Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

Abstract

PurposeBerberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the hippocampus using gerbils.MethodsGerbils received berberine orally once a day for 14 consecutive days, starting one day after surgery. In this study, a step-down avoidance task was used to assess short-term memory. Furthermore, we employed the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate DNA fragmentation, immunohistochemistry to investigate glial fibriallary acidic protein, CD11b, and caspase-3, and western blot to assess PI3K, Akt, Bax, Bcl-2, and cytochrome c.ResultsOur results revealed that berberine treatment alleviated ischemia-induced short-term memory impairment. Treatment with berbeine also attenuated ischemia-induced apoptosis and inhibited reactive astrogliosis and microglia activation. Furthermore, berberine enhanced phospho-PI3K and phospho-Akt expression in the hippocampus of ischemic gerbils.ConclusionsBerberine exerted a neuroprotective effect against ischemic insult by inhibiting neuronal apoptosis via activation of the PI3K/Akt signaling pathway. The antiapoptotic effect of berberine was achieved through inhibition of reactive astrogliosis and microglia activation. Berberine may therefore serve as a therapeutic agent for stroke-induced neurourological problems.

Berberine ameliorates neonatal necrotizing enterocolitis by activating the phosphoinositide 3-kinase/protein kinase B signaling pathway

“…Inflammation serves an essential role in the development of neonatal NEC (22). Previous studies have reported that preventing inflammation is an effective method of protecting against myocardial ischemia-reperfusion injury and have highlighted it as a novel technique of diagnosing and treating patients with cardiac disease (23,24).…”

“…Berberine also exhibits anti-inflammatory effects on patients with acute coronary syndrome that have experienced percutaneous coronary intervention (26). Additionally, berberine prevents postsurgical intestinal adhesion and inhibits inflammation in a rat model by inhibiting the transforming growth factor β-activated kinase 1 (TAK1)/Jun N-terminal kinase and TAK1/NF-κB signaling pathways (22). Therefore, berberine may regulate inflammation in the progression of neonatal NEC via the PI3K/AKT signaling pathway.…”

“…Additionally, inhibiting NF-κB expression improves resolution of mucosal inflammation in the intestinal epithelium (20). Furthermore, it has been demonstrated that berberine inhibits ischemia-induced apoptosis by activating the PI3K/PKB signaling pathway (22). Therefore, various strategies aiming at preventing or mitigating the extent of apoptosis have been performed to try to protect the small intestine against apoptosis or necrosis (23,27,28).…”

Berberine protects against light-induced photoreceptor degeneration in the mouse retina

“…Activation of the PI3K/AKT/ERK pathway by 17-estradiol(Mo et al, 2013) and bacterial lipopolysaccharide (Bordone et al, 2012) showed neuroprotection in the light damage model. Interestingly, published studies showed BBR can protect the hippocampus from ischemia-induced apoptosis via enhancing phospho-PI3K and phospho-Akt production (Kim et al, 2014). Similarly, damage of endothelial progenitor cells in the coronary arteries was prevented by BBR through activation of the PI3K/AKT signaling pathway (Xiao et al, 2014).…”

Treadmill Exercise Improves Memory Function Depending on Circadian Rhythm Changes in Mice

“…Western blotting was conducted according to previously published methodology [8,16]. The hippocampal tissues were homogenized on ice and lysed in a lysis buffer.…”