ABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease of the central nervous system. It is currently believed that PD is related to factors such as age, gender, family inheritance, gene mutation and environment. The pathogenesis of PD is complex and is related to dysfunction and loss of dopaminergic neurons, involving accumulation of α-synuclein, neuroinflammation, oxidative stress, mitochondrial dysfunction and excessive accumulation of neuromelanin. In many ways, various factors act both independently and through cross-promotion, resulting in an ongoing pattern of brain tissue damage and progressing PD pathology. This article reviews the recent research on the pathogenic factors and pathogenesis of PD and explores new ideas and potential targets for PD treatment and drug development.
ABSTRACT
This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia model [MARADP= (41.67±4.55)%, MARAA= (53.22±2.83)%, MARTHR= (73.33±5.04)%] indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregation [MARADP= (26.13±4.60)%, MARAA= (35.53±13.73)%, P<0.01], while aspirin played a strong inhibitory effect on AA-induced platelet aggregation [MARAA= (8.13±2.99)%]. Salvianolic acid A (10 mg·kg-1) significantly improved the neurological function, cerebral infarction volume [(10.77±7.80)%] and brain edema [(79.72±0.83)%] compared with the model group [(43.50±12.69)%, (82.25±0.89)%] (P<0.01), while the effect of aspirin (100 mg·kg-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.
ABSTRACT
Parkinson disease(PD)is characterized by the loss of dopaminergic neurons in the substantia nigra and deposition of cytosolic inclusions in surviving neurons (Lewy bodies), resulting in motor deficits and non-motor symptoms.Although Levodopa remains the gold standard treatment for PD,side effects like dyskinesia followed by long-term use could notbe ignored.Consequently,there is a need for devel-opment new drugs. Baicalein is a flavonoid isolated from traditional Chinese herb, Scutellaria baicalensis Georgi.Our laboratory discovered that baicalein could effectively attenuate neurotoxicity of 6-hydroxy-dopamine(6-OHDA)and promote the differentiation of PC12 cells through high throughput drug screen-ing at the cellularlevel. In vivo studies have shown that baicalein exerts significant therapeutic effect, particularly in the attenuation of muscle tremor in 6-OHDA-lesioned rats.Based on the result from the so far acquired knowledge and previous findings from our laboratory, we could consider neuroprotec-tive mechanism of baicalein focus on the activities ofanti-oxidation and anti-inflammation. Baicalein could prevent oxidative stress and apoptosis through maintaining the mitochondrial function, inhibition of collapse of mitochondrial membrane potential, increase the activity of antioxidant enzymes and restraint of lipid peroxidation via several pathways such as Keap1/Nrf2/HO-1.Anti-inflammatory activity of baicalein exert by attenuating activation of astrocyte and microglia, as well as the production of cathepsin B and cytokines. Additionally, promoting the degradation of α-synuclein contributes to the neuroprotective effect of baicalein against Lewy bodies toxicity.Furthermore,baicalein also modulates the metabolic balance between glutamate(GLu)and gamma-aminobutyric acid(GABA).Overall,baica-lein could protect nervous systemby inhibiting oxidative damage and neuroinflammation caused by environmental and genetic factors.This article reviewed the developments of studies on pharmacody-namics and mechanism of baicalein in PD therapy and provideda reference for further exploration.
ABSTRACT
Platelets are fragments of cytoplasm that are released from the mature megakaryocyte of the bone marrow.The main function of platelets is coagulation and hemostasis.Platelets play a central role in formation of pathological thrombosis. Many ischemic diseases are caused by excessive activa-tion of platelets, which can lead to thrombosis and death. Salvia miltiorrhiza Bunge, the dry roots and rhizomes of the Salvia miltiorrhiza plants,includes some water-soluble compounds,which play positive effects on diverse diseases such as neurodegenerative diseases, diabetic complications or cardiovas-cular diseases.In this paper,the components of the water-soluble in Salvia miltiorrhiza,as well as the applications in thrombotic diseases are summarized. The results show that water-soluble compounds include salvianolic acid A,salvianolic acid B,protocatechuic aldehyde, Danshensu,etc.The water-soluble compounds are applied to ischemic stroke,myocardial infarction and other diseases caused by thrombus. We also discussed the mechanisms of water-soluble compounds on the platelets based on our research results and the data obtained from references. The results indicate that water soluble compounds in Salvia miltiorrhiza play the antiplatelet and antithrombotic effects via different mechanisms, for example, salvianolic acid A inhibits platelet aggregation without promoting bleeding by increasing cAMP, inhibiting phosphoinositide 3-kinase (PI3K) and affecting GPCRs (G protein-coupled receptors) signaling path-ways; salvianolic acid B inhibit platelets as a P2Y12 antagonist and PDE inhibitor; Danshensu inhibits platelet activity may be related to inhibition of calcium influx.In conclusion,thrombotic diseases seriously affect human life and health. The existing antiplatelet drugs have some disadvantages. For example, aspirin may cause intracranial hemorrhage, and clopidogrel may play a slower role. Salvia miltiorrhiza as a traditional Chinese medicine has positive pharmacological activity and exerts antiplatelet aggrega-tion through different mechanisms.In the future,we will develop the new drugs which prevent and treat thrombotic diseases with the further study of the pharmacological effects and mechanisms of Salvia miltiorrhiza.