人参多糖抗疲劳和抗抑郁作用及其机制的研究
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摘要
人参(Panax ginseng C.A.Meyer)是著名中药,具有多种药效。现代中药学研究表明人参具有抗疲劳、抗抑郁等作用。人参多糖是人参的有效成分,对人参的抗疲劳和抗抑郁活性起重要作用,有关这方面的研究还未见报导。
制备人参多糖是按照本实验室已经建立的方法进行的,人参根经过水提、醇沉、Sevag法脱蛋白得到人参总多糖WGP。WGP用DEAE-Cellulose柱层析分离,蒸馏水洗脱得到未结合部分淀粉样葡萄糖WGPN; 0.5 M NaCl洗脱下结合部分人参果胶WGPA。实验室以前的工作已经证明WGPA含有RG-I、HG和AG结构的果胶。进一步通过DEAE-Cellulose柱纯化从WGPA中分离出中性的AG多糖WGPA-N,剩余部分为含有RG-I和HG型结构的果胶WGPA-A。将得到的人参多糖样品口服给予小鼠,研究了人参多糖抗疲劳、抗抑郁的作用及其机制。
本论文研究了WGP、WGPN及WGPA的抗疲劳作用及其剂量效应关系。小鼠的强迫游泳实验及血清生化实验结果表明WGP及WGPA具有抗疲劳活性,以剂量200 mg/kg效果最为明显,而中性的淀粉样葡聚糖几乎没有抗疲劳作用。通过小鼠的强迫游泳实验,血清生化检测及电子显微镜超微结构图像对比研究WGPA-N及WGPA-A的抗疲劳活性,结果表明具有RG-I和HG-型结构的WGPA-A具有更明显的抗疲劳活性,其活性主要是通过①直接的抗氧化过程或是修饰几种抗氧化酶的活性从而减少对细胞膜及细胞内线粒体膜的损伤,减少了氧化应激介导的疲劳；②促进脂肪动员,节约糖原,保持血糖浓度的稳态,减少了能源耗竭引起的疲劳；③减少疲劳代谢产物乳酸的蓄积,减少了毒性物质对中枢的抑制。
抑郁和疲劳有着密切的联系和许多共同的起因,在研究人参果胶WGPA抗疲劳的同时,本论文也通过小鼠口服给药方式研究了WGPA的抗抑郁作用及其可能的机制。自主活动测试,高架十字迷宫测试,社会干扰测试及强迫游泳测试系列行为学实验结果表明WGPA具有显著的抗抑郁活性。为了进一步确定人参果胶抗抑郁的机制,本论文研究了与抑郁密切相关的ERK及GSK-3β神经信号转导通路,通过Western Blotting实验分析了该通路下游的重要靶位BDNF、β-Catenin的蛋白表达,结果显示人参果胶抗抑郁活性可能是通过上调BDNF和β-Catenin的蛋白表达实现的。
Panax ginseng C. A. Meyer (ginseng) as a famous plant medicine has diverse phamacological effects. Specially, its anti-fatigue and antidepressant activities have been confirmed through the modern pharmacological research on traditional Chinese drug. Being the active components of ginseng, ginseng polysaccharides have effective anti-fatigue and antidepressant effects, but little research on the effects has ever been reported.
Ginseng polysaccharides were prepared following the methods built in our lab before, ginseng total polysaccharide WGP was prepared by hot water extraction, ethanol precipitation and destarch from the root of Panax ginseng C. A. Meyer. WGP was loaded on DEAE-cellulose column. The column was eluted first with distilled water to elute the unbound fraction WGPN and then with 0.5 M NaCl to elute the bound fraction WGPA. The polysaccharide components of WGPA-A have been confirmed as RG-I, HG and AG-rich pectin. WGPA was reloaded on DEAE-cellulose column, and it was isolated into the neural AG polysaccharide WGPA-N and the acid RG-I and HG-rich pectin WGPA-A. The anti-fatigue and antidepressant effects of the fractions of ginseng polysaccharide and their possible mechanisms were studied by orally administrated way in mice.
The anti-fatigue effects of WGP, WGPN and WGPA and their dose-effect relations were investigated through the results of the forced swimming test and the serum biochemical tests in mice. It was confirmed that 200 mg/kg is the most optimum dosage of the anti-fatigue effects of WGP and WGPA. The anti-faitgue effects of WGPA-A and WGPA-N were compared and the results showed the effects of WGPA-A whose structure is RG-I and HG pectin was more significant than that of WGPA-N. The resuts were evaluated by the forced swimming test, the serum biochemical tests and the morphological changes of mitochondria in striated skeletal muscle. The anti-fatigue mechanisms were mainly focused on①directly antioxidative effects or increasing the activities of antioxidant enzymes, reducing the myocardial damage of membrane structure of mitochondria or cells, alleviating the fatigue mediated by oxidative stress;②significantly promoting fat utilization of mice during exercising, sparing the consumption of blood glucose and therefore delaying fatigue mediated by energy exhaustion;③significantly decreasing the accumulation of lactic acid the metabolic products of fatigue, and decreasing its inhibition to central nervous systerm.
Based on the close connection and part of similar mechanisms between depression and fatigue, the antidepressant effects of ginseng pectin WGPA and its possible mechanisms were also studied in the present paper. WGPA was orally administrated to mice and some behavioral tests including the spontaneous activity test, the elevated plus-maze test, the social interaction test and the forced swimming test were performed, the results showed that WGPA has the significant antidepressant effects. To elucidate the antidepressant mechanisms of ginseng pectin, the neuronal signaling pathways of ERK and GSK-3βwere studied in the present paper. BDNF andβ-Catenin as the important targets of the pathways were tested with the Western Blotting analysis, the results showed that the antidepressant mechanisms of WGPA were mainly through up-regulating the expression of target protein BDNF andβ-Catenin in the ERK and GSK-3βsignaling pathway.
