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...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.展开更多
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 ...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.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry...Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.展开更多
基金supported by grants from National Natural Science Foundation of China(No.81260511)Guangxi First-Class Discipline(Pharmacy)Construction Project(No.GXFCDP-PS-2018)+1 种基金Nanning Science and Technology SMEs Technology Innovation Fund Project (No. 20183108)Guangxi Innovation Drive Development Special Project-Science and Technology Major Project(No.GK-AA17202050)
基金Supported by:Guangxi Scientific Research and Technological Development Program,No.0630002-2ADoctoral Research and Innovation Program of Guangxi Graduate Education,No, 2007105981007D10
文摘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.
基金Supported by: Guangxi Natural Science Foundation, No. 0447030Guangxi Scientific Research and Technological Development Projects, No. 0630002-2A
文摘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.
基金financially supported by the National Natural Science Foundation(No.82304393,China)Beijing Nova Program(Nos.Z211100002121127 and 20220484219,China)+1 种基金Beijing Natural Science Foundation(No.L212059,China)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-028,China)。
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treating type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermosensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly decreased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
