Review Article

Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism

Table 1

Summary of the efficacy of borneol for ischemic stroke.

Study
(author, years)
SpeciesWeightAnestheticConditions or model inductionMethod of administrationOutcome measures (sample)Intergroup differences
Treatment groupControl group

Chen et al. 2010 [20]Male, C57 BL/6J mice18–20 gChloral hydrate (300 mg/kg, ip)Temporary occlusion of bilateral common carotid arteries for 25 minBorneol, 0.01 g/kg, ig, at 30 min before model and once daily for 2 days after occlusionSame volume of 10% ethanol, ig, at 30 min before model and once daily for 2 days after occlusion(1) Brain EB content, 48 h (6/6)
(2) Brain water content, 24 h (6/6)
(3) Morris water maze test, 4 d (12/12)
(4) MDA, SOD, 4 d (6/6)
(5) GFAP, 4 d (3/3)
(1)
(2)
(3)
(4)
Dong 2018 [21] aMale, SD rats230–270 gNSPermanent middle cerebral artery occlusionL-borneol, 0.2 g/kg, ig, once daily for 3 days before occlusionSame volume of 5% Tween 80 solution, ig, once daily for 3 days before occlusion(1) Neurological function score, 24 h (12/12)
(2) Brain water content, 24 h (8/8)
(3) Cerebral infarction rate with TTC staining, 24 h (5/5)
(4) The ultrastructure of BBB, NS
(5) VEGF levels in the serum, 24 h (7/7)
(6) TNF-α levels in the serum, 24 h (7/7)
(7) Bax mRNA, 24 h (3/3)
(8) Bcl-2 mRNA, 24 h (3/3)
(9) Claudin-5 mRNA, 24 h (3/3)
(1)
(2)
(3)
(4) NS
(5)
(6)
(7)
(8)
(9)
Dong 2018 [21] bMale, SD rats230–270 gNSPermanent middle cerebral artery occlusionD-borneol, 0.2 g/kg, ig, once daily for 3 days before occlusionSame volume of 5% Tween 80 solution, ig, once daily for 3 days before occlusion(1) Neurological function score, 24 h (12/12)
(2) Brain water content, 24 h (8/8)
(3) Cerebral infarction rate with TTC staining, 24 h (5/5)
(4) The ultrastructure of BBB, NS
(5) VEGF levels in the serum, 24 h (7/7)
(6) TNF-α levels in the serum, 24 h (7/7)
(7) Bax mRNA, 24 h (3/3)
(8) Bcl-2 mRNA, 24 h (3/3)
(9) Claudin-5 mRNA, 24 h (3/3)
(1)
(2)
(3)
(4) NS
(5)
(6)
(7)
(8)
(9)
Dong 2018 [21] cMale, SD rats230–270 gNSPermanent middle cerebral artery occlusionSynthetic borneol, 0.6 g/kg, ig, once daily for 3 days before occlusionSame volume of 5% Tween 80 solution, ig, once daily for 3 days before occlusion(1) Neurological function score, 24 h (12/12)
(2) Brain water content, 24 h (8/8)
(3) Cerebral infarction rate with TTC staining, 24 h (5/5)
(4) The ultrastructure of BBB, NS
(5) VEGF levels in the serum, 24 h (7/7)
(6) TNF-α levels in the serum, 24 h (7/7)
(7) Bax mRNA, 24 h (3/3)
(8) Bcl-2 mRNA, 24 h (3/3)
(9) Claudin-5 mRNA, 24 h (3/3)
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Fang et al. 2004 [22]Male and female, SD rats200–300 g10% chloral hydrate (300 mg kg, ip)Temporary occlusion of bilateral common carotid arteries for 60 minBorneol, 0.2 g/kg, ig, once daily for 7 days before occlusionSame volume of normal saline, ig, once daily for 7 days before occlusion(1) Brain water content, NS (10/10)
(2) BAX, NS (10/10)
(3) BCL-XL, NS (10/10)
(1)
(2)
(3)
Huang et al. 2000 [23]Male and female, SD rats180–200 gNSTemporary obstruction of bilateral common carotid arteries for 45 minSynthetic borneol, 1 g/kg, ig, once daily for 7 days before model establishmentSame volume of distilled water, ig, once daily for 7 days before model establishment(1) Brain water content, 1 h (10/10)
(2) The ultrastructure of BBB, 1 h (10/10)
(1)
(2) NS
Jia 2014 [24]Male, Wistar rats240–280 g10% chloral hydrate (NS, ip)Transient occlusion of bilateral hemisphere for 20 min (Pulsinelli-4VO method)D-borneol, 0.2 g/kg, ig, once daily for 3 days before occlusionSame volume of 70% ethanol, ig, once daily for 3 days before occlusion(1) Brain EB content, 72 h (6/6)
(2) Brain water content, 72 h (6/6)
(3) ZO-1, 72 h (6/6)
(1)
(2)
(3)
Liu et al. 2007 [25]Male and female, SD rats260–300 g10% chloral hydrate (350 mg/kg, ip)Temporary middle cerebral artery occlusion for 2 hBorneol, 0.003 g/kg, ig, at 12 h, 30 min before model and at 12 h, 24 h after occlusionSame volume of 1% Tween, ig, at 12 hr, 30 min before model and at 12 hr, 24 hr after occlusion(1) Brain EB content, 24 h (5/5)
(2) Brain water content, 24 h (5/5)
(1)
(2)
Ni et al. 2011 [26]Male, SD rats280–320 g10% chloral hydrate (350 mg/kg, ip)Temporary middle cerebral artery occlusion for 2 hBorneol, 0.2 g/kg, ig, once daily for 3 days before occlusionSame volume of 5% Tween, ig, once daily for 3 days before occlusion(1) The ultrastructure of BBB, 22 h (NS/NS)
