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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.

Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization 1 , 2 . Challenges in global supplies have resulted in frequent shortages of these drugs 3 , 4 . Further vulnerabilities in supply chains have been revealed by events such as the Australian wildfires 5 and the COVID-19 pandemic 6 . Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval 7 , 8 are needed. Here we engineered baker’s yeast to produce the medicinal alkaloids hyoscyamine and scopolamine, starting from simple sugars and amino acids. We combined functional genomics to identify a missing pathway enzyme, protein engineering to enable the functional expression of an acyltransferase via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titres. Our integrated system positions more than twenty proteins adapted from yeast, bacteria, plants and animals across six sub-cellular locations to recapitulate the spatial organization of tropane alkaloid biosynthesis in plants. Microbial biosynthesis platforms can facilitate the discovery of tropane alkaloid derivatives as new therapeutic agents for neurological disease and, once scaled, enable robust and agile supply of these essential medicines. The alkaloid drugs hyoscyamine and scopolamine are synthesized from sugars and amino acids in yeast, using 26 genes from yeast, plants, bacteria and animals, protein engineering and a vacuole transporter to enable functional expression of a key acyltransferase.

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1β, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aβ and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

In this large, randomized trial, the investigators compared outcomes in patients with chronic obstructive pulmonary disease (COPD) treated with once-daily inhalation of tiotropium or placebo. There was no benefit of treatment on the rate of loss of lung function over time, although benefits were observed in some secondary end points. These investigators compared outcomes in patients with chronic obstructive pulmonary disease treated with once-daily inhalation of tiotropium or placebo. There was no benefit of treatment on the rate of loss of lung function over time, although benefits were observed in some secondary end points. Prospective studies testing effects on the progression of chronic obstructive pulmonary disease (COPD) through the evaluation of the slope of the forced expiratory volume in 1 second (FEV 1 ) have not shown that inhaled short-acting anticholinergic drugs, inhaled corticosteroids, or N -acetylcysteine alter this marker of disease progression. 1 – 7 To date, only smoking cessation has prospectively been shown to alter the rate of decline of FEV 1 in patients with COPD. 2 Tiotropium is a once-daily, inhaled anticholinergic drug that provides at least 24-hour improvements in airflow and hyperinflation in patients with COPD. 8 – 10 Clinical trials lasting 6 weeks to . . .

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Lycium barbarum is used both as a food additive and as a medicinal herb in many countries, and L. barbarum polysaccharides (LBPs), a major cell component, are reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer properties, and immune modulation. The effects of LBPs on neuronal function, neurogenesis, and drug-induced learning and memory deficits have not been assessed. We report the therapeutic effects of LBPs on learning and memory and neurogenesis in scopolamine (SCO)-treated rats. LBPs were administered via gastric perfusion for 2 weeks before the onset of subcutaneous SCO treatment for a further 4 weeks. As expected, SCO impaired performance in novel object and object location recognition tasks, and Morris water maze. However, dual SCO- and LBP-treated rats spent significantly more time exploring the novel object or location in the recognition tasks and had significant shorter escape latency in the water maze. SCO administration led to a decrease in Ki67- or DCX-immunoreactive cells in the dentate gyrus and damage of dendritic development of the new neurons; LBP prevented these SCO-induced reductions in cell proliferation and neuroblast differentiation. LBP also protected SCO-induced loss of neuronal processes in DCX-immunoreactive neurons. Biochemical investigation indicated that LBP decreased the SCO-induced oxidative stress in hippocampus and reversed the ratio Bax/Bcl-2 that exhibited increase after SCO treatment. However, decrease of BDNF and increase of AChE induced by SCO showed no response to LBP administration. These results suggest that LBPs can prevent SCO-induced cognitive and memory deficits and reductions in cell proliferation and neuroblast differentiation. Suppression of oxidative stress and apoptosis may be involved in the above effects of LBPs that may be a promising candidate to restore memory functions and neurogenesis.

The journal retracts the article \"The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights\" [...].The journal retracts the article \"The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights\" [...].

•Scopolamine was found unexpectedly in a series of cases of scopolamine-facilitated robberies, by non-targeted analysis.•Scopolamine blood concentrations and amounts are presented and compared to the (scarce) data in literature.•In a fatal case, the heart blood concentration was raised considerably postmortem by diffusion from the stomach.•Obtaining timely samples for toxicology may be a problem in drug-facilitated crimes. The use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair.