Table 1.
Polyphenols active in preclinical stroke models.
| Polyphenol Class | Polyphenol | Type of Stroke | Experimental Model | Effective Dose and Treatment | Findings | References | |
|---|---|---|---|---|---|---|---|
| Flavonols | Quercetin | Ischemic Stroke | tMCAO rat model | Post; 20 mg/kg; daily for 3 days Pre; 25 mg/kg; daily for 21 days |
↓brain damage, oxidative stress, apoptosis, neurological deficits | [69,70] | |
| Ischemic Stroke | pMCAO rat model | Post; 30 mg/kg; single administration | ↓brain damage | [71] | |||
| Ischemic Stroke | Photothrombotic rat model | Post; 25 µmol/kg; every 12 h for 3 days Post; 50 mg/kg; every 12 h for 3 days |
↓BBB damage, neurological deficits | [72,73] | |||
| Ischemic Stroke | 2VO mouse model | Pre; 50 mg/kg; 30 min before and immediately after stroke, then daily for 2 days | ↓ brain damage, BBB damage | [74] | |||
| ICH | Collagenase infusion rat model | Post; 30 mg/kg; single administration Post; 50 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [75,76] | |||
| SAH | Blood infusion rat model | Post; 10 mg/kg; every 8 h for 2 days Post; 50 mg/kg; 30 min, 12 h and 24 h after SAH |
↓brain damage, oxidative stress, vasospasm, apoptosis, neurological deficits | [77,78] | |||
| Myricetin | Ischemic Stroke | OGD SH-SY5Y cells | Pre; 0.1 nM | ↓toxicity | [80] | ||
| Ischemic Stroke | OGD human BMVECs | Pre; 30 µM | ↓oxidative stress, inflammation, endothelial permeability | [82] | |||
| Ischemic Stroke | tMCAO rat model | Pre; 20 mg/kg; 2 h before and daily for 2 days after stroke Pre; 25 mg/kg; daily for 7 days |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [80,81] | |||
| Kaempferol | Ischemic Stroke | tMCAO rat model | Pre; 100 and 200 µM; 30 min before and immediately after reperfusion Post; 10 and 7.5 mg/kg; single administration Post; 100 mg/kg; daily for 7 days |
↓brain damage, oxidative stress, apoptosis, inflammation, BBB damage, neurological deficits | [84,85,86] | ||
| Fisetin | Ischemic Stroke | tMCAO mouse model | Pre; 50 mg/kg; single administration Post; 50 mg/kg; single administration |
↓brain damage, inflammation | [89] | ||
| Ischemic Stroke | pMCAO rat model | Post; 30 mg/kg; single administration | ↓brain damage | [71] | |||
| Ischemic Stroke | SCE rabbit model | Post; 50 mg/kg; single administration | ↓ neurological deficits | [88] | |||
| Morin | Ischemic Stroke | tMCAO rat model | Post; 30 mg/kg; daily for 7 days Post; 30 mg/kg; single administration |
↓brain damage, BBB damage, inflammation, oxidative stress, apoptosis, neurological deficits | [91,92] | ||
| Flavan-3-ols | EGCG | Ischemic Stroke | OGD PC12 cells | Pre; 2 µM | ↓toxicity, apoptosis | [97] | |
| Ischemic Stroke | tMCAO mouse model | Post; 50 mg/kg; single administration | ↓brain damage, MPPs | [98] | |||
| Ischemic Stroke | tMCAO rat model | Post; 50 mg/kg; single administration Post; 50 mg/kg; single administration Post; 50 mg/kg; daily for 3 days Post; 50 mg/kg; single administration Post; 20 mg/kg; single administration Pre; 40 mg/kg; daily for 3 days |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [99,100,101,102,103,104] | |||
| Ischemic Stroke | 2VO gerbil model | Post; 25 and 30 mg/kg; single administration Pre; 50 mg/kg; 30 min before and immediately after stroke |
↓brain damage, oxidative stress | [105,106] | |||
| Ischemic Stroke | tMCAO rat model treated with rtPA | Post; 20 mg/kg; single administration | ↓brain damage, BBB damage, neurological deficits | [107] | |||
| SAH | Hb PC12 cells | Pre; 1–50 µM Pre; 1–50 µM Pre, 50 µM |
↓cell proliferation | [108,109,110] | |||
