Composición química y actividad Butirilcolinesterasa selectiva del aceite esencial de Piper arboreum Aubl. de Ecuador / Chemical composition and selective BuChE activity of the essential oil of Piper arboreum Aubl. from Ecuador

The aim of this study was to identify the chemical composition of the Piper arboreum Aubl. essential oil (EO), and to evaluate its inhibitory activity in vitro against the enzymes butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The EO was obtained by steam distillation of the leaves, which were collected in Pindal canton of the Loja province in southern Ecuador. The chemical composition was analyzed using the gas chromatography technique coupled to a mass spectrometry detector (GC-MS) and gas chromatography coupled to a flame ionization detector (GC-FID). A total of 41 compounds were identified, the major components found in the oil were limonene (31,46%), ß-selinene (12,01%), (E)-caryophyllene (7,53%), bicyclogermacrene (6,72%), germacrene D (3,83%) and ß-elemene (3,63%). In in vitro analyzes, the EO showed high selective inhibition for BuChE with an IC50 inhibition value of 29,3±3,3 µg/mL. By contrast, the EO was not active against the AChE enzyme (IC50was 100,1±15,2 µg/mL).

El objetivo del presente estudio consistió en identificar la composición química del aceite esencial de la especie Piper arboreum Aubl. y evaluar su actividad inhibitoria in vitro frente a las enzimas butirilcolinesterasa (BuChE) y acetilcolinesterasa (AChE). El aceite esencial (AE) se obtuvo mediante destilación por arrastre de vapor de las hojas de la planta, que se colectaron en el cantón Pindal de la provincia de Loja al sur de Ecuador. La composición química se analizó mediante la técnica de cromatografía de gases acoplado a un detector de espectrometría de masas (GC-MS) y cromatografía de gases acoplado a un detector de ionización de llama (GC-FID). Se identificaron en total 41 compuestos, siendo los mayoritarios, el limoneno (31,46%), ß-selineno (12,01%), (E)-cariofileno (7,53%), biciclogermacreno (6,72%), germacreno D (3,83%) y ß-elemeno (3,63%). En los análisis in vitro, el AE mostró una alta inhibición selectiva para BuChE con un valor de inhibición CI50 de 29,3±3,3 µg/mL. Por el contrario,el AE no resultó activo frente a la enzima AChE con un valor de inhibión CI50= 100,1±15,2 µg/mL.

Some bis (3-(4-nitrophenyl)acrylamide derivatives: Synthesis, characterization, DFT, antioxidant, antimicrobial properties, molecular docking and molecular dynamics simulation studies-Supplemenntary data

Alzheimer's disease, which is a progressive neurologic disorder, is the most common form of dementia. Although there are various treatment options for Alzheimer’s disease, there is no definite treatment for this disease yet. In this study it was aimed to investigate the treatment potentials of three bis(3-(4-nitrophenyl)acrylamide) derivatives, two of which are known and one is new, for Alzheimer's disease. The study consists of three parts; in the first part of the study, synthesis and characterization studies of the investigated compounds were carried out. In the characterization of the compounds, IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis techniques were used. In the second part of the study, the compounds were investigated computationally with the assistance of various computational techniques including density functional theory (DFT) calculations, molecular docking and molecular dynamics simulations. In this part, binding free energy calculations were also performed on the investigated compounds. Results of computational studies showed that synthesized compounds interacted with AChE effectively and can be promising structures as AChE inhibitors. In the last part of the study, antioxidant and antimicrobial properties of the compounds were investigated. Antioxidant activities were determined by DPPH? and ABTS?? radical scavenging methods. According to the DPPH? test, the most active compound was found to be 2, while the most active compound was found to be 3 according to the ABTS? test, showing that these methods for antioxidant assay were not significantly correlated with each other. On the other hand, the results of the antimicrobial activity tests showed that compound 3 was the most active compound, which exhibited both antioxidant and antimicrobial activity.

