The low solubility and permeability of drugs, in general, leads to unsatisfactory pharmacokinetics profile of drugs. Polymer conjugation has attracted increasing interest in pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. The objective of this work was to find a method to overcome the solubility and permeability problems using the conjugation strategy. In this regard, hydroxyethyl starch (HES), a highly biocompatible semi-synthetic biopolymer, was used as a drug carrier. N- Arylsulfonylbenzimidazolones were selected as antidiabetic compounds of choice for coupling with HES. The experiments established the viability of a covalent coupling between polymer and N-arylsulfonylbenzimidazoles using a suitable coupling strategy. As a requirement for the desired coupled products, HES must have Mw that is suitable for drug delivery and excretion through the kidney. Therefore, HES needs to undergo a selective degradation. In the present study, two different methods for hydrolysis, i.e. acidic and enzymatic, were used for selective degradation of HES. It was found that the enzymatic hydrolysis method is superior to acidic hydrolysis. The enzymatic method was used to obtain HES of Mw as low as ≈ 10,000 g/mol. The selectively degraded HES was oxidized to generate carboxylic acid groups at the chain ends to serve as a coupling site for N-arylsulfonylbenzimidazolones, the selected antidiabetic compounds. For oxidation of HES, potassium permanganate and sodium oxychloride were tried as oxidizing agents. The sodium oxychloride method was found advantageous over permanganate method. The degraded and oxidized products were characterized using GPC, IR and NMR techniques. N-Arylsulfonylbenzimidazolones were synthesized using a multistep sequence to serve as antidiabetic compounds. The structures of all the synthesized arylsulfonylbenzimidazolne products and intermediates were established using spectroscopic techniques and the purity ascertained by elemental analysis. The synthesized arylsulfonylbenzimidazolnes were coupled to oxidized HES of molecular weights 17,490 g/mol and 10,067 g/mol by creating an amide linkage between the two units. iiThe coupled products were characterized using GPC, IR, 1 H NMR and 13 C NMR spectroscopy. The coupled products were screened for their antidiabetic potential on male albino rats of the Sprague–Dawley albino family at a dose of 20 mg and 40 mg per Kg body weight of the rats. It was observed that all the synthesized compounds were highly active. 2,3-Dihydro-3-(4- nitrobenzensulfonyl)-2-oxo-1H-benzimidazole (63) was found most potent with a 54 % reduction in blood glucose level of the rats as compared to 41 % reduction produced by tolbutamide and 38 % by glucophage. The coupling of these antidiabetic compounds with oxidized HES resulted in an increase of the hypoglycemic activity of all the compounds. The activity of compound 63 on coupling to HES 10,067 increased to 67 % reduction in blood glucose level.
The Immensely Merciful to all, The Infinitely Compassionate to everyone.
67:01 a. Blessed is HE WHO holds the reins of Sovereignty over all existence in HIS Hand, b. and HE Manifests Sovereignty over all existence.
67:02 a. The One WHO created the phenomenon of the death and the life. b. So that HE may test you between life and death to see which one of you would be most virtuous in deeds that pleased HIM. c. And HE is The Almighty, The Ever-Forgiving.
67:03 a. It is also HE WHO created the seven celestial realms, one above the other in full harmony with one another. b. You will not see any imperfection in this creation of The Immensely Merciful. c. Then turn up your sight again! d. Can you see any discrepancy or flaw?
67:04 a. Then turn up your sight again and again! b. Your sight will come back to you bewildered and fatigued, unable to find any discrepancy or flaw.
67:05 a. And, indeed, WE adorned the lowest sky to the earthly life with lamps, b. and WE made such shooting stars/meteors that would fend off every approaching satanic evil force, c. and, additionally, WE have prepared for them the punishment of the Blazing Fire.
67:06 a. And for those who disbelieve in their Rabb- The Lord is the punishment of Hell. b. And it is going to be an awful and woeful destination!
