Scopolamine Research Articles

Electroacupuncture Reduces Ocular Surface Neuralgia in Dry-Eyed Guinea Pigs by Inhibiting the Trigeminal Ganglion and Spinal Trigeminal Nucleus Caudalis P2X3R-PKC Signaling Pathway

Purpose To observe the effects of electroacupuncture on ocular surface neuralgia and the P2X3R-PKC signaling pathway in guinea pigs with dry eye. Methods A dry eye guinea pig model was established by subcutaneous injection of scopolamine hydrobromide. Guinea pigs were monitored for body weight, palpebral fissure height, number of blinks, corneal fluorescein staining score, phenol red thread test, and corneal mechanical perception threshold. Histopathological changes and mRNA expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis were observed. We performed a second part of the experiment, which involved the P2X3R-specific antagonist A317491 and the P2X3R agonist ATP in dry-eyed guinea pigs to further validate the involvement of the P2X3R-protein kinase C signaling pathway in the regulation of ocular surface neuralgia in dry eye. The number of blinks and corneal mechanical perception threshold were monitored before and 5 min after subconjunctival injection and the protein expression of P2X3R and protein kinase C was detected in the trigeminal ganglion and spinal trigeminal nucleus caudalis of guinea pigs. Results Dry-eyed guinea pigs showed pain-related manifestations and the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis was upregulated. Electroacupuncture reduced pain-related manifestations and inhibited the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis. Subconjunctival injection of A317491 attenuated corneal mechanoreceptive nociceptive sensitization in dry-eyed guinea pigs, while ATP blocked the analgesic effect of electroacupuncture. Conclusions Electroacupuncture reduced ocular surface sensory neuralgia in dry-eyed guinea pigs, and the mechanism of action may be associated with the inhibition of the P2X3R-protein kinase C signaling pathway in the trigeminal ganglion and spinal trigeminal nucleus caudalis by electroacupuncture.

Promnesic, Anxiolytic and Antioxidant Effects of Glaucosciadium cordifolium (Boiss.) Burtt & Davis Essential Oil in a Zebrafish Model of Cognitive Impairment.

The purpose of this study was to investigate the effect of Glaucosciadium cordifolium essential oil (GCEO, 25 and 150 µL/L) on anxiety and learning and memory impairment induced by scopolamine (SCOP) in zebrafish. The chemical composition was analyzed by GC-MS, and the results showed that the highest content was limonene followed by α- and β-pinene, p-cymene and α-phellandrene. The dementia model was induced by SCOP (100 µM), whereas GCEO and galantamine (GAL, 1 mg/L) were delivered to the SCOP-induced model. It was found that GCEO significantly improved memory impairment and anxiety-like response induced by SCOP through the Y-maze, novel object recognition (NOR) test, and novel tank diving tests (NTT). Biochemical analyses showed that GCEO reduced SCOP-induced oxidative damage. Additionally, the cholinergic system activity was improved in the SCOP-induced model by decreasing the acetylcholinesterase (AChE) activity following the exposure to GCEO. It was clear that as a mixture, GCEO displays positive action in improving memory impairment through restoring cholinergic dysfunction and brain antioxidant status.

Therapeutic potential of blackberry extract in the preventing memory deficits and neurochemical alterations in the cerebral cortex, hippocampus and cerebellum of a rat model with amnesia.

The blackberry (Rubus sp.) is a popular fruit that has a high concentration of phenolic compounds. Pharmacological investigations have demonstrated the important biological activities of the blackberry extract, such as neuroprotective actions. This study aimed to evaluate the effects of blackberry extract on memory and neurochemical parameters in rats subjected to scopolamine (SCO)-induced amnesia. Male rats were divided into five groups: I, control (saline); II, SCO; III, SCO + Rubus sp. (100mg/kg); IV, SCO + Rubus sp. (200mg/kg); and V, SCO + donepezil (5mg/kg). Blackberry extract and donepezil were orally administered for 10days. On day 11, group I received saline, and groups II, III, IV, and V received SCO (1mg/kg) intraperitoneally after object recognition behavioral training. Twenty-four hours after the training session, animals were subjected to an object recognition test. Finally, the animals were euthanized, and the cerebral cortex, hippocampus, and cerebellum were collected to evaluate the oxidative stress and acetylcholinesterase (AChE) activity. Rubus sp. extract prevented memory impairment induced by SCO in a manner similar to that of donepezil. Additionally, Rubus sp. extract and donepezil prevented the increase in AChE activity induced by SCO in all the evaluated brain structures. SCO induced oxidative damage in the cerebral cortex, hippocampus, and cerebellum, which was prevented by Rubus sp. and donepezil. Our results suggest that the antioxidant and anticholinesterase activities of Rubus sp. are associated with memory improvement; hence, it can potentially be used for the treatment of neurodegenerative diseases.

Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer's disease in rats: Mechanistic approach to prevent inflammation.

The most common form of dementia, Alzheimer's disease (AD), is characterized by gradual declines in cognitive abilities and behavior. It is caused by a combination of factors, including amyloid-β (Aβ) accumulation, acetylcholine (ACh) loss, oxidative stress, and inflammation. Phenolic compounds have a variety of health benefits, including antioxidant activities. Thus, the purpose of this study was to investigate how resveratrol (RES) alone and in combination with vitamin E affected rats with AD using scopolamine (SCO). Animals are categorized into groups; (i) control, (ii) SCO (1mg/kg i.p.), (iii) SCO + donepezil, (iv) SCO + RES (50mg/kg, p.o.), (v) SCO + RES (75mg/kg, p.o.), (vi) SCO + RES (50mg/kg + vitamin E 1mg/kg, p.o.) for 17days. In rats, studied behavioural (NOR and EPM) and biochemical characteristics. In addition, brain histopathology was examined to investigate any damage to the hippocampus and neuroprotection. SCO-induced changes in acetylcholinesterase, protein carbonyl, and TNF-α improved after resveratrol treatment. RES increased antioxidant levels, decreased SCO-induced lipid peroxidation, and reversed SCO-mediated changes compared with the drug donepezil. The results indicated that RES and vitamin E had nootropic action in the NOR and EPM tests, measured by the recognition index and the inflection ratio. This study supports the efficacy of RES as a preventive and treatment agent for AD. Vitamin E showed a synergistic effect on RES, which helps in managing cognitive impairment AD.

Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia

This study describes the effects of translationally controlled tumor protein (TCTP) on mice with memory impairment caused by scopolamine (SCO) administration. Specifically, memory functions and expression levels of hippocampal synaptic proteins in 7- to 12-month-old SCO-treated wild-type (WT-SCO) mice were compared to those of TCTP-overexpressing (TG) and TCTP knocked-down (KD) mice similarly treated with SCO. Passive-avoidance tasks were performed with WT, TG, and KD mice for four weeks after intraperitoneal injection of SCO or saline followed by an acquisition test. After completing behavioral studies, hippocampi of all mice groups were collected and their synaptic protein contents were subjected to Western blotting or immunohistochemical analyses, and compared with those of 5x familial Alzheimer's disease (5xFAD) mice and postmortem AD patients. Results of passive avoidance tests revealed that SCO-induced memory impairment was repaired in TCTP-TG mice, but not in TCTP-KD mice. Hippocampal expression levels of synaptophysin, synapsin-1, and PSD-95 were increased in TCTP-TG mice treated with SCO (TG-SCO) but decreased in TCTP-KD mice treated with SCO (KD-SCO). Decreased levels of TCTP, synaptophysin, and PSD-95 were also found in hippocampi of 5xFAD mice and AD patients. Expression levels of p-CREB/CREB and brain-derived neurotrophic factor (BDNF) in TCTP-TG and TG-SCO mice were similar to or increased compared to those in WT mice, but decreased in TCTP-KD and KD-SCO mice. BDNF immunoreactivity was restored in CA1 regions of hippocampi of TG-SCO mice, but not in KD-SCO mice. These results suggest that TCTP can restore damaged memory in mice possibly through restored synaptic protein expression.