Some bis (3-(4-nitrophenyl)acrylamide derivatives: Synthesis, characterization, DFT, antioxidant, antimicrobial properties, molecular docking and molecular dynamics simulation studies

Alzheimer's disease, which is a progressive neurologic disorder, is the most common form of dementia. Although there are various treatment options for Alzheimer’s disease, there is no definite treatment for this disease yet. In this study it was aimed to investigate the treatment potentials of three bis(3-(4-nitrophenyl)acrylamide) derivatives, two of which are known and one is new, for Alzheimer's disease. The study consists of three parts; in the first part of the study, synthesis and characterization studies of the investigated compounds were carried out. In the characterization of the compounds, IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis techniques were used. In the second part of the study, the compounds were investigated computationally with the assistance of various computational techniques including density functional theory (DFT) calculations, molecular docking and molecular dynamics simulations. In this part, binding free energy calculations were also performed on the investigated compounds. Results of computational studies showed that synthesized compounds interacted with AChE effectively and can be promising structures as AChE inhibitors. In the last part of the study, antioxidant and antimicrobial properties of the compounds were investigated. Antioxidant activities were determined by DPPH? and ABTS?? radical scavenging methods. According to the DPPH? test, the most active compound was found to be 2, while the most active compound was found to be 3 according to the ABTS? test, showing that these methods for antioxidant assay were not significantly correlated with each other. On the other hand, the results of the antimicrobial activity tests showed that compound 3 was the most active compound, which exhibited both antioxidant and antimicrobial activity.

Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder / 中国中药杂志

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

Curative effects of traditional Chinese medicine paste combined with Baduanjin in treatment of osteoporotic vertebral compression fracture after PVP / 药学实践与服务

Objective To study the curative effects of traditional Chinese medicine paste combined with Baduanjin in treatment of osteoporotic vertebral compression fracture (OVCF) after percutaneous vertebroplasty (PVP). Methods 120 OVCF patients treated with PVP in our hospital from January 2016 to September 2017 were divided into the observation group (60 cases) and the control group (60 cases) according to the random number table method. The control group was given calcium carbonate D3 chewable tablets orally with routine guidance. In addition to the same treatment as the control group, the observation group received the traditional Chinese medicine paste orally with Baduanjin exercise. Both groups were treated for 6 months and followed-up for 3 years. The curative effects in the two groups after 6 months treatment and the low back pain after 1, 3 and 6 months of treatment were recorded. The changes of bone mineral density (BMD), kyphosis angle (Cobb angle), anterior wall height of vertebral body (AVBH) and level of bone metabolism indexes in the two groups were compared before and after treatment for 6 months. The follow-up times and the incidences of push-back fracture after PVP during follow-up were recorded. Results After 6 months of treatment, the clinical cure rate of the observation group was 73.33%, which was higher than 53.33% of the control group(P<0.05). Compared with pretreatment, the scores of visual analogue scale (VAS) in the two groups gradually decreased after 3 and 6 months of treatment, and the observation group had a lower scores than the control group (P<0.05). After 6 months treatment, BMD and AVBH of lumbar vertebrae and femoral neck in both groups increased, and the observation group was higher than that in the control group. The Cobb angle and serum levels of Type I procollagen degradation products (β-Cross I), the n-terminal middle osteocalcin (N-MID Ost) and parathyroid hormone (PTH) decreased in both groups, and the observation group was lower than those in the control group (P<0.05). There was no significant difference in fracture incidence after PVP in the year 1, year 1 to 3 follow up between the two groups (P>0.05). During the 3 years follow-up, the incidence of push-body fracture after PVP in the observation group was 3.33%, which was lower than that in the control group 20.00%( P<0.05). Conclusion Traditional Chinese medicine paste combined with Baduanjin reduced the serum levels of β-Cross I, N-MID Ost and PTH, regulated bone metabolism, improved BMD and AVBH of lumbar vertebrae and femoral neck, reduced Cobb angle, promoted the recovery of lumbar function, alleviated patients' back pain, lowered the incidence of push-body fracture after PVP. The curative effects were remarkable.

