Four-Dimensional Label-Free Quantitative Proteomics of Ginsenoside Rg2 Ameliorated Scopolamine-Induced Memory Impairment in Mice through the Lysosomal Pathway.

Alzheimer's disease (AD) is a neurodegenerative disease. Ginsenoside Rg2 has shown potential in treating AD, but the underlying protein regulatory mechanisms associated with ginsenoside Rg2 treatment for AD remain unclear. This study utilized scopolamine to induce memory impairment in mice, and proteomics methods were employed to investigate the potential molecular mechanism of ginsenoside Rg2 in treating AD model mice. The Morris water maze, hematoxylin and eosin staining, and Nissl staining results indicated that ginsenoside Rg2 enhanced cognitive ability and decreased neuronal damage in AD mice. Proteomics, western blot, and immunofluorescence results showed that ginsenoside Rg2 primarily improved AD mice by downregulating the expression of LGMN, LAMP1, and PSAP proteins through the regulation of the lysosomal pathway. Transmission electron microscopy and network pharmacology prediction results showed a potential connection between the mechanism of ginsenoside Rg2 treatment for AD mice and lysosomes. The comprehensive results indicated that ginsenoside Rg2 may improve AD by downregulating LGMN, LAMP1, and PSAP through the regulation of the lysosomal pathway.

A novel neuroprotective peptide YVYAETY identified and screened from Flammulina velutipes protein hydrolysates attenuates scopolamine-induced cognitive impairment in mice.

Flammulina velutipes protein hydrolysates are known for their abundant amino acids and excellent developmental values. This study aimed to identify and screen neuroprotective peptides from F. velutipes protein hydrolysates in vitro and validate the protective effects of YVYAETY on memory impairment in scopolamine-induced mice. The F. velutipes protein was hydrolyzed by simulated gastrointestinal digestion, followed by purification through ultrafiltration and gel chromatography. The fraction exhibiting the strongest neuroprotective activity was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main identified peptides (SDLKPADF, WNDHYY, YVYAETY, and WFHPLF) effectively mitigated excessive ROS production by increasing SOD and GSH-px activities while inhibiting cell apoptosis and mitochondrial membrane potential (MMP) collapse against oxidative stress in Aß25-35-induced HT22 cells. By molecular docking, the interaction between peptides and the active site of the Keap1-Kelch domain reveals their capacity to regulate the Keap1/Nrf2/HO-1 pathway. In vitro, the peptide YVYAETY had the best effect and can be further validated in vivo. The behavioral tests showed that YVYAETY improved scopolamine-induced cognitive impairment in mice. YVYAETY also alleviated neuron damage including neuron vacuolation and pyknotic nuclei in the hippocampus. Furthermore, it significantly inhibited oxidative stress and suppressed the activation of the Nrf2 pathway. Therefore, this study revealed that YVYAETY had the potential to serve as a novel neuroprotective agent.

Butin attenuates behavioral disorders via cholinergic/BDNF/Caspase-3 pathway in scopolamine-evoked memory deficits in rats.

OBJECTIVE: Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins. RESULTS: When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin. CONCLUSIONS: This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.

Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia.

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.

Preparation and characterization of brain-targeted polymeric nanocarriers (Frankincense-PMBN-lactoferrin) and in-vivo evaluation on an Alzheimer's disease-like rat model induced by scopolamine.

Experiments have demonstrated that frankincense may offer protection against scopolamine-induced Alzheimer's disease by mitigating cholinergic dysfunction and inhibiting inflammatory mediators. Nevertheless, its instability and limited water solubility lead to diminished medicinal efficacy. In this study, we utilized PMBN (poly [MPC-co-(BMA)-co-(MEONP)]) as a nanocarrier for targeted brain drug delivery of frankincense, employing lactoferrin as a ligand for precise targeting. Characterization of nanoparticle properties was conducted through FTIR and FESEM analysis, and the in-vitro drug release percentage from the nanoparticles was quantified. To induce Alzheimer's-like dementia in rats, scopolamine was intraperitoneally administered at a dose of 1 mg/kg/day for 14 days. Subsequently, behavioral assessments (Y-maze, passive avoidance test, tail suspension test) were performed, followed by evaluations of acetylcholinesterase (AChE), reduced glutathione (GSH), catalase (CAT), and brain histopathology at the conclusion of the treatment period. The results revealed that the nanoparticles had a size of 106.6 nm and a zeta potential of -3.8 mV. The maximum release of frankincense in the PBS environment from PMBN nanoparticles was 18.2 %, in accordance with the Peppas model. Behavioral tests indicated that targeted drug nanoparticles (F-PMBN-Lf) exhibited the capability to alleviate stress and depression while enhancing short-term memory in scopolamine-induced animals. Additionally, F-PMBN-Lf counteracted the scopolamine-induced elevation of AChE activity and GSH levels. However, it resulted in decreased activity of the antioxidant enzyme CAT compared to the scopolamine group. Histological analysis of brain tissue suggested that F-PMBN-Lf exerted a notable neuroprotective effect, preserving neuronal cells in contrast to the scopolamine-induced group. It appears that the polymer nanoparticles containing this plant extract have introduced a novel neuroprotective approach for the treatment of Alzheimer's disease.