Rodent models for dry eye syndrome: Standardization using benzalkonium chloride and scopolamine hydrobromide

Dry eye disease is a highly prevalent ocular condition that significantly affects the quality of life and presents a major challenge in ophthalmology. Animal models play a crucial role in investigating the pathophysiology and developing effective treatments. The goal of this study was to compare and standardize two dry eye disease rodent models and explore their recovery aspects. We have standardized benzalkonium chloride and scopolamine-induced dry eye disease models which represents two different classes of the dry eye i.e., evaporative dry eye and aqueous deficient dry eye, respectively. After the development of dry eye conditions, a self-recovery period of seven days was granted to assess the reversal of the induced changes. The dry eye condition was assessed by measuring tear volume, corneal slit lamp imaging, and histological examination of the cornea, the lacrimal and the harderian gland. The study indicated the development of chronic inflammation of the cornea and lacrimal gland in the case of benzalkonium after five days of the treatment, while the scopolamine treated group showed chronic inflammation of the lacrimal gland after five days and corneal inflammation after seven days of administration. The recovery study suggested that after discontinuation of inducing agent, the dry eye symptoms were still persistent suggesting the utility of the model in evaluating dry eye treatments. The study highlights the comparative changes in both models along with recovery which can serve as a base for drug discovery and development against dry eye disease.

Serum lipidomics reveal the mechanism of memory disorder improvement by Qifu decoction.

Memory disorder (MD) is a neurodegenerative disease that seriously affects the quality of life of the elderly in China. It is characterized by cognitive deficits and psychiatric symptoms. In addition to oxidative damage, neurotransmitter disorders, and other factors, Ca2+ homeostasis and lipid metabolism are among the major pathways of MD etiology. Studies have shown that Ca2+ influx, causing Ca2+ overload, leads to neuronal apoptosis and alterations in lipid metabolites at all MD stages. Qifu decoction (QFD) is one of the classic compounds for the traditional treatment of dementia, which has been shown to significantly improve MD caused by dementia and Alzheimer's disease (AD). So far, it is not clear whether QFD can regulate Ca2+ homeostasis and lipids to improve MD. In this study, we developed a scopolamine hydrobromide MD mouse model and performed neurobehavioral experiments and examinations of brain tissue pathology, Ca2+ homeostasis-related factor levels, and non-targeted lipidomics to explore the mechanism of QFD action in improving MD. The results showed that four weeks of intragastric administration of QFD resulted in significant increases in the cognitive ability and spatial memory ability of the mice with MD. Furthermore, the damage to nerve cells was reduced, the levels of Ca2+ and CaM in the serum were decreased, whereas the content of CaMKII was increased, and the Ca2+ homeostasis was regulated. Non-targeted lipidomics detected four lipid subclasses and 17 potential differential metabolites. Metabolic pathway analysis revealed that QFD significantly regulated sphingolipid metabolism and improved MD. In summary, QFD improves scopolamine hydrobromide memory impairment in mice by regulating the Ca2+ signaling pathway and sphingolipid metabolism. This study provides new insights into the beneficial mechanism of QFD on MD from the perspective of lipidomics.

Gut microbiome and brain transcriptome analyses reveal the effect of walnut oil in preventing scopolamine-induced cognitive impairment.

Walnut Oil (WO) is recognized for its potential to improve cognition, but the mechanisms of its action related to improving cognitive impairment are not yet clear. In this study, the components of walnut oil were measured, and it was found that WO supplementation for 8 weeks could significantly prevent cognitive behavioral deficits and synaptic dysfunction induced by intraperitoneal injection of scopolamine (SCOP) in mice. By comparing and analyzing the changes in the hippocampal synaptic structure, oxidative stress, neurotransmitter fluctuations, brain transcriptome, inflammatory factors and gut microbiota in mice from different treatment groups, we observed a significant correlation between synaptic transmission genes, gut microbiota and neurotransmission in the WO supplemented group. It was found that WO supplementation could influence the secretion of neurotransmitters Ach and 5-HT by modulating the gut microbiota in vivo, thereby improving cognitive impairment through the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis regulation.

Modulation of ocular surface desiccation in a murine model by histatin-5 application.