制备人参多糖是按照本实验室已经建立的方法进行的,人参根经过水提、醇沉、Sevag法脱蛋白得到人参总多糖WGP。WGP用DEAE-Cellulose柱层析分离,蒸馏水洗脱得到未结合部分淀粉样葡萄糖WGPN; 0.5 M NaCl洗脱下结合部分人参果胶WGPA。实验室以前的工作已经证明WGPA含有RG-I、HG和AG结构的果胶。进一步通过DEAE-Cellulose柱纯化从WGPA中分离出中性的AG多糖WGPA-N,剩余部分为含有RG-I和HG型结构的果胶WGPA-A。将得到的人参多糖样品口服给予小鼠,研究了人参多糖抗疲劳、抗抑郁的作用及其机制。
本论文研究了WGP、WGPN及WGPA的抗疲劳作用及其剂量效应关系。小鼠的强迫游泳实验及血清生化实验结果表明WGP及WGPA具有抗疲劳活性,以剂量200 mg/kg效果最为明显,而中性的淀粉样葡聚糖几乎没有抗疲劳作用。通过小鼠的强迫游泳实验,血清生化检测及电子显微镜超微结构图像对比研究WGPA-N及WGPA-A的抗疲劳活性,结果表明具有RG-I和HG-型结构的WGPA-A具有更明显的抗疲劳活性,其活性主要是通过①直接的抗氧化过程或是修饰几种抗氧化酶的活性从而减少对细胞膜及细胞内线粒体膜的损伤,减少了氧化应激介导的疲劳；②促进脂肪动员,节约糖原,保持血糖浓度的稳态,减少了能源耗竭引起的疲劳；③减少疲劳代谢产物乳酸的蓄积,减少了毒性物质对中枢的抑制。
抑郁和疲劳有着密切的联系和许多共同的起因,在研究人参果胶WGPA抗疲劳的同时,本论文也通过小鼠口服给药方式研究了WGPA的抗抑郁作用及其可能的机制。自主活动测试,高架十字迷宫测试,社会干扰测试及强迫游泳测试系列行为学实验结果表明WGPA具有显著的抗抑郁活性。为了进一步确定人参果胶抗抑郁的机制,本论文研究了与抑郁密切相关的ERK及GSK-3β神经信号转导通路,通过Western Blotting实验分析了该通路下游的重要靶位BDNF、β-Catenin的蛋白表达,结果显示人参果胶抗抑郁活性可能是通过上调BDNF和β-Catenin的蛋白表达实现的。
Panax ginseng C. A. Meyer (ginseng) as a famous plant medicine has diverse phamacological effects. Specially, its anti-fatigue and antidepressant activities have been confirmed through the modern pharmacological research on traditional Chinese drug. Being the active components of ginseng, ginseng polysaccharides have effective anti-fatigue and antidepressant effects, but little research on the effects has ever been reported.
Ginseng polysaccharides were prepared following the methods built in our lab before, ginseng total polysaccharide WGP was prepared by hot water extraction, ethanol precipitation and destarch from the root of Panax ginseng C. A. Meyer. WGP was loaded on DEAE-cellulose column. The column was eluted first with distilled water to elute the unbound fraction WGPN and then with 0.5 M NaCl to elute the bound fraction WGPA. The polysaccharide components of WGPA-A have been confirmed as RG-I, HG and AG-rich pectin. WGPA was reloaded on DEAE-cellulose column, and it was isolated into the neural AG polysaccharide WGPA-N and the acid RG-I and HG-rich pectin WGPA-A. The anti-fatigue and antidepressant effects of the fractions of ginseng polysaccharide and their possible mechanisms were studied by orally administrated way in mice.
The anti-fatigue effects of WGP, WGPN and WGPA and their dose-effect relations were investigated through the results of the forced swimming test and the serum biochemical tests in mice. It was confirmed that 200 mg/kg is the most optimum dosage of the anti-fatigue effects of WGP and WGPA. The anti-faitgue effects of WGPA-A and WGPA-N were compared and the results showed the effects of WGPA-A whose structure is RG-I and HG pectin was more significant than that of WGPA-N. The resuts were evaluated by the forced swimming test, the serum biochemical tests and the morphological changes of mitochondria in striated skeletal muscle. The anti-fatigue mechanisms were mainly focused on①directly antioxidative effects or increasing the activities of antioxidant enzymes, reducing the myocardial damage of membrane structure of mitochondria or cells, alleviating the fatigue mediated by oxidative stress;②significantly promoting fat utilization of mice during exercising, sparing the consumption of blood glucose and therefore delaying fatigue mediated by energy exhaustion;③significantly decreasing the accumulation of lactic acid the metabolic products of fatigue, and decreasing its inhibition to central nervous systerm.
Based on the close connection and part of similar mechanisms between depression and fatigue, the antidepressant effects of ginseng pectin WGPA and its possible mechanisms were also studied in the present paper. WGPA was orally administrated to mice and some behavioral tests including the spontaneous activity test, the elevated plus-maze test, the social interaction test and the forced swimming test were performed, the results showed that WGPA has the significant antidepressant effects. To elucidate the antidepressant mechanisms of ginseng pectin, the neuronal signaling pathways of ERK and GSK-3βwere studied in the present paper. BDNF andβ-Catenin as the important targets of the pathways were tested with the Western Blotting analysis, the results showed that the antidepressant mechanisms of WGPA were mainly through up-regulating the expression of target protein BDNF andβ-Catenin in the ERK and GSK-3βsignaling pathway.
引文
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