mitochondrial dysfunction	[26]
Curcumin	Pure chemical	STZ-induced diabetic rats	NRF2↑, FOXO-3a↑, PKCβII↓, NF-κB↓	PKC βII/p 66 Shc axis	Antioxidative stress	[27]
Notoginsenoside R1	Pure chemical	db/db diabetic mice, HK-2 cells	ROS↓, NRF2↑, HO-1↑	NRF2 pathway	Inhibition of apoptosis and renal fibrosis caused by oxidative stress	[28]
Oleanolic acid and N-acetylcysteine	Pure chemical	Type 2 diabetic rat model, mesangial cells	ROS↓, NRF2↑, TGF-β/smad2/3↓, α-SMA↓	NRF2/Keap1 system	Inhibition of oxidative stress and ER stress	[29]