| SAH | Hb mouse model | Pre; 50 mg/kg; daily for 14 days Pre; 50 mg/kg; daily for 14 days |
↓brain damage, oxidative stress, mitochondrial dysfunction, apoptosis, neurological deficits | [109,110] | |||
| ECG | Ischemic Stroke | OGD PC12 cells | Pre; 2 µM | ↓toxicity, apoptosis | [97] | ||
| Ischemic Stroke | OGD human BMVECs | Pre; 2 µM | ↓oxidative stress, apoptosis | [111] | |||
| EC | Ischemic Stroke | OGD mouse neurons | Pre; 100 µM | ↓toxicity, oxidative stress | [113] | ||
| Ischemic Stroke | tMCAO mouse model | Pre; 30 mg/kg; single administration Post; 30 mg/kg; single administration |
↓brain damage, neurological deficits | [112] | |||
| Ischemic Stroke | pMCAO mouse model | Pre; 15 mg/kg; single administration | ↓brain damage, inflammation | [113] | |||
| ICH | Hb mouse astrocytes | Pre; 100 µM | ↓oxidative stress | [114] | |||
| ICH | Collagenase infusion mouse model | Post; 15 mg/kg; 3 h after ICH and daily for 3 days | ↓brain damage, oxidative stress, neurological deficits | [115] | |||
| ICH | Blood infusion mouse model | Post; 15 mg/kg; 3 h after ICH and daily for 3 days | ↓brain damage, oxidative stress, neurological deficits | [115] | |||
| ICH | Thrombin infusion mouse model | Post; 15 mg/kg; 3 h after ICH and daily for 3 days | ↓brain damage, oxidative stress, neurological deficits | [115] | |||
| Flavanones | Eriodictyol | Ischemic Stroke | OGD rat astrocytes | Pre; 20–80 µM | ↓toxicity | [120] | |
| Ischemic Stroke | tMCAO rat model | Pre; 30 mg/kg; daily for 5 days | ↓brain damage, neurological deficits | [120] | |||
| Ischemic Stroke | pMCAO mouse model | Pre; 4 mg/kg; 30 min before, 2 h and daily for 5 days after stroke | ↓brain damage, inflammation, neurological and memory deficits | [119] | |||
| Naringenin | Ischemic Stroke | OGD rat neurons | Pre; 80 µM Post; 80 µM |
↓toxicity, oxidative stress, apoptosis, mitochondrial dysfunction | [122,123] | ||
| Ischemic Stroke | OGD human MSCs | Post; 40 and 80 µM | ↓ inflammation | [124] | |||
| Ischemic Stroke | pMACO rat model | Pre; 100 mg/kg; daily for 4 days | ↓brain damage, inflammation, neurological deficits | [126] | |||
| Ischemic Stroke | tMCAO rat model | Post; 80 µM; single administration Pre; 50 mg/kg; daily for 21 days |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [123,125] | |||
| Ischemic Stroke | Stroke-prone spontaneously hypertensive rats | 9.0 and 17.7 mg/kg; daily for 4 weeks | ↓blood pressure, thrombotic tendency, oxidative stress | [127] | |||
| Hesperetin | Ischemic Stroke | tMCAO rat model | Pre; 50 mg/kg; daily for 15 days | ↓brain damage, oxidative stress, inflammation, neurological and behavioral deficits | [129] | ||
| Ischemic Stroke | 2VO rat model | Pre; 20 mg/kg; daily for 14 days | ↓brain damage, oxidative stress, inflammation | [130] | |||
| Ischemic Stroke | Stroke-prone spontaneously hypertensive rats | 14.5 (hesperidin), 16.2 and 31.6 (glucosyl hesperidin) mg/kg; daily for 4 weeks | ↓blood pressure, thrombotic tendency, oxidative stress | [127] | |||
| SAH | Blood infusion rat model | Post; 50 and 100 mg/kg; daily for 2 days | ↓vessel wall thickness, ↑vessel luminal diameter | [131] | |||
| Pinocembrin | Ischemic Stroke | OGD rat neurons | Post; 0.1, 1 and 10 µM | ↓toxicity, oxidative stress, apoptosis | [133] | ||
| Ischemic Stroke | OGD rat BMVECs | Post; 1 and 10 µM | ↓toxicity | [134] | |||
| Ischemic Stroke | OGD human BMECs and astrocytes | Post; 1 µM | ↓endothelial permeability | [135] | |||