ⅣMep⁃S as a novel dual⁃binding AChEI to ameliorate scopolamine⁃induced learning and memory impairment in mice / 安徽医科大学学报

Objective @#To explore the effect of ( - ) Ⅳmeptazinol⁃serotonin hybrid , [( - ) ⅣMep⁃S] on scopolamineinduced learning and memory impairment in mice.@*Methods@#The binding of ( - ) ⅣMep⁃S and hAChE was analyzed by molecular docking. The effect of ( - ) ⅣMep⁃S on AChE activity was observed in vivo and in vitro. The effect of ( - ) ⅣMep⁃S on learning and memory impairment induced by scopolamine was examined in Morris water maze test in mice. The effect of ( - ) ⅣMep⁃S on the motor behaviors of mice was detected by open field test. @*results@#Molecular docking analysis revealed that ( - ) ⅣMep⁃S binded to human AChE. In parallel , ( - ) ⅣMep⁃S overtly inhibited the activity of AChE derived from mouse forebrain and SH⁃SY5Y neuronal cells , and IC50 values were lower than those of the positive control drug rivastigmine. In the Morris water maze test , mice treated with ( - ) ⅣMep⁃S (2. 5 mg/kg) showed significantly reduced latency on day 4 (P < 0. 05) . Moreover, they exhibited significantly greater percentage of distance travelled and percentage of time spent in the target quadrant in the probe trial on day 5 (P < 0. 05) . ( - ) ⅣMep⁃S at 0. 5 mg/kg did not show any significant effects. In addition , ( - ) Ⅳ Mep⁃S inhibited the enhancement of forebrain AChE activity induced by scopolamine (P < 0. 05) . The open field test showed that the effect of ( - ) ⅣMep⁃S on scopolamine⁃induced learning and memory impairment was not due to the difference on the motor behaviors of mice.@*Conclusion@#( - ) ⅣMep⁃S can effectively inhibit AChE activity and ameliorate scopolamineinduced learning and memory impairment in mice.

Research progress on the treatment of gingival pigmentation / 口腔疾病防治

@#Gingival pigmentation is a nonplaque gum disease. Patients are often afraid to communicate with others because of gum color problems, which affect the social and mental health of patients. The commonly used treatment methods for gingival pigmentation include scalpel excision, gingival grinding, laser therapy, cryosurgery and electrosurgery. In this paper, the progress of gingival pigmentation treatment was reviewed in terms of bleeding, pain, tissue healing and recoloring. The results showed that the clinical effect of laser treatment was better. Among them, the semiconductor laser had more advantages in reducing bleeding, pain and the restaining rate, while the Er:Cr:YSSG/Er:YAG laser performed better for promoting tissue healing. Clinicians can choose the best kind of laser to use according to the actual situation. For patients with thin gingival biotypes, floating gingival transplantation or substitute materials can be selected to restore the gingival morphology. With the in-depth study of melanin regulation mechanisms, various drugs, such as ascorbic acid, natural peptides, synthetic peptides and derivatives, may be the main research direction for the treatment of gingival pigmentation in the future.

A Siddha Literature Review on Parallel Analysis of Netriculai Vatam with Frontal Sinusitis

The poetic medical philosophies of Siddha were presented in palm scripts cannot be easily interpreted by common man. According to this system, the disease classification is based on the concepts of Tridosha pathology (Vatham, Pitham and Kabham). The Siddha concept of tri-humoural theory seems poles apart from those of the International Classification of Diseases (ICD) when viewed afar. This review article is an attempt to correlate clinically, the symptoms of “Net?ic?laivatam”, a disease given in the Siddha text Y?ki vaittiya cint?ma?i - 800 with that of the common ailment Sinusitis mentioned in contemporary science. Through meticulous interpretation and parallel analysis of the condition it can be concluded that the signs and symptoms of ‘Net?ic?laivatam’ can be correlated well with that of Sinusitis. This parallel analysis would further pave way for better perceptive, diagnosis and management of the disease ‘Net?ic?laivatam’ as mentioned in Siddha literature

Protective effect of huperzine A on phenytoin induced cognition impairment: Behavioral and biochemical study