The Anti-Inflammatory Effect of Multi-Wavelength Light-Emitting Diode Irradiation Attenuates Dry Eye Symptoms in a Scopolamine-Induced Mouse Model of Dry Eye.

Dry eye disease is a common condition in patients of all ages, causing discomfort and potential visual problems. Current treatments, including artificial tears and anti-inflammatory drugs, have certain limitations, encouraging research into alternative therapies. We investigated the therapeutic potential of multi-wavelength light-emitting diode (LED) irradiation of mice with dry eye. First, we showed that multi-wavelength LED irradiation was non-toxic to human corneal epithelial cells and improved cell viability. We then used a scopolamine-induced mouse model of dry eye to assess the effects of multi-wavelength LED irradiation on various clinical parameters. This treatment increased the tear volume and reduced corneal irregularity, thus improving dry eye. Histological analysis revealed that multi-wavelength LED irradiation protected against corneal epithelial damage and the associated reduction in epithelial thickness and would thus improve the corneal health of dry eye patients. Multi-wavelength LED irradiation significantly reduced the corneal levels of pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α; the treatment was thus anti-inflammatory. Our results suggest that multi-wavelength LED irradiation may serve as a safe and effective treatment for dry eye, alleviating symptoms, reducing inflammation, and promoting corneal health.

Neuropharmacological Study on Capsaicin in Scopolamine-injected Mice.

AIM: To evaluate the potential beneficial role of Capsaicin in cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice. BACKGROUND: Capsaicin is the chief phenolic component present in red chili and is responsible for its pungent and spicy flavor. It affects TRPV1 channels in nociceptive sensory neurons and is present in the hippocampus, and hypothalamus of the brains of rodents and humans. OBJECTIVE: The main objective is to investigate the effective role of capsaicin in attenuating cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice and examine the feasible mechanisms. METHODS: Various doses of capsaicin (5, 10, and 20 mg/kg) were given orally to mice daily for 7 consecutive days after the administration of scopolamine. Various behavioral tests (motor coordination, locomotor counts, hole board test) and biochemical assay (Pro-inflammatory cytokines, catalase, lipid peroxidation, nitrite, reduced glutathione, and superoxide dismutase), mitochondrial complex (I, II, III, and IV) enzyme activities, and mitochondrial permeability transition were evaluated in the distinct regions of the brain. RESULTS: Scopolamine-treated mice showed a considerable reduction in the entries and duration in the light zone as well as in open arms of the elevated plus maze. Interestingly, capsaicin at different doses reversed the anxiety, depressive-like behaviors, and learning and memory impairment effects of scopolamine. Scopolamine-administered mice demonstrated substantially increased pro-inflammatory cytokines levels, impaired mitochondrial enzyme complex activities, and increased oxidative damage compared to the normal control group. Capsaicin treatment reinstated the reduced lipid peroxidation, nitric oxide, catalase, superoxide dismutase, reduced glutathione activity, decreasing pro-inflammatory cytokines and restoring mitochondrial complex enzyme activities (I, II, III, and IV) as well as mitochondrial permeability. Moreover, the IL-1ß level was restored at a dose of capsaicin (10 and 20 mg/kg) only. Capsaicin reduced the scopolamine-induced acetylcholinesterase activity, thereby raising the acetylcholine concentration in the hippocampal tissues of mice. Preservation of neuronal cell morphology was also confirmed by capsaicin in histological studies. From the above experimental results, capsaicin at a dose of 10 mg/kg, p.o. for seven consecutive days was found to be the most effective dose. CONCLUSION: The experiential neuroprotective effect of capsaicin through the restoration of mitochondrial functions, antioxidant effects, and modulation of pro-inflammatory cytokines makes it a promising candidate for further drug development through clinical setup.

