Liuwei Dihuang decoction(LW), a classic formula in traditional Chinese medicine(TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists...Liuwei Dihuang decoction(LW), a classic formula in traditional Chinese medicine(TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6herbs including Dihuang[prepared root of Rehmannia glutinosa(Gaertn) DC], Shanyao(rhizome of Dioscorea polystachya Turcz), Shanzhuyu(fruit of Cornus officinalis Siebold Zucc), Mudanpi(root bark of Paeonia × suffruticosa Andrews),Zexie(rhizome of Alisma plantago-aquatica L) and Fuling(scleorotia of Wolfiporia extensa(Peck) Ginns)LW-active fraction combination(LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. There are 3 fractions in LW-AFC, a polysaccharide fraction(LWB-B), a glycoside fraction(LWD-b) and an oligosaccharide fraction(CA-30). Our previous results indicate that LW-AFC has similar pharmacological effects to LW, modulating the balance of the NIM network. LW-AFC has positive effects in many animal models of kidney deficiency or disturbance of the NIM network. LW-AFC could improve the cognitive ability in Alzheimer′s disease(AD) animal models(APP/PS1, SAMP8), where modulating immune function and balancing the NIM network may play an important role in its cognition improving effects. Our study also showed that LW-AFC had protective effects on stress-induced disturbances of the NIM network. However, the underlying mechanisms remain elusive and need further investigation. OBJECTIVE This study evaluated the effects of LW-AFC and the active fractions(polysaccharide, LWB-B;glycoside, LWD-b;oligosaccharide,CA-30) on corticosterone(Cort)-induced long-term potentiation(LTP) impairment in vivo. METHODS LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration(ig, ip, 7 d) or single administration(icv, ig, ip). Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS) to induce LTP impairment. Moreover, in order to research on the possible effective pathways, an antibiotic cocktail and an immunosuppressant were also used. RESULTS Chronic administration(ig) of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Single administration(icv, ig, ip) of any of the active fractions had no effect on Cort-induced LTP impairment, while chronic administration(ig, ip) of LWB-B or LWD-b showed positive effects against Cort. Interestingly, CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition, when the intestinal microbiota was disrupted by application of the antibiotic cocktail, CA-30 showed little protective effects against Cort. The effects of LW-AFC were also abolished when the immune function was inhibited. In the hippocampal tissue, Cort treatment increased corticosterone and glutamate, and LW-AFC could inhibit the Cort-induced elevation of corticosterone and glutamate;there was little change in D-serine in Cort-treated animals, but LW-AFC could increase the D-serine levels. CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Their protective effects are unlikely by a direct way, and immune modulation might be the common pathway. CA-30 could protect LTP from impairment via modulating the intestinal microbiota. Decreasing corticosterone and glutamate and increasing D-serine in the Cort-treated animals’ hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC. Further study is needed to understand the underlying mechanisms.展开更多
OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal mo...OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal models.In this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on LTP.METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP impairment.RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment.The effect of LW-AFC was abolished when the immune function was inhibited.Single administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP impairment.Consecutively intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment.Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal injection.In addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against Cort.CONCLUSION In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota.Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.展开更多
OBJECTIVE Liuwei Dihuang Decoction(LW)-active fraction combination(LW-AFC,consist of 3 fractions polysaccharide,LWB-B;glycoside,LWD-b;oligosaccharide,CA-30)is extracted from LW,it is effective for the treatment of kid...OBJECTIVE Liuwei Dihuang Decoction(LW)-active fraction combination(LW-AFC,consist of 3 fractions polysaccharide,LWB-B;glycoside,LWD-b;oligosaccharide,CA-30)is extracted from LW,it is effective for the treatment of kidney yin deficiency in many animal models.This study evaluated the effects and mechanisms of LW-AFC and the active fractions on corticosterone(Cort)-induced long-term potentiation(LTP)impairment in vivo.METHODS LTP was used to evaluate the synaptic plasticity.LW-AFC was orally administered for seven days.The active fractions were given by either chronic administration(ig,ip,7 d)or single administration(icv,ig,ip).Cort was injected subcutaneously 1h before the high-frequency stimulation(HFS)to induce LTP impairment.Moreover,in order to research on the possible effective pathways,an antibiotic cocktail and an immunosuppressant were also used.RESULTS Chronic administration(ig)of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Single administration(icv,ig,ip)of any of the active