The pharmacological effects of isatin on Parkinson's disease / 中国药理学通报

Parkinson's disease (PD) is a kind of senile neurodegenerative disease. Dopaminergic drugs and anticholinergic drugs are the two major therapeutic drugs for PD. In the past several decades, great progress has been achieved on dopamines (DAs) and their synergists including monoamine oxidase B (MAO-B) inhibitors, catechol oxygen methyl transferase inhibitors, ergot and nonergot DA receptor agonists, DA precursor drugs, cannabis and isatin. Isatin is the inhibitor of endogenous specific anti-aging enzyme MAO-B, which has a variety of pharmacological activities. Moreover, the pharmacological mechanism of isatin may be associated with the regulatory functions of various protein activities.

Virtual Screening and Pharmacokinetic Studies of Potential MAO-B Inhibitors from Traditional Chinese Medicine

Parkinson’s disease (PD) is a chronic neurological disorder of the nervoussystem, initiated by lessened production of dopamine (DA) in the substantia nigra, itaffects circa 50 percent more men than women. Theories reveal that age, genetic andenvironmental factors are involved in PD etiology but age seems to be the mostprominent risk factor. Monoamine oxidase B (MAO-B) play prominent role in theoxidative deamination of DA in the striatum. Inhibition of MAO-B in the brain maydecrease the exhaustion of DA stores and increase endogenous DA level. Glide-XPdocking, Quantum-mechanics Polarized Ligand Docking (QPLD), pharmacokineticstudies and biological activity prediction studies were utilized to explain the bindingmode, molecular interaction, inhibitory potential and pharmacokinetic properties ofTraditional Chinese Medicine (TCM) compounds on MAO-B and compared to standarddrugs used for treatment of PD, selegiline and rasagiline. Molecular docking resultsshowed Rutaecarpine and Chrysophanol to have relatively better inhibitory activitiesthan selegiline and rasagiline. Pharmacokinetic studies revealed that Rutaecarpine andChrysophanol show comparative result with selegiline and rasagiline. Also,Rutaecarpine and Chrysophanol PASS prediction for their monoamine inhibitoryactivity showed greater Pa than Pi value. Our results have shown that Rutaecarpine andChrysophanol can be a better therapeutic candidate in the treatment of PD.

Synthesis and monoamine oxidase B inhibitory activities of isoquiritigenin derivatives / 中国中药杂志

Isoquiritigenin,one of the active constituents in the Chinese herb liquorice,is found to have moderate inhibitory activity against rat monoamine oxidase B(MAO-B,IC5047. 2 μmol·L-1). However,the structure-activity relationship(SAR) remains unclear until now. In an attempt to reveal the SAR of inhibition by isoquiritigenin,and to identify more potent and selective inhibitors of MAOB,a series of 13 derivatives based on the scaffold of isoquiritigenin were prepared,and their purities and structures were confirmed by UPLC,1 H-NMR,13 C-NMR and HRMS. These compounds were then evaluated for their ability to inhibit the enzymatic activity of human MAO-B. The SAR of inhibition was summarized and a potent compound C8 with high inhibitory activity(IC501. 4 μmol·L-1) and selectivity(>57 folds over MAO-A) was identified. Enzyme kinetics studies suggested that C8 acted as a competitive inhibitor. In addition,C8 showed little cytotoxicity to glial cells in vitro,which could be a promising lead compound for further study.

Effects of a Silkworm Extract on Dopamine and Monoamine Oxidase-B Activity in an MPTP-induced Parkinsons Disease Model / 한국실험동물학회지

The protective efficacy of a silkworm extract (SE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism and its possible mechanisms were studied in C57BL/6 mice. Mice were administrated intraperitoneally with SE (20 mg/kg/day) for 15 days and MPTP (10 mg/kg/day) was administrated subcutaneously into the mice for the first 6 consecutive days 1 hour before SE treatment. All animals were sacrificed 24 hours after the last SE treatment. Then the parameters related to general toxicity and neurobiochemical markers, such as the dopamine level and the activities of monoamine oxidase (MAO)-B, were measured in various regions of the brain. Treatment of mice with SE effectively attenuated the MPTP-induced decline of striatal dopamine level. MAO-B activity in SE-pretreated mice was inhibited in whole brain, cerebellum and substantia nigra. These results suggest that SE plays an effective role in attenuating MPTP-induced neurotoxicity in animal model. These neuroprotective effects of SE are likely the result from the inhibitory effect on MAO-B activity in mouse brain.

