Table 1.
The in vivo mechanism underlying the inhibition of MPTP opening-induced neuronal apoptosis by authorized drugs in the treatment of ischemic stroke.
| Agents | Objects | Gender | Weight (g) | Animal model | Dose | Time periods | Mechanisms | References |
|---|---|---|---|---|---|---|---|---|
| XueShuanTong injection | SD | Both | 270–320 | MCAO (2 h)/R (46 h) | 25 mg/kg, i.p. | Pretreatment for 5 min and 12/24/36 h after MCAO | Caspase-1/3↓, TUNEL-positive neurons↓ | Li et al., 2009 |
| Cerebralcare granule | Mongolian gerbils | Male | 65–90 | MCAO (0.5 h)/R (5 d) | 0.4 and 0.8 g/kg, i.g. | 3 h after the reperfusion, 5 d, q.d. | Bcl-2↑; leukocyte adhesion↓, fluorescence intensity of DHR↓, albumin leakage↓, Caspase-3↓, Bax↓, TUNEL-positive neurons↓ | Sun et al., 2010 |
| AnGong NiuHuang wan. | SD | Male | 250–280 | MCAO (1.5 h)/R (24 h) | 0.065, 0.125, and 0.25 g/kg, i.g. | Pretreatment 3 d, q.d., and 1 d, q.d. after reperfusion | Bcl-2↑; Bax↓, Caspase-3↓, TUNEL-positive neurons↓ | Wang G. et al., 2014 |
| SD | Male | 260–280 | MCAO (2 h)/R (22 h) | 257 mg/kg, i.g. | Single dose before reperfusion | Bcl-2↑, ZO-1↑, claudin-5↑, eNOS↑; Bax↓, p47phox↓, iNOS↓, 3-NT↓, MMP-2↓, MMP-9↓, iNOS↓ | Tsoi et al., 2019 | |
| QingKaiLing injection | KM/C57BL/6 | Male | 25–28/25–30 | MCAO (1.5 h)/R (28 h) | 3 ml/kg, i.v. | 4 h after reperfusion, and once every 12 h, three times | Procaspase-12↑; Caspase-3↓, p-eIF2α↓, ROS↓, Ca2+↓, TUNEL-positive neurons↓ | Cheng et al., 2012 |
| DangGui Jakyak san | SD | Male | —— | pMCAO (28 d) | 50, 100, and 200 mg/kg, i.g. | 24 h after surgery, 28 d, q.d. | STAT3↑, Pim-1↑, GSH↑, SOD↑, CAT↑; MDA↓, Caspase-3↓, PARP↓, NT↓, 4-HNE↓ | Kim et al., 2016 |
| YiQi FuMai powder injection | C57BL/6J | Male | 18–22 | pMCAO (24 h) | 1.342 g/kg, i.p. | Single dose after pMCAO onset | cerebral blood flow↑, Bcl-2↑; Caspase-12↓, GRP78↓, CHOP↓, ATF-4/6↓, p-eIF2α/eIF2α↓, XBP-1↓ | Cao et al., 2016 |
| SD | Male | 280–300 | tMCAO (1.5 h)/R (24 h) | 0.957 g/kg, i.p. | Single dose after tMCAO onset | Bcl-2↑, cytosolic Drp1↑; Bax↓, cleaved Caspase-9↓, mtDrp1↓, total p-Drp1 and Drp1↓ | Xu Y. et al., 2017 | |
| TongXinLuo | SD | Male | 200–220 | MCAO (1.5 h)/R (24 h) | 0.4, 0.8, and 1.6 g/kg, i.g. | Pretreatment for 3 d, b.i.d., and after MCAO for 1 d, b.i.d. | p-PTEN/PTEN↑, p-PDK1/PDK1↑, p-AKT/AKT↑, p-Bad/Bad↑, p-c-Raf/c-Raf↑; cleaved Caspase-3↓, TUNEL-positive neurons↓ | Yu et al., 2016 |