Phenytoin, a drug of choice for Epilepsy is also known for its adverse effects. The most common adverse effect due to phenytoin is cognition impairment. Cognition impairment is a serious problem in society as it debars the person's social life. Thus to overcome such a problem demand for a solution arises. Huperzine, sesquiterpene alkaloids having immense neuroprotective properties. Thus in this study, it was aimed to evaluate the effectiveness of huperzine on Phenytoin- induced Cognition Impairment. The protective effect of huperzine on phenytoin-induced cognition impairment was evaluated in rats. The effect of Huperzine on phenytoin-induced cognitive impairment was evaluated by behavioral, biochemical, and histopathological studies. The co-administration of huperzine with phenytoin showed significant results. The treatment of Huperzine with phenytoin resulted in significant improvement in learning and memory. The oxidative stress induced by Phenytoin was reversed by huperzine. A significant decrease in cholinesterase activity was also observed. The histopathology showed damaged neuronal cells in periventricular regions and cortex due to phenytoin which was altered by Huperzine. Thus, the present study demonstrates the protective effect of huperzine on phenytoin-induced cognition impairment.

The Relationship Between Neuroprotective Activity and Antigenotoxic and Acetylcholinesterase Inhibitory Effects of Glaucium corniculatum Extracts

Abstract The purpose of this study was to investigate the relationship between the acetylcholinesterase (AChE) inhibitory and antigenotoxic effect with the neuroprotective activity of Glaucium corniculatum methanol and water extracts rich in rutin and quercetin flavonoids. Neuroprotective activity in terms of cell survival and development against oxidative damage was measured by MTT assay and microscopic analysis in H2O2-induced NGF-differentiated PC12 (dPC12) cells. QRT-PCR and western blot hybridization method was employed for the determination of AChE inhibition of the extracts in the same cell model, and the genotoxic and antigenotoxic effects were identified with Comet assay with human lymphocytes. H2O2-induced vitality loss in dPC12 cells was inhibited in pre-treated cells with these plant extracts. Moreover, extracts stimulated neurite formation and prevented the oxidative stress-induced reduction in neurite growth. In general, it was determined that G. corniculatum methanol extract containing higher amounts of rutin and quercetin was more effective than water extract in terms of AChE inhibitory, antigenotoxic and also neuroprotective effect. In this study, it was shown for the first time that both AChE inhibitory and antigenotoxic effects of G. corniculatum may be effective in neuroprotection and it's protective and therapeutic effects against neurodegeneration may be related to the flavonoid content.

Expression of / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acetylcholinesterase (AChE) is a key enzyme used to detect organophosphorus pesticide residues by the enzyme inhibition method. An accidental discovery of a mutant strain with AChE activity was made in our laboratory during the process of AChE expression by

Prevalência da dor em estudantes universitários: uma revisão sistemática / Prevalence of pain in university students: a systematic review

Objetivo: revisar estudos sobre a prevalência e os fatores relacionados a dor em estudantes universitários brasileiros. Métodos: revisão sistemática com registro na Prospero (CRD42020204197), de artigos publicados em periódicos nacionais e internacionais, nas bases Pubmed, Ebsco, Lilacs, Medline, Portal da BVS, Google Acadêmico e SciELO. Descritores: "Pain", "Chronic Pain", Students", "Students, Health Occupations" e "Universities". Incluídos: a) estudos observacionais; b) transversais; c) publicados em periódicos nacionais ou internacionais; d) redigidos em inglês ou português; e) desenvolvidos com acadêmicos, em instituições de ensino superior brasileiras; f) que tenham avaliado a prevalência e fatores relacionados a dor; g) Tais estudos deviam estar disponíveis na íntegra. Não foram realizadas restrições quanto ao período de publicação dos estudos. Excluídos: h) estudos que não relataram a metodologia aplicada para mensuração do desfecho; i) estudos com instrumentos que não avaliaram a dor como desfecho primário, posteriormente apresentando dados insuficientes para análise dos resultados; j) estudos com acadêmicos de outros países; e k) estudos com inconsistência dos dados relacionados a amostra e seus principais resultados. O risco de viés foi avaliado com a escala Downs and Black e a proposta por Hoy. Resultados: as buscas identificaram 67 artigos, contudo, após análise, 10 foram incluídos. Esses eram estudos transversais, publicados entre 2011 e 2019, sendo cinco deles da região Nordeste. A amostra totalizou 3.268 acadêmicos, sendo 68% mulheres. A prevalência da dor variou entre 14,4% e 98% e a dor crônica entre 11,5% e 59,7%. A maior percepção da dor autorrelatada foi de 4,12 ± 2,15. As principais queixas álgicas foram nas regiões de lombar e de membros superiores. Na análise metodológica, os estudos possuem moderado a alto risco de viés. Conclusões: por fim, as evidências indicam uma alta prevalência de dor, bem como sua cronificação em universitários. Contudo, estudos com adequado rigor metodológico ainda são necessários para a confirmação dos resultados apresentados.