Effects of a Silkworm Extract on Dopamine and Monoamine Oxidase-B Activity in an MPTP-induced Parkinsons Disease Model / 한국실험동물학회지

The protective efficacy of a silkworm extract (SE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism and its possible mechanisms were studied in C57BL/6 mice. Mice were administrated intraperitoneally with SE (20 mg/kg/day) for 15 days and MPTP (10 mg/kg/day) was administrated subcutaneously into the mice for the first 6 consecutive days 1 hour before SE treatment. All animals were sacrificed 24 hours after the last SE treatment. Then the parameters related to general toxicity and neurobiochemical markers, such as the dopamine level and the activities of monoamine oxidase (MAO)-B, were measured in various regions of the brain. Treatment of mice with SE effectively attenuated the MPTP-induced decline of striatal dopamine level. MAO-B activity in SE-pretreated mice was inhibited in whole brain, cerebellum and substantia nigra. These results suggest that SE plays an effective role in attenuating MPTP-induced neurotoxicity in animal model. These neuroprotective effects of SE are likely the result from the inhibitory effect on MAO-B activity in mouse brain.

Effects of β-amyloid peptide on the monoamine oxidase-B, interleukin-6 in the brain of mice and the interfering effect of traditional Chinese medicine / 中国康复理论与实践

@#ObjectiveTo observe the changes of monoamine oxidase-B (MAO-B), interleukin-6(IL-6) in the cortex and hippocampus of Alzheimer's disease model mice and the effect of traditional Chinese medicine Naofucong.MethodsAlzheimer's disease model was induced in mice by β-amyloid(Aβ)25-35 icv. Space learning and memorial ability was tested in Morris water maze. The activity of MAO-B was measured by colorimetric method. IL-6 was observed with the immnuohistochemical stain.ResultsMice in the model group presented longer latent periods of Morris water maze(81.3±13.4)s, higher activities of MAO-B in brain cortex and hippocampus (120.12±10.15,83.60±5.29) compare with that of the control group, which was (34.2±10.9)s,(93.09±10.54) and (50.39±9.16)(P<0.05～0.01).There were many IL-6 positive cell in dentate gyrus of hippocampus of the model group. After administration with Naofucong grain, latent periods (43.7±12.7) s and activities of MAO-B (47.11 ± 6.57)in hippocampus were recovered(P<0.05～0.01), and the IL-6 positive cell in dentate gyrus decreased.ConclusionNaofucong grain can antagonize the Aβ25-35 toxicity by decreasing the overactivition of MAO-B and the excretion of inflammatory medium by microglia, as well as improve the memory function.

Effects of Pine Needle Butanol Fraction on Acetylcholine (ACh) and Its Related Enzymes in Brain of Rats

This study was designed to investigate the effects of buthanol (BuOH) fraction of pine (Pinus densiflora Sieb et Zucc) needle on cholesterol and lipofuscin (LF) accumulations, acetylcholine (ACh) and its related enzyme activities such as choline acetyltransferase (CAhT) and acetylcholinesterase (AChE), and monoamone oxidase-B (MAO-B) activity, which destroyed the catecholamine-related neurotransmitters in brain membranes of Sprague-Dawley (SD) rats. Male SD rats were fed basic diets (control group) or experimental diets (BuOH-25, BuOH-50 and BuOH-100) for 45 days. Cholesterol accumulations in mitochondria and microsomes were significantly inhibited (about 14 - 17% and 23 - 34%, respectvely) in BuOH-50 and BuOH-100 groups, whereas LF levels were significantly inhibited (about 10 - 14%) in BuOH-50 and BuOH-100 groups compared with control group. ACh levels and ChAT activities were significantly increased (about 11 - 17% and 11 - 23%, respectively) in membranes of BuOH-50 and BuOH-100 groups compared with control group. AChE activities were significantly increased (about 14 - 17%) in membranes of BuOH-50 and BuOH-100 groups. There was no significant difference in MAO-B activities between control and experimental diet groups. The results suggest that butanol fraction of pine needle may play an effective role in an antiaging effect and improving a learning and memory impairments.