Desfecho clínico do paciente com síndrome de Kounis após ingestão de escopolamina: relato de caso / Clinical outcome of patient with Kounis syndrome after ingestion of scopolamine: case report

A Síndrome de Kounis é uma condição que se manifesta como uma síndrome coronária aguda (SCA) em um contexto de reação de hipersensibilidade a diversos alérgenos. O mecanismo fisiopatológico central desta síndrome está associado ao vasoespasmo coronário. No caso, trata-se de um paciente com dor abdominal inespecífica que durante a administração da escopolamina, desenvolveu sintomas indicativos de síndrome coronária aguda, sem elevação do segmento ST no eletrocardiograma, porém com aumento da troponina ultrassensível. O paciente foi submetido a estratificação não invasiva para SCA, que não demonstrou doença coronária. Palavras-chave: Síndrome de Kounis. Vasoespasmo coronário. Dor no peito. Hipersensibilidade a Drogas. Escopolamina.

Investigation of the Asyogh's rectangular device for learning and memory testing in Wistar rats.

This study aimed to design Asyogh's rectangular device that is used for memory testing in rodents. It was found that scopolamine (3 mg/kg i.p.) and diazepam (1 mg/kg i.p.) caused significant memory deficits in rats, as evidenced by increased transfer latency times. However, these memory deficits were significantly reversed when the rats were pretreated with Donepezil. It further demonstrates that pretreated donepezil is able to effectively restore the memory deficits induced by scopolamine and diazepam, as indicated by the significant recovery in TLT. The present study showed that the device used to measure transfer latency time that was a valuable tool for assessing memory and cognitive function in rodents.

Mechanism of Tibetan medicine Ershiwuwei Shanhu Pills on scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway / 中国中药杂志

This study aims to investigate the mechanism of the Tibetan medicine Ershiwuwei Shanhu Pills(ESP) in improving scopolamine-induced learning and memory impairment in mice based on Keap1/Nrf2/HO-1 signaling pathway. ICR mice were randomized into blank group, model group, low-dose(200 mg·kg~(-1)), medium-dose(400 mg·kg~(-1)), and high-dose(800 mg·kg~(-1)) ESP groups, and donepezil hydrochloride group. The learning and memory impairment was induced in mice by intraperitoneal injection of scopola-mine. The learning and memory abilities of mice were detected by Morris water maze test, and the damage of hippocampal neurons and cortical neurons was detected based on Nissl staining. The expression of neuron specific nuclear protein(NeuN) in hippocampus and cortex of mice was determined by immunofluorescence assay, and the content of acetylcholine(Ach) and the activity of acetylcholines-terase(AchE) in hippocampus of mice by kits. Moreover, the content of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in serum of mice was detected. The content of Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase 1(HO-1) in hippocampus was determined by Western blot. The results showed that there were significant differences in the trajectory map of mice among different groups in the behavioral experiment. Moreover, the latency of ESP groups decreased significantly compared with that in the model group. The hippocampal neurons in the high-dose ESP group were significantly more than those in the model group and the cortical neurons in the high-dose and medium-dose ESP groups were significantly more than those in the model group. The expression of NeuN in the model group was significantly decreased compared with that in the blank group, and the expression in the ESP groups was significantly higher than that in the model group. The AchE activity and MDA level were significantly decreased, and Ach content and levels of SOD, CAT, and T-AOC in the ESP groups were significantly increased in the ESP groups compared with those in the model group. The expression of Keap1 in the model group was significantly increased compared with that in the blank group, and the Keap1 expression increased insignificantly in ESP groups compared with that in the model group. The expression of Nrf2 and HO-1 was significantly lower in the model group than in the blank group, and the expression was significantly higher in the medium-dose ESP group than in the model group. In conclusion, ESP protected mice against the scopolamine-induced learning and memory impairment by regulating the Keap1/Nrf2/HO-1 signaling pathway.

Sumisión química con escopolamina, a propósito de un brote de tres casos / Drug-facilitated crime with scopolamine, a presentation of three cases

En los últimos años, la Sumisión Química con escopolamina, conocida popularmente como Burundanga, ha recibido una importante atención de los medios de comunicación de masas en nuestro país sin una clara correlación con el número de casos notificados en la literatura científica. Esta ausencia de casos notificados puede ser debida en parte a la dificultad de obtener un diagnóstico analítico que permita confirmar la presencia de la misma en los sujetos que la padecen. Presentamos tres casos de varones con Sumisión Química confirmada con escopolamina atendidos en nuestro centro

In recent years, Drug-facilitated crime with Scopolamine, popularly known as Burundanga, has received significant attention from the mass media in our country without a clear correlation with the number of cases reported in the scientific literature. The absence of reported cases may be due in part to the difficulty of obtaining an analytical diagnosis that allows confirming its presence. We present three cases of confirmed Drug-facilitated crime with Scopolamine in our center

Enduring amnesia induced by ICV scopolamine is reversed by sesame oil in male rats