To determine the efficacy of Histatin-5 (Hst5) peptide treatment in ameliorating dry eye disease (DED) phenotype in an in-vivo mouse model of scopolamine and desiccating stress (SDS) dry eye. SDS was induced in female C57BL/6 mice by subcutaneous injections of scopolamine hydrobromide and exposure to low relative humidity and forced air draft for five days. Mouse eyes were topically treated with synthetic Hst5 peptide or balanced salt solution (BSS) twice a day for four days. Control mice were not exposed to SDS induction and did not receive any treatments. Oregon green dextran (OGD) staining was used to evaluate corneal permeability. Histologically, staining with periodic acid schiff (PAS), immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), were used to quantify the number of goblet cells (GC), CD45+ immune cells and apoptotic cells respectively in formalin fixed paraffin embedded (FFPE) mouse whole eye sections. Compared to treatment with BSS, Hst5 treatment significantly lowered corneal epithelial permeability, prevented conjunctival epithelial GC loss, decreased conjunctival CD45+ immune cell infiltration and reduced conjunctival epithelial cell apoptosis. Hst5 peptide topical treatment significantly improves the clinical parameters observed in SDS experimental model of DED. This is the first report of the efficacy of Hst5 treatment of dry eye phenotype, and potential novel treatment for DED in the clinic. Hst5 represents a new class of efficacious therapeutic agents, demonstrating pro-epithelial and anti-inflammatory activities at the ocular surface.

MHRA issues drug safety warning on hyoscine bromide patches

MHRA issues drug safety warning on hyoscine bromide patches

Alpha-Mangostin Attenuates Oxidative Stress and Apoptosis in Scopolamine-Induced Amnesic Rat Brains

The extract from Garcinia mangostana L. pericarp was reported to scavenge radicals, inhibit acetylcholinesterase (AChE) activity, and improve spatial memory in scopolamine (SCOP)-induced amnesic rats. This study investigated α-mangostin (α-MG) neuroprotective effects against SCOP-induced neurotoxicity.The compound was evaluated for anti-AChE and antioxidant properties in vitro, and its preventive effect on apoptosis and oxidative stress in SCOP-treated rat brains. AChE inhibitory property of α-MG was assessed by fast blue B (FB) salt and β-naphthyl acetate (NA) and Ellman’s assays. The antioxidant properties of α-MG were assessed by ferric reducing antioxidant power (FRAP), scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid] (ABTS•+) radicals. Brain levels of malondialdehyde (MDA), lipid peroxidation marker, and activities of the caspase-3 enzyme, an apoptosis-related marker, were determined in SCOP-treated rats pretreated with donepezil (DPZ) and α-MG. IC50 of α-MG and DPZ for AChE activity were 64.23±0.22 and 32.46±0.14 mg/mL, respectively. α-MG and DPZ (100-600 µg/mL) gave FRAP values within the range of 20-410 µmol Fe2+/L. The IC50 of α-MG and DPZ for ABTS were 21.52±3.45 and 14.53±1.86 µg/mL, and for DPPH were 38.12±8.36 and 29.44±5.13 µg/mL, respectively. Prior given to SCOP-induced rats, DPZ and α-MG (50 and 100 mg/kg) reduced MDA levels, and pretreatment of DPZ and α-MG (50 mg/kg), but not α-MG (100 mg/kg), attenuated the increase of caspase-3 activity in cerebral cortex and hippocampus (P<0.05), but not in the basal forebrain. The present study is the first report of α-MG as a potential neuroprotective candidate, and its mechanism might be involved in ameliorating scopolamine-induced neurotoxicity via inhibition of lipid peroxidation and caspase-3 enzyme activity in the cerebral cortex and hippocampus.

An Objective Measure of Recovery.

