Streptozotocin mechanisms and its role in rodent models for Alzheimer’s disease

Chik, Mazzura Wan; Ramli, Nur Adiilah; Hazalin, Nurul Aqmar Mohamad Nor; Singh, Gurmeet Kaur Surindar

doi:10.1080/15569543.2022.2150646

Cited by 5 publications

(4 citation statements)

References 82 publications

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“…Acetylcholine depletion disrupts communication between nerve cells, impairing memory formation and cognitive processes. STZ administration has been shown to induce hyperactivation of AChE in rodent brain, which accelerates the breakdown of acetylcholine, resulting in cholinergic impairment and poor cognition (Chik et al, 2022; Kaur et al, 2017). In line with these studies, elevated AChE activity was observed in STZ‐treated animals.…”

Section: Resultsmentioning

confidence: 99%

“…Oxidative stress has also been identified as an important factor leading to dementia (Chik et al, 2022). STZ administration leads to increased oxidative stress by disrupting the balance between the production of ROS and the body's antioxidant defense mechanisms.…”

Section: Resultsmentioning

confidence: 99%

“…Administration of 5k significantly decreased STZ induced cognitive impairment by means of restoring the ELT (Figure 3) and TSTQ (Figure 4). Oxidative stress has also been identified as an important factor leading to dementia (Chik et al, 2022). STZ administration leads to increased oxidative stress by disrupting the balance between the production of ROS and the body's antioxidant defense mechanisms.…”

Section: In Vivo Activitymentioning

confidence: 99%

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N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation

Sharma,

Singh,

Singh

2023

Chem Biol Drug Des

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The series of N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfuctional agents against Alzheimer's disease that have been designed, synthesized and then evaluated biologically using in vitro assays for the inhibition of acetylcholinesterase (AChE) activity, AGEs, and free radical formation. The majority of synthesized compounds inhibited AChE & AGEs with additional free radical scavenging activities at nanomolar concentrations. Among these, compound 5k was found to have potent AChE inhibitory activity (IC50 = 11.6 nM), superior than the reference compound donepezil (15.68 nM) along with the good anti‐AGEs and free radical formation effect. Its potency was justified by docking studies that revealed its dual binding characteristic with both catalytic active site and peripheral anionic site of AChE, simultaneously. Furthermore, the in vivo evaluation of 5k against streptozotocin (STZ)‐induced dementia in rats also showed improvement of memory functions (Morris water maze test) in animals. Also, 5k inhibited STZ‐inudced brain AChE activity and oxidative stress which further strengthen the observed in vitro effects. The stability of the ligand‐protein complex was then analyzed using a simulation‐based interaction protocol. The results revealed that these N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives could be considered for potential polyfunctional anti‐Alzheimer's molecules.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: In Vivo Activitymentioning

confidence: 99%

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N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation

Sharma,

Singh,

Singh

2023

Chem Biol Drug Des

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“…The STZ model (i.c.v., 3 mg/kg) is commonly used to study AD in animals [ 44 , 45 , 46 ]. The intracerebroventricular injection of STZ, at two sub-diabetogenic doses, induces a range of symptoms including impaired cognition, metabolic and molecular changes, and neuropathological symptoms in rodents which are often found in AD subjects.…”

Section: Resultsmentioning

confidence: 99%

Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease

Sharma,

Singh,

Singh

et al. 2023

Molecules

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No drug on the market, as a single entity, participates in different pathways involved in the pathology of Alzheimer’s disease. The current study is aimed at the exploration of multifunctional chalcone derivatives which can act on multiple targets involved in Alzheimer’s disease. A series of novel aminoethyl-substituted chalcones have been developed using in silico approaches (scaffold morphing, molecular docking, and ADME) and reported synthetic methods. The synthesized analogs were characterized and evaluated biologically using different in vitro assays against AChE, AGEs, and radical formation. Among all compounds, compound PS-10 was found to have potent AChE inhibitory activity (IC50 = 15.3 nM), even more than the standard drug (IC50 = 15.68 nM). Further, the in vivo evaluation of PS-10 against STZ-induced dementia in rats showed memory improvement (Morris Water Maze test) in rats. Also, PS-10 inhibited STZ-induced brain AChE activity and oxidative stress, further strengthening the observed in vitro effects. Further, the molecular dynamic simulation studies displayed the stability of the PS-10 and AChE complex. The novel aminoethyl-substituted chalcones might be considered potential multifunctional anti-Alzheimer’s molecules.

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Hippocampal sharp-wave ripples and hippocampal-prefrontal synchrony regulate memory-enhancing effects of intranasal insulin in an STZ-induced Alzheimer's model

Karimani,

Asgari Taei,

Kaveh

et al. 2024

Life Sciences

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Streptozotocin mechanisms and its role in rodent models for Alzheimer’s disease

Cited by 5 publications

References 82 publications

N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation

N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation

Recent Development of Novel Aminoethyl-Substituted Chalcones as Potential Drug Candidates for the Treatment of Alzheimer’s Disease

Hippocampal sharp-wave ripples and hippocampal-prefrontal synchrony regulate memory-enhancing effects of intranasal insulin in an STZ-induced Alzheimer's model

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