Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 (p < 0.001) and h3 (p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT (p < 0.001) in EPM, while (p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased (p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.
Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.
Background and objective: Leukemia is one of the fatal diseases and their morbidity and mortality rates increases day by day all over the world. This piece of research study was designed in order to find out the prevalence of different types of leukemia in Khyber Pakhtunkhwa, Pakistan during January 2015 to December 2016. Material and Method: The retrospective research study was carried out at Institute of Radiotherapy and Nuclear Medicine (IRNUM) Peshawar. A data of 400 admitted patients of leukemia were evaluated. Result: It was observed that acute leukemia (80%) was more prevalent than chronic leukemia (20%). Amongst types of leukemia, Acute Lymphocytic Leukemia (ALL) 49.5% (n=198) was more prevalent than Acute Myelogenous Leukemia (AML) 31.25% (n=125), Chronic Myelogenous Leukemia (CML) 10% (n=40) and Chronic Lymphocytic Leukemia (CLL) 9.25% (n=37) was less prevalent in this study. It was also found that leukemia was more prevalent in male patients 64.5% (n=258) as compared to females 35.5% (n=142) and male to female ratio was 1.8:1. Most of the patients were under the age of 20 years. Conclusion: Acute leukemia was more prevalent than chronic leukemia during this study in this part of the country and needs to be address. Bangladesh Journal of Medical Science Vol.18(2) 2019 p.222-227
Depression is a serious psychiatric disorder that affects millions of individuals all over the world, thus demanding special attention from researchers in order to investigate its effective remedies. Curcumin, along with its synthetic derivatives, is recognized for its incredible pharmacological activities. In this study, methyl, methoxy and chloro-substituent synthetic curcumin analogues C1–C3 were respectively tested for free radical-scavenging activity. Behavioral studies were performed using chemical-induced and swimming endurance tests as stress models, and forced swim tests (FSTs) and tail suspension tests (TSTs) as depression mice models. Biochemical examinations were performed after a scopolamine-induced stress model by decapitating the mice, and brain tissues were isolated for biochemical assessment of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The curcumin analogue C2 exhibited higher DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazo-line-6-sulphonate) free radical-scavenging potential, having IC50 values of 45.18 µg/mL and 62.31 µg/mL, respectively, in comparison with reference curcumin and tocopherol. In the chemical-induced test, C2 (80.17%), C3 (72.79%) and C1 (51.85%) revealed higher antistress responses by significantly reducing the number of writhes, whereas the immobility time was significantly reduced by C2 and C3 in the swimming endurance test, indicating excellent antistress potential. Similarly, C2 and C3 significantly reduced the immobility times in FST and TST, demonstrating their antidepressant properties. The biomarkers study revealed that these compounds significantly enhanced hippocampus CAT, SOD and GSH, and reduced MDA levels in the scopolamine-induced stress mice model. These findings suggest the potential of curcumin analogues (C2 and C3) as antistress and antidepressant agents.
The antidiarrheal effect of methanolic extract of T. govanianum was studied at doses of 12.5, 25, and 50 mg/kg in different animal models of diarrhea including castor oil (6 mL/kg), magnesium sulfate (2 gm/kg), sodium picosulfate (2 mL/kg) and lactitol (0.25 mL/kg). The antispasmodic effect of T. govanianum was studied on isolated rabbit's jejunum, using acetylcholine as tissue stabilizer and verapamil as calcium channel blocker. T. govanianum strongly attenuated the diarrhea by producing a significant decrease in the number and weight of stool, and an increase in stool latency time. T. govanianum completely inhibited both spontaneous as well as high potassium induced contractions of isolated rabbit's jejunum, which was analogous to verapamil. Moreover, T. govanianum produced a right shift in calcium concentration response curve, confirming its calcium channel blocking activity. These findings scientifically endorsed that T. govanianum has strong antidiarrheal and antispasmodic properties and involves the blockade of calcium channels.
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