ڈیرہ غازی خان کی مذہبی و معاشرتی زندگی میں صوفیا کرام کی تعلیمات کے اثرات

Islam is the religion of peace and love for the humanity. It always ordered to his followers to treat other with kind and tolerance. The Holy prophet always proved himself the prophet of mercy as the Holy Quran Said, but we sent you as a mercy to the worlds. Islam spread through politeness. In Subcontinent the advent of Islam is a great achievement of the noble saints and sufis. D۔G Khan which was a purely Hindu area in the past and the several sufis came to this part of Punjab in the initial stage of Islam. They played glorious role in the advent of Islam in the region. Sufism is a deter-mine effort towards unity. His main purpose is to bring humanity close with one another, separated as it is into so many different units, closer together in the deeper understanding of life. The main task is to bring about brotherhood among races, nations and faiths and to respect one another's faith, scripture and teacher. Sufi is to confer Sympathy on these lives, to impart Love, Compassion and Kindhearted-ness on all creations. The Sufi message is the resonance of the same Divine message which has always come and will always come to inform humanity. This research paper highlights the services of sufis who influenced on socio religious life of the people of D۔G Khan. 

Activity Guided Synthesis and Sar Study of Flavonols As Nootropic Agents

Cognitive dysfunction or brain fog is a major public health concern of 21st century associated with many neuropsychiatric and neurodegenerative disorders like Alzheimer Disease (AD). Memory is the key function of brain where the neural circuitry necessary for memory and learning is present in hippocampus of the brain. Nootropic drugs help in boosting cognitive skills while amnestic drugs disturb memory and learning process. The potential pharmacological role of flavonoids with special emphasis on their nueroprotective and nootropic effects is still uneplored. In this connection, the current research study was planned to synthesize flavonols with substitution and were subjected to a series of tests to examine their antioxidant potentials, safety and enzyme inhibition, molecular docking, nootropic activity and their biomarker studies. A simple and convenient methodology for flavonol derivatives (OF1-OF12) was used to synthesize the flavonols from ketone and substituted benzaldehyde. Initially electronically and chemically different flavonol derivatives (OF1-OF6) were synthesized. OF1 being the parent flavonol has hydrogen on its para position. The OF2 (N,N-dimethyl, N(CH3)2, strong electron donating and activating ), OF3 (chlorine, Cl, halogen), OF4 (methyl group, CH3, slightly electron donating and slightly activating), OF5 (methoxy group, OCH3, strong electron donating and strong activating) and OF6 (trifluoromethyl, CF3, strong electron withdrawing and strong deactivating) were synthesized and characterized. Similarly, flavonol derivatives OF7 and OF8 by changing the position of methoxy group from para to ortho and meta position followed by synthesis of dimethoxy derivatives of flavonols (OF9-OF12) in order to see the effect of 2nd methoxy group. The flavonol derivatives (OF1-OF12) studied in the acute and sub acute toxicity at different dose levels in phases were safe and suggested to be virtually nontoxic. The molecular docking studies of different flavonol derivatives attested the in-vitro cholinesterase (acetylcholinesterase and butyrylcholinesterase) studies. The assessment of nootropic potentials of the selected synthetic flavonols (OF1-OF12) at the dose of 12.5, 25 and 50 mg/kg was done out by applying well established passive avoidance step through test, passive avoidance step down test and novel object recognition (NORT) assay models. At a dose of 12.5, 25 and 50 mg/kg, all the tested flavonol exhibited a significant (*P<0.05, **P<0.01, ***P<0.001, n=8) step through latency (STL) that are comparable to amnesic group (scopolamine treated). Among the different flavonol derivatives, OF5 and OF11 were found the most potent flavonols suggesting that methoxy group is important for activity. The OF5 has methoxy group (OCH3) at para position and OF11 has methoxy groups (OCH3) at ortho and para position which is strong electron donating and activating group. In the passive avoidance step down test, the step down latency and in NORT, the percent discrimination index DI was also significant when mice were treated with flavonols (OF1-OF12) and tested against these models. In addition, it showed that synthetic flavonols (OF1-OF12) is decreasing the acetyl cholinesterase activity while also increasing the acetylcholine levels in the brain of test animals. The synthetic flavonols (OF1-OF12) significantly increased antioxidant enzyme activities (SOD, GSH and CAT) and reduced lipid peroxidation (MDA level) in the frontal cortex and hippocampus of brain. Pretreatment of mice with synthetic flavonols (OF1-OF12) produced significant change in SOD activity (2.94 to 2.25 folds) in the hippocampus and frontal cortex when compared with scopolamine treated (amnesic) group. Moreover, treatment of OF5 and OF11 significantly increased (P< 0.001) SOD activity by 2.82 (29.83±2.01, n=8) and 2.94 (31.07±1.92, n=8) folds compared to amnesic group. Moreover, the pretreatment of mice treated with 50 mg/kg of synthetic flavonols (OF1- OF12) significantly increased catalase levels in the hippocampus (4.06 to 2.93 folds) and frontal cortex (3.35 to 2.65 folds) when compared to amnesic. The synthetic flavonols (OF1-OF12) prevented scopolamine-induced elevation in MDA level as indicated by significantly (P<0.05, P<0.01, P<0.001, n=8) less MDA level in mice brain regions (hippocampus and cortex). There was significant rise (P<0.05, P<0.01 and P<0.001) in level of GSH in brain regions (hippocampus 3.66 to 3.44 folds and frontal cortex 3.22 to 2.73 folds) of group treated with synthetic flavonols (OF1-OF12) in comparison to scopolamine group. In short, the correlation of in-vitro study, in-vivo and ex-vivo animal study of synthetic flavonols (OF1-OF12) at the dose of 12.5, 25 and 50 mg/kg significantly improved the memory of mice and reversed the amnesic response induced by scopolamine.