| Ischemic Stroke | tMCAO rat model | Post; 3–30 mg/kg; single administration Post; 1–10 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, neurological deficits | [133,136] | |||
| Ischemic Stroke | pMCAO rat model | Post; 3, 10 and 30 mg/kg; single administration | ↓brain damage, apoptosis, inflammation, neurological deficits | [137] | |||
| Ischemic Stroke | 2VO rat model | Pre; 10 mg/kg; daily for 7 days | ↓brain damage, oxidative stress, apoptosis, inflammation | [138] | |||
| Ischemic Stroke | 4VO rat model | Post; 1–10 mg/kg; single administration | ↓brain and BBB damage, neurological deficits | [134] | |||
| Ischemic Stroke | Thromboembolic rat model treated with rtPA | Post; 10 mg/kg; single administration or daily for 7 days | ↓brain and BBB damage, neurological deficits | [135] | |||
| ICH | Collagenase infusion mouse model | Post; 5 mg/kg; 2 h after ICH and every 12 h for 3 days | ↓brain damage, inflammation, neurological deficits | [139] | |||
| Flavones | Luteolin | NHIB | OGD rat neurons | Pre; 10–30 µM | ↓toxicity, oxidative stress, apoptosis | [142] | |
| Ischemic Stroke | OGD mouse neurons | Post; 0.1–1 µM | ↓toxicity | [143] | |||
| Ischemic Stroke | OGD mouse MCs | Pre; 10 and 100 nM | ↓MC degranulation | [143] | |||
| Ischemic Stroke | OGD human BMVECs | Post; 90 µM | ↓toxicity, apoptosis | [144] | |||
| Ischemic Stroke | tMCAO rat model | Post; 20–80 mg/kg; 0 and 12 h after stroke | ↓brain damage, inflammation, neurological deficits | [145] | |||
| Ischemic Stroke | pMCAO rat model | Post; 10 and 25 mg/kg; single administration Post; 10 and 25 mg/kg; single administration Post; 10 and 25 mg/kg; 0 h and daily for 3 days after stroke |
↓brain damage, oxidative stress, apoptosis, neurological deficits | [144,146,147] | |||
| ICH | Hb rat neurons | Post; 10 µM | ↓toxicity | [148] | |||
| ICH | Hb rat neurons and microglia | Post; 10 and 20 µM | ↓ microglia activation and induced neurotoxicity | [149] | |||
| ICH | Blood infusion rat model | Post; 10 and 20 mg/kg; single administration Post; 10 and 20 mg/kg; 30 min, 12 h and 24 h after ICH |
↓brain damage, inflammation, neurological and memory deficits | [148,149] | |||
| Apigenin | Ischemic Stroke | OGD human BMVECs | Pre; 5 µM | ↓toxicity, apoptosis, autophagy | [151] | ||
| Ischemic Stroke | tMCAO rat model | Post; 25 mg/kg; daily for 7 or 14 days Post; 20 and 40 mg/kg; daily for 28 days |
↓brain damage, neurological and memory deficits | [151,152] | |||
| SAH | Endovascular perforation rat model | Post; 20 mg/kg; single administration | ↓brain and BBB damage, inflammation, neurological deficits | [153] | |||
| Nobiletin | Ischemic Stroke | Hypoxia HepG2 cells | Post; 100 µg/mL | ↓toxicity | [160] | ||
| Ischemic Stroke | tMCAO rat model | Post; 15 mg/kg; 0 and 1 h after stroke | ↓brain damage, apoptosis, inflammation, neurological deficits | [157,160] | |||
| Ischemic Stroke | 2VO mouse model | Pre; 50 mg/kg; daily for 7 days before and 7 days after stroke | ↓brain damage, memory deficits | [156] | |||
| Tangeretin | Ischemic Stroke | OGD human BMVECs | Post; 2.5, 5 and 10 µM | ↓toxicity, oxidative stress, apoptosis | [159] | ||
| Ischemic Stroke | Hypoxia HepG2 cells | Post; 10 and 100 µg/mL | ↓toxicity | [160] | |||
| Baicalein | Ischemic Stroke | OGD SH-SY5Y cells | Pre; 0.1, 1 and 10 µM | ↓toxicity | [163] | ||
| Ischemic Stroke | tMCAO rat model | Post; 25 and 50 mg/kg; single administration Post; 50, 100 and 200 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, neurological deficits | [163,164] | |||
| Ischemic Stroke | 2VO gerbil model | Post; 100 and 200 mg/kg; single administration | ↓brain damage, oxidative stress, apoptosis | [165] | |||