Objective: to review studies on the prevalence and factors related to pain in Brazilian university students. Methods: systematic review with PROSPERO record (CRD42020204197), of articles published in national and international journals, in PUBMED, EBSCO, LILACS, MEDLINE, VHL Portal, Google Scholar and SciELO. Descriptors: "Pain", "Chronic Pain", Students "," Students, Health Occupations "and" Universities ". Included: a) Observational studies; b) transversal; c) published in national or international journals; d) written in English or Portuguese; e) developed with academics, in Brazilian higher education institutions; f) who have assessed the prevalence and factors related to pain; g) Such studies should be available in full. There were no restrictions on the period of publication of the studies. Excluded: h) studies that did not report the methodology applied to measure the outcome; i) studies with instruments that did not evaluate pain as a primary outcome, subsequently presenting insufficient data to analyze the results; j) studies with academics from other countries and k) studies with inconsistent data related to the sample and its main results. The risk of bias was assessed using the Downs and Black scale and proposed by Hoy. Results: searches identified 67 articles, however, after analysis 10 were included. These were cross-sectional studies, published between 2011 and 2019, 5 of them from the Northeast region. The sample totaled 3,268 students, 68% of whom were women. The prevalence of pain varied between 14.4% and 98% and chronic pain between 11.5% and 59.7%. The highest perception of self-reported pain was 4.12 ± 2.15. The main pain complaints were in the lower back and upper limbs. In the methodological analysis, studies have a moderate to high risk of bias. Conclusions: finally, the evidence indicates a high prevalence of pain, as well as its chronicity in university students. However, studies with adequate methodological rigor are still needed to confirm the results presented.

Effect of Ultrafine Powder of Gastrodiae Rhizoma in Improving Learning and Memory Ability of Vascular Dementia Rats by Regulating Cholinergic System / 中国实验方剂学杂志

Objective:To investigate whether ultrafine powder of Gastrodiae Rhizoma （UPG） can alleviate the learning and memory impairment of vascular dementia rats and delay the process of VD， and whether this effect is related to the release of acetylcholine （Ach） through the regulation with acetylcholinesterase （AChE） and choline acetyltransferase （ChAT） and control of cholinergic system. Method:SD rats were randomly divided into sham operation group， UPG low dose group （0.45 g·kg-1）， UPG high dose group （1.8 g·kg-1） and Huperzine A group （80 μg·kg-1）， with 12 rats in each group. The drug administration groups were given orally drugs once a day for 8 weeks， and sham group and model group were given orally the same amount of distilled water. The learning and memory ability of the rats with VD were evaluated by the Morris water maze. Htoxylin eosin（HE） staining was used for pathomorphological observation of hippocampus CA1 area of the rats. The content of Ach was determined by enzyme-linked immunosorbent assay（ELISA）， AChE and ChAT protein expressions were detected by Western blot， and expression of ChAT in hippocampus CA1 area was observed by immunohistochemistry. Result:Compared with the sham operation group， the escape latency of the model group was significantly increased （P<0.01）， and the frequency of crossings platform and the time of staying in the target quadrant were reduced significantly （P<0.01）. HE staining of hippocampal tissues from VD rat showed neuron disorders， loss and degeneration and necrosis， pyknosis of the nucleus and light coloration of the cytoplasm. The level of acetylcholine in the hippocampus was significantly decreased by ELISA （P<0.05）， the expression level of AChE protein was significantly up-regulated， and the expression level of ChAT protein was significantly down-regulated （P<0.01）. Compared with model group， each administration group could significantly reduce the escape latency of the model rats， and significantly increase the frequency of crossing platform and the time of staying in the target quadrant （P<0.01）， the content of Ach was significantly increased （P<0.05）， the expression of AChE protein was significantly down-regulated （P<0.01）， while the expression of ChAT protein was significantly up-regulated （P<0.01）. Conclusion:UPG improves the learning and memory ability of vascular dementia rats， and its mechanism may be related to the increase of Ach， ChAT level and the decrease of AChE level.