Effective ambulatory anesthesia is based on a predictable pattern of recovery. This, of course, varies with the agent used, the inherent differences in how patients metabolize or detoxify a drug, as well as the duration and dosage of the drug administered. The development of a straightforward objective test to measure recovery accurately was undertaken in an effort to provide reliable and reproducible data.Other methods of measuring psychomotor performance have been used. These include testing special sensory functions such as vision and hearing,1 various verbal, drawing and bead threading parameters,2 as well as the use of a complex reaction timer developed by the American Automobile Association.3 Other studies of recovery from methohexital anesthesia have involved measuring waking time, the ability to speak rationally and coherently,4 as well as the use of a driving simulator.5 Porteus mazes and ‘“draw a person test” have also been proposed. All available methods are very involved, and require special equipment or personnel.The Bender Motor Gestalt Test, a series of drawings developed by Lauretta Bender in 1938, was copyrighted in 1946.6 This test is used on children and adults as a maturational test involving visual-motor gestalt function. The main aim of the test is to determine the individual’s capacity to experience visual-motor stimuli (gestalten). It has been used to explore mental retardation, regression, loss of function, organic brain damage and personality deviations. Clinical psychologists made extensive use of the Bender tests in cases of neuroses in World War II Army medical installations. Both fatigue and central nervous system depression tend to magnify the sensory-motor disturbances seen in the performance of the Bender Motor Gestalt Test.One of the figures of the Bender Test was selected and modified. Dots were substituted for the continuous lines and spaced approximately 12–13 mm. (See Fig. 1.) In this way, fine motor coordination and perception of the entire outline form could be measured.Patients admitted to the Oral Surgical Clinic were requested to carry out the drawing test, to provide their own pre-operative, pre-anesthetic baseline. Patients were asked to simply “connect the dots in Figure 1.” All patients in this study received either intravenous sedation consisting of pentobarbital sodium or hydroxyzine and meperidine hydrochloride, with scopolamine hydrobromide or atropine sulfate and/or general anesthesia (methohexital) in addition to a local anesthetic. (No oral or intramuscular pre-medications were administered). Ten patients who received only local anesthesia served as one control.This same drawing test was then repeated at appropriate intervals before and after the anesthesia experience to evaluate recovery. Patients were observed and timed in their performance of this test. Their position, cooperativeness and general attitude were noted and scaled.Immediately following the operation, as soon as the patient became conscious and responsive, a second test was administered. Ten minutes later a third test was given. The decision to discharge the patient was made by the doctor and was based on his clinical assessment of recovery. At that time, the final drawing was administered.Scoring: Data processing was done on the IBM 7094 computer. Pearson Correlation Coefficients with 50 variables in Matrix form; variances and standard deviations as well as multidimensional analysis of variance and quadratic and linear trends were computed and analyzed, and are reported elsewhere.8Recovery was taken as the period from awakening to discharge for those patients who received general anesthesia; or from the end of the surgical procedure to discharge for those patients receiving only intravenous sedation.It was determined that performance of this test is directly and significantly related to recovery time. Connecting the series of dots, proved to be a reliable and reproducible index of psychomotor performance. (Subsequent studies of drug effects, utilizing this modified Bender test have repeatedly demonstrated its validity and reliability.)Visual-motor incoordination appears most frequently in the production of sweeping, uninhibited lines, the substitution of dashes for lines, exaggeration or minimization of curves, and fragmentation.7 These aberrations, together with the psychological trauma resulting from the surgery and drug infusion, become evident in the patient’s performance. The following illustrations demonstrate the obvious deviations in performance and eventual return to baseline with recovery.This study provides statistical and clinical evidence in support of the validity of a simple, direct, self-administered, objective test to measure recovery time from ambulatory anesthesia. This test measures sensory-motor performance, which is a critical determinant of recovery. With the aid of this test, the patient’s return towards his own pre-anesthetic baseline becomes more evident and objective. It may also serve as a helpful medical-legal record of recovery from anesthetic influence.Postscript: Detailed data generated from this experiment were published in Anesth. & Analg., 1969.8 This simple drawing test has been effectively used since its development, in subsequent studies which involve comparison of various anesthetic and pre-anesthetic agents. It may provide a helpful tool for both the researcher and the clinician in anesthesiology.