| Acacetin | Ischemic Stroke | tMCAO mouse model | Post; 25 mg/kg; single administration | ↓brain damage, inflammation, neurological deficits | [167] | ||
| Isoflavone | Genistein | Ischemic Stroke | OGD rat neurons | Concomitant, 1 mM | ↓toxicity, apoptosis | [172] | |
| Ischemic Stroke | OGD PC12 cells | Concomitant, 30 µM | ↓toxicity, apoptosis | [173] | |||
| Ischemic Stroke | tMCAO mouse and rat models | Pre; 5 and 10 mg/kg; daily for 14 days Pre; 10 mg/kg; daily for 14 days Pre; 500 mg/kg (genistein), 250 mg/kg (equol); daily for 14 days Pre; 500 mg/kg; daily for 28 days before and 1 day after stroke Post; 10 mg/kg; daily for 3 days Post; 1 and 2 mg/kg; single administration Pre; 10 mg/kg; daily for 14 days |
↓brain damage, oxidative stress, apoptosis, neurological deficits ↑circulatory function | [174,175,176,177,178,179,180] | |||
| Ischemic Stroke | pMCAO rat model | Post; 10 mg/kg; single administration | ↓brain damage, oxidative stress, apoptosis, neurological deficits | [181] | |||
| Ischemic Stroke | Photothrombotic rat model | Pre; 16 mg/kg; every 6 h from 24 h before to 24 h after stroke | ↓brain and BBB damage | [182] | |||
| Ischemic Stroke | 2VO mouse model treated with streptozotocin | Pre; 5 and 10 mg/kg; daily for 14 days before and 1 day after stroke | ↓brain damage, oxidative stress, apoptosis, neurological deficits | [183] | |||
| Ischemic Stroke | 4VO rat model | Pre; 0.1 mg/kg; daily for 7 days before and 7 days after stroke Post; 1 mg/kg; single administration Pre; 15 mg/kg; 30 min before and 24 h after stroke |
↓brain damage, oxidative stress, apoptosis, neurological deficits | [184,185,186] | |||
| Ischemic Stroke | 2VO gerbil model | Post; 3 and 10 mg/kg; single administration | ↓brain damage, oxidative stress, behavioral and memory deficits | [187] | |||
| SAH | Blood infusion rat and dog models | Post; 10 µM; single administration Post; 14.0 and 17.2 µM; single administration |
↓vasospasm | [188,189] | |||
| Daidzein | NHIBI | OD rat NSCs | Pre; 20–100 µM | ↓toxicity, apoptosis | [194] | ||
| Ischemic Stroke | OGD rat astrocytes | Concomitant, 12 and 48 µg/mL | ↓toxicity, apoptosis | [195] | |||
| Ischemic Stroke | tMCAO mouse and rat models | Post; 10 mg/kg; daily for 7 days, then every other day up to 1 month Pre; 50 and 100 mg/kg; daily for 7 days Pre; 36 and 54 mg/kg; daily for 5 days Pre; 50 and 100 mg/kg; single administration Post; 50 and 100 mg/kg; daily for 14 days |
↑cholesterol homeostasis, ↓brain damage, inflammation, neurological, motor and memory deficits | [191,196,197,198,199] | |||
| Ischemic Stroke | pMCAO mouse and rat models | Post; 0.10 mg/kg; daily for 14 days Post; 10 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, behavioral deficits | [190,192] | |||
| Ischemic Stroke | Stroke-prone spontaneously hypertensive rats | 100 mg/kg; daily for 14 days | ↓arterial dysfunction, blood pressure | [200] | |||
| SAH | Endovascular perforation mouse model | Pre; 100 mg/kg; single administration | ↓brain and BBB damage, oxidative stress, apoptosis, neurological deficits | [201] | |||
| Biochanin A | Ischemic Stroke | tMCAO mouse and rat models | Pre; 5 and 10 mg/kg; daily for 4 weeks Pre; 10, 20 and 40 mg/kg; daily for 14 days |
↓brain damage, oxidative stress, neurological deficits | [203,204] | ||
| SAH | Blood infusion rat model | Post; 20 and 40 mg/kg; single administration | ↓brain damage, apoptosis, inflammation, neurological and memory deficits | [205] | |||
| Anthocyanins | Cyanidin | Ischemic Stroke | OGD PC12 cells | Concomitant, 10 µg/mL | ↓toxicity | [209] | |
