Neuroprotective Effect of Dauricine after Transient Middle Cerebral Artery Occlusion in Rats: Involvement of Bcl-2 Family Proteins

Abstract

Previous studies have shown that the bisbenzyl isoquinoline alkaloid dauricine can protect the brain against ischemic damage. We investigated here whether dauricine could inhibit neuronal apoptosis and modulate Bcl-2 family protein levels in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats underwent a 60 min temporary occlusion of the middle cerebral artery (MCAO). Two doses of dauricine (5 and 10 mg/kg as low and high dose respectively) were administered intraperitoneally at 1 hour after MCAO. After neurological deficits were assessed at 3 hours and 24 hours of reperfusion, rats were killed and brain samples were collected. Apoptotic changes were evaluated by TUNEL method. The immunohistochemistry and Western blot were used to assess the protein expressions of Bcl-2 and Bax. RT-PCR was used to determine Bcl-2 and Bax mRNA expressions. Dauricine (5 and 10 mg/kg) treatment improved neurological deficits, diminished DNA fragmentation, increased Bcl-2 expression and reduced Bax expression in the penumbra. The infarct-reducing effects of dauricine may be due, in part, to the inhibition of apoptotic cell death via modulation Bcl-2 family protein in the penumbra.

Neuroprotective Effects of Ischemic Preconditioning and Postconditioning on Global Brain Ischemia in Rats through the Same Effect on Inhibition of Apoptosis

“…The Bcl-2 family proteins are located at outer mitochondria membranes, and it controls the activation of downstream caspases, thus representing a critical proximal intracellular checkpoint in the mitochondria-mediated apoptosis pathway [26,27]. Therefore, western blotting was used to detect the protein of caspases and Bcl-2.…”

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke

“…Dauricine was purchased from MUST (ChengDu, China, A0315), dissolved in DMSO for cell experiments, and dissolved in saline with 0.9% NaCl. Considering the limitation of drug administration capacity in mice and previous studies, 11 , 16 dauricine was dissolved in 0.9% NaCl saline with severe vortexing and finally presented as a turbid liquid. There are many studies of dauricine about transient focal cerebral ischaemia in rat and mouse, and the neuroprotective dose is from 5 to 10 mg/kg, so we chose the dosage of 10 mg.kg −1 in this study.…”

“…There are many studies of dauricine about transient focal cerebral ischaemia in rat and mouse, and the neuroprotective dose is from 5 to 10 mg/kg, so we chose the dosage of 10 mg.kg −1 in this study. 16 After intragastric administration, the dosage was 10 mg.kg −1 , and the dosing capacity was 10 mL/kg. The first administration at reperfusion after focal cerebral ischemia within 30 min, once a day, continued until the end of the experiment.…”

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling

“…Menispermum dauricum DC., commonly known as "Bei Dou Gen" in China, has been used extensively to treat swelling and pain caused by sore throat, enteritis, and rheumatic arthralgia (Su et al, 2016;Sun et al, 2014). Dauricine (Dau) is a type of bibenzyl-tetrahydroisoquinoline alkaloid present in the roots of Menispermum dauricum D.C. Dau has a variety of biological effects, including antiproliferative (Wang, Li, Zu, Chen, & Qi, 2012), anti-inflammatory (Qiao et al, 2019), and anti-ischemic (Yang, Liu, Zhang, Jiang, & Gong, 2010) effects. Previous studies have demonstrated the role of Dau in cancer cells; one ground-breaking report showed that, in combination with tetrandrine, Dau could significantly reduce the resistance to doxorubicin in human leukemia cells, which is likely to be mediated by P-glycoprotein that pumps antitumor drugs out of cancer cells (He, Meng, & Zhang, 1996).…”