This dissertation encompasses the phytochemical and pharmacological role of Viola canescens, Ziziphus oxyphylla and Rosa webbiana. The objective of this study was to authenticate folk uses of these plants in liver diseases, by isolating active pure compounds and to test them for hepatoprotection. The crude methanolic extracts of the selected plants were fractionated into n-hexane, chloroform, ethyl acetate and water. These extracts were qualitatively screened for various chemical constituents such as alkaloids, carbohydrates, polyphenols, flavonoids, saponins, tannins, triterpenes, proteins, fixed oils, essential oils and fats. The polyphenols and flavonoids were determined quantitatively. The crude extracts were tested for acute toxicity study and hepatoprotective activity in BALB/c mice. All the plant extracts were found safe upto 2000 mg/kg body weight. Among various fractions, the ethyl acetate fraction of Viola canescens, and chloroform fraction of Ziziphus oxyphylla and Rosa webbiana exhibited more pronounced hepatoprotection. Therefore, these fractions were subjected to isolation and purification of compounds responsible for hepatoprotective activity. Structures of pure compounds were elucidated by NMR and mass spectrometric techniques and placed in group of triterpenes, flavonoid and sterol. The isolated compounds were screened for acute toxicity, anti-inflammatory and hepatoprotective activity. Antioxidant activity of solvent extracts was evaluated by DPPH and H2O2 scavenging assays. In DPPH assay, ethyl acetate subfraction (EAF + Me) of Viola canescens exhibited DPPH scavenging action (86.89 ± 0.16%, IC50=12 μg/ml), while chloroform fraction (CF) of Rosa webbiana (RW) exhibited (84.7 ± 0.3 %) activity. IX In H2O2 scavenging assay, Viola canescens EAF + Me exhibited excellent scavenging of H2O2 (IC50, 5 μg/ml), the IC50 value for CF of RW was 100 μg/ml. Hepatoprotective activity was evaluated in carbon tetrachloride (CCl4) induced hepatotoxicity by determination of hepatic biomarkers, antioxidant parameters, changes in body and liver weight and histopathology of liver. Seven days treatment with CCl4 caused elevation in ALT (195.6 ± 1.4 U/L), ALP (315.3 ± 1.7 U/L), total bilirubin (2.73 ± 0.07 mg/dl) and decline in total protein (3.91 ± 0.47 g/dl). Viola canescens (EAF + Me) reduced the levels of ALT (50.67 ± 0.67), ALP (187 ± 0.68), TB (0.7 ± 0.05) while TP was enhanced (4.78 ± 0.25). Ziziphus oxyphylla (CF) reduced ALT level to (57 ± 0.13), ALP (204 ± 0.17), TB (0.82 ± 0.18) and increased TP level (4.50 ± 0.16). Rosa webbiana (CF) reduced the level of these parameters to 97.3 ± 1.2, 204 ± 1.34, 1.01 ± 0.11 and 4.35 ± 0.21 respectively. In order to probe into mechanism of hepatoprotection, antioxidant enzymes (CAT, SOD), lipid peroxidation and phenobarbital induced sleeping time (PST) was determined. It was observed in the current study that CCl4 caused decrease in activities of CAT (15.87 ± 0.24) and SOD (18.3 ± 0.95) while MDA level was increased (43.5 ± 0.45). Viola canescens subfraction (EAF + Me) enhanced the level of CAT (40.17 ± 0.08), SOD (53.3 ± 0.28) while MDA level declined (15.1 ± 0.1). Ziziphus oxyphylla (CF) enhanced the level of CAT, SOD and MDA upto 39.8 ± 0.23, 51.7 ± 0.15 and 17.4 ± 0.24 respectively. CCl4 induced prolongation of phenobarbital sleeping time (130 ± 3.88) in comparison to normal group (85 ± 2.26); however, in Viola canescens (EAF + Me) treated animals sleeping time was reduced (96 ± 1.15 minutes). Chloroform fraction (CF) of Ziziphus oxyphylla also reduced righting reflex (94 ± 0.88 minutes). X Furthermore, the hepatoprotective mechanism was also investigated for the ability of extracts to stabilize