Neuroprotective Effects of Bromelain on Acute Ischemic Stroke in Rats

Ischemic stroke (IS) is a severe neurological disorder that develops as a result of the interruption of cerebral blood flow and leads to high rates of mortality and morbidity. This study examined the neuroprotective potential of bromelain (Brm) in a rat model of IS induced by middle cerebral artery occlusion (MCAO). Three-month-old male Sprague Dawley rats were divided into four groups: Sham, IS, Brm20 + IS, and Brm40 + IS (n = 10 per group). Brm (20 or 40 mg/kg) or vehicle was administered orally for seven days prior to surgery, followed by 60 min of transient MCAO and 24 h of reperfusion. During reperfusion, neurological deficit scores and rotarod performance were assessed, and infarct volume was determined using 2,3,5-triphenyltetrazolium chloride staining. In the IS group, neurological deficits and infarct volume were significantly increased. The oxidative stress marker malondialdehyde (MDA) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) were elevated, whereas the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the anti-apoptotic protein Bcl-2, were reduced. In addition, apoptotic markers (Bax, caspase-3) and angiogenic markers, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), were increased, while the activity of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling was suppressed. Brm treatment attenuated these pathological alterations by reducing angiogenesis, inflammation, and apoptosis, enhancing antioxidant defense, and restoring PI3K/Akt signaling activity. In conclusion, the present study demonstrated that Brm exerts multifaceted neuroprotective effects in experimental IS by targeting key mechanisms including oxidative stress, inflammation, apoptosis, angiogenesis, and PI3K/Akt signaling. These findings suggest that Brm may represent a potential pharmacological candidate for the treatment of IS, pending validation in future advanced preclinical and clinical studies.