A 1H NMR spectroscopic metabolomic study of the protective effects of irbesartan in a rat model of chronic mountain sickness.

Chronic mountain sickness (CMS) is a significant pathology in most high-altitude regions globally, affecting the cardiopulmonary system and its mechanism is largely unknown. A metabonomic approach using 1H nuclear magnetic resonance spectroscopy allows for detecting differential metabolites, which provides a global view and mechanisms during CMS development. In this study, we simulated a high-altitude environment to establish a rat model of CMS. Irbesartan was administered to CMS rats at three doses (6.75, 13.5, and 27 mg/kg) once a day for 15 days. HE staining and transmission electron microscopy were used to evaluate the effect of changes on the lung. Based on 1H NMR spectra obtained from serum samples, partial least squares-discriminant analysis (PLS-DA) and its variant orthogonal PLS-DA (OPLS-DA) models were applied to distinguish the different groups. Histopathological sections showed that the alveolar structure was abnormal, inflammatory infiltration occurred in CMS rats, and CMS induced notable metabolic disorder according to the 1H NMR result. However, irbesartan reversed the imbalanced metabolites via energy metabolism, amino acid metabolism, and taurine metabolism pathways, and its effect was also confirmed by the general signs and morphology of the lung. The results revealed that irbesartan as an effective therapeutic agent to improve CMS is warranted.

Cognitive enhancement and neuroprotective effects of a traditional Chinese herbal compound medicine on Aß1-42 induced Alzheimer's disease in rats.

INTRODUCTION: We aimed to explore the role of a novel traditional herbal compound medicine (HCM) in Alzheimer's disease (AD). MATERIAL AND METHODS: 72 rats were randomized into control, AD, Donepezil and HCM groups. Injection of -amyloid peptide (A1-42) into the lateral ventricle was used to induce AD in rats. Rats in treatment groups received HCM (1.5, 3.0 and 6.0 g/kg) and Donepezil (0.92 mg/kg) for 21 days, respectively. The spatial learning and memory ability were observed by Morris water maze (MWM) test. Haematoxylin-eosin (HE) staining was carried out for pathological morphology. The contents of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the hippocampus were determined using the spectrophotometric method. A expression was measured by immunohistochemistry and Western blotting. RESULTS: Rats in HCM groups spent less time to locate the platform and performed better in spatial learning and memory than the AD group (p < 0.05). Hippocampus in the HCM (6.0 g/kg) group had a complete pyramidal cell layer, in which the structure of morphology was normal and the number of neurons was larger than in the AD group (p < 0.01). The contents of SOD, CAT, GSH-Px were notably increased and MDA content was significantly decreased in the hippocampus in HCM groups than in the AD group (p < 0.01). The expression levels of A1-42 in HCM groups were markedly decreased than in the AD group (p < 0.01). CONCLUSIONS: HCM has a protective effect on the learning and memory capacity in AD in rats, indicating that HCM had cognitive enhancing potentials on AD.