| SD | Male | 240–270 | MCAO (1.5 h)/R (14 d) | 0.1 g/kg, i.g. | Pretreatment for 5 d and 14 d after MCAO, q.d. | Connexin 43↓, Calpain II↓, Bax↓, cleaved Caspase-3↓, TUNEL-positive neurons↓ | Cheng et al., 2017 | |
| QianCao NaoMaiTong mixture | SD | 180–200 | MCAO (2 h)/R | 2.7, 5.4, and 10.8 ml/kg | Pretreatment for 28 d | Bcl-2/Bax↑, SOD↑, CAT↑, BDNF↑, ICAM-1↑, NGF↑, MDA↓, IL-6↓ | Lu et al., 2016 | |
| DanHong injection | SD | Male | 250–280 | MCAO (1 h)/R (24 h) | 4 ml/kg, i.p. | 4 h after MCAO | claudin-5↑, occludin↑, ZO-1↑, Bcl-2↑; Bax↓, Caspase-3↓, MMP-9↓, PAI-1↓, P-selectin↓ | Li M. et al., 2018 |
| XingNaoJing injection | SD | Male | 250–280 | MCAO (2 h)/R (24 h) | 5, 10, and 15 ml/kg, i.p. | 24 h after reperfusion | Bcl2/Bax↑, p-PI3K/PI3K↑, p-AKT (308 and 473)/AKT↑, p-eNOS/ eNOS↑, NO↑, p-PI3K/AKT↑ | Zhang Y. et al., 2018 |
| PienTzeHuang capsule | SD | Male | 240–260 | MCAO (1.5 h)/R (24 h) | 180 mg/kg, i.g. | Pretreatment 4 d before MCAO |
NeuN↑, mtCyto-c↑, Bcl-xl↑, p-AKT↑, p-GSK-3β↑; IL-1β↓, IL-6↓, TNF-α↓, cytosolic Cyto-c↓, Bax↓, p53↓, cleaved Caspase-3/9↓, TUNEL-positive neurons↓ | Zhang X. et al., 2018 |
| XueSaiTong | C57BL/6 | Male | 20–25 | MCAO (45 min)/R (14 d) | 15 µg/g, i.v. | Immediately after reperfusion, 14 d, q.d. | arginase-1↑, CD206↑, CD206/Iba-1↑, IL-10↑, TGF-β1↑; IL-1β↓, p-STAT3/STAT3↓, CD16↓, CD16/Iba-1↓, iNOS↓, TUNEL-positive neurons↓ | Li et al., 2019 |
| NaoLuoTong capsule | Wistar | Male | 250–280 | MCAO (2 h)/R (22 h) | 75, 150, and 300 mg/kg, i.g. | Pretreatment for 7 d, q.d. | Bcl-2↑, NGF↑; TNF-α↓, IL-1β↓, IL-6↓, Bax↓, Caspase-3↓, ICAM-1↓, NF-κBp65↓ | Bai M. et al., 2019 |
| ZhenLong XingNao capsule | Wistar | Male | 200–250 | MCAO (1.5 h)/R (24 h) | 125 and 250 mg/kg, i.g. | Pretreatment 14 d, q.d. | T-AOC↑, T-SOD↑, Bcl-2↑, Bcl-2/Bax↑; Caspase-3↓, NF-кB↓, p38↓, Bax↓, MDA↓, GABA↓, Glu↓, Tau↓ | Wei X. et al., 2019 |
| ErShiWei ChenXiang pills | SD | Male | 260–300 | MCAO (2 h)/R (24h) | 1.33 and 2.00 g/kg, i.g. | Pretreatment 14 d, q.d. | Bcl-2↑, CaMK II↑; Bax↓, cleaved Caspase-3↓, Cyto-c↓, ATF4↓, c-Jun↓, TUNEL-positive neurons↓ | Hou et al., 2020 |
| AnNao tablets | SD | Male | 250–270 | MCAO (2 h)/R (7 d) | 300, 600, and 1,200 mg/kg, i.g. | 1 h after reperfusion, 1 d or 7 d, q.d. | Drp1↑, OPA1↑, PINK1↑, Parkin↑, Bcl-2↑, Bcl-2/Bax↑; Bax↓ | Zhang et al., 2020 |
↑, upgrade; ↓, downgrade.