Aspirin(AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun.dred million,but many persons wer...Aspirin(AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun.dred million,but many persons were died from interned bleeding.We found salvianolic acids(salvianolic acid B 57%,salvianolic acid A 1%,rosmarinic acid,35%,SA) was much better than AS in preventing in.cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows:(1) both AS and AS have same anti-platelet aggregation ef.fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2 only;(2) For established thrombosis,SA could dissolved it,AS showed no effect.The thrombolytic mechanism of SA has been elucidated.(3) In SHRSP rats,the incidence of stroke and death rate in SA group was distinct less that of AS group;(4) In MCAO rats,SA and Sal B decreased stroke index and neural im.pairment.AS showed no such ability;(5) There is microcirculatory disturbance in cardio-cerebral ischemic disease.SA could improve circulatory disturbance induced by LPS,adrenaline,ROS and I/r.there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis.turbance models;(6) Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease.SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin) and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7) Thereis overproduc.tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro.bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8) According to literatures,1/3 patients who take AS for long time will have hemorrhage,we found in normal rats and mice(coagulating and hemodynamics)SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases;(9) As well known,neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation,inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre.ventive effect on cardio-cerebral vascular diseases.SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in.hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.展开更多
Clausenamide(clau)is one of seven novel compounds isolated from Clausena lansium(Lour)skeels.Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers.After identification of the configurati...Clausenamide(clau)is one of seven novel compounds isolated from Clausena lansium(Lour)skeels.Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers.After identification of the configuration of these enantiomers,the synthesis of 16 enantiomers,including optically active clau and(+)and(-)clau was carried out.During this study,many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated.Production scale is now sufficient to meet the needs of clinical practice.In a pharmacological study numerous models and indicators showed that(-)clau is the active enantiomer,while(+)clau is inactive and elicits greater toxicity than(-)clau.The principal pharmacological effects of(-)clau are to increase cognition,demonstrated in ten models of memory impairment,as well as to inhibitβ-amyloid(Aβ)toxicity,blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein.This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia.(-)Clau is considered to be a promising drug candidate for treatment of Alzheimer's disease and other neurodegenerative disorders.展开更多
文摘Aspirin(AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun.dred million,but many persons were died from interned bleeding.We found salvianolic acids(salvianolic acid B 57%,salvianolic acid A 1%,rosmarinic acid,35%,SA) was much better than AS in preventing in.cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows:(1) both AS and AS have same anti-platelet aggregation ef.fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2 only;(2) For established thrombosis,SA could dissolved it,AS showed no effect.The thrombolytic mechanism of SA has been elucidated.(3) In SHRSP rats,the incidence of stroke and death rate in SA group was distinct less that of AS group;(4) In MCAO rats,SA and Sal B decreased stroke index and neural im.pairment.AS showed no such ability;(5) There is microcirculatory disturbance in cardio-cerebral ischemic disease.SA could improve circulatory disturbance induced by LPS,adrenaline,ROS and I/r.there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis.turbance models;(6) Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease.SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin) and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7) Thereis overproduc.tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro.bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8) According to literatures,1/3 patients who take AS for long time will have hemorrhage,we found in normal rats and mice(coagulating and hemodynamics)SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases;(9) As well known,neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation,inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre.ventive effect on cardio-cerebral vascular diseases.SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in.hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.
文摘Clausenamide(clau)is one of seven novel compounds isolated from Clausena lansium(Lour)skeels.Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers.After identification of the configuration of these enantiomers,the synthesis of 16 enantiomers,including optically active clau and(+)and(-)clau was carried out.During this study,many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated.Production scale is now sufficient to meet the needs of clinical practice.In a pharmacological study numerous models and indicators showed that(-)clau is the active enantiomer,while(+)clau is inactive and elicits greater toxicity than(-)clau.The principal pharmacological effects of(-)clau are to increase cognition,demonstrated in ten models of memory impairment,as well as to inhibitβ-amyloid(Aβ)toxicity,blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein.This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia.(-)Clau is considered to be a promising drug candidate for treatment of Alzheimer's disease and other neurodegenerative disorders.
