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Acetylcholinesterase inhibitors (AChEIs) isolated from plants have become the mainstream of clinical treatment for Alzheimer’s disease because of their high efficiency and low toxicity. At present, the production of galantamine and huperzine A still mainly rely on plant extraction since they are not chemically synthesized on a large scale in industry. However, with the sharp rise of social demand, the contradiction between supply and demand has become increasingly prominent due to the difficulty in cultivation and the poor abundance of effective substances. Developing new alternative resources and taking the advantage of metabolic engineering for the production of AChEIs such as galantamine and huperzine are the efficient ways to alleviate the current contradiction. Here, the current development status of alternative resources was summarized and the progress of biosynthesis of galantamine and huperzine A during the past few years was reviewed.
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Alzheimer's disease ( AD) is the most common type of dementia. Currently, there is a lack of drugs that could effectively slow and halt the progression of AD. The present review describes the advancements in the treatment of AD, mainly including drugs for symptomatic control, drugs that control the behavioral and psychological symptoms of dementia, and some other drugs for AD and the non-pharmaceutical treatments. It is hoped that early diagnosis, early intervention and comprehensive therapy could relieve the symptoms and slow the progression of AD.
ABSTRACT
Alzheimer's disease ( AD) is the most common type of dementia. Currently, there is a lack of drugs that could effectively slow and halt the progression of AD. The present review describes the advancements in the treatment of AD, mainly including drugs for symptomatic control, drugs that control the behavioral and psychological symptoms of dementia, and some other drugs for AD and the non-pharmaceutical treatments. It is hoped that early diagnosis, early intervention and comprehensive therapy could relieve the symptoms and slow the progression of AD.
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Objective: To explore the optimum condition for complex enzyme-assisted extraction of galanthamine from Lycoris aurea by L9 (34) orthogonal array design and separation effect of cation exchange resin on galanthamine. Methods: Cellulase and pectinase solution was used as the extraction solvent. The effects of pH value of enzyme, amount of complex enzyme, dissociation time, and enzymatic hydrolysis temperature on the extraction results were investigated. Results: The optimal conditions were obtained as follows: ratio of solid to liquid (g: mL) 1:10, pH value 4.5, amount of complex enzymes 4%, enzymatic hydrolysis temperature 50 °C, and reaction time 2.0 h. Under these conditions, the extraction yield of galanthamine was 0.0294%. In addition, D-001 cation exchange resin was selected for separation of galanthamine. The separation conditions were that adsorption flow rate was 3 BV/h with reagent of pH 2 and the desorption flow rate was 3 BV/h with 70% ethanol solution containing 1.5 mol/L ammonia. After separation, the content of galanthamine was increased to 12.31%. Conclusion: The results provide a reference for industrial production of galanthamine.
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Objective: To investigate the culture conditions for the establishment of cell suspension culture system for Lycoris radiata callus and its alkaloid accumulation. Methods: Using the bulbs of L. radiata as explants for callus induction, calli with good quality were selected for suspension cultivation. The factors influencing the establishment of L. radiata cell suspension culture system, such as hormone, inoculum amount, inositol, and conditional culture, were investigated. The alkaloid content in cell suspension culture system of L. radiata was determined by HPLC. Results: The optimal medium for the cell suspension culture was MS+0.5 mg/L 2, 4-D+0.1 mg/L KT+300 mg/L inositol and the inoculum size was 15%. The lag phase of the cell suspension culture system could be evidently shortened by the medium of logarithmic growth. The galanthamine contents in the cell suspension culture system and the medium were 4.18 and 0.69 times of those in the bulbs of L. radiata, respectively. Conclusion: The cell suspension culture system of L. radiata is established and it is a feasible way to gain galanthamine.
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@#ObjectiveTo explore the effect of galanthamine on motor function of patients with cerebral infarction.Methods78 patients were randomly divided into the galanthamine treatment group (40 cases) and the control group (38 cases). Patients in the control group were given clinical routine treatment and rehabilitation training, while the galanthamine treatment group took galanthamine orally in addition. Evaluations were done in pre-treatment and post 6 weeks. Motor function was assessed with Fugl-Meyer motor scale (FMMS).ResultsThe increase of FMMS scores in each group had a significant difference ( P<0.05-0.01), while the process of scores in the galanthamine treatment group was superior to that in the control group (P<0.01).Conclusions Galanthamine hydrobromide is an effect drug on improving activities of motor function and ameliorating the therapeutic efficacy of rehabilitation to patients with cerebral infarction.