erythrocyte membrane. The membrane stabilizing effect of Viola canescens EAF was (IC50 3.4 ± 0.15 mg/ml), while CF of Ziziphus oxyphylla exhibited 72.5 ± 2.04% inhibition of erythrocyte lysis as compare to sodium salicylate (76.43 ± 3.22%). Protective effect of the solvent extracts of Viola canescens on CCl4 induced DNA damage in the liver tissue of mice was evaluated by polyacrylamide gel electrophoresis. In CCl4 treated mice liver tissue, severe DNA damage was observed. Administration of Viola canescens solvent extracts prevented DNA damage as compare to silymarin. Histopathological study was performed to confirm hepatoprotective effects of extracts. Administration of CCl4 caused severe fatty changes, extensive hepatocyte necrosis, lymphocytic infiltration and sinusoidal congestion. Treatment of mice with Viola canescens (EAF + Me) exhibited significant recovery from fatty changes, necrosis, lymphocytic infiltrations and sinusoidal congestion which is comparable to normal. While CF of Ziziphus oxyphylla resulted in near to normal histomorphology of liver. In case of CF of Rosa webbiana only mild cellular infiltration was observed. Moreover, the crude extracts were screened for anti-inflammatory activity via xylene and carrageenan models in mice. VCME (400 mg/kg body weight) resulted in inhibition of ear edema (53.41 ± 0.7%) induced by xylene as compare to diclofenac sodium (73.64 ± 1.14%). Paw edema in mice caused by carrageenan was reduced upto 59.46 ± 0.29% at 400 mg/kg body weight at 4th h. The standard drug (diclofenac sodium) reduced paw edema upto 62.4 ± 0.26% at 10 mg/kg body weight. RWME (400 mg/kg body weight) inhibited xylene induced ear edema (40.02 ± 0.23%). While carrageenan induced paw edema was reduced upto 52.75 ± 0.04% at 400 mg/kg. XI Compound 6 (ARW1) at 50 mg/kg inhibited 62.9 ± 0.15% xylene induced ear edema and 66.6 ± 0.17% carrageenan induced paw edema. Compound 3 (AZO2) and 4 (AZO3) isolated from Ziziphus oxyphylla, inhibited xylene induced ear edema at 50 mg/kg 51.33% and AZO3 58.66% respectively as compare to diclofenac sodium (72.66% inhibition). In carrageenan induced paw edema, compound 3 (AZO2) and 4 (AZO3) provided 33.3 ± 0.21 and 39.21 ± 0.15% inhibition respectively at 50 mg/kg. In acetic acid induced analgesic activity, compound 3 (AZO2) and 4 (AZO3) produced 64.28% and 65.35% inhibition of writhing at 50 mg/kg. Based on folk uses, the Viola canescens extract was subjected to antipyretic and antidiarrheal activity. Subcutaneous injection of brewer yeast suspension caused marked increase of body temperature of mice which was reduced in dose dependant manner by V. canescens at 100, 200 and 400 mg/kg orally. Treatment of animals with paracetamol and VCME at 100, 200 and 400 mg/kg caused reduction of pyrexia at 1st, 2nd, 3rd and 4th h in comparison to control group. Evaluation of phytotoxic effect by percent radish seed inhibition and root length inhibition shown by VCME was 59.33 ± 0.23 and 62.43 ± 0.25 respectively at 1000 ppm with IC50 240 and 125 ppm respectively. The percent cytotoxic activity of VCME was 65 ± 2.1% at 1000 ppm. VCME showed 40% antidiarrheal activity at 300 mg/kg that was enhanced to 80% at 1000 mg/kg as compare to loperamide (100% activity). It may be concluded from our findings that Viola canescens and Ziziphus oxyphylla provided good hepatoprotection while Rosa webbiana exhibited poor hepatoprotection as compare to silymarin. Compound 3 (AZO2) and 4 (AZO3) isolated from Ziziphus oxyphylla exhibited antioxidant, analgesic, anti-inflammatory and XII hepatoprotective activity while compound 6 (ARW1) isolated from Rosa webbiana showed antioxidant, anti-inflammatory and hepatoprotective activity.