| Ischemic Stroke | tMCAO mouse model | Post; 150 and 300 mg/kg; daily for 7 days Post; 10 mg/kg; single administration |
↓brain damage, oxidative stress | [208,209] | |||
| Ischemic Stroke | 2VO rat model | Pre; 10 mg/kg; 1 h before stroke/post; 10 mg/kg; 0.5 h after reperfusion Pre; 10 and 20 mg/kg; 10 min before stroke and during reperfusion |
↓brain damage, oxidative stress, microvascular permeability | [210,212] | |||
| Ischemic Stroke | pMCAO mouse model | Pre; 2 and 5 mg/kg; 1 h before stroke/post; 2 mg/kg; 3 h after stroke | ↓brain damage, oxidative stress, neurological deficits | [211] | |||
| Phloretin | Ischemic Stroke | tMCAO rat model | Pre; 40 and 80 mg/kg; daily for 14 days | ↓brain damage, oxidative stress, neurological deficits | [214] | ||
| Dihydrochalcones | GSPE | NHIBI | Carotid ligation mouse model | Pre; 30 mg/kg; single administration | ↓brain damage, apoptosis, neurological deficits | [216] | |
| Proanthocyanidins | Procyanidins | Ischemic Stroke | tMCAO mouse, rat models | Post; 20 and 40 mg/kg; daily for 2–14 days Pre; 50 mg/kg; daily for 14 days |
↓brain and BBB damage, oxidative stress, apoptosis, neurological deficits | [217,218] | |
| SAH | Blood infusion rabbit model | Post; 10 and 50 mg/kg; daily for 3 days | ↓vasospasm | [219] | |||
| Hydroxycinnamic acids | Caffeic acid | NHIBI | Carotid ligation mouse model | Pre; 40 mg/kg; 30 min before and daily for 7 days after stroke/post; 40 mg/kg; single administration | ↓brain damage, apoptosis, inflammation | [223] | |
| Ischemic Stroke | tMCAO rat model | Pre; 50 mg/kg; 30 min before, 0 h, 1 h and 2 h after stroke, then every 12 h for 4 days Pre; 0.1–10 µg/kg; single administration |
↓brain damage, inflammation, neurological deficits | [224,227] | |||
| Ischemic Stroke | pMCAO rabbit model | Pre; 10 µmol/kg; daily for 7 days | ↓brain damage, oxidative stress, neurological deficits | [226] | |||
| Ischemic Stroke | Photothrombotic mouse model | Post; 2 and 5 mg/kg; 1 and 6 h after stroke | ↓brain damage, inflammation | [225] | |||
| Ischemic Stroke | 2VO rat model with hypotension | Post; 10, 30 and 50 mg/kg; single administration | ↓brain damage, oxidative stress, memory deficits | [228] | |||
| Ferulic acid | Ischemic Stroke | OGD PC12 cells | Pre; 80 and 100 µM | ↓toxicity, oxidative stress | [230] | ||
| Ischemic Stroke | tMCAO rat model | Post; 28, 56 and 112 mg/kg; daily for 5 days Post; 100 and 200 mg/kg; daily for 7 days Concomitant; 100 mg/kg; single administration Concomitant, 80 and 100 mg/kg/post; 100 mg/kg; single administrations |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological and memory deficits | [231,232,233,234] | |||
| Ischemic Stroke | 4VO rat model | Pre; 20 and 25 mg/kg; daily 4 days before, immediately after stroke and during reperfusion | ↓brain damage, oxidative stress, neurological and memory deficits | [230] | |||
| Sinapic acid | Ischemic Stroke | 4VO rat model | Post; 3 and 10 mg/kg; 0 and 90 min after stroke or daily for 14 days | ↓brain damage, memory deficits | [236] | ||
| p-Coumaric acid | Ischemic Stroke | pMCAO rat model | Post; 100 mg/kg; single administration | ↓brain damage, oxidative stress, apoptosis, neurological deficits | [238] | ||
| Ischemic Stroke | 2VO mouse model | Pre; 100 mg/kg; daily for 14 days | ↓brain damage, oxidative stress | [239] | |||
| Chlorogenic acid | Ischemic Stroke | tMCAO rat model | Post; 30 mg/kg; 0 and 2 h after stroke Post; 30 mg/kg; 0 and 2 h after stroke Pre; 15, 30 and 60 mg/kg; daily for 7 days |
