Effects of Bushen-Yizhi formula on age-related inflammation and oxidative stress in senescence-accelerated mice.

The present study aimed to investigate the possible effects and underlying molecular mechanism of Bushen­Yizhi formula (BSYZ), a traditional Chinese medicine, on age­related degeneration of brain physiology in senescence­accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and step­down tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferator­activated receptor­Î³ and B­cell lymphoma extra­large, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase­2, nuclear factor­κB and interleukin­1ß in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against age­related neurodegenerative diseases.

Berberine Improves Diabetic Encephalopathy Through the SIRT1/ER Stress Pathway in db/db Mice.

The association between diabetes and dementia has been well demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related protein expression (PSD95, SYN, and NGF) and decreased the protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the protein expression of SIRT1 and downregulated ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the SIRT1/ER stress pathway might be a crucial mechanism in the neuroprotective effect of BBR against DE.

Ferulic acid attenuates brain microvascular endothelial cells damage caused by oxygen-glucose deprivation via punctate-mitochondria-dependent mitophagy.

Ferulic acid (FA) has an important effect on scavenging free radicals, which is related to the alleviation of various neurodegenerative diseases. However, there are few studies about its effects on vascular dementia. In this study, we demonstrated the effect of FA on oxidative damage of brain microvascular endothelial cells (BMECs) which underwent oxygen-glucose deprivation (OGD) for 2h. Our data showed that FA significantly reversed the oxidative stress state of OGD-treated BMECs and reduced mitochondrial dysfunction. In further study, we found that FA upregulated the expression of LC3-II, a marker of autophagy. Besides, mitophagy was observed by transmission electron microscopy. The mechanism of FA inducing autophagy was found to be related to mitochondrial fission, according to the effects of siRNA and inhibitor of dynamin-related protein 1, which was responsible for fission. All above suggested that FA mitigated OGD-induced mitochondrial oxidative damage by punctate-mitochondria-dependent autophagy.

A novel assay for high-throughput screening of anti-Alzheimer's disease drugs to determine their efficacy by real-time monitoring of changes in PC12 cell proliferation.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the accumulation of senile plaque and neurofibrilary tangle formation in the brain, including the cerebral cortex and hippocampus. Nowadays, the first-line treatment for AD is the application of acetylcholinesterase inhibitors. However, acetylcholinesterase inhibitors are basically anti-symptomatic for a limited aspect of AD pathology and are associated with serious side-effects. With the advantage of multiple targets, pathways and systems, Chinese herbal compounds hold promising potential for the development of drugs for the treatment of AD. Over the past few years, with the development of Chinese herbal compounds and in vitro pharmacological studies, cell-based disease models are one of the main methods used to screen Chinese herbal compounds for potential efficacy. Testing the efficacy of possible anti-Alzheimer's disease drugs and the development of new drugs are hindered by the lack of objective high-throughput screening methods. Currently, the assessment of the effects of drugs is usually made by MTT assays, involving laborious, subjective, low-throughput methods. Herein, we suggest a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess the effective composition of Chinese herbal compounds by assessing amyloid-ß peptide Aß1-42-induced apoptosis in PC12 cells. We detected the proliferation and motility of the cells using a fully automated high-throughput and real-time system. We quantitatively assessed cell motility and determined the real-time IC50 values of various anti-AD drugs that intervene in several developmental stages of Aß1-42-induced apoptosis in PC12 cells, Then, we identified the optimal time phase by curative efficacy. Our data indicate that this technique may aid in the discovery and development of novel anti-Alzheimer's disease drugs. It is possible to utilize a similar technique to measure changes in electrical impedance as cells attach and spread in a culture dish covered with a gold microelectrode array that covers approximately 80% of the area on the bottom of a well. As cells attach and spread on the electrode surface, it leads to an increase in electrical impedance of 9-12. The impedance is displayed as a dimensionless para-meter termed the cell index, which is directly proportional to the total area of tissue culture well that is covered by the cells. Hence, the cell index can be used to monitor cell adhesion, spreading, morphological variation and cell density.

[Influence of acupoint-catgut-implantation on blood pressure and cardiac function in chronic congestive heart failure rats].

OBJECTIVE: To observe the effect of acupoint-catgut-implantation on blood pressure and cardiac function in chronic heart failure (CHF) rats. METHODS: A total of 60 SD female rats were randomly divided into sham-operation group (sham), CHF model group, catgut-implantation group, Captopril group. CHF model was established by suprarenal abdominal artery constriction. Surgical catgut (No. 3-0, 2-3 mm length piece) was implanted into bilateral "Neiguan" (PC 6), "Xinshu" (BL 15) and "Zusanli" (ST 36) twice for 7 weeks. Rats of the Captopril group were treated with intragastric infusion of Captopril from the 50= day on after the operation, once daily for 7 weeks. Blood pressure (BP) including the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP), heart rate (HR) and the left ventricular ejection fraction (LVEF) were detected respectively by cardiac sonography. RESULTS: On the 14th week after modeling, in comparison with the sham group, the SBP, DBP, MBP and HR in rats of the model group were increased significantly (P<0. 01, P<0. 05), while LVEF of the model group was decreased considerably (P<0. 01). Compared with the model group, the SBP, DBP, MBP and HR after 7 weeks' treatment in rats of the catgut-implantation and Captopril groups were decreased considerably (P<0. 01), while the LVEF of the catgut-implantation group was increased evidently (P<0. 05). No significant differences were found between the catgut-implantation and Captopril groups in the SBP, DBP, MBP and HR levels, and between the model and Captopril groups in LVEF values (P>0. 05). CONCLUSION: Acupoint-catgut-implantation can down-regulate BP and HR, and increase LVEF in chronic congestive heart failure rats, which may contribute to its effect in ameliorating the cardiac function.

[Advances in study on the pharmacological effects of active components of Chinese herbs on Alzheimer's disease].

Based on the pharmacological research of Chinese herbs on AD and some famous hypothesis on AD, such as dysfunction of nervous transmitter metabolism, apoptosis, inflammation etc, we consulted and analyzed relevant papers. We found the effective mechanism of Ginsenoside, Osthol, Rhodosin, and (-) Clausenamide were related to many pathological channels of AD, and Ginsenoside had effect on many pathological channels. The results have provided some clues for selecting effective herbs on AD.