3۔ تحفظ عقل اللہ تعالیٰ نے جہاں انسان کو لا تعداددوسری نعمتوں سے نوازا ،وہاں عقل وشعور جیسی نعمت سے نواز کر اس پر خاص فضل فرمایا۔ اسی کی بدولت حضرت انسان کو اشرف المخلوقات کا رتبہ ملا۔ اسی کی وجہ سے وہ شر اور خیر میں فرق محسوس کرتا ہے ۔ اسی وجہ سے وہ مکلف بنا اور اللہ تعالیٰ کا نائب، کیونکہ بے عقل اور مجنون کو مرفوع القلم قرار دیا گیاہے ،جیسا کہ قرآن مجیدمیں حکم ربانی ہے ﴿كَذَلِكَ يُبَيِّنُ اللَّهُ لَكُمْ آَيَاتِهِ لَعَلَّكُمْ تَعْقِلُونَ۔ ﴾237 "اسی طرح تمہارے لیے اپنی نشانیاں بیان کرتا ہے تاکہ تم عقل سے کام لو۔ " نشہ آور چیزوں میں سے جو عقل و فہم اور شعور کے لئے مہلک ہیں۔ ان میں سے شراب نوشی کو نمایاں مقام حاصل ہے اور دوسری نشہ آور چیزیں انہی کے حکم میں آتی ہیں ۔ زمانہ جاہلیت میں شراب پینے ، پلانے کا رواج عام تھا۔ رسول اللہ ﷺ کی آمد سے امت اور انسانیت کی اصلاح کام شروع ہوا تو جہاں زندگی کے دوسرے گوشوں کی اصلاح کا انتظام ہوا وہاں شراب نوشی کے سلسلے میں بھی رسول اللہ ﷺ نے ہدایات دیں اوراس کے نقصانات بتلائے ۔ قرآن مجید میں شراب نوشی کے مفسدات یوں بیان ہوئے ﴿إِنَّمَا يُرِيدُ الشَّيْطَانُ أَنْ يُوقِعَ بَيْنَكُمُ الْعَدَاوَةَ وَالْبَغْضَاءَ فِي الْخَمْرِ وَالْمَيْسِرِ وَيَصُدَّكُمْ عَنْ ذِكْرِ اللَّهِ وَعَنِ الصَّلَاةِ فَهَلْ أَنْتُمْ مُنْتَهُونَ۔ ﴾238 "شیطان تو یہ چاہتا ہے کہ شراب اور جوئے کے سبب تمہارے میں دشمنی اور رنجش ڈلوادےاور تمہیں اللہ کی یاد سے اور نماز سے روک دے تو تم کو (ان کاموں سے ) باز رہنا چاہیے۔ " حضرت ابن عمر(م:73ھ) سے مروی ہے کہ آپ ﷺ نے فرمایا " كُلُّ مُسْكِرٍ خَمْرٌ وَكُلُّ خَمْرٍ حَرَامٌ۔ "239 "ہر نشہ آور چیز خمر یعنی شراب ہے اور ہر...
Quran is the word of Allah Almighty, therefore, in order to understand it in the true sense, a person has to sharpen his or her intellectual ability as well as increase the knowledge. When one is at a particular intellectual level, only then can he or she start understanding the true message, which Allah Almighty conveyed through words of Quran. Pertaining to the explanation of Quran for the understanding of general audience, different people have tried to write the Tafseer of Quran. Although Muslims recite Quran and try reading it with translation, however, the reading of Tafseer has its own importance. “Tafseer Dawat-Ul-Quran” is written by Abu Nauman Saifullah Khalid and published from Dar-Ul_Undalus Lahore in 2010. This Tafseer has been written in the light of the Quran, Hadith, and the sayings of the companions of Prophet. In this Tafseer correct tradit-ions has been included and unauthentic traditions has been avoided. In theological interpretations, the words of Qur'an are explained in the context of the Qur'an itself or the sayings of The Holy Prophet(ﷺ). This type of interpretation is called “Tafseer Bilmasur”.“Tafseer Dawat-Ul-Quran”is representative of Tafseer Bilmasur. In this research article, the Salient features of “Tafseer Dawat-Ul-Quran” are discussed.