↓brain and BBB damage, oxidative stress, MMPs level, behavioral deficits | [240,241,242] | ||
| Ischemic Stroke | 2VO rat model | Post, 100 and 500 mg/kg | ↓brain damage, oxidative stress, apoptosis, MMPs level, memory deficits | [243] | |||
| Ischemic Stroke | SCE rabbit model treated with rtPA | Post; 50 mg/kg; single administration | ↓behavioral deficits | [244] | |||
| Rosmarinic acid | Ischemic Stroke | OGD SH-SY5Y cells | Pre; 1 and 10 µM Post; 3–81 µM |
↓toxicity, apoptosis | [246,247] | ||
| Ischemic Stroke | tMCAO mouse model | Post; 20 and 40 mg/kg; single administration | ↓brain damage, oxidative stress, apoptosis | [248] | |||
| Ischemic Stroke | tMCAO rat model treated with streptozotocin | Post; 50 mg/kg; single administration | ↓brain and BBB damage, neurological deficits | [247] | |||
| Ischemic Stroke | pMCAO mouse model | Pre; 1 and 20 mg/kg; 30 min before, 1 h after stroke and then daily for 5 days | ↓brain damage, inflammation, neurological and memory deficits | [249] | |||
| Hydroxybenzoicacids | Gallic acid | Ischemic Stroke | OGD rat neurons | Concomitant, 50 µM | ↓toxicity | [251] | |
| Ischemic Stroke | tMCAO rat model | Pre; 50 mg/kg; daily for 7 days Pre; 50 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, inflammation, mitochondrial dysfunction, neurological deficits | [251,252] | |||
| Ischemic Stroke | 4VO rat model exposed to particulate matter | Pre; 100 mg/kg; daily for 10 days | ↓BBB damage, oxidative stress, behavioral deficits | [253] | |||
| Ischemic Stroke | 2VO mouse model | Post; 25 and 50 mg/kg; daily for 7 days | ↓oxidative stress, depressive symptoms | [254] | |||
| Stilbenes | Resveratrol | NHIBI | Carotid ligation mouse and rat models | Post; 100 mg/kg; 0, 8 and 18 h after stroke Pre; 0.2 and 20 mg/kg; single administration/post; 20 mg/kg; single administration Pre; 20 mg/kg; single administration |
↓brain damage, apoptosis, inflammation, behavioral deficits | [260,261,262] | |
| Ischemic Stroke | OGD mouse and rat neurons, PC12 cells | Pre, post, pre and post; 5–25 µM Post; 30 µM Pre and post, post; 10–80 µM Pre; 40 µM |
↓toxicity, oxidative stress, apoptosis | [263,264,265,268] | |||
| Ischemic Stroke | tMCAO mouse, rat models | Post; 6.8 mg/kg; single administration Post; 6.8 mg/kg; single administration Pre; 20 and 30 mg/kg; daily for 5 days Pre; 30 mg/kg; daily for 7 days and 30 min before stroke Post; 1.9 mg/kg; single administration |
↓brain and BBB damage, apoptosis, neurological deficits | [264,266,267,268,269] | |||
| ICH | Collagenase infusion mouse model | Post; 10 mg/kg; single administration | ↓brain damage, apoptosis, inflammation, neurological deficits | [270] | |||
| SAH | Blood infusion rat model | Post; 10 mg/kg; daily for 3 days Post; 60 mg/kg; 2 and 24 h after SAH |
↓vasospasm, apoptosis | [271,272] | |||
| SAH | Endovascular perforation rat model | Post; 30 mg/kg; 0 and 6 h after SAH Pre; 100 mg/kg; single administration |
↓brain and BBB damage, apoptosis, neurological deficits | [273,274] | |||
| Curcuminoids | Curcumin | NHIBI | Carotid ligation mouse model | Pre; 100 µg/kg; single administration/post; 50–200 µg/kg; single administration | ↓ brain damage, oxidative stress, apoptosis, inflammation | [277] | |
| Ischemic Stroke | OGD rat neurons | Pre; 0.5–8 µM | ↓toxicity, apoptosis, inflammation | [276] | |||
| Ischemic Stroke | tMCAO rat model | Post; 100 and 300 mg/kg; single administration Post; 300 mg/kg; single administration Post; 300 mg/kg; single administration Post; 300 mg/kg; daily for 7 days Post; 100, 300 and 500 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [278,279,280,281,282] | |||
