scholarly journals Ethanol extract of Curcuma longa leaf, a potential drug candidate against Bacillus species mediated infections

2021 ◽  
Vol 22 (5) ◽  
pp. 2782 ◽  
Author(s):  
Johanna Michael ◽  
Julia Zirknitzer ◽  
Michael Stefan Unger ◽  
Rodolphe Poupardin ◽  
Tanja Rieß ◽  
...  

Alzheimer’s disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling—more specifically, the leukotriene receptors—has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.


2013 ◽  
Vol 6 (1) ◽  
pp. 89-99 ◽  
Author(s):  
Daniela Košťálová ◽  
Lýdia Bezáková ◽  
Lucia Račkovác ◽  
Silvia Mošovská ◽  
Ernest Šturdík

Abstract Extensive research over the past half century has shown that curcumin (diferuloylmethane), a polyphenolic compound of turmeric (Curcuma longa L.), can modulate multiple cell signaling pathways. Extensive clinical trials have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in human. Curcumin, known for thousand years as a subject of Ayurvedic medicine, has undergone in recent times remarkable transformation into a drug candidate with prospective multipotent therapeutic application. Characterized by high chemical reactivity, resulting from an extended conjugated double bond system prone to nucleophilic attack, curcumin has been shown to interact with a plethora of molecular targets, in numerous experimental observations. In clinical trials, has been used either alone or in combination with other agent. However, its clinical advance has been limited by its short biological half-life, fast metabolism and poor systemic bioavailability after oral administration. To mitigate the above limitations, recently various formulation of curcumin, including nanoparticles, micelles, liposomes, phytosomes delivery system has been examined. The present review has been devoted towards better understanding of the phytonutraceutic properties of curcumin and turmeric based on their disease specific indications and enhancing their prophylactic and therapeutic nutraceutical qualities. The article deals with the biological activity, mode of action, toxicity and forthcoming application of these leads.


2015 ◽  
Vol 14 (1) ◽  
pp. 36
Author(s):  
ManalH Shabana ◽  
EmanM Shahy ◽  
MonaM Taha ◽  
GehanM Mahdy ◽  
MahaH Mahmoud

2018 ◽  
Vol 4 (1) ◽  
pp. 1472197 ◽  
Author(s):  
Aziz-ur Rehman ◽  
Khadija Nafeesa ◽  
Muhammad Athar Abbasi ◽  
Sabahat Zahra Siddiqui ◽  
Shahid Rasool ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Ju Eun Kim ◽  
Abinash Chandra Shrestha ◽  
Hyo Shin Kim ◽  
Ha Neul Ham ◽  
Jun Hyeong Kim ◽  
...  

Alzheimer's disease (AD) is linked to an extensive neuron loss via accumulation of amyloid-beta (Aβ) as senile plaques associated with reactive astrocytes and microglial activation in the brain. The objective of this study was to assess the therapeutic effect of WS-5 ethanol extract in vitro and in vivo against Aβ-induced AD in mice and to identify the extract’s active constituents. In the present study, WS-5 exerted a significant inhibitory effect on acetylcholinesterase (AChE). Analysis by transmission electron microscopy (TEM) revealed that WS-5 prevented Aβ oligomerization via inhibition of Aβ1-42 aggregation. Evaluation of antioxidant activities using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) demonstrated that WS-5 possessed a high antioxidant activity, which was confirmed by measuring the total antioxidant status (TAS). Furthermore, the anti-inflammatory properties of WS-5 were examined using lipopolysaccharide-stimulated BV-2 microglial cells. WS-5 significantly inhibited the lipopolysaccharide–induced production of nitric oxide and two proinflammatory cytokines, TNF-α and IL-6. The memory impairment in mice with Aβ-induced AD was studied using the Morris water maze and passive avoidance test. Immunohistochemistry was performed to monitor pathological changes in the hippocampus and cortex region of the mouse brain. The animal study showed that WS-5 (250 mg/kg) treatment improved learning and suppressed memory impairment as well as reduced Aβ plaque accumulation in Aβ-induced AD. HPLC analysis identified the extract’s active compounds that exert anti-AChE activity. In summary, our findings suggest that WS-5 could be applied as a natural product therapy with a focus on neuroinflammation-related neurodegenerative disorders.


2020 ◽  
Vol 114 (4) ◽  
pp. 194-204 ◽  
Author(s):  
Watcharapong Mitsuwan ◽  
Chooseel Bunsuwansakul ◽  
Theodore Ebenezer Leonard ◽  
Sawanya Laohaprapanon ◽  
Kruawan Hounkong ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81634 ◽  
Author(s):  
Adriana Monserrath Orellana-Paucar ◽  
Tatiana Afrikanova ◽  
Joice Thomas ◽  
Yelaman K. Aibuldinov ◽  
Wim Dehaen ◽  
...  

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