. 2024 Dec 20;30:265. doi: 10.1186/s10020-024-01020-5

Table 1.

NPs to target apoptosis as a means of combating DKD

Name	Sources	Structure	In vitro/In vivo	Model	Dose and Duration	Correlated target	Mechanisms	References
Z. officinale	Z. officinale	NA	In vivo	STZ induced Wistar rats	400, 800 mg/kg 6 weeks	Apoptosis, inflammation, oxidative stress	↓Cytc,caspase-3 ↓TNF-α, IL-1β ↑SOD,GSH,CAT ↓BUN, SCr	Al Hroob et al. (2018)
HSYA	Carthamus tinctorius L		In vivo	STZ induced Wistar rats	120 mg/kg 8 weeks	Apoptosis, inflammation, oxidative stress	↓Bax ↑Bcl-2 ↓caspase-3, ROS ↑SOD ↓TNF-α ↓FFA, LDH	Lee et al. (2020)
PN	Phylanthus niruri	NA	In vivo	STZ induced Wistar rats	200, 400 mg/kg 28 days	Apoptosis, inflammation, oxidative stress, fibrosis	↓Bax ↑Bcl-2 ↓caspase-3/9 ↓ TNF-α, IL-1β ↑SOD, GSH, CAT ↓VEGF, TGF-β	Giribabu et al. (2017)
Mangiferin	Mangifera indica		In vivo	STZ induced Wistar rats	40 mg/kg 4 weeks	Mitochondrial dependent apoptotic pathways	↓caspase-8, tBid ↓PARP ↓Bax, Cyt C ↓caspase-3/9 ↑Bcl-2, MMP ↓NF-κB, TNF-α ↓TGF-β1, MAPK	Pal et al. (2014)
Quercetin	Bupleuri		In vitro	40 mM HG induced MPCs	10, 20, 40 μM 24 h	EGFR	↓Bax ↓caspase-3 ↑Bcl-2 ↓BUN, UACR ↑Renin	Liu et al. (2021c)
Quercetin	Bupleuri		In vivo	C57BL/KSJ db/db rats	50, 100, 150 mg/kg 8 weeks	EGFR	↓Bax ↓caspase-3 ↑Bcl-2 ↓BUN, UACR ↑Renin	Liu et al. (2021c)
Emodin	Rhubarb		In vitro	30 mM HG induced MPCs	20, 40 μM 24 h	PERK/eIF2α/ATF4	↑GPR78 ↓PERK, eIF2α ↓CHOP, ATF4 ↓Bax ↑Bcl-2 ↓BUN, SCr	Tian et al. (2018)
Emodin	Rhubarb		In vivo	C57BL/6J rats	40,80 mg/kg 8 weeks	PERK/eIF2α/ATF4	↑GPR78 ↓PERK, eIF2α ↓CHOP, ATF4 ↓Bax ↑Bcl-2 ↓BUN, SCr	Tian et al. (2018)
AS-IV	Astragalus		In vitro	palmitate induced MPCs	20, 40, 80 μM 12 h	SERCA/SERCA2b/ER/mitochondrion	↑SERCA ↑SERCA2b ↑GPR78, Bcl-2 ↓ATF6, IRE1α, ↓PERK, eIF2α ↓CHOP, Ca²⁺ ↓Bax, Cyt c	Guo et al. (2016)
AS-IV	Astragalus		In vivo	db/db rats	2, 6, 18 mg/kg 8 weeks	SERCA/SERCA2b/ER/mitochondrion		Guo et al. (2016)
AS-IV	Astragalus		In vitro	HG induced MPCs	10, 20, 40 μM 1 h	TRPC6/Ca²⁺	↓TRPC6 ↓Ca²⁺ ↓ NFAT2, Bax	Yao et al. (2016)
AS-IV	Astragalus		In vitro	HG induced MPCs	3, 10, 20, 40, 80, 100 μM 24 h	Nrf2-ARE/TFAM	↑Nrf2-ARE/TFAM ↓Bax, Cyt c ↓caspase-3 ↓ROS ↑SOD, GSH-Px ↑Nrf2, HO-1 ↑PGC-1α, ETC	Shen et al. (2023)
AS-IV	Astragalus		In vivo	STZ induced C57BL/6J rats	6 mg/kg 10 weeks	Nrf2-ARE/TFAM		Shen et al. (2023)
Berberine	Coptis chinensis		In vitro	Palmitate induced MPCs	0.4 μM 12 days	Drp1	↓Drp1 ↑PGC-1α, Bcl-2 ↓Bax, Cyt c ↓caspase-3,ROS ↓MMP-9 ↑SOD	Qin et al. (2019)
Berberine	Coptis chinensis		In vivo	db/db rats	300 mg/kg 8 weeks	Drp1		Qin et al. (2019)
Rb1	Ginseng		In vitro	HG stimulated MPCs	10 μM 72 h	AR	↓AR ↓ROS ↓Bax, Cyt c ↓caspase-3/9 ↓BUN, SCr	He et al. (2022)
Rb1	Ginseng		In vivo	FVB rats	40 mg/kg 7 weeks	AR	↓AR ↓ROS ↓Bax, Cyt c ↓caspase-3/9 ↓BUN, SCr	He et al. (2022)