| Ischemic Stroke | pMCAO mouse and rat models | Post; 50 mg/kg; single administration Post; 150 mg/kg; 0 and 24 h after stroke |
↓brain damage, inflammation, neurological and behavioral deficits | [283,284] | |||
| Ischemic Stroke | Stroke-prone spontaneously hypertensive rats | 100 mg/kg; daily for 4 weeks | ↓arterial dysfunction, oxidative stress, ↑survival | [285] | |||
| Lignans | Pinoresinol | Ischemic Stroke | 2VO rat model | Pre; 1 and 2 mg/kg; 10 min before stroke and during reperfusion | ↓microvascular damage, oxidative stress | [289] | |
| Ellagitannins and ellagic acid | Ellagic acid | Ischemic Stroke | OGD rat neurons | Post; 10 and 30 µM | ↓ toxicity, apoptosis | [290] | |
| Ischemic Stroke | Photothrombotic rat model | Pre; 10 and 30 mg/kg; 24 h before and immediately after stroke | ↓neurological deficits | [290] | |||
| Urolithin A | Ischemic Stroke | OGD mouse neurons and N2a cells | Pre; 3–30 µM | ↓ toxicity | [291] | ||
| Ischemic Stroke | tMCAO mouse model | Pre; 2.5 and 5.0 mg/kg; 24 and 1 h before stroke | ↓ brain damage, neurological deficits | [291] | |||
| Punicalagin | Ischemic Stroke | tMCAO rat model | Pre; 15 and 30 mg/kg; daily for 7 days Pre; 15 and 30 mg/kg; daily for 7 days |
↓brain damage, oxidative stress, apoptosis, inflammation, neurological deficits | [292,293] | ||
| Coumarins | Auraptene | Ischemic Stroke | 2VO mouse model | Post; 25 mg/kg; daily for 8 days Pre; 10 and 25 mg/kg; daily for 5 days |
↓brain damage, inflammation | [300,301] | |
| Umbelliferone | Ischemic Stroke | tMCAO rat model | Pre; 15 and 30 mg/kg; daily for 7 days | ↓brain damage, oxidative stress, inflammation, neurological deficits | [303] | ||
| Esculetin | Ischemic Stroke | tMCAO mouse model | Pre; 50 and 100 mg/kg; single administration/post; 100 mg/kg; single administration |
↓brain damage, apoptosis, neurological deficits | [305] | ||
| Imperatorin | Ischemic Stroke | OGD SH-SY5Y cells | Concomitant, 2.56 µM | ↓apoptosis | [307] | ||
| Ischemic Stroke | tMCAO rat model | Pre; 10 mg/kg; single administration | ↓brain damage, neurological deficits | [307] | |||
| Scopoletin | Ischemic Stroke | tMCAO rat model | Pre; 1 mg/kg; single administration | ↓brain damage | [309] | ||
| Osthole | Ischemic Stroke | tMCAO rat model | Pre; 100 mg/kg; 30 min before stroke and immediately after reperfusion Pre; 40 mg/kg; single administration Pre; 20 and 40 mg/kg; single administration |
↓brain damage, oxidative stress, apoptosis, MMPs levels, neurological deficits | [311,312,313] | ||
| Daphnetin | NHIBI | Carotid ligation rat model | Pre; 10 mg/kg; single administration/post; 10 mg/kg; single administration | ↓brain damage | [314] | ||
| Ischemic Stroke | tMCAO mouse model | Pre; 1 mg/kg; single administration | ↓brain damage, apoptosis, inflammation, neurological deficits | [314,315] | |||
BMVECs: brain microvascular endothelial cells; EC: (−)-epicatechin; ECG: (−)-epicatechin-3-gallate; EGCG: epigallocatechin-3-gallate; GSPE: grape seed proanthocyanidin extract; Hb: hemoglobin; ICH: intracerebral hemorrhage; MCs: mast cells; MMPs: metalloproteinases; MSCs: mesenchymal stem cells; NHIBI: neonatal hypoxic–ischemic brain injury; NSCs: neural stem cells; OD: oxygen deprivation; OGD: oxygen and glucose deprivation; pMCAO: permanent middle cerebral artery occlusion; rtPA: recombinant tissue plasminogen activator; SAH: subarachnoid hemorrhage; SCE: small clot embolism; tMCAO: middle cerebral artery occlusion; 2VO: two-vessel occlusion; 4VO: four-vessel occlusion.