Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in scopolamine-induced senescence in mice

Abstract

Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of six herbs has been reported to possess a neuroprotective effect. The present study aimed to investigate the effects of BSYZ on learning and memory abilities, as well as oxidative stress and neuronal apoptosis in the hippocampus of scopolamine (SCOP)-induced senescence in mice, in order to reveal whether BSYZ is a potential therapeutic agent for Alzheimer’s disease (AD). A high-performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP-induced memory impairment for two weeks. The learning and memory abilities were determined by the Morris water maze test. The oxidant stress-related indices, such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were examined in hippocampus of SCOP-treated mice. The cell death ratio was assessed by TUNEL staining, while apoptotic-related proteins including Bcl-2 and Bax were determined by immunofluorescent staining and western blot analysis. Caspase-3 was determined by western blot analysis. Consequently, a chromatographic condition, which was conducted at 35°C with a flow rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to yield common fingerprint chromatography under 203 nm with a similarity index of 0.986 within 10 batches of BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive ability, restored the abnormal activity of SOD and increased the levels of MDA and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of SCOP-treated mice was reversed by BSYZ by regulating the expression of Bcl-2, Bax and caspase-3. The results demonstrated that BSYZ had neuroprotective effects in SCOP-induced senescence in mice by ameliorating oxidative stress and neuronal apoptosis in the brain, supporting its potential in AD treatment.

Ferulic Acid Reverses the Cognitive Dysfunction Caused by Amyloid β Peptide 1-40 Through Anti-Oxidant Activity and Cholinergic Activation in Rats

“…A previous study demonstrated that continuous intracisternal infusion of Aβ 1-40 in rats resulted in significantly decreased protein expressions of Mn-SOD, GSH, glutathione disulfide (GSSG) in the rat brain, suggesting that Aβ 1-40 impairs anti-oxidant capacity (Tsai et al, 2010). Another study showed that SCOP-induced changes in reactive oxygen species (ROS), malondialdehyde (MDA), and AChE activity in mice (Hou et al, 2014;Lee et al, 2014). Data show that intracisternal injection of Aβ 1-40 infusion for 14 days decreased Mn-SOD expression and increased Cu, Zn-SOD activity.…”

Oxidative Stress in Neurodegenerative Diseases

“…MDA, HNE, or TBARS were enhanced in all of those models in the cerebral cortex or/and hippocampus or/and the whole brain [237][238][239][240][241][247][248][249][250][251][252][253][254][255]. Oxidative modification of proteins has also been demonstrated in the cortex and whole brain homogenate of transgenic AD mice [253,255] and in the cerebral cortex and hippocampus of an Aβ 1-42 mouse model [247].…”

“…Diminished levels of GSH in the cerebral cortex or hippocampus or in whole brain lysates have been demonstrated in pharmacologically induced AD animal models [237,238,240,241,247,250,254,256].…”

“…Furthermore, the activities of enzymes connected with GSH metabolism, such as GPx and GR, and the enzymes involved in antioxidant defense (SOD and CAT) were reduced in the hippocampus and cerebral cortex in pharmacological and genetic models [237,238,241,248,249,[254][255][256]. It should be noted that some studies demonstrated no change in CAT and SOD activity in whole brain lysates in Wistar rats in the streptozotocin model [240], while enhanced SOD, GPx, and GR were observed in the mouse cerebral cortex and hippocampus following i.c.v.…”

“…)), Aβ (i.c.v. ), or apolipoprotein E (APOE) in transgenic models is used to study sporadic AD, while amyloid precursor protein (APP) and presenilin 1 (PSEN1) and PSEN2 transgenic models are used to examine familial AD [237][238][239][240]. For detailed descriptions of AD animal models, see [241][242][243][244][245][246].…”