Abstract
We recently reported the protective effects of chlorogenic acid (CGA) in a transient middle cerebral artery occlusion (tMCAo) rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA) was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion) were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP)-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p.) dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB) leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.
Highlights
Coffee is a widely consumed beverage worldwide
We previously reported the protective effects of chlorogenic acid (CGA) against brain edema, as well as brain infarction, in a transient focal cerebral ischemia rat model via inhibition of matrix metalloproteinase (MMP)-2 and -9 expression and activities [4]
In the brain of the vehicle-treated rat, white area could be seen in whole sections, which extended from the ischemic core to the penumbra, after middle cerebral artery occlusion (MCAo)
Summary
Coffee is a widely consumed beverage worldwide. The beneficial activities on human diseases, especially on vascular diseases and cerebral ischemia, have been well documented [1]. We previously reported the protective effects of CGA against brain edema, as well as brain infarction, in a transient focal cerebral ischemia rat model via inhibition of matrix metalloproteinase (MMP)-2 and -9 expression and activities [4]. CA is a well-known anti-oxidant component and has protective effects on various cerebral ischemia animal models [8,9]. Caffeic acid phenethyl ester, which is the mostly studied derivative of CA, showed protective effects on various cerebral ischemia models through anti-inflammatory and anti-oxidative mechanisms [8,9]. DHCA, a metabolite of CGA ( of CA), is a well-known anti-oxidant component, and there are several studies on the beneficial activities of DHCA, such as anti-oxidative [10,11], anti-Alzheimer’s [12], neuroprotective [13], arousal [14], and lipid-lowering effects [15]. We analyzed the effects of DHCA on MMP-2 and MMP-9 expression and activity to study the mechanisms of action [4]
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