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1.
Indian J Biochem Biophys ; 2023 Mar; 60(3): 167-176
Article | IMSEAR | ID: sea-221627

ABSTRACT

Imatinib is the most effective therapy for chronic myeloid leukemia (CML), but many patients eventually develop resistance to it after an initial satisfactory response. This study investigated the potential of three miRNAs (miR-106b-5p, miR-145-5p, miR-203a-5p) in overcoming imatinib resistance in leukemic cells. The imatinib-resistant K562 (IR-K562) cells were developed and transfected with one of the three miRNAs to evaluate their potency in overcoming imatinib resistance. The changes in the metabolic profile were studied using flux balance analysis (FBA) and the data was validated using qRT-PCR.Among the three miRNAs, the ectopic expression of either miR-145-5p or miR-203a-5p was able to sensitize the IR-K562 cells to imatinib. The concentration of key oncometabolites; glucose, lactate, and glutamine, in the culture media of the miR-transfected IR-K562 cells, reverted to the same levels as seen in imatinib-sensitive K562 cells. In addition, the FBA analysis revealed that the metabolism of lipid, fatty acids, and electron transport chain were significantly altered in resistant cells. The FBA data was also validated at the molecular level. Interestingly, the imatinib treatment coupled with the transfection of miR-145-5p or miR-203a-5p cells could reverse the metabolic flux of IR-K562 to the levels seen in imatinib-sensitive K562 cells. This study highlights the key metabolic changes that occur during development of imatinib resistance. It also identifies the specific miRNAs which can be targeted to overcome imatinib resistance in CML.

2.
Indian J Biochem Biophys ; 2023 Mar; 60(3): 167-176
Article | IMSEAR | ID: sea-221625

ABSTRACT

Imatinib is the most effective therapy for chronic myeloid leukemia (CML), but many patients eventually develop resistance to it after an initial satisfactory response. This study investigated the potential of three miRNAs (miR-106b-5p, miR-145-5p, miR-203a-5p) in overcoming imatinib resistance in leukemic cells. The imatinib-resistant K562 (IR-K562) cells were developed and transfected with one of the three miRNAs to evaluate their potency in overcoming imatinib resistance. The changes in the metabolic profile were studied using flux balance analysis (FBA) and the data was validated using qRT-PCR.Among the three miRNAs, the ectopic expression of either miR-145-5p or miR-203a-5p was able to sensitize the IR-K562 cells to imatinib. The concentration of key oncometabolites; glucose, lactate, and glutamine, in the culture media of the miR-transfected IR-K562 cells, reverted to the same levels as seen in imatinib-sensitive K562 cells. In addition, the FBA analysis revealed that the metabolism of lipid, fatty acids, and electron transport chain were significantly altered in resistant cells. The FBA data was also validated at the molecular level. Interestingly, the imatinib treatment coupled with the transfection of miR-145-5p or miR-203a-5p cells could reverse the metabolic flux of IR-K562 to the levels seen in imatinib-sensitive K562 cells. This study highlights the key metabolic changes that occur during development of imatinib resistance. It also identifies the specific miRNAs which can be targeted to overcome imatinib resistance in CML.

3.
Indian J Biochem Biophys ; 2022 Dec; 59(12): 1184-1189
Article | IMSEAR | ID: sea-221610

ABSTRACT

We report the efficacy of the Iron nanoparticles (IONPs) and assessed two different approaches for the synthesis of IONPs i.e. Polyol and co-precipitation method and further, evaluate their antimicrobial properties. Ferrous sulphate heptahydrate salts were reduced with ethylene glycol to obtain IONP and Fe+2 and Fe+3 co-precipitation reaction was performed with KOH at optimum heating. Further, synthesized (IONPs) were characterized by hydrodynamic radii measurement done by DLS clearly indicating the size of IONPs is 79.75nm in polyol based and 135.1 nm in co-precipitation method. The biological efficacy in terms of antimicrobial activity was assessed by the Kirby Bauer method, applied for both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Escherichia coli, respectively. The ZOI values i.e. Zone of inhibition diameter was found to be clearly visible in both S. aureus and E. coli, indicating bactericidal activity. Further growth kinetics studies and bacterial genotoxicity was also assessed. Hence, IONPs synthesized are proposed to have great potential as an antibacterial agent and can be used in drug delivery.

