4'-O-β-D-glucosyl-5-O-methylvisamminol, an active ingredient of Saposhnikovia divaricata, attenuates high-mobility group box 1 and subarachnoid hemorrhage-induced vasospasm in a rat model.

Chih-Zen Chang,Aij-Lie Kwan,Shu-Chuan Wu,Chih-Lung Lin

doi:10.1186/s12993-015-0074-8

Abstract

BackgroundHigh-mobility group box 1 (HMGB1) was observed to be an important extracellular mediator involved in vascular inflammation associated with subarachnoid hemorrhage (SAH). This study is of interest to examine the efficacy of 4′-O-β-d-glucosyl-5-O-methylvisamminol (4OGOMV), C22H28O10, on the alternation of cytokines and HMGB1 in an animal model.MethodsA rodent double hemorrhage SAH model was employed. Administration with 4OGOMV was initiated 1 h after animals were subjected to SAH. Basilar arteries (BAs) were harvested and cortexes examined for HMGB1 mRNA, protein expression (Western blot) and monocyte chemoattractant protein-1 (MCP-1) immunostaining. Cerebrospinal fluid samples were collected to examine IL-1β, IL-6, IL-8 and MCP-1 (rt-PCR).ResultsMorphological findings revealed endothelial cell deformity, intravascular elastic lamina torture, and smooth muscle necrosis in the vessels of SAH groups. Correspondently, IL-1β, IL-6 and MCP-1 in the SAH-only and SAH-plus vehicle groups was also elevated. 4OGOMV dose-dependently reduced HMGB1 protein expression when compared with the SAH groups.(p < 0.01) Likewise, 400 μg/kg 4OGOMV reduced IL-1β, MCP-1 and HMGB1 mRNA levels as well as MCP-1(+) monocytes when compared with the SAH groups..Conclusion4OGOMV exerts its neuro-protective effect partly through the dual effect of inhibiting IL-6 and MCP-1 activation and also reduced HMGB1 protein, mRNA and MCP-1(+) leukocytes translocation. This study lends credence to validating 4OGOMV as able to attenuate pro-inflammatory cytokine mRNA, late-onset inflammasome, and cellular basis in SAH-induced vasospasm.

Highlights

High-mobility group box 1 (HMGB1) was observed to be an important extracellular mediator involved in vascular inflammation associated with subarachnoid hemorrhage (SAH)
Subarachnoid hemorrhage (SAH)-induced cerebral vasospasm persists as a major cause of morbidity and mortality in patients suffering from aneurysm rupture [1,2,3,4,5,6,7]
Tissue morphometry and MCP‐1 immunostaining The internal elastic lamina (IEL) in the basilar artery (BA) of SAH and SAH+vehicle groups showed substantial corrugation when compared with that obtained from the controls (Fig. 1, upper panel)

Summary

Introduction

High-mobility group box 1 (HMGB1) was observed to be an important extracellular mediator involved in vascular inflammation associated with subarachnoid hemorrhage (SAH). Even if the systemic inflammation has been recognized in the pathogenesis of cerebral vasospasm, the putative importance of intracranial sterile inflammatory activity has not been fully emphasized. Various inflammosomes, including adhesion molecules, cytokines, leukocytes, immunoglobulins, and complements, were observed in the pathogenesis of SAH-induced cerebral infarct and vasospasm [1, 7, 8, 17,18,19,20]. HMGB1 is able to induce the expression of vascular cell-adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and E-selectin, and lead to up-regulating the recruitment of leukocytes [21, 23, 24]. It is rational to postulate that HMGB1 can mediate cerebral inflammation and play a putative role in SAHinduced delayed vasoconstriction

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