(2) VEGF, 22 h (8/8)
(3) MMP-9, 22 h (8/8)
(1) NS
(2)
(3)
Tian 2013 [27] aMale, SD rats280–350 g10% chloral hydrate (350 mg/kg, ip)Temporary middle cerebral artery occlusion for 2 hL-borneol, 0.20 g/kg, ig, once daily for 3 days before occlusionSame volume of normal saline, ig, once daily for 3 days before occlusion(1) Rate of cerebral edema, 22 h (8/8)
(2) MDA, 22 h (8/8)
(3) SOD, 22 h (8/8)
(4) P-GP, 22 h (8/8)
(5) The ultrastructure of BBB, 22 h (2/2)
(1)
(2)
(3)
(4)
(5) NS
Tian 2013 [27] bMale, SD rats280–350 g10% chloral hydrate (350 mg/kg, ip)Temporary middle cerebral artery occlusion for 2 hSynthetic borneol, 0.20 g/kg, ig, once daily for 3 days before occlusionSame volume of normal saline, ig, once daily for 3 days before occlusion(1) Rate of cerebral edema, 22 h (8/8)
(2) MDA, 22 h (8/8)
(3) SOD, 22 h (8/8)
(4) P-GP, 22 h (8/8)
(5) The ultrastructure of BBB, 22 h (2/2)
(1)
(2)
(3)
(4)
(5) NS
Shao 2018 [28]Male & female, SD rats300–400 gNSPermanent ligation of bilateral common carotid arteriesBorneol, 0.5 g/kg, ig, once daily for 7 days before model establishmentSame volume of normal saline, ig, once daily for 7 days before model establishment(1) Brain EB content, 24 h (10/10)
(2) SOD, NS (10/10)
(3) MPO, NS (10/10)
(4) TNF-α, NS (10/10)
(1)
(2)
(3)
(4) NS
Wang 2011 [29]Male and female, SD rats180–220 g10% chloral hydrate (300 mg/kg, ip)Permanent ligation of bilateral common carotid arteriesSynthetic Borneol, 0.2 g/kg, ig, once daily for 3 days before model establishmentSame volume of normal saline, ig, once daily for 3 days before model establishment(1) Brain water content, 3 h (9/10)
(2) SOD, Na+-K+-ATPase, 3 h (9/10)
(3) MDA, 3 h (9/10)
(4) LDH, 3 h (9/10)
(1)
(2)
(3)
(4)
Xu and Zhang 2015 [30]Male, SD rats g10% chloral hydrate (NS, NS)Temporary middle cerebral artery occlusion for 2 hNatural borneol, 0.028 g/kg, ig, once daily for 3 days before occlusionSame volume of normal saline, ig, once daily for 3 days before occlusion(1) Brain EB content, 24 h (5/5)
(2) ZO-1, 24 h (5/5)
(3) Claudin-5, 24 h (5/5)
(1)
(2
(3)
Yao et al. 2011 [31]Male and female, Kunming mice g4% chloral hydrate (400 mg/kg, ip)Permanent ligation of bilateral common carotid arteriesSynthetic borneol, 0.0666 g/kg, ig, once daily for 3 days before occlusionSame volume of normal saline, ig, once daily for 3 days before occlusionBrain EB content, 20 min (8/6)
Zhang et al. 2011 [32]Male, SD rats250–280 g10% chloral hydrate (350 mg/kg, ip)Permanent middle cerebral artery occlusionBorneol, 0.4 g per animal, ig, once daily for 7 days before occlusionSame volume of 1% Tween, ig, once daily for 7 days before occlusion(1) Brain water content, 24 h (9/9)
(2) Neurological function score, NS (9/9)
(3) Infarction volume, NS (9/9)
(1)
(2)
(3)
Zhang et al. 2011 [33]Male and female, ICR mice18–22 g4% chloral hydrate (0.4 mg/kg, NS)Temporary occlusion of bilateral common carotid arteries for 20 minBorneol, 0.5 g per animal, ig, once daily for 8 days before occlusionSame volume of 1% Tween, ig, once daily for 8 days before occlusion(1) Brain water content, 10 min (11/10)
(2) SOD, 10 min (11/10)
(3) MDA, 10 min (11/10)
(1)
(2)
(3)
Zhu et al. 2007 [34]Male, SD rats200–250 g10% chloral hydrate (400 mg/kg, ip)Permanent ligation of bilateral common carotid arteriesBorneol, 0.020 g/kg, iv, once daily for 4 days before model establishmentSame volume of normal saline, iv, once daily for 4 days before model establishmentBrain water content, 3 h (8/8)

Note: BBB: the blood-brain barrier; increased: a significantly increasing blood-brain barrier permeability after the administration of borneol; decreased: a significantly decreasing blood-brain barrier permeability after the administration of borneol; ND: no statistical difference between treatment and control groups; Increased? or decreased?: the efficacy result was reported as increasing or decreasing blood brain barrier permeability with the absence of statistical analysis or available original data; ig: intragastric administration; ip: intraperitoneal administration; iv: intravenous injection; NS: not stated; SOD: superoxide dismutase; MDA: malondialdehyde; ET: endothelin; NO: nitric oxide; LDH: lactated hydrogenase; EB: Evans blue; ZO-1: zonula occludens-1; GFAP: gliofibrillar acid protein; BAX: Bcl-2 associated X protein; BCL: B-cell lymphoma; VEGF: vascular endothelial growth factor; MMP-9: matrix metalloproteinase-9; P-GP: P-glycoprotein.