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of as well as experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions.

Virtual screen of effective AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking / 中国中药杂志

This research is to predict anti-Alzheimer's disease active constituents on the target of acetylcholinesterase(AChE) from Glycyrrhizae Radix et Rhizoma with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Glycyrrhizae Radix et Rhizoma were established by collecting literature. Then the constituents from Glycyrrhizae Radix et Rhizoma were screen for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between compounds screened from pharmacophore model and AChE protein(PDB ID:4 EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Glycyrrhizae Radix et Rhizoma contains 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma were considered to be the promising compounds according to the results of searching 3 D database of pharmacophore model. The molecular docking was possessed and the interaction patterns were given to show the detail interactions. The compounds screening from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking was reliable.

Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

Alzheimer disease (AD) is characterized by a low level of acetylcholine, beta-amyloid (Aβ) aggregation and oxidative stress. Donepezil is the core medicine used for the treatment of AD. Various structural modifications of donepezil have been carried out. Benzylpiperidine part of donepezil has been replaced with benzylpyridine, pyridyl methylpiperidine, benzylpiperazine, pyrimidyl piperazine. These derived molecules showed promising activities as anti-Alzheimer agents. Replacement of indanone part by other heterocyclic rings such as pyridine resulted in the formation of compounds which exhibited monoamine oxidase (MAO) as well as acetylcholinesterase (AChE) inhibition. Propargylamine containing derivatives displayed AChE as well as MAO inhibition properties. Attachment of donepezil with natural compounds like ferulic acid, flavonoids, and curcumin showed antioxidant activities in addition to inhibition of the AChE. Benzylpiperidine and benzylpiperazine have also been combined with condensed heterocyclic rings and these compounds displayed promising anti-Alzheimer properties. This review highlights the important structural modifications of donepezil and their influence on biological activities as anti-Alzheimer agents.

Comparative study on efficacy of Ketorolac in the management of post-operative pain when administered intravenously or intramuscularly