Advances in pharmacogenetics of anti-Parkinson's drugs treatment / 中国药理学通报

Parkinson's disease(PD)is a neurodegenerative disease that predominantly affects the elderly.Dopamine mimicking drug is the mainstay in the treatment of Parkinson's disease.However,there is a large of interindividual variability in response to anti-Parkinson's disease drugs.It is thought that genetic variability in dopamine system genes is one of the important factors in determining interindividual variability in drug response.There are a lot of studies focused on the relationship between the risk of Parkinson's disease and genetic variations in domestic,while it is a lack of the pharmacogenetics study on Parkinson's disease.This review summarizes the relationship between the polymorphism of genes encoding dopamine transporter,dopamine-metabolizing enzymes and dopamine receptors and Parkinson's disease treatment.

Neurotoxicity of chronic aluminum overload and protective effects of nimodipine in rats / 第三军医大学学报

Objective To study the neurotoxicity of chronic aluminum overload and the protective effects of nimodipine in rats.Methods The brain damage models of rats were established via intragastric administration of aluminum gluconate(element aluminum 400 mg/kg)once a day,5 d/week for 12 weeks.The step-down test and programmed Morris water maze test were used to evaluate the changes of learning and memory functions of rats.Pathomorphological changes of hippocampi of rats were observed.The activities of SOD,ChAT,AchE,MAO-B and the contents of MDA of brain tissue in rats were also measured.Nimodipine(80 mg/kg)were intragastrically administered 4 h after aluminum administration every time for 12 weeks.Results Chronic aluminum administration induced the impairment of avoidance learning and memory ability and spatial oriental ability.Consistent with the behavioral changes,neuronal death in the hippocampi,decreased activities of SOD and ChAT,increased content of MDA,and increased activity of MAO-B and AchE were detected in the aluminum-overload mice.The administration of nimodipine could significantly protect rats from the brain damage,and behavioral and biochemical changes above caused by aluminum overload were in a dose-dependent manner.Conclusion These results suggest that changes of cellular calcium overload and oxide stress and MAO-B activities are involved in pathophysiological mechanisms of brain injury induced by chronic aluminum overload.Nimodipine has a protective effect on neurotoxicity of chronic aluminum overload.

Effects of indole-2,3-dione on the content and release of monoamine neurotransmitters in rat brain / 中国海洋药物

Objective To study the effect of indole- 2,3-dione on the content and release of monoamine neurotransmitters in rat brain.Methods The Wistar rats were given indole-2,3-dione (50,200mg?kg~(-1),ip), and the content of acetylcholine(Ach) and dopamine(DA) in corpus striatum were detected two hours later;the releases of DA,5-hydroxy-tryptamine(5-HT) and norepinephrine(NE) in cortex and corpus striatum slices were examined before and after perfusion with the artificial cerebrospinal fluid(ACSF)that contained indole-2,3-dione. Results The rats given indole-2,3-dione were observed higher concentration of Ach and DA in their corpus striatum compared with that in cortex. Moreover the results also showed indole- 2,3-dione promoted the release of DA in cortex and corpus striatum slices. Conclusion Indole-2,3-dione can regulate the balance between Ach and DA release in rat brain.

Effect of total alkaloids in Equisetum pratense on activity of MAO-B in mice brain / 中草药

Object To study the effects of total alkaloids in Equisetum pratense Ehrh. (TAEP) on the activity of monoamine oxidase B (MAO B) in mice brain, to reveal the mechanism of its inhibitory action on the central nervous system (CNS). Methods The activity of MAO B was determined by UV spectrophotometry. Results TAEP can markedly activate MAO B in cerebrum and antagonise the inhibition of MAO B activity by nialamide. Conclusion TAEP is a MAO B agonist with an action for the evacuation of monoamine, this may be considered as one of the mechanisms of TAEP sedative and tranquilizing action on CNS.

