Key gene and protein changes in the beta-amyloid pathway following Longyanshen polysaccharides treatment in a mouse model of Alzheimer's disease

BACKGROUND： During onset and development of Alzheimer＇s disease, β-amyloid （Aβ） precursor protein （APP）, β-site amyloid precursor protein cleaving enzyme （BACE）, and β-amyloid are key genes and proteins in the Aβ pathway, and over-expression of these genes can lead to Aβ deposit/on in the brain. OBJECTIVE： To observe the influence of Longyanshen polysaccharides on expression of BACE, APP, and Aβ in the senescence-accelerated mouse prone/8 （SAMP8） brain, and to compare these effects with huperzine A treatment. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiochemical experiment was performed at the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University from September 2005 to January 2008. MATERIALS： Longyanshen polysaccharfdes powder was extracted from the dried slices of the medicinal plant Longyanshen. The active component, Longyanshen polysaccharides, was provided by the Department of Pharmacology, Guangxi Medical University; huperzine A was purchased from Yuzhong Drug Manufactory, China. METHODS： Healthy SAMP8 mice were used to establish a model of Alzheimer＇s disease. A total of 50 SAMP8 mice were randomly assigned to 5 groups （n = 10）： SAMP8, huperzine A, low-, middle-, and high-dose polysaccharides. In addition, 10 senescence-accelerated mouse resistant 1 （SAMR1） mice were selected as normal controls. SAMP8 and SAMR1 mice were administered 30 mL/kg normal saline; the huperzine A group was administered 0.02 mg/kg huperzine A; the low-, middle-, and high-dose polysaccharides groups were respectively administered 45, 90, and 180 mg/kg Longyanshen polysaccharides. Each group was treated by intragastric administration, once per day, for 50 consecutive days. MAIN OUTCOME MEASURES： One hour after the final administration, immunohistochemical analysis was used to determine Aβ expression in the cortex and hippocampus of SAMP8 mice. Reverse-transcription polymerase chain reaction was used to determine mRNA levels of BACE and APP in SAMP8 brain tissue. RESULTS： Compared with the SAMR1 group, Aβ expression in the cerebral cortex and hippocampus, as well as expression of BACE, APP mRNA in the brain was significantly increased in the SAMP8 group （P 〈 0.05-0.01）. Compared with the SAMP8 group, Aβ expression, as well as BACE and APP mRNA expression, were significantly decreased in the cerebral cortex and hippocampus of huperzine A and low-, middle-, and high-dose polysaccharides groups （P 〈 0.05-0.01）. In particular, the effect of high-dose polysaccharides was the most significant （P 〈 0.05-0.01 ）. CONCLUSION： Longyanshen polysaccharides reduced or inhibited over-expression of BACE, APP, and Aβ in SAMP8 mice in a dose-dependent manner, and the effect was not worse than huperzine A.

Effects of Longyanshen polysaccharides on free radical metabolism in senescence accelerated-prone mice

BACKGROUND： Along with aging, antioxidase activity decreases and oxygen-derived free radicals greatly accumulate, resulting in cellular senescence, or even cell death. This is manifested by hypomnesia and disordered metabolism of free radicals. Studies have reported that Longyanshen polysaccharides have the function of antioxidation and improved brain memory. OBJECTIVE： To observe the effects of Longyanshen polysaccharides on free radical metabolism in brain tissue to verify the anti-aging mechanisms in senescence accelerated-prone （SAMP8） mice. DESIGN, TIME AND SETTING： The randomized, controlled, biochemical experiment was performed in the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University （China） from September 2005 to January 2008. MATERIALS： Forty SAMP8 mice were randomized into four groups： SAMP8 control group, as well as low-, mid-, and high-dose polysaccharide, with 10 mice in each group. Ten senescence accelerated-resistantprone （SAMR 1） mice served as the normal control group. Longyanshen polysaccharides, extracted from the medical plant Longyanshen, were supplied by the Department of Pharmacology, Guangxi Medical University Superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, malonaldehyde （MDA）, nitric oxide （NO）, and total protein test kitwere purchased from Nanjing Jiancheng Bioengineering Institute （China）. METHODS： SAMP8 mice were used to establish a dementia animal model. SAMP8 and SAMR1 control mice were administered 30 mL/kg saline. The low-, middle-, and high-dose polysaccharide groups were administered 45, 90, and 180 mg/kg Longyanshen polysaccharides, respectively. Each group was treated by intragastric administration, once daily, for 50 continuous days. MAIN OUTCOME MEASURES： One hour after the last administration, mouse brain tissues were collected, and retro orbital blood sampling was performed. Spectrophotometry was used to measure SOD and GSH-Px activity, as well as MDA and NO concentration in sera and brains of SAMP8 mice. RESULTS： SOD and GSH-Px activity decreased significantly, and MDA and NO concentration increased significantly, in SAMP8 control group brain tissues, compared with the SAMP1 control group （P 〈 0.05）. Compared with the SAMP8 control group, Longyanshen polysaccharide-treated groups exhibited enhanced SOD and GSH-Px activity, as well as decreased MDA and NO concentration, in serum and brain tissue （P 〈 0.05）. Longyanshen polysaccharides exerted a similar effect on SOD, GSH-Px, MDA, and NO concentrations in serum and brain tissues of SAMP8 mice. CONCLUSION： Longyanshen polysaccharides scavenged free radicals effectively, reduced NO concentration and ameliorated NO toxicity, thereby influenced aging and stress, as well as improving memory capacity in the brain.

Averrhoa carambola extractive inhibits breast cancer via regulating CEPT1 and LYPLA1

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD, i.e., Averrhoa carambola extractive) liposomes(HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading(up to 83%)with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests,HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κ B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.