ABSTRACT
A molecular thermodynamic model is developed to predict DNA melting in ionic and crowded solutions. Each pair of nucleotides in the double-stranded DNA and each nucleotide in the single-stranded DNA are respectively represented by two types of charged Lennard-Jones spheres. The predicted melting curves and melting temperatures T(m) of the model capture the general feature of DNA melting and match fairly well with the available simulation and experimental results. It is found that the melting curve is steeper and T(m) is higher for DNA with a longer chain. With increasing the fraction of the complementary cytosine-guanine (CG) base pairs, T(m) increases almost linearly as a consequence of the stronger hydrogen bonding of the CG base pair than that of adenine-thymine (AT) base pair. At a greater ionic concentration, T(m) is higher due to the shielding effect of counterions on DNA strands. It is observed that T(m) increases in the presence of crowder because the crowder molecules occupy a substantial amount of system volume and suppress the entropy increase for DNA melting. At a given concentration, a larger crowder exhibits a greater suppression for DNA melting and hence a higher T(m). At the same packing fraction, however, a smaller crowder leads to a higher T(m).
Subject(s)
DNA/chemistry , Solutions/chemistry , Base Pairing , Hydrogen Bonding , Models, Molecular , Nucleic Acid Denaturation , Osmolar Concentration , Thermodynamics , Transition TemperatureABSTRACT
AIM: To study the effects of SSF, an effective part isolated from Scutellaria baicalensis George, on memory impairments and the pathological changes of neural and immunological systems in senescent mice induced by chronic galactose. METHODS: Senescent performance in mice was induced by consecutive administration of D-galactose (120 mg/kg, ip) for 47 d. The behavioral tests of mice used water maze task. The neural and immunological changes were assessed by alterations of cerebral cortex morphology and immune tissue index. The improving effects of SSF (50, 100, and 200 mg/kg, ig, 47 d) on above changes in the senescent mice were detected. Piracetam (PIR) was as reference drug. RESULTS: D-Galactose (120 mg/kg, ip, 47 d) resulted in an increase in the latencies to find the terminal platform and the number of errors entering non-exits in water maze, neuropathological changes and immune tissue index (spleen index) deducted in mice as compared with saline treated group. Both PIR (200 mg/kg, ig, 47 d) and SSF (50, 100, and 200 mg/kg, ig, 47 d) could significantly reverse the increased latencies and number of errors and improve the pathological alterations of neural and immunological systems. CONCLUSION: SSF could ameliorate the cognitive deficits and pathological alterations of neuron and immune systems in senescent mice induced by chronic galactose.
Subject(s)
Aging , Drugs, Chinese Herbal/therapeutic use , Memory Disorders/drug therapy , Scutellaria baicalensis/chemistry , Aging/immunology , Aging/pathology , Animals , Cerebral Cortex/pathology , Cognition/drug effects , Drugs, Chinese Herbal/pharmacology , Female , Galactose , Maze Learning , Memory Disorders/chemically induced , Memory Disorders/immunology , Memory Disorders/pathology , Mice , Neurons/pathology , Random AllocationABSTRACT
AIM: To determine the memory-improving properties of huperzine A in aged rats with memory impairments naturally occurring or induced by scopolamine. METHODS: Morris water maze was used to investigate the effects of huperzine A on the acquisition and memory impairments. RESULTS: During 7-day acquisition trials, aged rats took longer latency to find the platform. Huperzine A (0.1-0.2 mg/kg, s.c.) could significantly reduce the latency. In the probe trials on the eighth day, huperzine A (0.1, 0.2 and 0.4 mg/kg, s.c.) significantly increased the time in the quadrant where plateform had disappeared in aged rats. In the acute experiment, scopolamine (0.1 mg/kg, i.p.) significantly impaired spatial memory in the trained aged rats. Huperzine A (0.4 mg/kg, s.c.) significantly reversed the memory deficits induced by scopolamine. CONCLUSION: Huperzine A ameliorates the impaired memory naturally occurring or induced by scopolamine in aged rats.
Subject(s)
Aging/drug effects , Cholinesterase Inhibitors/pharmacology , Memory Disorders/drug therapy , Memory/drug effects , Sesquiterpenes/pharmacology , Alkaloids , Animals , Male , Maze Learning/drug effects , Rats , Rats, Sprague-Dawley , Scopolamine/antagonists & inhibitorsABSTRACT
AIM: To study the effects of huperzine A on lipid peroxidation and superoxide dismutase (SOD) in hippocampus, cerebral cortex, and serum of aged rats. METHODS: The level of lipid peroxidation was determined by thiobarbituric acid reactive substance method and represented as the concentration of malondialdehyde (MDA) in wet tissue. The activity of SOD was determined by xanthine-xanthine oxidase method and represented as the nitrite unit per gram protein in wet tissue. RESULTS: The levels of MDA and the manganese-SOD (Mn-SOD) activities in hippocampus, cerebral cortex, and serum of aged male rats were 2.3-2.8 times and 1.8-2.8 times, respectively, higher than those of adult male rats. Huperzine A (0.05 mg/kg, ig) lowered markedly the levels of MDA and the activities of Mn-SOD in aged male rats following 7-14 d consecutive administrations. The MDA levels in hippocampus, cerebral cortex, and serum decreased 44.7-52.8% (7 d) and 52.6-54.7% (14 d). The Mn-SOD activities in hippocampus, cerebral cortex, and serum lowered 25.0 -57.6% (7 d) and 56.0-74.2% (14 d). In adult rats, no marked change was found after 7-14 d consecutive administrations of huperzine A at a dose of 0.05 mg/kg. CONCLUSION: Huperzine A improved the abnormal free radicals in aged rats.