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Oxidative stress is an essential factor in the development and progression of Alzheimer's disease (AD). An excessive amount of reactive oxygen species (ROS) induces the peroxidation of lipid membranes, reduces the activity of antioxidant enzymes and causes neurotoxicity. In this study, we investigated the antioxidant and cholinesterase inhibitory potential of a novel galantamine-curcumin hybrid, named 4b, administered orally in two doses (2.5 mg/kg and 5 mg/kg) in scopolamine (SC)-induced neurotoxicity in mice. To evaluate the effects of 4b, we used galantamine (GAL) (3 mg/kg) and curcumin (CCN) (25 mg/kg) as positive controls. Ex vivo experiments on mouse brains showed that the higher dose of 4b (5 mg/kg) increased reduced glutathione (GSH) levels by 46%, catalase (CAT) and superoxide dismutase (SOD) activity by 57%, and glutathione peroxidase (GPx) activity by 108%, compared with the SC-treated group. At the same time, 4b (5 mg/kg) significantly reduced the brain malondialdehyde (MDA) level by 31% and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities by 40% and 30%, respectively, relative to the SC-impaired group. The results showed that 4b acted as an antioxidant agent and brain protector, making it promising for further experimental research in the field of neurodegenerative diseases.

Acupuncture mitigates ocular surface inflammatory response via α7nAChR/NF-κB p65 signaling in dry eye guinea pigs

To observe the effect of electroacupuncture (EA) on the ocular surface inflammation and α7 nicotinic acetylcholine receptor (α7nAChR) / nuclear factor kappa-B (NF-κB) p65 signal pathway in guinea pigs with dry eye, so as to explore its underlying mechanism. A total of 32 male British tricolor short haired guinea pigs were randomized into blank control, model, EA and sham acupuncture groups, with 8 guinea pigs in each group. The dry eye model was established by subcutaneous injection of scopolamine hydrobromide solution (0.6 mg/0.2 mL each time, 4 times a day for 10 days). Guinea pigs of the EA group was treated with EA at bilateral "Cuanzhu" (BL2) and "Taiyang" (HN5), and manual acupuncture at bilateral "Jingming" (BL1), "Sizhukong" (SJ23), "Tongziliao" (GB1) for 15 min, once daily for 14 days. For animals of the sham acupuncture group, a blunt needle was used to prick the skin surface of the acupoints, the acupoint selection and stimulation time were the same as those in the EA group. Before and after modeling and after the intervention, the breakup time (BUT) of lacrimal film, sodium fluorescein coloring (Fl) state of corneal epithelium and phenol red thread (PRT) moist length were recorded for assessing the severity of dry eye. The density of activated immune cells around the corneal epithelial stromal cells was determined by corneal confocal microscopy. The contents of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor α (TNF-α) in the cornea and lacri-mal gland tissues were determined by ELISA, and the expression levels of α7nAChR and NF-κB p65 in the cornea and lacrimal gland were detected by immunohistochemistry and Western blot, separately. Compared with the blank control group, the corneal Fl, density of activated immune cells of corneal epithelium, contents of IL-6, IL-10 and TNF-α in both corneal and lacrimal gland tissues, NF-κB p65 cell positive rate and protein expression of lacrimal gland and corneal tissues were significantly increased (P<0.01, P<0.05), while the BUT, PRT and lacrimal gland α7nAChR cell positive rate considerably decreased (P<0.01) in the model group. In comparison with the model group, the level of corneal Fl, density of the activated immune cells of corneal epithelium, contents of corneal and lacrimal IL-6 and TNF-α, and corneal and lacrimal NF-κB p65 cell positive rates and protein expressions were remarkably down-regulated in the EA group (P<0.01, P<0.05), rather than in the sham acupuncture group (P>0.05) except content of corneal IL-10, lacrimal NF-κB p65 cell positive rate and lacrimal α7nAChR protein expression, whereas the levels of BUT, PRT, corneal and lacrimal IL-10 and corneal and lacrimal α7nAChR cell positive rates and protein expressions significantly up-regulated in the EA group (P<0.01, P<0.05), rather than in the sham acupuncture group (P>0.05) except corneal TNF-α and corneal NF-κB p65 protein expression. EA can improve corneal and lacrimal function in dry eye guinea pigs, which may be associated with its actions in increasing the expression of α7nAChR, inhibiting the nuclear translocation of NF-κB, and reducing the activated immune cells and inflammatory reaction.

Synthesis of deoxy-Andrographolide Triazolyl Glycoconjugates for the Treatment of Alzheimer's Disease.