ABSTRACT PURPOSE: To evaluated the long-term effect of scopolamine and sesame oil on spatial memory. METHODS: Memory impairment induced by Intracerebroventricular (ICV) injection of scopolamine hydrochloride (10 μg/ rat). Animals were gavaged for 4 weeks with saline, sesame oil (0.5, 1, or 2 mL/kg/day), or 3 weeks with memantine (30 mg/kg/day) in advance to induction of amnesia. Morris water maze (MWM) test was conducted 6 days after microinjection of scopolamine. Then, blood and brain samples were collected and evaluated for the malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and total antioxidant status (TAS) and ferric reducing ability of plasma (FRAP). RESULTS: Scopolamine significantly decreased traveled distance and time spent in target quadrant in probe test. Pretreatment of rats with sesame oil (0.5 mg/kg) mitigated scopolamine-induced behavioral alterations. Measurement of MDA, SOD, and GPX in brain tissue, and FRAP and TAS in blood showed little changes in animals which had received scopolamine or sesame oil. CONCLUSIONS: Intracerebroventricular injection of scopolamine has a residual effect on memory after six days. Sesame oil has an improving effect on spatial memory; however this effect is possibly mediated by mechanisms other than antioxidant effect of sesame oil.

Efectos neurotóxicos inducidos por administración tópica de ciclopléjicos. Caso clínico y revisión de la bibliografía / Neurotoxic effects induced by the topical administration of cycloplegics. A case report and review of the literature

Introducción. Se describe el caso de un paciente que presentóun cuadro confusional agudo con alucinaciones visuales trasla exposición a un colirio ciclopléjico y se revisa además la bibliografíaexistente con respecto a esta complicación del uso de dichotipo de colirios. Caso clínico. Varón de 61 años que sufrió en dosocasiones un cuadro de confusión, desorientación temporoespacialy alucinaciones visuales vívidas tras exposición a un colirio ciclopléjicoque contenía atropina al 2%, escopolamina al 0,5% y fenilefrinaal 4%. Se realizó una búsqueda bibliográfica de complicacionesneurológicas de los colirios ciclopléjicos utilizando las basesde datos PubMed y los servicios de la Biblioteca Virtual de laAgencia Laín Entralgo. Se analizan los datos clínicos de todasaquellas publicaciones en las que se tuvo acceso al documento original.Hemos documentado los datos clínicos correspondientes a29 casos debidos a ciclopentolato, 19 a atropina, 18 a escopolamina,7 a homatropina y 2 a tropicamida. Nuestro caso sería el cuartoregistrado en España; en todos éstos es responsable el mismotipo de colirio. Los síntomas que se han descrito con mayor frecuenciason alucinaciones visuales, trastornos de conducta/psicosisaguda, alteración de nivel de conciencia/confusión, inquietudmotora/hiperactividad, ataxia/incoordinación motora y alteracionesdel lenguaje. La mayoría de los casos publicados correspondea niños y ancianos. En algunas ocasiones se ha descrito mortalidad,especialmente relacionada con atropina. Conclusiones. Laneurotoxicidad debida al efecto anticolinérgico de los agentes ciclopléjicosno es infrecuente, si bien es poco conocida en nuestromedio; puede llegar a causar la muerte. La exposición a dichos fármacosdebe tenerse en cuenta en el diagnóstico diferencial de loscuadros confusionales

Introduction. We report a patient who developed an acute confusional state with hallucinations after exposure tocycloplejic eye drops, and review the current literature regarding neurotoxicity due to this type of eye drops. Case report. A 61year-old man who developed in two occasions confusion, disorientation and vivid visual hallucinations following exposure toa cyclopejic eye drop containing atropine 2%, scopolamine 0.5% and phenylephrine 4%. We performed a literature searchregarding neurological complications of cycloplegic eye drops using the PubMed Database and the services of the VirtualLibrary ‘Agencia Laín Entralgo’. The clinical features of all reports in which the original document was obtained areanalyzed and summarized. We have summarized the clinical features of 29 patients with neurotoxicity due to cyclopentolate,19 to atropine, 18 to scopolamine, 7 to homatropine, and 2 to tropicamide. Our patient should be the fourth reported in Spain,being the offending drug in the four cases the same eye drop. The most commonly reported symptoms are visual hallucinations,behavioral disorders/acute psychosis, alterations of consciousness/confusion, restlessness/hyperactivity, ataxia and speechdisorders. Many of the patients reported are children and elder. There have been reported some fatal cases, specially relatedwith atropine. Conclusions. Neurotoxicity related with anticholinergic effects of cycloplegic agents is not infrequent, althoughit is not well known in our setting; and can cause death in some cases. Exposure to these drugs should be taken in account inthe differential diagnosis of acute confusional syndromes