scholarly journals Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer’s Disease Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1626
Author(s):  
Line Séguy ◽  
Léna Guyon ◽  
Manon Maurel ◽  
Pascal Verdié ◽  
Audrey Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vitro Assays ◽  
Titration Calorimetry ◽  
Therapeutic Effects ◽  
Disease Treatment ◽  
Cellular Effects ◽  
Irritable Bowel ◽  
The Stability

Background and Purpose: The activation of 5-HT4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer’s disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood–brain barrier shuttle peptide. Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C18/HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties. Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

scholarly journals Experimental Therapeutic Effects of Hybrid Liposomes on the Alzheimer's Disease in Vitro

2011 ◽  
Vol 131 (5) ◽  
pp. 775-782 ◽  
Author(s):  
Keiko ZAKO ◽  
Maki SAKAGUCHI ◽  
Yuji KOMIZU ◽  
Hideaki ICHIHARA ◽  
Koichi GOTO ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Effects

scholarly journals Nepeta menthoides Boiss. & Buhse, an endemic species in Iran: A review of traditional uses, phytochemistry and pharmacology

2019 ◽  
Vol 8 (3) ◽  
pp. 194-204
Author(s):  
Zahra Memariani ◽  
Atena Rahimi ◽  
Mohammad Hosein Farzaei ◽  
Niloofar Zakaria Nejad
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endemic Species ◽  
Scientific Evidence ◽  
Therapeutic Effects ◽  
Lavandula Stoechas ◽  
Traditional Persian Medicine ◽  
Memory Enhancing

Nepeta menthoides Boiss & Buhse is one of the endemic species in Iran. Named Ostokhodus, it is almost used as substitute of the Lavandula stoechas –the original Ostokhodus- in traditional Persian medicine (TPM) over the time and widely used for the management of some ailments such as anxiety, depression, dementia and chronic pain. The aim of this study is to review the pharmacological and phytochemical evidence on Nepeta menthoides for the assessment of the recommended traditional indications of this herb. In this review, all the relevant articles that met our inclusion criteria [English or Persian articles, having full text, evaluating therapeutic effects of N. menthoides and dated mainly from the year 1980 to 2018] were included by searching studies in PubMed, Scopus, Google Scholar, Web of Science, and SID. The search terms were "Nepeta menthoides, "Ostokhodus". Triterpenes and monoterpenes were the most chemicals reported from essential oil of N. menthoides. Several pharmacological properties via in vitro, in vivo and clinical studies have been reported including antioxidant, anti-inflammatory, anti-nociceptive, antidepressant and anxiolytic, anticholinesterase, neuroprotective, memory enhancing, anti-Alzheimer’s disease, anticancer and effect on opioid dependence. Some proposed traditional indications of this herb in TPM books are in accordance with pharmacological evidence like anti-nociceptive, anti-seizure, anti-Alzheimer’s disease, memory enhancing, neuroprotective, antidepressant, anxiolytic activity and anti-infective properties. Although some properties in TPM, such as anti-tussive and gastrotonic effects are not supported by scientific evidence, they need more investigations.

scholarly journals A Snapshot on the Current Status of Alzheimer’s Disease, Treatment Perspectives, in-Vitro and in-Vivo Research Studies and Future Opportunities

2019 ◽  
Vol 67 (10) ◽  
pp. 1030-1041
Author(s):  
Gizem Tezel ◽  
Selin Seda Timur ◽  
İsmail Bozkurt ◽  
Ö. Faruk Türkoğlu ◽  
İpek Eroğlu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Current Status ◽  
Disease Treatment ◽  
Research Studies

scholarly journals Neurotrophin-3 Promotes the Neuronal Differentiation of BMSCs and Improves Cognitive Function in a Rat Model of Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhongrui Yan ◽  
Xianjing Shi ◽  
Hui Wang ◽  
Cuiping Si ◽  
Qian Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neuronal Differentiation ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease ◽  
Neurotrophin 3

