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Home > Isolation, Characterization and Biological Evaluation of Bioactive Compounds from Grewia Optiva

Isolation, Characterization and Biological Evaluation of Bioactive Compounds from Grewia Optiva

Thesis Info

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Author

Wasim Ul Bari

Program

PhD

Institute

University of Malakand

City

Malakand

Province

KPK

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/12361/1/Wasim%20Ul%20Bari%20chemistry%202019%20uom%20malakand%20prr.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726550668

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Species of Grewia are mostly usesd for the typhoid, malaria, diarrhea, dysentery, small pox, fever, cough, eczema etc. On the basis of ethno medicinal survey, this study was designed to evaluate Grewia optiva as possible therapy of Alzheimer’s, oxidative stress and other neurodegenerative diseases. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), Alpha-glucosidase and alpha-amylase inhibitory activities of crude methanolic extract, n-hexane, chloroform, ethyl acetate, aqueous fraction and isolated compounds of G. optiva were investigated using Ellman’s spectrophotometric and other standard protocol. Antioxidant potential of G. optiva was determined using DPPH and ABTS free radicals scavenging assays. Total phenolic and flavonoids contents of plant extracts were determined and expressed in mg GAE/g dry weight and mg QE/g of dry sample respectively. Antibacterial activity of crude extract was determined using agar well diffusion method. In the in vivo experiments, methanol extract was orally administered to mice (n = 5) at four doses of 500, 400, 300 and 200 mg kg–1 for 30 days and its effect on glucose, triglycerides, total cholesterol etc were investigated. Finally, based on HPLC fingerprinting results, chloroform and ethyl acetate fractions were subjected silica gel column isolations. The isolated compounds were characterized by different spectroscopic techniques. The in vitro pharmacological activities of isolated compounds were also determined. To validate the experimental data, molecular docking simulation software was used (only for those compounds having low IC 50 values) Phytochemical analysis showed that alkaloids, flavonoids, glycosides, tannins, sterols and saponins were present in crude extract of G. optiva. Amongst various fractions crude extract and ethyl acetate fraction exhibited highest inhibitory activity against AChE (89.08 ± 2.35, 77.18 ± 1.45%) and BChE (86.32 ± 1.71, 74.16 ± 1.30%) enzymes at 1000 µg/ml with IC50 values of 120 and 185 μg/mL for AChE while 100 and 235 μg/mL for BChE respectively. Galanthamine causing 95.22 ± 0.81 and 94.30 ± 0.74% inhibition of AChE and BChE at 1000 µg/ml concentration with IC50 values of 45 and 60 μg/mL respectively. In antioxidant assays, Crude methanolic extract and ethyl acetate fraction demonstrated highest radicals scavenging activities against DPPH and ABTS which were comparable to that of ascorbic acid. Crude extract was found most potent with IC50 of 75 and 88 μg/mL against DPPH and ABTS free radicals respectively. Crude methanolic extract and ethyl acetate fraction also showed moderate inhibition against alpha glucosidase (69.02 ± 1.02, 64.29± 2.41) and alpha amylase (65.12 ± 2.02, 63.29± 1.41) when compared with standard acarbose. Chloroform, ethyl acetate and aqueous fractions showed high phenolic and flavonoid contents. The phenolic and flavonoid contents of different extracts were correlated with their antioxidant, anticholinesterase, and antidiabetic activities. The phenolic compounds in the crude extract and fractions were determined using HPLC standard method and secondary metabolites like: morine, ellagic Acid, kaempferol-3-(pcoumaroyl- diglucoside)-7-glucoside, apigenin-7-O-rutinoside, quercetin-3-(caffeoyldiglucoside)-7-glucoside etc. were detected at different retention times. A significant decrease in cholesterol, triglyceride and blood glucose levels shown in mice after treating with plant extract. However, levels of MCHC, MCV, RBC, WBC total protein and blood urea were not more affected. Based on in vivo and in vitro results of extracts, it was concluded that G. optiva possess antilipidemic, antioxidant and antidiabetic potentials as it is a good source phytochemicals, some of which may probably possess anticholinesterase, anti-glucosidase, and anti-amylase activities, and can be used to treat oxidative stress, neurological disorders, and diabetes mellitus. Phytochemical investigation of the ethyl acetate and chloroform fractions led to the isolation of eleven compounds namely β- sitosterol, betulinic acid, 1, 2, 3 benzene triol , 7- O-methyl cathachin, docosanoic acid, glutaric acid, trihydroxyl-4H chromen -4`- one, 3,5 dihydroxy phenyl acrylic acid, hexa methyl-icosahydro-1H cylopenta chrysene-2-ol, (2,5 dihydroxyl phenyl) 3`,6`,8` trihydroxyl-4H chromen -4`- one and hexanedioic acid reported first time from the Grewia genus except β-sitosterol, while methanetriol mano formate isolated from the said plant is a new compound firstly reported from natural sources. In antioxidant assays, 7-O-methyl cathachin demonstrated highest percent radicals scavenging against DPPH and ABTS (86.11 ± 2.20, 85.23 ± 1.61) at 1000 µg/mL with 63 µg/mL of IC50, which was very near to the standard ascorbic acid IC50 value (35 µg/mL). All other testing compounds also have very good percent inhibition and IC50 values. All the isolated compounds also showed excellent potential against AChE and BChE but β- sitosterol exhibited highest percent inhibition (87.66 ± 1.93, 85.71 ± 1.17) at 1000 µg/mL with 62 µg/mL of IC50, which is very close to the standard galanthamine IC50 value. Molecular docking studies also support the binding of β-sitosterol, trihydroxyl-4H chromen -4`- one and 3,5 dihydroxy phenyl acrylic acid with the target enzyme. In silico docking studies with AChE and BChE predicted possible binding modes for these active compounds. The para hydroxy of the phenolic moiety is predicted to form hydrogen bonds with the active site water molecule and the side chain carbonyl of residues. The remaining part of the active compound binding in a shallow pocket close picking up an H-bond interaction. Compound 1, 2, 3 benzene triol and 7-O-methyl Cathachin, showed good inhibition against alpha glucosidase with IC50 of 82 and 87 µg/mL respectively, while glutaric acid and hexanedioic acid have moderate effect against alpha amylase (IC50=85 µg/mL ) when compared with standard acarbose.
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خواجہ کمال الدین

