In this study the crude methanolic extract of Paeonia emodi (P. emodi) and Solanum xanthocarpum (S. xanthocarpum), (Pe-CR, Sx-CR)and its subsequent fractions, like n-hexane (Pe-HEX, Sx-HEX), chloroform (Pe-CF, Sx-CF), ethyl acetate (Pe-EA, Sx-EA) and aqueous (Pe-AQ, Sx.AQ) were initially screened for its cardioprotective potentials at a dose of 500 mg/kg in mice. The Isoproterenol hydrochloride (ISO) was used to induce myocardial infarction (MI) in mice. During MI, the enzymes such as Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Lactate Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) leaks from the damaged cardiac cells into blood which are important markers of cardiac injury. The effect of plant extracts on the level of these biomarkers was determined in mice and Pe-EA was found most active by reducing the serum levels of ALT, AST, CPK and LDH to 71.53 ± 1.37, 78.50 ± 1.14, 84.66 ± 1.92 and 243.66 ± 6.17 which are comparable with standard group. The Pe-EA was further tested at lower doses of 75, 150 and 300 mg/kg for its cardioprotective potentials and a dose of 300mg/kg significantly reduced the serum levels of ALT (p < 0.001), AST (p < 0.001), CPK (p< 0.05) and LDH (p < 0.001) as compared to ISO treated group. In order to understand the underlying mechanism, the same fraction was subjected to relevant in-vivo and in-vitro experiments including anti-hyperlipidemic, anti-oxidant, membrane stabilization, thrombolytic, calcium channel blocking and DNA ladder assay. As Total Cholesterol (TC), Triglycerides (TG) and low density lipoprotein cholesterol (LDL) plays major role in hyperlipidemia and results in progression of atherosclerotic plaque which leads to MI. In this study Poloxamer-407 (P-407) was used for induction of hyperlipidemia and Pe-EA fraction was tested at a dose of 75, 150 and 300 mg/kg in hyperlipidemic mice. The Pe-Ea exhibited prominent effect 300mg/kg dose by reducing the serum levels of TC, TG and LDL to 113.33 ± 3.32, 121.50 ± 4.58 and 57.20 ± 3.33 mg/dl respectively, almost similar to the standard drug used. To know the possible antihyperlipidemic mechanism, Pe-EA was tested against pancreatic lipase, cholesterol esterase and HMG-CoA reductase at a concentration of 125, 250 and 500 µg/mL. The HMG-CoA reductase inhibitory activity at concentration of 500 µg/mL demonstrated best potential (67.04 ± 1.12%), which suggests its mechanism is same like statins used in treating hyperlipidemia. Similarly, the Pe-EA was tested for the membrane stabilization activity at different doses which showed good stabilizing potential with an IC50 value of 850 µg/mL. Platelets aggregation and formation of thrombus leads to permanent obstruction of blood flow in MI. In order to know thrombolytic potential of Pe-EA, it was screened for thrombolytic effect and was tested at several concentrations where the highest thrombolytic potential of 53.22% was observed at highest concentration (800µl). Recent studies reported that elevated cytosolic free calcium overload majorly contributes to MI. Calcium channel blocking effect of Pe-EA was investigated at different concentrations on isolated rabbit jejunum which exhibited best activity at a dose of 1 mg/mL. Similarly, DNA damage of cardiac myocytes occurs during MI and DNA fragmentation assay was carried out to check the DNA protection ability of Pe-EA. The Pe-EA fraction protected DNA from damaging effects during MI. Bioguided isolation of compounds was carried out from the same fraction through column chromatography. Different subfractions were obtained which were screened for cardioprotective potential. Among all, subfraction Pe-EA 40 exhibited best cardioprotective potential by reducing serum levels of biomarkers responsible for MI. The Pe-EA 40 was used for the synthesis of gold nanoparticles (Pe-EA40-AuNPs) and was screened for cardioprotective potential. Pe-EA 40 was also used for the preparation of herbal formulation (Tablets) and tested in rabbits for cardioprotective potential at optimized dose (80 mg/kg). It decreased the serum levels of ALT, AST, CPK and LDH to 53.37 ± 1.83, 47.65 ± 1.29, 145.34 ± 1.28 and 248.83 ± 4.13 IU/L as compared togroup treated with ISO only. Pure compounds were isolated from Pe-EA 40 on the bases of good cardioprotective potential. The isolated compounds IB-1, IB-2 and IB-3 were screened for cardioprotective potential. The compound IB-1 (10 mg/kg) showed significant cardioprotective potential and lowered the serum levels of ALT, AST, CPK and LDH to 63.42 ± 1.72, 78.59± 1.34, 84.00 ± 2.66 and 229.54 ± 4.76 IU/L. Results of the current research work provides evidence that Pe-EA produced its cardioprotective potential via multiple mechanisms including antihyperlipidemic, antioxidant, membrane stabilizing, thrombolytic, calcium channel blocking and DNA protective effect. The cardioprotective effect of Pe-EA was increased two folds upon its formulation in gold nanoparticles (Pe-EA 40-AuNPs). It can be concluded from this study that P. emodi has the cardioprotective potential and can be used for the management and treatment of MI