67:07 a. As they would be flung into it, they will hear its furor - as it boils up,
Almighty Allah bestowed honors and respect to mankind. Keeping in view the honor of mankind, Allah SWT blessed them also a purified, cleanse and Halal [permissible & Lawful] food. Moreover, the religious teachings are very clear and transparent in this regard to highlight the difference between what is beneficial and useful for them and what is harmful and injurious. Almighty Allah is very kind and compassionate to his servants and described definite commands and orders about such Animals which are adequate and effective to mankind and counts them in Halal category and otherwise are considered Restricted and Haram [impressible & unlawful]. So all kinds of animals which are harmful are prohibited with exception of their some body organs and which are useful are described with their all qualities are halal in mentioned divine religions i.e. Judaism, Christianity and Islam coupled with little changes in rulings about the use of body organs of impermissible animals like use of bones or skin etc. The paper emphasis on describing the disparities of three divine religions regarding the use of organs, skin of animals, bones and highlight their procedures of making them safe and useable for mankind. This study will lead us to know that which divine religion is more applicable and provides cleanse food to their followers along with having the status of eternity strength among three.
The present investigation was an attempt to explore the nutraceutical potential of pomegranate peel and bagasse extracts based value added/functional drinks against various metabolic syndromes. Three different pomegranate varieties namely Kandhari, Desi and Badana were nutritionally characterized followed by punicalagin quantification, product development and finally the bio-efficacy trial was carried to evaluate health benefits of respective drinks against hypercholesterolemia and diabetes. The nutritional analysis revealed that pomegranate peel and bagasse are a good source of protein, fiber, fat, potassium (K) and calcium (Ca). For the extraction of polyphenols three types of solvent were used i.e. methanol (50%), ethanol (50%) and ethyl acetate (50%). Amongst tested pomegranate peels & bagasses, Kandhari variety demonstrated the highest total phenolic contents (TPC) [259.05±27.40 & 30.67±4.72 mg/g gallic acid equivalent (GAE)], total flavonoid contents (TFC) [53.53±6.14 & 8.86±1.91 mg/g rutin equivalent (RE)] and 2,2-diphenyl-1-picrylhydrazyl [DPPH (70.66±7.44 & 42.30±5.75%)], likewise, maximum TPC (272.68±17.03 & 31.72±4.75 mg/g GAE), TFC (54.90±3.89 & 8.74±2.48 mg/g RE) and DPPH (72.41±5.87 & 43.34±5.97%) were noticed in methanolic extract of all varieties. The pomegranate peels and bagasses of all varieties were quantified by HPLC that depicted 110.59±8.84 mg/g and 1.77±0.41 mg/g of punicalagin, respectively. Afterwards, in product development phase, three types of value added drinks were formulated as drink containing pomegranate peel extract (D1), drink containing bagasse extract (D2) alongside with control (D0) for comparison purpose. The prepared drinks were subjected to physicochemical characterization during two months storage interval. In this milieu, storage intervals and treatments imparted significant effect on color tonality parameters of value added drinks. Moreover, storage interval substantially affected pH and acidity of drinks except for total soluble solids (TSS). Sensory scores of formulated value added drinks decreased with the progression of storage time however, the scores remained within acceptable range throughout the course of study. The efficacy trial was conducted on male Sprague Dawley rats. Accordingly, three types of studies were designed i.e. study I (normal rats), study II (hypercholesterolemic rats) and study III (diabetic rats). Additionally, each study was further divided into three groups G-1, G-2 and G-3 depending on the drinks i.e. D0, D1 and D2 that they were subjected to respectively. The body weights of experimented rats were affected substantially due to the application of value added drinks in all studies. The pomegranate peel extract based drink (D1) resulted in maximum decline in serum cholesterol values during study I, II & III by 3.09, 14.52 & 10.26% likewise a pronounced reduction in LDL and triglyceride levels was evaluated due to utilization of drink D1 (3.75, 14.86 & 11.75% and 3.12, 9.99 & 7.05%) followed by D2 (2.02, 10.74 & 7.72% and 2.89, 5.63 & 4.22%), respectively. Similarly, HDL increases significantly due to administration of value added drinks in study II and III. As far as antidiabetic perspectives are concerned, a substantial decline (p˂0.05) in serum glucose level was observed in study II (7.50 & 5.11%) and study III (13.28 & 8.71%) due to consumption of drink D1 & D2, correspondingly. Nevertheless, a substantial increase in insulin level was documented in D1 (5.66 & 8.74%) and D2 (3.38 & 4.37%) administrated groups during study II & III. Moreover, for the assessment of anti-oxidative markers, glutathione level was enhanced and thiobarbituric acid reactive substances (TBARS) level was reduced by utilization of value added drinks. The results of liver and kidney functioning tests as well as hematological attributes ensured the safety of value added drinks. It is inferred from the present exploration that Kandhari pomegranate peel was more effective as compared to Kandhari bagasse based drinks to mitigate hypercholesterolemia and diabetes.