The Antioxidant Cerebralcare Granule Attenuates Cerebral Microcirculatory Disturbance During Ischemia-Reperfusion Injury

Abstract

Cerebralcare Granule (CG) is a compound Chinese medicine used for treatment of headache and dizziness associated with cerebrovascular diseases. To clarify the mechanism underlying the clinical outcome of CG, this study investigated the effects of CG on the structure and function of cerebral microvasculature during I/R injury. A total of 138 Mongolian gerbils were included and divided into four groups, each composed of 36 or 30 animals, for evaluating various parameters of concern. A skull window was prepared for microcirculatory observation in animals, which were subjected to I/R with or without pretreatment with CG (0.4 or 0.8 g/kg). The velocity of red blood cells in the venules was observed by a high-speed video camera system, along with intravital confocal microscopic measurements of microvascular diameters, adherent leukocytes, and albumin leakage in the brain cortex. Changes in the fluorescence intensity of dihydrorhodamine 123 in cerebral microvessels and malondialdehyde level in the cortex were measured. The ultrastructure of the microvessels in the cerebral cortex was analyzed using both transmission and scanning electron microscopy. In addition, cerebral blood flow was monitored using the laser Doppler imaging technique. Pretreatment with CG (0.4 or 0.8 g/kg) significantly alleviated I/R injury-induced disorders in cerebral microvasculature, as evidenced by the data observed at 60 min of reperfusion wherein the values in CG (0.4 g/kg) pretreatment group, CG (0.8 g/kg) pretreatment group, and I/R group were 2.43 +/- 0.24, 2.28 +/- 0.18, and 6.00 +/- 0.35 for leukocyte adhesion, 2.51 +/- 0.40, 2.33 +/- 0.29, and 4.77 +/- 0.24 for albumin leakage, 7.06 +/- 0.81, 5.93 +/- 0.42, and 28.38 +/- 2.70 for dihydrorhodamine 123 fluorescence intensity in cerebral microvessels, 16.35 +/- 0.52, 14.34 +/- 0.68, and 21.46 +/- 0.71 for malondialdehyde level in the cortex, and 0.43 +/- 0.07, 0.46 +/- 0.02, and 0.17 +/- 0.08 for cerebral blood flow, respectively. I/R injury-elicited ultrastructural alterations in microvessels in cerebral cortex were also mitigated impressively by CG administration, manifested as attenuation of the reduced number of opening capillaries and the altered fine structures in endothelium, which were characterized by rough inner surface, increased intracellular vesicles, hypertrophy of digitations of intercellular contact, and swollen perivascular astroglial processes. Cerebralcare Granule is able to attenuate I/R injury-induced functional and structural changes in microvessels in the cerebral cortex of gerbils, an ability that is most likely correlated with its antioxidant potential.

Therapeutic effect of Yang-Xue-Qing-Nao granules on sleep dysfunction in Parkinson’s disease

“…The improved NA associated with YXQN, but not with nocturnal levodopa, may be attributed to differences in the pharmacologic actions on dopamine receptor subtypes or the effects of YXQN on other neurotransmitter systems [15]. The UPDRS scores improved slightly after YXQN administration (Table 2), and the observed benefits might be caused by the sleep effects, rather than direct motor effects, in patients with PD.…”

“…As a CM compound for treating headache and dizziness associated with serious sleep disturbances, Yang-Xue-Qin-Nao granules (YXQN) attenuate cerebral microcirculatory disturbances during ischemia-reperfusion injury in vivo [15], which might improve the sleep dysfunction in PD patients. YXQN (Tianjin Tasly Pharmaceutical Co. Ltd., Tianjin, China) is a newly developed compound medicine that was approved in 1996 by the China State Food and Drug Administration for the treatment of headache and dizziness associated with cerebrovascular diseases.…”

“…The granules are composed of 11 herbs: Radix angelicae sinensis ( Dang Gui ), 6.76%; Rhizoma chuanxiong ( Chuan Xiong ), 6.76%; Radix paeoniae alba ( bai shao ), 5.41%; Ramulus uncariae cum uncis ( Gou Teng ), 13.51%; Caulis spatholobi ( Ji Xue Teng ), 13.51%; Spica prunellae ( Xia Ku Cao ), 13.51%; Concha margaritifera usta ( Zhen Zhu Mu ), 13.51%; Radix rehmanniae preparata ( Di Huang ), 5.41%; Semen cassiae ( Jue Ming Zi ), 13.51%; Rhizoma corydalis yanhusuo ( Yan Hu Suo ), 6.76%; and Herba asari ( Xi Xin ), 1.35%. Available evidence from in vitro studies has revealed that at least six chemicals derived from these herbs exhibit antioxidant potential, inhibit neutrophil adhesion to endothelial cells and decrease infarct size and brain tissue damage [15]. YXQN was reported to show effects on functional and structural changes in microvessels in the cerebral cortex of gerbils induced by ischemia-reperfusion injury [15].…”

“…Available evidence from in vitro studies has revealed that at least six chemicals derived from these herbs exhibit antioxidant potential, inhibit neutrophil adhesion to endothelial cells and decrease infarct size and brain tissue damage [15]. YXQN was reported to show effects on functional and structural changes in microvessels in the cerebral cortex of gerbils induced by ischemia-reperfusion injury [15]. These granules might improve non-motor symptoms, such as dizziness, headache and even depression [16,17].…”

Mechanism of Cerebralcare Granule® for Improving Cognitive Function in Resting-State Brain Functional Networks of Sub-healthy Subjects

“…On the other hand, a clinical study of post-stroke patients showed that CG use led to greater cognitive improvement than aspirin (Zhao et al, 2017). Other groups demonstrated that ischemia-induced cognitive impairment could be ameliorated by CG (Xu et al, 2009; Sun et al, 2010; Zhang X. X. et al, 2016). In addition, CG has been widely used to treat chronic cerebral circulation insufficiency (Xiong et al, 2011; Wu C. H. et al, 2013), which is often associated with cognitive impairment (Hirai, 1991).…”