ABSTRACT
To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum, jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results, all of the five oligosaccharides were absorbed in the whole intestine, and their absorption rates were affected by the pH of the perfusion solution, drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments, without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.
Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Intestine, Small/metabolism , Morinda/chemistry , Oligosaccharides/pharmacokinetics , Animals , Drugs, Chinese Herbal/chemistry , Intestinal Absorption , Male , Oligosaccharides/chemistry , Perfusion , Rats , Rats, Sprague-DawleyABSTRACT
ETHNOPHARMACOLOGICAL RELEVENCE: Neurodegenerative diseases (NDs) caused by neurons and/or myelin loss lead to devastating effects on patients׳ lives. Although the causes of such complex diseases have not yet been fully elucidated, oxidative stress, mitochondrial and energy metabolism dysfunction, excitotoxicity, inflammation, and apoptosis have been recognized as influential factors. Current therapies that were designed to address only a single target are unable to mitigate or prevent disease progression, and disease-modifying drugs are desperately needed, and Chinese herbs will be a good choice for screening the potential drugs. Previous studies have shown that bajijiasu, a dimeric fructose isolated from Morinda officinalis radix which was used frequently as a tonifying and replenishing natural herb medicine in traditional Chinese medicine clinic practice, can prevent ischemia-induced neuronal damage or death. MATERIALS AND METHODS: In order to investigate whether bajijiasu protects against beta-amyloid (Aß25â35)-induced neurotoxicity in rats and explore the underlying mechanisms of bajijiasu in vivo, we prepared an Alzheimer׳s disease (AD) model by injecting Aß25-35 into the bilateral CA1 region of rat hippocampus and treated a subset with oral bajijiasu. We observed the effects on learning and memory, antioxidant levels, energy metabolism, neurotransmitter levels, and neuronal apoptosis. RESULTS: Bajijiasu ameliorated Aß-induced learning and memory dysfunction, enhanced antioxidative activity and energy metabolism, and attenuated cholinergic system damage. Our findings suggest that bajijiasu can enhance antioxidant capacity and prevent free radical damage. It can also enhance energy metabolism and monoamine neurotransmitter levels and inhibit neuronal apoptosis. CONCLUSION: The results provide a scientific foundation for the use of Morinda officinalis and its constituents in the treatment of various AD. Future studies will assess the multi-target activity of the drug for the treatment of AD.
Subject(s)
Alzheimer Disease/drug therapy , Disaccharides/therapeutic use , Neuroprotective Agents/therapeutic use , Alzheimer Disease/metabolism , Amyloid beta-Peptides , Animals , Behavior, Animal/drug effects , Biogenic Monoamines/metabolism , Brain/cytology , Brain/drug effects , Brain/metabolism , Catalase/metabolism , Cell Count , Disaccharides/pharmacology , Disaccharides/toxicity , Disease Models, Animal , Female , Glutathione Peroxidase/metabolism , Hydroxyindoleacetic Acid/metabolism , Male , Malondialdehyde/metabolism , Maze Learning/drug effects , Memory/drug effects , Morinda , Neurons/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/toxicity , Peptide Fragments , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Toxicity Tests, AcuteABSTRACT
Alzheimer's disease irreversibly and progressively damages the brain, but the treatments in clinical trials are too slow. So, we hypothesized that the presence of erythrocyte variants with AD could be used as a noninvasive means to predict or trigger for administration of the preventive therapeutics, and the aim of this study is to develop a method using Raman spectroscopy in a rat model of Aß25-35-induced neurotoxicity, and then evaluate the protective effect of bajijiasu by this method. Results showed that the Raman spectra fingerprints of the erythrocyte of model group were obvious different from those of the normal control, as peaks around the region 650 cm(-1) belonged to the s-s makers, 1605 cm(-1) corresponded to the high spin (deoxygenated-Hb) marker, 1374 cm(-1) arises from ν4 as a sign of concentration of O2, and 1123 and 1033 cm(-1) are associated with the trans stretching vibrations of CAC skeleton. Results also showed that bajijiasu can make these changes recover. Our study also suggested that erythrocyte variants detected using Raman spectroscopy should be tested in a specific longitudinal study for the association with AD diagnosis, and if positive, can be used as a prognostic marker.