fractions had no effect on Cort-induced LTP impairment,while chronic administration(ig,ip)of LWB-B or LWD-b showed positive effects against Cort.Interestingly,CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition,when the intestinal microbiota was disrupted by application of the antibiotic cocktail,CA-30 showed little protective effects against Cort.The effects of LW-AFC were also abolished when the immune function was inhibited.In the hippocampal tissue,Cort treatment increased Cort and glutamate,and LW-AFC could inhibit the Cort-induced elevation of Cort and glutamate;there was little change in D-serine in Cort-treated animals,but LW-AFC could increase the D-serine levels.CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Their protective effects are unlikely by a direct way,and immune modulation might be the common pathway.CA-30 could protect LTP from impairment via modulating the intestinal microbiota.Decreasing Cort and glutamate and increasing D-serine in the Cort-treated animals'hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC.Further study is needed to understand the underlying mechanisms.展开更多
OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed t...OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment.The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms.METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS)to induce LTP impairment.NMDA receptor antagonists and agonists were administrated by icv.RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice.Corticosterone increased the glutamate level in hippocampal tissues,neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP,while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone,suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone.Further results showed that the level of D-serine and its precursor L-serine did not change.D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1(ASC-1)in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone.CONCLUSION Taken together,this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction,which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.展开更多
OBJECTIVE To evaluate the neuroprotective effects of 4 components from Uncaria rhynchophylla(297,307,315 and 327)on long-term potentiation(LTP)deficit in neuroinflammation animal model induced by lipopolysaccha⁃ride(L...OBJECTIVE To evaluate the neuroprotective effects of 4 components from Uncaria rhynchophylla(297,307,315 and 327)on long-term potentiation(LTP)deficit in neuroinflammation animal model induced by lipopolysaccha⁃ride(LPS).METHODS Male BALB/c 18-22 g mice were divided into control group,model group and component treat⁃ment group(1μg per mouse,icv);each group contained 5 mice,model group and compound treatment group were intra⁃peritoneally injected LPS(50μg·kg^-1,ip)4 h before LTP induction.LTP of perforant path-dentate gyrus pathway in hippo⁃campus was induced by high frequency stimulation and used to evaluate the effects on synaptic plasticity.RESULTS Compared with control group,the LTP of the model group was significantly impaired.Compound 297,327,and 307 could significantly improve LPS-induced LTP impairment.315 had no significant effect on LPS-induced LTP impairment.CONCLUSION Hippocampal synaptic plasticity could be impaired by LPS.Compounds 297,327 and 307 have protec⁃tive effects against LPS induced LTP impairment,and 315 has little effect on LPS induced LTP impairment.These re⁃sults suggested that 297,327 and 307 might have potential effects on neuroinflammation induced memory deficits.展开更多
目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给...目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给予大鼠双侧海马分别注射4 nmol/L Aβ25-35或等体积生理盐水每侧2μl,手术后恢复2周,每只大鼠依次进行行为学和电生理两部分实验。首先,利用Morris水迷宫进行空间学习、记忆功能测试;之后,进行在体海马CA1区场兴奋性突触后电位(fEPSP)引导记录实验,观察突触可塑性指标长时程增强(LTP)的改变。结果:与对照组相比,海马内注射Aβ25-35大鼠的空间学习记忆功能和在体海马突触可塑性LTP均有改变,其中:逃避潜伏期和逃避距离明显增加(P<0.01);目标象限内游泳时间和距离明显缩短(P<0.01);在体海马LTP幅度显著降低(P<0.01)。结论:海马内注射Aβ25-35可导致大鼠空间学习记忆功能障碍;联合实验中Aβ25-35同样可引起在体海马LTP改变。提示同批动物先后进行行为学和电生理学测试的方法是可行的,行为学实验不会影响后续LTP的实验结果。因此,本实验为行为学改变后进行在体LTP机制探讨提供了实验依据,为有效开展行为学和电生理学实验提供了思路。展开更多
文摘Liuwei Dihuang decoction(LW), a classic formula in traditional Chinese medicine(TCM), has been used for nearly one thousand years for various diseases with characteristic features of kidney yin deficiency. LW consists of 6herbs including Dihuang[prepared root of Rehmannia glutinosa(Gaertn) DC], Shanyao(rhizome of Dioscorea polystachya Turcz), Shanzhuyu(fruit of Cornus officinalis Siebold Zucc), Mudanpi(root bark of Paeonia × suffruticosa Andrews),Zexie(rhizome of Alisma plantago-aquatica L) and Fuling(scleorotia of Wolfiporia extensa(Peck) Ginns)LW-active fraction combination(LW-AFC) is extracted from LW, it is effective for the treatment of kidney yin deficiency in many animal models. There are 3 fractions in LW-AFC, a polysaccharide fraction(LWB-B), a glycoside fraction(LWD-b) and an oligosaccharide fraction(CA-30). Our previous results indicate that LW-AFC has similar pharmacological effects to LW, modulating the balance of the NIM network. LW-AFC has positive effects in many animal models of kidney deficiency or disturbance of the NIM network. LW-AFC could improve the cognitive ability in Alzheimer′s disease(AD) animal models(APP/PS1, SAMP8), where modulating immune function and balancing the NIM network may play an important role in its cognition improving effects. Our study also showed that LW-AFC had protective effects on stress-induced disturbances of the NIM network. However, the underlying mechanisms remain elusive and need further investigation. OBJECTIVE This study evaluated the effects of LW-AFC and the active fractions(polysaccharide, LWB-B;glycoside, LWD-b;oligosaccharide,CA-30) on corticosterone(Cort)-induced long-term potentiation(LTP) impairment in vivo. METHODS LTP was used to evaluate the synaptic plasticity. LW-AFC was orally administered for seven days. The active fractions were given by either chronic administration(ig, ip, 7 d) or single administration(icv, ig, ip). Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS) to induce LTP impairment. Moreover, in order to research on the possible effective pathways, an antibiotic cocktail and an immunosuppressant were also used. RESULTS Chronic administration(ig) of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Single administration(icv, ig, ip) of any of the active fractions had no effect on Cort-induced LTP impairment, while chronic administration(ig, ip) of LWB-B or LWD-b showed positive effects against Cort. Interestingly, CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition, when the intestinal microbiota was disrupted by application of the antibiotic cocktail, CA-30 showed little protective effects against Cort. The effects of LW-AFC were also abolished when the immune function was inhibited. In the hippocampal tissue, Cort treatment increased corticosterone and glutamate, and LW-AFC could inhibit the Cort-induced elevation of corticosterone and glutamate;there was little change in D-serine in Cort-treated animals, but LW-AFC could increase the D-serine levels. CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment. Their protective effects are unlikely by a direct way, and immune modulation might be the common pathway. CA-30 could protect LTP from impairment via modulating the intestinal microbiota. Decreasing corticosterone and glutamate and increasing D-serine in the Cort-treated animals’ hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC. Further study is needed to understand the underlying mechanisms.
文摘OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang Decoction.Previous studies have showed that LW-AFC could improve learning&memory ability in amny animal models.In this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on LTP.METHODS In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP impairment.RESULTS The results showed that LW-AFC could ameliorate Cort-induced LTP impairment.The effect of LW-AFC was abolished when the immune function was inhibited.Single administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP impairment.Consecutively intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP impairment.Intragastric administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal injection.In addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against Cort.CONCLUSION In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal microbiota.Further studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.
文摘OBJECTIVE Liuwei Dihuang Decoction(LW)-active fraction combination(LW-AFC,consist of 3 fractions polysaccharide,LWB-B;glycoside,LWD-b;oligosaccharide,CA-30)is extracted from LW,it is effective for the treatment of kidney yin deficiency in many animal models.This study evaluated the effects and mechanisms of LW-AFC and the active fractions on corticosterone(Cort)-induced long-term potentiation(LTP)impairment in vivo.METHODS LTP was used to evaluate the synaptic plasticity.LW-AFC was orally administered for seven days.The active fractions were given by either chronic administration(ig,ip,7 d)or single administration(icv,ig,ip).Cort was injected subcutaneously 1h before the high-frequency stimulation(HFS)to induce LTP impairment.Moreover,in order to research on the possible effective pathways,an antibiotic cocktail and an immunosuppressant were also used.RESULTS Chronic administration(ig)of LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Single administration(icv,ig,ip)of any of the active fractions had no effect on Cort-induced LTP impairment,while chronic administration(ig,ip)of LWB-B or LWD-b showed positive effects against Cort.Interestingly,CA-30 only showed protective effects via ig administration,and there was little effect when CA-30 was administered ip In addition,when the intestinal microbiota was disrupted by application of the antibiotic cocktail,CA-30 showed little protective effects against Cort.The effects of LW-AFC were also abolished when the immune function was inhibited.In the hippocampal tissue,Cort treatment increased Cort and glutamate,and LW-AFC could inhibit the Cort-induced elevation of Cort and glutamate;there was little change in D-serine in Cort-treated animals,but LW-AFC could increase the D-serine levels.CONCLUSION LW-AFC and its three active fractions could ameliorate Cort-induced LTP impairment.Their protective effects are unlikely by a direct way,and immune modulation might be the common pathway.CA-30 could protect LTP from impairment via modulating the intestinal microbiota.Decreasing Cort and glutamate and increasing D-serine in the Cort-treated animals'hippocampal tissue might be one of the mechanisms for the neural protective effects of LW-AFC.Further study is needed to understand the underlying mechanisms.