4.
Indian J Biochem Biophys ; 2022 Nov; 59(11): 1106-1112
Article | IMSEAR | ID: sea-221599

ABSTRACT

Zinc oxide nanoparticles (ZnO NPs) are one of the most abundant metal oxides nanoparticles. It provides excellent thermal, electrical and chemical stabilities with low biotoxicity; its photo-oxidising and photo-catalytic impact on biological and chemical species is of great importance, thereby making it a promising candidate to be used for in-vitro and in-vivo studies in biomedical field. Hereby, ZnO NPs were synthesized using precipitation method with zinc acetate and sodium hydroxide as starting materials. This study has characterized the synthesized ZnO NPs using different techniques such as UV-Visible spectroscopy indicating a peak at 365 nm wave length, size of ZnO NPs was determined to be 286.7 nm by measuring hydrodynamic radii using Dynamic Light Scattering (DLS) phenomena. Further predominant charge existing at surface of the synthesised ZnO NPs was evaluated to be 31.6mV. Anti-microbial activity of ZnO NPs was determined by Kirby-Bauer method for both Gram-positive and Gram-negative bacteria, S. aureus and E. colirespectively. Anti-microbial activity was determined as Zone of Inhibition that measures both bactericidal and bacteriostatic activity of ZnO NPs and was found to be more potent for Gram-positive (S. aureus)bacteria and its activity increased with increasing concentration of nanoparticles. Growth kinetics was studied to determine percentage growth inhibition, for this optical density was recorded as a function of time in bacterial culture broth with and without treatment. Further DNA fragmentation assay was performed to determine genotoxicity caused by nanoparticles and its effect on genomic DNA of bacteria. Highlighting its potential role as a nano-carrier system for leading antibacterial drugs for enhanced effectiveness of the antibacterial therapies

5.
Indian J Biochem Biophys ; 2022 May; 59(5): 509-520
Article | IMSEAR | ID: sea-221526

ABSTRACT

Cancer is the leading cause of death among individuals due to its poor prognosis. Various therapeutics treatments are available in form radiation therapy, chemotherapy, or immunotherapy but major point of concern is the treatment of cancer resistant cell lines. Homozygous loss of the p53 gene is virtually present in every type of cancer. Mutation in DNA binding domain of p53 leads to formation of mutant forms having altered amino acid sequence which lacks DNA binding activity. Berberine is chemo-sensitizing isoquinoline quaternary alkaloid molecule obtained from Berberis vulgaris. Berberine has the capability to suppress the growth of broad range of tumors. It exhibits pharmacological, biochemical and anticancer properties which can potentiate the activities of the existing therapeutics available in a way that it can re-sensitize the cancer resistant clones. Berberine has an immanent potential to bind with DNA and can communicate with several cellular targets, further it also shows hormetic effect which refers to biphasic dose response curve in order to determine dose dependent stimulatory and inhibitory effect. Mode of action involved is yet not well understood but mechanistic pathway involved are autophagy, up-regulation of tumor-suppressor gene (p53) and epigenetic alterations in the viral DNA. In this review, versatility of berberine can be utilized ideally or in combination with chemotherapeutics drugs to potentiate chemo sensitization of the resistant cancer cell line. Further, cancer cell specific receptor targeting can also be employed in combination with berberine for therapeutic treatment of metastasizing cancer cells.

6.
Indian J Biochem Biophys ; 2022 Apr; 59(4): 455-460
Article | IMSEAR | ID: sea-221520

ABSTRACT

We report the efficacy of the gold nanoparticles (AuNPs) synthesized using the leaf extracts of Syzygium cumini (common name Jamun) with auric chloride (AuCl4) which was used as both reducing and capping agent at room temperatures- 25°C. Synthesized AuNPs were characterized using UV-Vis spectroscopy indicating a peak in the range of 520-540 nM. The hydrodynamic radii measured by DLS clearly indicated the size of AuNPs in the range of 14-64 nM. The biological efficacy in terms of antimicrobial activity was assessed by the Kirby Bauer method, applied for both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus and Escherichia coli, respectively. The Zone of inhibition (ZOI) diameter was found to be 4 mM and 3 mM in S. aureus and E. coli, as indicated by the bactericidal activity. Hence, AuNPs synthesized by green synthesis are proposed as economical, environment friendly with immense potential as an antibacterial agent and for drug delivery.

