Piperine suppresses cerebral ischemia–reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model

Abstract

The pathophysiological mechanisms leading to neuronal injury in middle cerebral artery occlusion (MCAO) model of cerebral stroke are complex and multifactorial that form the bases of behavioral deficits and inflammation mediated damage. The present study demonstrates the effect of piperine pretreatment (10 mg/kg b wt, once daily p.o. for 15 days) on cerebral ischemia-induced inflammation in male Wistar rats. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 h. A maximum infarct volume (57.80 %) was observed in ischemic MCAO group. However, piperine administration prior to ischemia showed a significant reduction in infarct volume (28.29 %; p < 0.05) and neuronal loss (12.72 %; p < 0.01). As a result of piperine pretreatment, a significant improvement in behavioral outputs of MCAO rats (p < 0.05-0.01) was observed. Piperine successfully reduced the level of proinflammatory cytokines IL-1β, IL-6 and TNF-α, in ischemic group (p < 0.01). Ischemic group brain has shown edematous morphology with vacuolated architecture and pyknotic nuclei in H & E staining which was successfully ameliorated by piperine administration. Moreover, piperine also succeeded in lowering the expression of COX-2, NOS-2, and NF-κB (p < 0.01). Both cytosolic and nuclear NF-κB were down-regulated in ischemic group pre-administered with piperine (p < 0.01). The present study suggests that piperine is able to salvage the ischemic penumbral zone neurons by virtue of its anti-inflammatory property, thereby limiting ischemic cell death.

SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion-induced injury via targeting p53/microRNA-22

“…COX exists in tissues in the forms of two subtypes. COX-1 is structural and has certain activities in normal conditions with the basic functions of maintaining physiological processes and the stability of the inner environment (33). COX-2 is inducible and is rarely expressed in normal tissues, while it is highly expressed in tissues during inflammation (34).…”

“…COX-2 is inducible and is rarely expressed in normal tissues, while it is highly expressed in tissues during inflammation (34). Many inflammation simulating factors, such as LPS, IL-1, TNF, serum, epidermal growth factor-α and platelet-activating factor can induce the genetic expression of COX-2 and trigger an increase in the levels of PGE2, PGI2 and PGE1 at inflammatory sites (33). COX and its metabolites can aggravate CIRI at the vasculature, blood-brain barrier and neurons (33).…”

“…Many inflammation simulating factors, such as LPS, IL-1, TNF, serum, epidermal growth factor-α and platelet-activating factor can induce the genetic expression of COX-2 and trigger an increase in the levels of PGE2, PGI2 and PGE1 at inflammatory sites (33). COX and its metabolites can aggravate CIRI at the vasculature, blood-brain barrier and neurons (33). The present study clearly demonstrated that SIRT1 exerted neuroprotective effects by suppressing COX-2 protein expression in rats with CIRI.…”

Involvement of attenuated antioxidant and Bcl2 signalling property in UV-R/ sunlight irradiated piperine treated ischemia/reperfusion rat model. Highlights

“…6,7 PIP is a dietary spice alkaloid derived from piper (piper nigrum) and exhibits multifunctional antioxidant, antiinflammatory, anti-ischemic and antifibrotic properties. [6][7][8][9] In addition to this PIP has tendency to act as bioavailability enhancer, inhibitory effect on p-glycoprotein and drug metabolizing enzyme. [10][11][12][13][14][15][16] Further, intravenously administered PIP was found to be 97% bioavailability compare to other route.…”

“…9 The recent interest on the relationship of PIP and stroke is focused for the development of novel neuroprotective agents. [7][8][9] However, due to its light sensitive nature and cis-trans geometric isomerisation at 254 nm UV radiation, we hypothesized that the exposure predominant UV-R irradiation may alter the functional properties of PIP influencing its neuroprotective effects.…”