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has the potential to be developed into an effective treatment for neurodegenerative diseases such as Alzheimer's disease (AD). However, the therapeutic effects of BMSCs are limited by their low neural differentiation rate. We transfected BMSCs with neurotrophin-3 (NT-3), a neurotrophic factor that promotes neuronal differentiation, and investigated the effects of NT-3 gene overexpression on the differentiation of BMSCs into neurons in vitro and in vivo. We further studied the possible molecular mechanisms. We found that overexpression of NT-3 promoted the differentiation of BMSCs into neurons in vitro and in vivo and improved cognitive function in rats with experimental AD. By contrast, silencing NT-3 inhibited the differentiation of BMSCs and decreased cognitive function in rats with AD. The Wnt/β-catenin signaling pathway was involved in the mechanism by which NT-3 gene modification influenced the neuronal differentiation of BMSCs in vitro and in vivo. Our findings support the prospect of using NT-3-transduced BMSCs for the development of novel therapies for AD.

scholarly journals Rational design of a conformation-specific antibody for the quantification of Aβ oligomers

2020 ◽  
Vol 117 (24) ◽  
pp. 13509-13518 ◽  
Author(s):  
Francesco A. Aprile ◽  
Pietro Sormanni ◽  
Marina Podpolny ◽  
Shianne Chhangur ◽  
Lisa-Maria Needham ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Rational Design ◽  
Design Method ◽  
Amyloid Β ◽  
In Vitro Assays ◽  
Aβ Oligomers ◽  
Detection And Quantification

Protein misfolding and aggregation is the hallmark of numerous human disorders, including Alzheimer’s disease. This process involves the formation of transient and heterogeneous soluble oligomers, some of which are highly cytotoxic. A major challenge for the development of effective diagnostic and therapeutic tools is thus the detection and quantification of these elusive oligomers. Here, to address this problem, we develop a two-step rational design method for the discovery of oligomer-specific antibodies. The first step consists of an “antigen scanning” phase in which an initial panel of antibodies is designed to bind different epitopes covering the entire sequence of a target protein. This procedure enables the determination through in vitro assays of the regions exposed in the oligomers but not in the fibrillar deposits. The second step involves an “epitope mining” phase, in which a second panel of antibodies is designed to specifically target the regions identified during the scanning step. We illustrate this method in the case of the amyloid β (Aβ) peptide, whose oligomers are associated with Alzheimer’s disease. Our results show that this approach enables the accurate detection and quantification of Aβ oligomers in vitro, and inCaenorhabditis elegansand mouse hippocampal tissues.

scholarly journals Tongqiaohuoxue Hinders Development and Progression of Atherosclerosis: A Possible Role in Alzheimer’s Disease

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 363
Author(s):  
Eunyoung Ha ◽  
Mikyung Kim ◽  
Jaemoo Chun ◽  
Chang-Seob Seo ◽  
YouMee Ahn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Intercellular Adhesion Molecule ◽  
In Vitro Assays ◽  
High Cholesterol Diet ◽  
Therapeutic Effects ◽  
Endothelial Cell Activation ◽  
Progression Of Atherosclerosis

Atherosclerosis is closely associated with Alzheimer’s disease (AD). Tongqiaohuoxue decoction (THD) is a classical herbal prescription in traditional Chinese medicine widely used for the prevention and treatment of cerebrovascular disease. This study aimed to explore the therapeutic effects of THD on atherosclerosis and AD. Eight-week-old C57BL6/J wild-type and ApoE-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for eight weeks, followed by oral phosphate-buffered saline vehicle or THD treatment for eight weeks further. In ApoE-/- mice, THD attenuated lipid deposition in the aorta and the brain, and abrogated atherosclerotic changes without affecting serum lipid profiles while decreasing amyloid plaque formation. In vitro assays undertaken to understand THD’s effects on lipid clearance in the aorta and brain vessels revealed that THD treatment inhibited the lipid uptake, stimulated by oxidized low-density lipoprotein, resulted in decreased endothelial cell activation through reduction in intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 levels. Serum analysis revealed inhibitory effects of THD on resistin production, which has important roles in the development of both atherosclerosis and AD. In conclusion, the current study demonstrates beneficial effects of THD on the development and progression of atherosclerosis, and a possible protective role against AD.

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