7.
Article | IMSEAR | ID: sea-207906

ABSTRACT

Background: The changing lifestyle has led to a rise in obesity, diabetes and hypertension in India which the most important risk factors for developing uterine cancer. The treatment of uterine cancer is evolving and requires proper evaluation and often adjuvant treatment for better survival. The disease being associated with symptoms of abnormal uterine bleeding often ends up being inadequately managed by non-oncologists practicing in a generalist setting in India. The current study was aimed to audit and observe any difference in outcome of patients primarily treated in the oncology set-up of the Chittaranjan National Cancer Institute, which is a regional cancer center in India versus those receiving primary treatment in a non-oncological set-up.Methods: Retrospective data was collected from hospital records after setting inclusion and exclusion criteria for the study.Results: There is poor correlation between the endometrial biopsy and histopathology findings of patients operated in non-oncological setting as compared to that in the institute. The overall survival of patients operated in the institute was superior to those treated outside.Conclusions: Patients having risk factors and symptoms akin to that of uterine carcinoma must be treated in an oncological set-up ideally.

8.
Article | IMSEAR | ID: sea-207435

ABSTRACT

Background: Abnormal uterine bleeding is one of the commonest clinical presentation ac-counts for 33% gynaecological consultations and this proportion rises to 70% in perimenopausal and postmenopausal age group in any gynaecology clinic. The most probable etiology of abnormal uterine bleeding relates to the patients reproductive age. Various diagnostic techniques have been evolved over the periods to determine the etiology of abnormal uterine bleeding in perimenopausal women, but their accuracy has not been compared properly. The aim of study is to evaluate the endometrium by transvaginal ultrasonography and hysteroscopy and its correlation with histopathology in perimenopausal patients with abnormal uterine bleeding.Methods: Total 96 patients in perimenopausal age group, admitted with chief complaints of ab-normal uterine bleeding were included. All patients underwent transvaginal ultrasonography and hysteroscopy, followed by hysteroscopy guided biopsy and histopathological examination. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated for both methods and compared, considering histopathological diagnosis as gold standard.Results: Mean age of patients was 44.05±3.29. Hysteroscopy has high accuracy, sensitivity, specificity, positive predictive value and negative predictive value than Transvaginal sonography for diagnosis of all endometrial and intrauterine pathologies.Conclusions: Hysteroscopy results are more consistent with the results of histopathology. Hysteroscopy and hysteroscopy guided biopsy has been proven as gold standard for endometrial evaluation of patients with abnormal uterine bleeding. TVS can be used as most cost effective first step investigation in cases of perimenopausal bleeding.

9.
International Eye Science ; (12): 1126-1131, 2020.
Article in Chinese | WPRIM | ID: wpr-823635

ABSTRACT

?AIM: To determine the vitamin D levels in vernal keratoconjunctivitis ( VKC) patients in Indian population.?METHODS:A total of 30 non-atopic healthy children and 30 children having VKC were included in the study. The serum vitamin D levels and the time spent outside was compared between the two groups ( P<0.05) .?RESULTS:The mean serum vitamin D level in the VKC group was significantly lower ( mean 19.17± 10.76 ng/mL) compared to the control group ( mean 31.19± 9.09 ng/mL) ( P = 0.0003 ) . The vitamin D levels were found to be deficient ( 10 - 20 ng/mL ) in 43.33%, whereas severe deficiency (<10 ng/mL ) was found in 20% of the VKC patients. The deficiency of vitamin D correlated with the level of severity of VKC ( P<0.02) . The time spent outside in the VKC group was 1.07± 0.76h, whereas in the healthy subjects it was 2.08±0.72h (P<0.0001), and it showed a significant correlation with the serum 25 ( OH ) D3 levels ( r=0.478, P<0.001) .?CONCLUSION:The study shows that children with VKC had a significantly lower serum vitamin D levels as compared to the healthy children which correlated with time spent outside. The severity of VKC also correlated with the severity of vitamin D deficiency which suggests that vitamin D plays an important role in maintaining ocular surface health.

10.
J Biosci ; 2019 Sep; 44(4): 1-12
Article | IMSEAR | ID: sea-214439

ABSTRACT

Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency ofreceptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was tocompare BAT activity in RAGE knock out (Ager-/-, RKO) and wild-type (WT) mice after treated with HFD or LFD.[18F]FDG PET-CT imaging under identical cold-stimulated conditions and mean standard uptake values (SUVmean), ratio ofSUViBAT/SUVmuscle (SUVR, muscle as the reference region) and %ID/g were used for BAT quantification. The resultsshowed that [18F]FDG uptake (e.g., SUVR) in WT-HFD mice was significantly reduced (three-fold) as compared to that inWT-LFD (1.40 ± 0.07 and 4.03 ± 0.38; P = 0.004). In contrast, BAT activity in RKO mice was not significantly affectedby HFD, with SUVRRKO-LFD: 2.14 ± 0.10 and SUVRRKO-LFD: 1.52 ± 0.13 (P = 0.3). The uptake in WT-LFD was almostdouble of that in RKO-LFD (P = 0.004); however, there was no significant difference between RKO-HFD and WT-HFDmice (P = 0.3). These results, corroborating our previous findings on the measurement of mRNA transcripts for UCP1 inthe BAT, suggest that RAGE may contribute to altered energy expenditure and provide a protective effect against HFD byAger deletion (Ager -/-).

11.
Article | IMSEAR | ID: sea-183756

ABSTRACT

Introduction: Acute dyspnea is one of the most common reasons for admission to emergency rooms. It could be due to potentially life-threatening cardiac or respiratory conditions. Differentiation among these three disorders is frequently needed. In the condition of heart failure, where there is clinical need for early and appropriate treatment but no objective method for rapid diagnosis, the potential benefits are enormous for any biomarker that can reliably rule in or rule out this syndrome. Objectives: The objectives of this study are as follows: (i) To evaluate the role of point of care of brain natriuretic peptide (BNP) in acute dyspnea and (ii) To determine the cutoff level of BNP to differentiate between cardiogenic and noncardiogenic causes of dyspnea. Materials and Methods: This was an in-hospital cross-sectional study conducted at a tertiary care center. Patients were evaluated using predetermined performa. All these patients were subjected to routine blood investigations, digital chest X-ray, and 12-lead electrocardiography. At the same time point of care, BNP was done in each patient after obtaining informed written consent. All patients with BNP >100 or clinical suspicion for heart failure underwent two-dimensional echocardiography (ECHO) with color Doppler. Results: A cross-sectional study was conducted on 238 patients presenting with acute dyspnea. Almost all patients with BNP level >415 pg/ml had <45% ejection fraction, but patients with BNP level <415 pg/ml had echocardiographic findings not suggestive of heart failure. Conclusion: This study gives us a reliable cutoff level of 415 pg/ml of BNP which clearly distinguishes between cardiogenic versus noncardiogenic dyspnea.

12.
Journal of Pharmaceutical Analysis ; (6): 258-264, 2018.
Article in Chinese | WPRIM | ID: wpr-700380

ABSTRACT

Silver nanoparticles (AgNPs) are known to have bacteriostatic and bactericidal effects. The present study highlights the extracellular synthesis of AgNPs and its antibacterial properties. The AgNPs were synthesized using Pseudomonas sp. THG-LS1.4 strain which had been isolated from soil. The AgNPs werecharacterized by field emission-transmission electron microscopy (FE-TEM), X-ray diffraction (XRD),Fourier transform-infrared (FT-IR) spectroscopy, and particle size distribution (DLS). The AgNPs displayed maximum absorbance at 412 nm and were irregular in shape ranging from 10 to 40 nm. The XRD spectroscopy results demonstrated the crystalline nature of nanoparticles. The AgNPs showed antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Candida tropicalis, Vibrio parahaemolyticus,Escherichia coli and Pseudomonas aeruginosa. Furthermore, the AgNPs were also evaluated for their increased antibacterial activities with various antibiotics against Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Additionally, AgNPs showd biofilm inhibition activity. The biosynthesized AgNPs were found to be a potent agent against tested pathogens. More importantly, we highlight the applications of AgNPs as an antimicrobial agent.

13.
Indian J Ophthalmol ; 2016 Oct; 64(10): 772-774
Article in English | IMSEAR | ID: sea-181306

ABSTRACT

Hand, foot, and mouth disease (HFD) is a common systemic infection occurring in childhood or immunocompromised adults caused by enteroviruses, the most common being coxsackievirus A16 and enterovirus 71. It is characterized by maculopapular eruptions over the hands and feet and ulcerative stomatitis. Ocular involvement is a rare complication and commonly manifests as inflammatory macular pathology. We report a case of HFD in an immunocompetent adult male with unilateral ocular involvement presenting as hemorrhagic maculopathy and its management with complete anatomical and functional recovery.