文摘OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation(LTP)and cognitive impairment induced by stress or corticosterone.However,other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment.The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms.METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation(HFS)to induce LTP impairment.NMDA receptor antagonists and agonists were administrated by icv.RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice.Corticosterone increased the glutamate level in hippocampal tissues,neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP,while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone,suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone.Further results showed that the level of D-serine and its precursor L-serine did not change.D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1(ASC-1)in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone.CONCLUSION Taken together,this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction,which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.
基金Open Fund from the State Key Laboratory of Phytochemistry and Plant Resources in West China(P2017-KF13)National Science and Technology Major Project of China(2016ZX09J16104)
文摘OBJECTIVE To evaluate the neuroprotective effects of 4 components from Uncaria rhynchophylla(297,307,315 and 327)on long-term potentiation(LTP)deficit in neuroinflammation animal model induced by lipopolysaccha⁃ride(LPS).METHODS Male BALB/c 18-22 g mice were divided into control group,model group and component treat⁃ment group(1μg per mouse,icv);each group contained 5 mice,model group and compound treatment group were intra⁃peritoneally injected LPS(50μg·kg^-1,ip)4 h before LTP induction.LTP of perforant path-dentate gyrus pathway in hippo⁃campus was induced by high frequency stimulation and used to evaluate the effects on synaptic plasticity.RESULTS Compared with control group,the LTP of the model group was significantly impaired.Compound 297,327,and 307 could significantly improve LPS-induced LTP impairment.315 had no significant effect on LPS-induced LTP impairment.CONCLUSION Hippocampal synaptic plasticity could be impaired by LPS.Compounds 297,327 and 307 have protec⁃tive effects against LPS induced LTP impairment,and 315 has little effect on LPS induced LTP impairment.These re⁃sults suggested that 297,327 and 307 might have potential effects on neuroinflammation induced memory deficits.
文摘目的:探讨海马内注射β-amyloid protein 25-35(Aβ25-35)所致Alzheizer’s病(AD)模型大鼠空间学习记忆功能障碍的海马突触可塑性长时程增强(LTP)机制,为联合开展AD动物行为学和在体电生理学研究提供实验证据。方法:在脑立体定位仪上给予大鼠双侧海马分别注射4 nmol/L Aβ25-35或等体积生理盐水每侧2μl,手术后恢复2周,每只大鼠依次进行行为学和电生理两部分实验。首先,利用Morris水迷宫进行空间学习、记忆功能测试;之后,进行在体海马CA1区场兴奋性突触后电位(fEPSP)引导记录实验,观察突触可塑性指标长时程增强(LTP)的改变。结果:与对照组相比,海马内注射Aβ25-35大鼠的空间学习记忆功能和在体海马突触可塑性LTP均有改变,其中:逃避潜伏期和逃避距离明显增加(P<0.01);目标象限内游泳时间和距离明显缩短(P<0.01);在体海马LTP幅度显著降低(P<0.01)。结论:海马内注射Aβ25-35可导致大鼠空间学习记忆功能障碍;联合实验中Aβ25-35同样可引起在体海马LTP改变。提示同批动物先后进行行为学和电生理学测试的方法是可行的,行为学实验不会影响后续LTP的实验结果。因此,本实验为行为学改变后进行在体LTP机制探讨提供了实验依据,为有效开展行为学和电生理学实验提供了思路。