خواجہ کمال الدین
عیسوی سال کے خاتمہ پر ۲۸؍ دسمبر ۱۹۳۳؁ء کو عیسوی مذہب کے سب سے بڑے نقاد اور عیسوی ممالک میں اسلام کے مشہور مبلغ خواجہ کمال الدین نے افسوس ہے کہ وفات پائی، وہ کئی برس سے سل کے مرض میں مبتلا تھے اور اس حالت میں بھی وہ تصنیف و تالیف میں ہمیشہ مصروف رہے، احمدی جماعت میں ہمارے نزدیک وہ عام مسلمانوں سے سب سے زیادہ قریب تھے، اس لئے ان کے مشن کا بار اٹھانے میں عام مسلمان اور امراء نے بھی شرکت کی تھی اور شاید یہ راز نہ ہو کہ مسیح الملک حکیم اجمل خان مرحوم اور مولانا شبلی مرحوم نے ان کی امدادی تحریکوں میں سب سے زیادہ دلچسپی لی، مولانا مرحوم نے ایک دفعہ علماء کے بالمقابل نوجوان تعلم یافتوں میں سے خواجہ صاحب کے عزم تبلیغ کو سامنے رکھ کر یہ شعر خود انہیں کے خط میں لکھا تھا:
کامل اس فرقہ زہاد سے اٹھا نہ کوئی
کچھ ہوئے تو یہی رندانِ قدح خوار ہوئے
گوہم کو خواجہ صاحب کے بہت سے خیالات اور تاویلات سے اتفاق نہیں تاہم یہ کہنا اظہار واقعہ ہے کہ انہوں نے ۱۹۱۲؁ء سے لے کر ۱۹۳۲؁ء تک اپنی پوری بیس برس کی زندگی اسلام کی تبلیغ اور اس کے محاسن کی اشاعت اور یورپ میں اسلامی لٹریچر کی فراہمی میں صرف کی اور نیز یہ کہ ان تصنیفات کے بڑے حصہ کا موضوع ’’احمدیت‘‘ نہیں ’’محمدیت‘‘ ہے، افسوس کہ ان کی موت سے دنیا کی مذہبی بزم میں ایک اہم جگہ خالی ہوگئی۔ اﷲ تعالیٰ ان کے ان اعمال صالحہ کے صدقہ میں ان کو اپنی مغفرت سے نوازے اور ان کی لغزشوں سے درگزر فرمائے۔
میں نے ان کو سب سے پہلے ندوہ کے اس اجلاس لکھنؤ ۱۹۱۲؁ء میں دیکھا جس میں مصر کے عالم سید رشید رضا صدر...

Terrorism and its Elimination an Islamic Perspective

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