14.
Indian J Ophthalmol ; 2015 Oct; 63(10): 779-784
Article in English | IMSEAR | ID: sea-178945

ABSTRACT

Background: Pterygium is an ocular surface disorder with prevalence rates ranges from 0.3% to 29% in different parts of the world. Vascular endothelial growth factor (VEGF) has been detected in increased amounts in pterygium epithelium, compared with normal conjunctiva. Bevacizumab is a recombinant, humanized anti‑VEGF antibody suggested as a possible adjunctive therapy for pterygium excision that appears to have a role in prevention of recurrence. We conducted this study to evaluate the role of subconjunctival bevacizumab in primary pterygium surgery in Indian patients. Methods: In this randomized prospective clinical study, the patients were randomized into two groups of 30 patients each. Study group received 1.25 mg/0.05 ml subconjunctival bevacizumab 1 week before pterygium surgery with conjunctival autograft. Control group received 1.25 mg (0.05 ml) subconjunctival normal saline 1 week prior to pterygium surgery with conjunctival autograft. Patients were followed up at day 1, day 7, 1 month and 3 months. The main outcome measures were morphology of pterygium after injection, intra‑operative ease, recurrence of pterygia, and any complications. Results: After giving bevacizumab, there was statistically significant improvement in grade, color intensity, size of pterygium, and symptoms of patients. Intra‑operatively, less bleeding was observed by the surgeon. No statistically significant difference regarding reduction in astigmatism, improvement of visual acuity, and complications were observed in two groups. Recurrence was noted in five patients (8.33%) in total study population at the end of 3 months. It was present in two patients (6.67%) in Group A and three patients (10%) in Group B. Conclusion: Single preoperative administration of subconjunctival injection bevacizumab given 1 week before the pterygium excision with conjunctival autograft decreases the vascularity of newly formed blood vessels, hence may decrease recurrence rate though not in our study.

15.
Indian J Ophthalmol ; 2015 July; 63(7): 611-613
Article in English | IMSEAR | ID: sea-170416

ABSTRACT

Aim: To compare the surgical outcome of adjustable with the conventional recession in patients with horizontal comitant strabismus. Patients and Methods: A prospective comparative nonrandomized interventional pilot study was performed on patients with horizontal comitant strabismus. Fifty‑four patients (27 in each group) were allocated into 2 groups to undergo either adjustable suture (AS) recession or non‑AS (NAS) recession along with conventional resection. The patients were followed up for 6 months. A successful outcome was defined as deviation ±10 prism diopters at 6 months. The results were statistically analyzed by Chi‑square test, Fisher’s exact test, and Student’s t‑test. Results: A successful outcome was found in 24 (88.8%) patients in AS and 17 (62.9%) in NAS group (P = 0.02). The postoperative adjustment was done in 13 (48.1%) patients in AS group. There was one complication (tenon’s cyst) in AS group. Conclusion: AS recession may be considered in all cooperative patients undergoing strabismus surgery for comitant deviations.

16.
Article in English | IMSEAR | ID: sea-175928

ABSTRACT

Classroom management techniques encourages students to attend all classes, on time and at the same time, ensure that if implanted, the faculty used a class roaster system that was required by university administration. But practically its been observed that students in university miss classes for various reasons. Hence, adding ICT enhanced technology to a classroom can equip teachers with a new range of classroom management issues. This research aimed at studying the student’s awareness towards Biometric technology system. Biometrics, an advance computer based technology is designed for automated recognition of humans using physiological or behavioral characteristics is much used device in classrooms. The study even focused on knowing the affect of awareness towards biometric technology system on its application on forty post graduate teacher trainees of Faculty of Education from Banasthali University. Four phase process was carried out in developing the inventory and procuring the data related to awareness towards biometric technological system and its application. The findings revealed low awareness towards physical feature and working nature of Biometric technological system. Yet the awareness towards biometric technological system did not have any affect on its usage.