Gastrodin	Gastrodia elata		In vitro	HG stimulated MPC5	0.1, 1, 10, 100 μM 24 h	AMPK/Nrf2	↑AMPK, Nrf2 ↓Bax ↑Bcl-2 ↓caspase-1/3/6/9 ↓TNF-α, NLRP3 ↓MDA ↑SOD	Huang et al. (2022d)
CCPs	Cordyceps cicadae	NA	In vivo	db/db rats	75, 150, 300 mg/kg 12 weeks	miR-30a-3p/TRIM16	↑miR-30a-3p ↓TRIM16, ROS ↓Bax, caspase-3 ↑Bcl-2, SOD ↓TNF-α, IL-1β	Zheng et al. (2024)
AS-IV	Astragalus		In vitro	HG induced MPCs	10, 20, 40 μM 4 h	Klotho/FoxO1	↑Klotho/FoxO1 ↓Bax, caspase-3 ↑Bcl-2 ↓ROS ↑SOD ↑Podocin ↑Nephrin	Xing et al. (2021)
AS-IV	Astragalus		In vivo	db/db rats	2, 6, 18 mg/kg 8 weeks	Klotho/FoxO1		Xing et al. (2021)
Hirudin	Leeches		In vivo	STZ induced SD rats	Injected with 5 U 8 weeks	p38 MAPK/NF-κB	↓p38 MAPK ↓NF-κB ↓TNF-α, IL-1β	Han et al. (2020)
AS-IV	Astragalus		In vivo	STZ induced SD rats	5 mg/kg 12 weeks	miR-378/TRAF5	↑miR-378 ↓TRAF5 ↓caspase-3	LeiZhangRen et al. (2018)
AS-IV	Astragalus		In vivo	STZ induced SD rats	5 mg/kg 12 weeks	lncRNA-TUG1/TRAF5	↑lncRNA- TUG1 ↓TRAF5 ↓caspase-3	LeiZhangLi et al. (2018)
FMN	Astragalus membranaceus		In vitro	HG induced HK-2 cells	10, 30 μM 48 h	SIRT1/PGC-1α	↑SIRT1/PGC-1α ↓Bax, caspase-3 ↑Bcl-2 ↓Drp1, Fis1 ↑Mfn2, MMP ↓ROS	Huang et al. (2022e)
FMN	Astragalus membranaceus		In vivo	STZ induced SD rats	20 mg/kg 8 weeks	SIRT1/PGC-1α		Huang et al. (2022e)
GSPE	Grape seed	NA	In vivo	db/db rats	30 mg/kg 12 weeks	TXNIP p38MAP/ERK1/2	↓TXNIP, Cyt c ↓Bax, caspase-3 ↑Bcl-2,p38MAPK ↑ERK1/2	Wei et al. (2018)
C3G	Folium mori		In vitro	HG induced HK-2 cells	50 μM 48 h	TXNIP p38MAP/ERK1/2	↓TXNIP, Cyt c ↓Bax, caspase-3 ↑Bcl-2,p38MAPK ↑ERK1/2 ↓ROS ↑MMP	Wei et al. (2018)
NGR1	Panax notoginseng		In vitro	AGEs induced HK-2 cells	25 μM 24 h	Nrf2/HO-1	↑Nrf2/HO-1 ↓TGF-β ↓Bax ↑Bcl-2 ↓caspase-3/9 ↓ROS ↑MMP	Zhang et al. (2019)
NGR1	Panax notoginseng		In vivo	db/db rats	30 mg/kg 20 weeks	Nrf2/HO-1	↑Nrf2/HO-1 ↓TGF-β ↓Bax ↑Bcl-2 ↓caspase-3/9 ↓ROS ↑MMP	Zhang et al. (2019)
AS-IV	Astragalus		In vitro	HG induced HK-2 cells	10, 20, 40 μM 24 h	Nrf2/ARE	↑Nrf2/ARE ↓Bax ↑Bcl-2 ↓caspase-3/9 ↑SOD, GSH-Px ↓LPO, ROS	Wang and Guo (2019)
Salidroside	Rhodiola rosea		In vitro	HG induced HK-2 cells	100 μM 48 h	Bim	↓Bim ↓Bax ↑Bcl-2 ↓caspase-3 ↓ROS ↓BUN,SCr	Guo et al. (2018)
Salidroside	Rhodiola rosea		In vivo	STZ induced Wistar rats	70 mg/kg 8 weeks	Bim	↓Bim ↓Bax ↑Bcl-2 ↓caspase-3 ↓ROS ↓BUN,SCr	Guo et al. (2018)
Osthole	Cnidium monnieri		In vitro	HG induced HBZY-1 cells	1, 5, 10 μM 24 h	TGF-β1/Smads	↓TGF-β1/Smads ↓α-SMA, ROS ↑SOD, GSH-Px ↓NF-κB, TNF-α ↓IL-6, IL-1β ↓Apoptosis ↓BUN, SCr	Li et al. (2024)
Osthole	Cnidium monnieri		In vivo	STZ induced SD rats	25, 50, 100 mg/kg 8 weeks	TGF-β1/Smads		Li et al. (2024)
PCS	Psoralea corylifolia L	NA	In vivo	STZ induced C57BL/6 rats	500 mg/kg 8 weeks	Apoptosis/renal fibrosis	↓ PARP, Bad ↓TGF-β1, PAI-1 ↓ROS	Seo et al. (2017)