4اپریل 1979ء کو بھٹو صاحب کو گڑھی خدا بخش دفن کر دیا گیا ۔6اپریل کو فوج کا پہرہ ختم ہوا تو پاکستان پیپلز پارٹی کے قائدین فاتحہ خوانی کے لیے گئے ۔ان میں بھٹو کے وکیل یحیٰ بختیار بھی تھے جب گائوں پہنچے تو لوگوں نے انہیں گھیر لیا اور پوچھنے لگے آپ تو ہمارے لیڈر کے سب سے قریب تھے ۔آخری وقت انہوں نے کوئی پیغام دیا یا کچھ کہا ۔یہ سن کر یحییٰ بختیار کی آنکھوں میں آنسو آگئے اور بولے بھٹو صاحب نے آخری ملاقات میں مجھ سے کہا ’’بزدل قوموں کے بہادر لیڈروں کا یہی انجام ہو تا ہے ‘‘
The aim of this research is to accumulate the literature related to an Islamic ideology for two of the basic components of a State, Governance and Judiciary; both have a strong impact on society. Pakistan is an Islamic ideological state, the only Islamic rule created on the name of religion after the state established by the Prophet Muhammad (Peace be Upon Him) in Medina. Its constitution and the style of governance should have its foundation based upon the principles of Islam; this is the main concept behind the creation of “Islamic Republic of Pakistan”. The paper will review some of the basic requirements for an administrative system to be qualified as Islamic way of governance and the judicial system in Islam includes the formulation of a comprehensive ideology of human equality and justice; the creation of a powerful incentive to adopt this ideology; and to establish a living example of equality and justice at all levels of life by defining the Islamic Judicial System & Its Legal Basis. Different Quranic verses, sayings and acts of Muslim jurists in this perspective are also studied. The paper has literature review in two major parts, first we will cover governance and Islam along with some basic terminologies from Islamic point of view and in the later part Judiciary, the concept of Justice and Judicial system in Islam will be discussed.
The potential of an indigenous white rot fungus Shyzophylum commune IBL-06 for the production of ligninolytic enzymes in solid state fermentation of banana stalk was investigated. The production process was further improved by optimizing some physical parameters (incubation time, moisture level, pH, temperature, inoculums size) and nutritional factors (carbon and nitrogen sources, carbon: nitrogen ratio, mediators and metal ions). By optimization of different parameters the maximum activities of enzyme synthesized by S. Commune IBL-06 were 3745 IU/mL of MnP, 2700 IU/mL of LiP and 345 IU/mL of Laccase after 3 days incubation at рH 4.5 and 35°C temperature with inoculum size, 3mL; moisture content, 60%; C: N ratio, 20:1(glucose and ammonium nitrate as carbon and nitrogen supplements), 1mM MnSO4 as mediator, 1mL and 1.25mM MgSO4 .7H2Oa, 1mL. The enzymes produced under optimum conditions were purified by (NH4SO4)2 precipitation, dialysis and Sephadex G-100 gel filtration chromatography. The purified enzymes were run on SDS-PAGE and characterized through kinetic studies. The purified MnP was a monomeric protein with mass of 40 kDa. The optimum pH and temperature for MnP were 5 and 40°C with 0.29 mM KM and 450mM/min Vmax using MnSO4 as substrate. The enzyme was activated by 1mM CuSO4 but was inhibited by CaCl2, EDTA, TEMED, β- Marcaptoethanol, AgNO3 and Pb(NO3)2. The molecular weight of purified LiP was 43KDa and it displayed a single band on SDS-PAGE. LiP showed optimum pH 5.0, optimum temperature, 35°C; KM, 0.5 mM and Vmax, 400 mM/min using varatryl alcohol as substrate. The enzyme was inhibited by CuSO4, MnSO4, CaCl2, EDTA, TEMED, β-Marcaptoethanol, AgNO3, Pb(NO3)2. Molecular mass of Laccase was 63 kDa and it had optimum рH 6.0, optimum temperature 40°C, KM value 0.25mM and Vmax 80mM/min using ABTS as substrate. The laccase activity was enhanced by 2mM CuSO4, and was inhibited by MnSO4, CaCl2, EDTA, TEMED, β-Marcaptoethanol, AgNO3, Pb(NO3)2. Crude ligninase extract decoulorized Novasol direct blue dye to 80%, followed by Novasol direct yellow dye to 60%, Novasol direct red to 38% and Novasol direct black to 37%. The effluent from Magna textile industry was maximally decolorized to 87% in 24 hours, followed by effluents from Crescent, Arzoo and Chenab textile industries. S. Commune IBL-06 produced high activities of MnP and LiP having higher catalytic activities as compared to most of the previously reported enzymes.