A new andrographolide-based terminal alkyne 3 was synthesized in good yield from deoxy-andrographolide 2, obtained from a natural compound andrographolide 1, which in turn was isolated from the leaves of the plant Andrographis paniculata. Copper(I)-catalyzed azide-alkyne cycloaddition reaction of alkyne 3 with azido-sugars 4a-f furnished a library of andrographolide-fastened triazolyl glycoconjugates 5a-f in good yields. The structures of these semisynthetic andrographolide derivatives were established by Fourier transform infrared, NMR, and mass spectroscopy. The compounds 5a-f were further evaluated against Alzheimer's disease (AD) using a scopolamine (SCOP)-induced memory impairment mice model. It was observed that antioxidant and anticholinesterase properties of these compounds contribute significantly toward their remarkable potential to improve cognitive functioning.

Acupuncture Alleviates Corneal Inflammation in New Zealand White Rabbits with Dry Eye Diseases by Regulating α7nAChR and NF-κB Signaling Pathway.

The purpose of this study is to determine the mechanism of improvement in dry eye diseases (DEDs) treated by acupuncture. The inflammatory molecules and related pathways will be analyzed in our study. In order to establish the animal model for DEDs, healthy New Zealand white rabbits were treated with scopolamine (Scop) hydrobromide for 21 consecutive days. After 21 days, acupuncture, fluorometholone (Flu), and α7nAChR antagonist (α-BGT) treatments were performed, and the Scop injections were continued until day 35. The therapeutic effect of acupuncture on DED inflammation was evaluated by corneal fluorescence staining, tear film rupture time, tear flow measurement, in vivo confocal microscopy (IVCM), corneal histopathology, and cytokine protein chip technology. The influence of acupuncture on the corneal pathology and inflammatory factors ACh, α7nAChR, and NF-κB was detected by enzyme-linked immunosorbent assay (ELISA) and western blot. Compared with the group Scop, acupuncture can significantly reduce corneal staining and increase the tear film rupture time and tear flow, which are accompanied by a decrease in corneal epithelial detachment and lymphocyte infiltration. Acupuncture can relieve the inflammation of corneal stroma and mitigate the expression of proinflammatory factors and chemokines. Acupuncture can upregulate the expression of ACh and α7nAChR and downregulate the expression of NF-κB. Our findings demonstrate that acupuncture can alleviate corneal inflammation in New Zealand white rabbits with DEDs via α7nAChR and NF-κB signaling pathway regulation. The expression indicates that α7nAChR/NF-κB signaling pathway may be active and that acupuncture is a potential therapeutic target for dry eye.

Expression analysis of synaptic plasticity genes in curcumin-treated amnesic mice model

Memories are formed and consolidated through an interplay of different synaptic plasticity genes. Amnesia is the state of memory loss, which can be due to several physiological and psychological causes. In this study, we were interested in checking the curcumin (Curcuma longa) effects on memory to treat chemically induced amnesia in the mice model. We analyzed the expression of synaptic plasticity genes (Arc, Zif268, Fmr1, and c-Fos) to see the effect of curcumin at the molecular level in the amnesic mice model. The 24 Swiss Albino male mice were randomly divided into four groups. The first group was a control; we induced amnesia in the other three groups by injecting Scopolamine hydrobromide (3 mg/kg). The administration of curcumin (50 mg/kg) was done pre-and post-treatment in the last two groups. We compared the expression of synaptic plasticity genes among different groups after Real-time PCR. We observed a significant change in the expression of synaptic plasticity genes (Arc and Fmr1) after curcumin treatment in scopolamine-induced amnesic mice. The significance of this study is that if the curcumin affects these synaptic plasticity genes to attenuate amnesia, it can be further developed for the therapeutic potential to prevent/cure neurodegenerative disorders related to amnesia.