Background: In the earlier periods analgesia was restricted to surgical and immediate postoperative period. However, this was associated with a lot of morbidities to the patient in terms of surgical stress and increased requirements for analgesia as the pain persisted. Patient’s attitude and concern about postoperative pain need to be addressed preoperatively. Early interventions are essential for better long-term outcomes. Because of the multiplicity of mechanisms involved in postoperative pain, a multimodal analgesia regimen, with a combination of opioid and non-opioid analgesic drugs is often used to enhance analgesic efficacy, reduce opioid requirements and its side effects. Aim of the study: To compare the efficacy of ketorolac in the management of postoperative pain when administered intravenously or intramuscularly, to assess the efficacy of ketorolac by two routes of administration namely Intravenous (IV) and Intramuscular (IM). Materials and methods: This comparative study was done in 2015 in Pondicherry Institute of Medical Sciences, Pondicherry. Totally 60 patients undergoing elective surgeries under ASA I/II was selected and they were divided into two groups of 30 patients each. Postoperatively the patients were examined at half hourly intervals for the first 6 hours for pain and it was graded using Visual Analogue Scale (VAS). If VAS score was > 3, inj. Tramadol 1mg/kg IV was given as rescue analgesic and the time was noted. Any adverse effect such as dizziness, vomiting, nausea was also Maria Varun Raj, R. Ahila, Sangiev Koshy George. Comparative study on efficacy of Ketorolac in the management of postoperative pain when administered intravenously or intramuscularly. IAIM, 2019; 6(3): 164-169. Page 165 noted at half hourly interval for the first six hours following surgery. Total dosage and frequency of rescue analgesic tramadol in the 24 hour period were also calculated. Use of anti-emetics was noted. Results: Postoperative VAS score between the two groups was comparable at zero hours and after the first hour. However, at the 4th and 5th hour, there was a statistically significant difference in the scores between the two groups showing a better analgesic effect with the intramuscular route of administration of ketorolac. The mean VAS score at the end of the 5 th hour showed a statistical difference between the two groups (p=0.001). Postoperative VAS score between the two groups was comparable. However, at the 4th and 5th hour, there was a statistically significant difference in the score between the two groups. The mean duration of analgesia produced by intramuscular routes was found to be high when compared with that of the intravenous route and is statistically significant (p=0.001). The mean duration of analgesia produced by intramuscular routes was found to be high when compared with that of the intravenous route and is statistically significant. (p=0.001). Conclusion: We conclude that ketorolac can be used for postoperative analgesia in place of opioids in patients where opioid has to be avoided. Intramuscular administration provided more effective and prolonged pain relief when compared to intravenous administration.

Effects of cluster needling at the scalp points on the expression of ChAT and AchE of hippocampus in rats with Alzheimer's disease / 中国针灸

OBJECTIVE@#To explore the effects of cluster needling at the scalp points on the expression of choline acetyl transferase (ChAT) and choline cholinesterase (AchE).@*METHODS@#A total of 60 Wistar rats were randomized into a sham-operation group, a model group, a medication group and a cluster needling group, 15 rats in each one. In the model group, the medication group and the cluster needling group, the models of Alzheimer's disease (AD) were established by the orienteering injection with Aβ1-42 in the bilateral hippocampal CA1 in the rats. In the sham-operation group, the distilled water was injected in bilateral hippocampus of rats. In the medication group, the lavage with aricept was adopted for the basic treatment, once a day, for 4 weeks consecutively. In the cluster needling group, on the base of the treatment as the medication group, the cluster needling at the scalp points was adopted, once a day, 6 times a week, for 4 weeks totally. In the sham-operation group and the model group, the normal feeding was provided. After intervention, the learning and memory ability was measured with Morris water maze in the rats of each group. The changes in the hippocampal gross structure were observed with HE staining. The changes in the positive expressions of hippocampal ChAT and AchE were determined with the immunohistochemical method.@*RESULTS@#Compared with the sham-operation group, the escape latency was prolonged and the percentage of the second quadrant and the frequency of platform leaping were reduced in the rats of the model group (all 0.05) and the expression of AchE was reduced (<0.05) in the medication group; the expression of ChAT was increased (<0.05) and that of AchE decreased (<0.01) in the cluster needling group. Compared with the medication group, the expression of ChAT was increased and that of AchE decreased in the cluster needling group (both <0.05).@*CONCLUSION@#The effect mechanism of cluster needling at the scalp points on AD could be related to the up-regulation of ChAT expression and down-regulation of AchE expression in the hippocampus. The combined treatment with the cluster needling and aricept achieves the better therapeutic effect on AD.

A pair of new tirucallane triterpenoid epimers from the stems of Picrasma quassioides / 中国天然药物

A pair of new tirucallane triterpenoid epimers, picraquassins M and N (1> and 2), were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses. In addition, their AChE inhibitory activity, cytotoxicity against five human tumour cell lines (SW480, MCF-7, HepG2, Hela, and PANC-1), and antimicrobial activity against two bacteria (Staphylococcus. aureus 209P and Escherichia coli ATCC0111) and two fungi (Candida albicans FIM709 and Aspergillus niger R330) were evaluated.