Escherichia coli lineage ST131 predominates across various spectra of extra-intestinal infections. Distinctive resistance profile, diverse armamentarium of virulence factors and rapid global dissemination of ST131 E. coli makes it an intriguing pathogen of significant importance. However, little is known about the prevalence and various attributes of ST131 associated with urinary tract infections in Pakistan. Evolutionary dimensions of ST131 linage and corresponding molecular markers encoding drug resistance remained largely unexplored and prevalence data are extremely scarce in South Asian countries. We scrutinized prevalence and various genetic attributes of E. coli ST131 isolates involved in urinary tract infections by processing 148 randomly selected samples during August 2012 and August 2014. Phylogenetic grouping, fumC/fimH and O-typing was done by PCR based methods. Antibiotic susceptibility assays and phenotypic detection of ESBLs were carried out according to the CLSI guidelines of year 2013 and ESBL isolates were screened for the prevalence of blaCTX-M-15. Plasmid encoded qnrA, qnrB and qnrS genes were identified by DNA amplification and sequencing. Mutations in genes gyrA, gyrB, parC and parE were identified among fluoroquinolone resistant isolates. Minimum inhibitory concentrations (MICs) for ciprofloxacin and levofloxacin were determined by using broth dilution method. Phylogenetic analysis was performed by PCR using three gene classification systems (Clermont et al., 2000). Overall, 59% of the UPEC isolates belonged to phylogenetic group B2 which was followed by group D=28%, B1=8% and A=5%. Among 18 different ST-types ST131 was the most dominant lineage as 46% of the isolates belonged to ST 131 lineage. By, CH-typing 46% of the ST 131 isolates belonged to sub-group H30. Higher numbers of identified ST 131 isolates 74% were MDR and 44% showed ESBL phenotypes while 100% of the isolates carried blaCTX-M-15. Overall, resistant patterns of ST 131 isolates confirmed least resistance against tigecycline, meropenam and amikacin. Likewise, resistance against tazocine, nitrofurantoin, sulzone and minocycline remained below threshold level. For fosfomycin, (FF) and gentamicin (CN) resistance were 13% and 28% respectively. Higher resistances was noticed against all four generations of cephalosporins, (53%-78%). Higher percentages of ST 131 isolates were resistant to co-trimoxazole (85%), amoxicillin clavulanic acid 65% and fluoroquinolones 60%. Overall, minimum inhibitory concentrations of ciprofloxacin remained above 256μg/ml in ST 131 and non ST 131 isolates. In comparison to MICs of ciprofloxacin, MICs of levofloxacin in most of the isolates varied between 8μg/ml-64μg/ml. In this study, majority of the fluoroquinolone resistant UPEC ST 131 isolates carried at least two or more non-synonymous mutations in gyrA, parC and parE genes. These isolates showed higher MICs for both ciprofloxacin and levofloxacin. Conclusively, higher percentages of the ST 131 isolates showed antibiotic resistance against trimethoprimsulphamethoxazolen, cephalosporin, fluoroquinolone, and majority of these isolates were multi-drug resistant. In addition, fluoroquinolone resistant UPECs isolates shared lineage of a clonal sub-group. An allelic combination of gyrA/parC/parE genes of sub-clone O25b-ST131 H30-R was associated with higher MICs of ciprofloxacin and levofloxacin. Overall, it is the first report from Pakistan that provides details insights about susceptibility patterns and genetic attributes of pandemic MDR ST131 strains involved in UTIs.