Effect of ginseng stem-leaf saponin on mice's brain aging / 中成药

Objective: To study ginseng stem leaf saponin's effect on brain aging. Methods: The natural aging mice were adopted, divided randomly groups by weight and fed with ginseng stem leaf saponiu for three months, learning and memory ability of mice, the content of MDA and the action of MAO B of brain tissue were determined. The mice was fed with drugs for 40 days, the action of SOD and GSH Px of brain tissues were determined. Bissecting and fecthing the brain of the adult and aging rats and preparing brain chondriosomes and microsomes, and MDA content of brain chondriosomes and microsomes by the method of Fe 2+ cysteine inducing oxidation reduction reaction were determined. Results: Ginseng stem leaf saponin can increase learning and memory ability of aging mice, decrease the content of lipid peroxide and inhibit the action of MAO B of brain tissues; increase the action of SOD and GSH Px of brain tissues; and also inhibit the content of LPO induced oxidation reduction reaction by Fe 2+ cysteine in brain chondriosomes and microsomes of the adult and aging rats. Conclusion:Ginseng stem leaf saponin can protect brain function and postpone brain aging by decreasing free radical's damage and increasing action of GSH Px and SOD of brain tissue.

Correlation between aluminum overload-induced brain neurodegeneration and monoamine oxidase B in mouse brain / 重庆医科大学学报

Objective:To adopt the brain lesion model of mouse induced by overload aluminum to study the relationship between monoamine oxidase B disorder and neurodegeneration induced by overload aluminum(Al).Method:Aluminum overload models were established by injection of 3?l AlCl3 into lateral ventricle of miceeach day for 5d.The AlCl3 solutions injected in different modelswere with different concentrations and they were 0.125%,0.25%,0.5%.On d10,d20,and d30 after the final administration of AlCl3 solution,the learning and memory function of mice,pathomorphology of hippocampi,and MAO-B activity were determined.Results:Aluminum overload elevated MAO-B activity,caused karyopyknosis and loss of neurons in CA1 area of hippocampi,in dose-and time-dependent manners.Conclusion:The results indicate that neurodegeneration induced by Al toxicity may be related to the monoamine oxidase B homeostasis interfered by Al overload.

EFFECTS OF PROCYANIDINS EXTRACTED FROM LOTUS SEEDPOD ON LEARNING AND MEMORY IMPAIRMENT IN MICE / 营养学报

Objective:To study the effects of LSPC on impairment of learning and memory in mice induced by scopolamine and alcohol,and its possible mechanism.Method:One hundred male Kun-Ming mice were randomly divided into 2 batches,50 in each.Each batch was then divided into 5 groups(n=10):control,model,LSPC of 22.5,45,90 mg/kg bw.Group 3-5 was treated with lotus seedpod procyanidins(LSPC,dissolved in normal saline,22.5,45,90 mg/kg bw)by ig.each day for 20 d,while group 1-2 was treated with ig.normal saline.The model of learning and memory impairment was established by ip.3 mg/kg bw scopolamine hydrobromide or ig.40% alcohol in 0.1 ml/10 g bw respectively.Then,effect of LSPC on learning and memory in mice were tested by Y-maze.As to the mice whose learning and memory ability was impaired by alcohol,their brains were dissected out after Y-maze experiment for detecting the level of MDA,the activity of SOD and MAO-B.Results:The learning and memory abilities of mice impaired by scopolamine were remarkably improved after22.5 and 90mg/kg bw LSPC treatment.In the alcohol experiment,the impairment was significantly improved after three different doses of LSPC administration.The level of MDA was reduced,the activity of SOD increased and the activity of MAO-B decreased in mice that learning and memory was impaired by alcohol.Conclusion:LSPC can improve learning and memory abilities of the mice impaired by alcohol and scopolamine,and the mechanism in alcohol experiment probably lay on its suppressive effect on MAO-B activity and protection of neurons from oxidative stress.