17.
Indian J Physiol Pharmacol ; 2014 Apr-Jun; 58(2): 147-151
Article in English | IMSEAR | ID: sea-152710

ABSTRACT

Medical courses in India are very demanding for the students thus making career in medical education very stressful. The study was designed to determine the prevalence of stress levels in 100 first year medical students and to explore the sources of stress & it‘s relationship across the male and female students. Demographic information and Qualitative data from investigator tailored Medical Student Stress Questionnaire (MSSQ) by self rating under supervision of investigators were subjected to a thematic analysis. Stress perceived was more in males students (82.2%) as compared to females (61.8%) and their MSSQ index score was significantly different (U=985; P=0.02). Moderate to high academic stress was present among 79% of students more so in males with the academic domain score significantly different from that of females (U=883; P=0.007). Females perceived more stress in inter personal domain (12.7%) with the score significantly different from males (U=953.5; P=0.02). Group and Teaching stress was equally present in males and females.

18.
Indian J Physiol Pharmacol ; 2014 Jan-Mar; 58(1): 100- 103
Article in English | IMSEAR | ID: sea-152686

ABSTRACT

Exposure of humans to radio frequency electromagnetic field (EMF) both during receiving and transmitting the signals has amplified public and scientific debate about possible adverse effects on human health. The study was designed with the objective of assessing the extent of mobile phone use amongst medical students and finding correlation if any between the hours of usage of mobile to sleep pattern and quality. hundred medical students grouped as cases (n=57) (>2 hours/day of mobile usage) and control (n=43) (≤2 hours/day of mobile usage) were examined for their sleep quality & pattern by Pittsburg sleep Quality Index (PSQI). Differences between groups were examined with the Mann Whitney “U” test for proportions (Quantitative values) and with Student‘t’ test for continuous variables. The association of variables was analyzed by Spearman Rank’s correlation. Probability was set at <0.05 as significant. Sleep disturbance, latency and day dysfunction was more in cases especially females. A significant association of hours of usage and sleep indices were observed in both genders (males r=0.25; p=0.04, females r=0.31; p=0.009). Evening usage of mobile phone in cases showed a statistically significant negative association (–0.606; p=0.042) with Sleep quality (higher PSQI means sleep deprivation). Students using mobile for > 2 hours/day may cause sleep deprivation and day sleepiness affecting cognitive and learning abilities of medical students.

19.
Article in English | IMSEAR | ID: sea-151699

ABSTRACT

Anxiety is a cardinal symptom of many psychiatric disorders and an inevitable component of many medical and surgical conditions. It is a universal human emotion, closely allied with appropriate fear presumably serving psycho biologically adaptive purposes. Anxiety is a normal emotional behaviour. When it is severe and/or chronic, it becomes pathological and can precipitate or aggravate cardiovascular and psychiatric disorders. Although many drugs are available in allopathic medicine to treat anxiety disorders, they produce various systemic side effects. Gallic acid has been identified as active ingredient found in gall nuts, sumac, witch hazel, tea leaves and oak bark. In the present study, we have attempted to evaluate the anti-anxiety- activity of Gallic acid in rats by employing, elevated plus maze and bright and dark arena. The rats were divided into five groups, each group containing six animals. The effects of the test drug Gallic acid (at 0.05, 0.1 and 0.2 mg/kg doses),the standard anxiolytic, diazepam (1.0 mg/kg) and control group 14% Dimethyl sulfoxide(10ml/kg) were assessed after repeated doses administration for ten days. The results suggest that, Gallic acid exhibited anxiolytic like activity comparable to diazepam.

20.
Indian J Biochem Biophys ; 2013 Apr; 50(2): 120-125
Article in English | IMSEAR | ID: sea-147295

ABSTRACT

Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pleiocarpine showed promising anti-cholinergic potential, while its amino derivative showed about six-fold higher anti-cholinergic potential than pleiocarpine. Pleiocarpine and its amino derivative were found to be better inhibitors of AChE, as compared to commonly used drugs tacrine (brand name: Cognex) and rivastigmine (brand name: Exelon), suggesting development of these molecules as potential therapeutics in future.


Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Alzheimer Disease/metabolism , Catalytic Domain , Chemistry, Pharmaceutical/methods , Cholinergic Antagonists/pharmacology , Cholinesterase Inhibitors/pharmacology , Crystallography, X-Ray/methods , Drug Design , Humans , Hydrogen Bonding , Ligands , Models, Chemical , Models, Molecular , Phytotherapy , Protein Binding , Protein Conformation , Quantitative Structure-Activity Relationship
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