Sesamol Attenuates Scopolamine-Induced Cholinergic Disorders, Neuroinflammation, and Cognitive Deficits in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive deficits accompanied by neuronal damage and cholinergic disorders. Sesamol, a lignan component in sesame oil, has been proven to have neuroprotective effects. This research aimed to investigate the preventive effects of sesamol on scopolamine (SCOP)-induced cholinergic disorders in C57BL/6 mice. The mice were pretreated with sesamol (100 mg/kg/d, p.o.) for 30 days. Behavioral tests indicated that sesamol supplement prevented SCOP-induced cognitive deficits. Sesamol enhanced the expression of neurotrophic factors and postsynaptic density (PSD) in SCOP-treated mice, reversing neuronal damage and synaptic dysfunction. Importantly, sesamol could balance the cholinergic system by suppressing the AChE activity and increasing the ChAT activity and M1 mAChR expression. Sesamol treatment also inhibited the expression of inflammatory factors and overactivation of microglia in SCOP-treated mice. Meanwhile, sesamol improved the antioxidant enzyme activity and suppressed oxidative stress in SCOP-treated mice and ameliorated the oxidized cellular status and mitochondrial dysfunction in SCOP-treated SH-SY5Y cells. In conclusion, these results indicated that sesamol attenuated SCOP-induced cognitive dysfunction via balancing the cholinergic system and reducing neuroinflammation and oxidative stress.

Effects of Anticholinergics on Death Rattle: A Systematic Review and Network Meta-Analysis.

Background: Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No quantitative summary of their effects is reported. Objective: This study aimed to systematically review and quantitatively synthesize the effect of anticholinergics on DR treatment and prophylaxis. Design: A systematic search was performed in the electronic databases (PubMed, Embase®, and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from inception to October 2021. Studies conducted to determine the effect of anticholinergics compared with other anticholinergics or placebo on noise reduction score in dying patients were included. A network meta-analysis was performed for DR treatment. The effect of anticholinergics at four hours was assessed. A pairwise meta-analysis was performed for DR prophylaxis. Results: A total of nine studies were included with 1103 patients. Six studies were randomized controlled trials, and three studies were cohort studies. Seven studies were conducted for DR treatment, while two studies were conducted for DR prophylaxis. For DR treatment, no statistically significant difference was observed between each anticholinergic (hyoscine hydrobromide, hyoscine butyl bromide, atropine, and glycopyrrolate) and placebo and among any anticholinergics. However, the surface under cumulative ranking curve indicated that hyoscine butyl bromide had the highest surface under the cumulative ranking curve (SUCRA) with 71.3%. For DR prophylaxis, the relative risk of DR occurrence for hyoscine butyl bromide was 0.23 (0.04, 1.18; I2 = 84.5%) compared with no treatment. Conclusion: This study showed no strong evidence of the regular use of anticholinergics for DR treatment. In addition, hyoscine butyl bromide appears to have a high potential for DR prophylaxis.

A Molecularly Imprinted Polymer-Disposable Pipette Tip Extraction-Capillary Electrophoresis (MISPE-DPX-CE) Method for the Preconcentration and Determination of Scopolamine in Synthetic Urine Samples

Alcoholic beverages contaminated with scopolamine (SCP) are often employed for criminal purposes due to their sedative effect. The determination of the residual levels of SCP in body fluids (e.g., urine) can help to track possible victims of induced ingestions. Biological sample analysis usually requires a preconcentration step to enhance their detectability and to provide sample clean-up. Molecularly imprinted polymers (MIPs) in lieu of conventional solid sorbents represent an enhancement of selectivity, due to their specific recognition sites. Additionally, the adaptation of the solid-phase extraction (SPE) cartridge into a disposable pipette tip extraction (DPX) contributes to the miniaturization of the sample preparation step. Herein, an analytical method for the determination of SCP in synthetic urine samples via the integration of molecularly imprinted solid-phase extraction (MISPE) with DPX as a preconcentration step prior to capillary electrophoresis analysis (also known as MISPE-DPX-CE) is presented. The extraction and elution steps were optimized using a factorial design. Using the optimized conditions, a preconcentration factor of 20 was obtained, leading to a working range of 0.5–6 µM with LOD of 0.04 µM and repeatability of 6.4% (n = 7) and adequate recovery values (84 and 101%) The proposed MISPE-DPX-CE approach was successfully applied to selective extraction, preconcentration, and determination of SCP in synthetic urine samples.