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BACKGROUND: The hydrolysis of mivacurium and succinylcholine is impaired in the presence of defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium- or succinylcholine-induced paralysis. In this study, the role of exogenous bovine pseudocholinesterases (BpChE) and/or neostigmine, pyridostigmine, edrophonium or galanthamine in the reversal of mivacurium- or succinylcholine-induced paralysis, were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Ninety five Sprague-Dawley rats (200 g, male) were divided into 14 groups (n = 10). The phrenic nerve-diaphragm preparation mounted in a bath containing oxygenated Krebs' solution. Twitch response from diaphragmatic muscle evoked by phrenic nerve stimulation were measured. After stabilization of the twitch responses, mivacurium (0.1 microgram/mlml) or succinylcholine (0.1 microgram/ml) was administered incrementally in the preparation to obtain more than 95% twitch inhibition. BpChE (0.1, 1.0 u/ml), and/or neostigmine (0.1, 1.0 microgram/ml), pyridostigmine (0.5, 5 microgram/ml), edrophonium (0.01, 0.1 microgram/ml) or galanthamine (0.1, 1.0 microgram/ml) were added for the reversal of mivacurium- and/or succinylcholine-induced block in each group and the twitch responses (0.1 Hz) were monitored for 60 min. The effect of BpChE (0.1 u/ml), in combination with each of the above four anticholinesterases at lower concentrations also were examined. Twitch heights more than 75% was considered an adequatereversal. RESULTS: BpChE 0.1 and 1.0 u/ml were effective in reversal of mivacurium-induced paralysis. When anticholinestrases were added, there was no effective improvement of twitch height at the end of 60 minutes. In succinylcholine-induced paralysis, BpChE was effective for reversal, but when anticholinesterases were added, BpChE potency was inhibited. CONCLUSIONS: BpChE will reverse mivacurium-induced block more effectively than anticholinesterase. BpChE is effective in reversing succinylcholine block. The addition of anticholinesterases inhibits the activity of pseudocholinesterase.
Subject(s)
Animals , Rats , Baths , Cholinesterase Inhibitors , Edrophonium , Galantamine , Hydrolysis , Neostigmine , Oxygen , Paralysis , Phrenic Nerve , Butyrylcholinesterase , Pyridostigmine Bromide , Rats, Sprague-Dawley , SuccinylcholineABSTRACT
OBJECTIVE:To study the bioavailability of single oral dose of galanthamine hydrobromide(GH) sustained-release pellet capsule (GHSRPC) in healthy dogs. METHODS: By a two-cycle crossover trial, 6 dogs were randomly assigned to receive GHSRPC or GH capsules respectively by ig. Blood samples were taken at different time and the plasma concentrations of GHSRPC and GH capsules were determined by HPLC, meanwhile their pharmacokinetic parameters were computed. RESULTS: After a single dose administration of GHSRPC and GH capsules, the pharmacokinetic parameters were as follows: AUC were (1 867.24?321.05) and (1 604.60?289.17) ng?h?mL-1; tmax were (5.42?2.24) and (0.73?0.62) h; Cmax were (89.62?11.23) and (162.82?15.35) ng?mL-1; t1/2 were (8.93?1.82) and (7.58?1.21) h, respectively. The relative bioavailability of the GHSRPC was 116.36%. CONCLUSION: The results showed significant sustained release characteristics of the GHSRPC, It’s bioequivalent with GH capsule.
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OBJECTIVE:To study the in vitro percutaneous permeability of galanthamine cream.METHODS:Using iso?lated mouse's skin as barrier to permeation,the promoting effect of azone in different concentrations on permeation of galanth_ amine was studied.RESULTS:Azone could obviously enhence the permeability of galanthamine through skin.The steady flux of galanthamine cream containing2%and5%azone increased56.12%and23.29%respectively.CONCLUSION:Galanthamine cream has good percutaneous permeability and2%azone promotes the permeability best.
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Aim To study the pharmacokinetics characteristics of galanthamine hydrohromide sustained release tablets and conventional tablets in healthy volunteers after a single and multiple oral doses. MethodsA single and multiple oral doses of galanthamine hydrohromide sustained release tablets and conventional tablets were given to 20 healthy male volunteers in a randomized cross-over study. We developed an LC-MS assay using naloxone as the internal standard to determine the plasma concentrations of galanthamine, calculate the pharmacokinetic parameters and evaluate the relative bioavailability and sustained release characteristics of galanthamine hydrohromide sustained release tablet. Results The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the single-dose study were as follows: the HVD_12 C_max(time span during which the plasma concentration is at least half of the C_max value)were (15.4?1.7) h and (5.4?2.5) h, the retard quotients (R△,the HVD_12 C_max ratio of sustained release tablets to conventional tablets) of sustained release tablet was 3.4?1.4, the T_max were (4.4?1.5) h and (1.3?1.2) h, the C_max were (27.5?2.9) ?g?L-1 and (53.7?12.7) ?g?L-1.Results showed significant sustained release characteristics of the sustained release tablet. The relative bioavailability of the sustained release tablet was (95.9?14.2) %。The pharmacokinetic parameters of the sustained release tablet and conventional tablet obtained from the multi-dose study were as follows: the T_max were (3.0?1.6) h and (0.9?0.3) h,the CSS_max were (58.8?9.4) ?g?L-1 and (52.0?6.9) ?g?L-1,the CSS_min were (16.2?4.0) ?g?L-1 and (22.5?5.0) ?g?L-1,the C_av were (39.0?3.9) ?g?L-1 and (37.1?5.0) ?g?L-1,the DF were 1.1 ?0.3 and 0.8?0.1, respectively. Results of two one-side t test showed that AUC_SS、CSS_max、C_av of two tablets were bioeqivalent. Conclusion Results showed that the sustained release tablet and the regular tablet were bioequivalent in absorbed extent, and the sustained release tablet exhibited a good retarding effect in release.