الأصوات العربية الفرعية في الدراسات الصوتية

يهدف هذا البحث إلى المساعدة على التعرف على كيفية تركيب الألفاظ العربية من حيث إتيان الحروف المجاورة في بنائها، وعند جمع أربعة أو أكثر في التلفظ بها. ويعين على تمييز الألفاظ الأعجمية التي لها ألفاظ عربية. واتبع الباحث المنهج الوصفي التحليلي في إجراء البحث. وفي ضوء ما تم تناوله تم التوصل إلى النتائج الآتية: 1- أن تصنيف الحروف الفرعية إلى مستحسن ومستقبح راجع عند القدماء لمبدأ الكثرة والقلة، فما كثر استعماله كان مستحسنا، وما قل استعماله وصف بالاستقباح. 2- تمثل الحروف الفرعية ألوانا من الآراء يعكس اختلاف القبائل العربية آدابها، وهي من صور الأداء المعروفة، مما جعل العلماء يقومون ببيان خواصها الصوتية. 3- جاءت هذه الحروف لإحداث نوع من التناسق والإنسجام في البنية الصوتية.

Isolation and Characterization of Biologically Active Compounds from Selected Medicinal Plants

The main objective of this study was to discover new cancer chemopreventive and cytotoxic compounds from the natural sources to combat cancer. For the purpose, after an extensive survey based on the information gathered from local healers, six medicinally-important plants of Pakistan were selected for investigation. These plants included Euphorbia wallichii Hook F., Bergenia ciliata (Haw.) Sternb, Acer oblongifolium Hort. ex Dippel, Aster thomsonii C. B. Clarke, Opuntia dillenii (Ker Gawl) Haw. and Withania coagulans (Stocks) Dunal. For initial screening, total 59 extracts/fractions were prepared by using the different techniques including maceration, solvent-solvent extraction, flash column chromatography and solid phase extraction. All the extracts/fractions were tested for their anticancer and cancer chemopreventive activity by employing seven independent assays. Overall the results of the initial screening were very encouraging and led to the selection of the most potent plant material for further investigation. NFĸB activity plays a critical role in cancer development, progression and therapy and two of our samples from Withania coagulans demonstrated greater than 90% inhibition of TNF-α induced activity of NFĸB. Aromatase inhibitors are known to be effective for the treatment and prevention of breast cancer. One fraction from aerial parts of each plant, W. coagulans and Euphorbia wallichii, inhibited aromatase by 100% and 73%, respectively. Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) plays critical role in inflammation, cell survival and tumor development and progression. Five of our samples, one from aerial parts of E. wallichii, one from Aster thomsonii, and three from fruit bearing aerial parts of W. coagulans, inhibited NO production significantly in lipopolysaccharide activated macrophage RAW 264.7 cells as a marker of iNOS inhibitor. No extracts or fractions was deemed active in RXRE assay. DPPH free radical scavenger has potential use to scavenge oxygen free radicals, which are the product of normal cellular metabolism and can attack and produce endogenous DNA lesions leading to genotoxicity, mutation and cancer. A total of 25 extracts/fractions exhibited ≥ 70% scavenging at 200 μg/ml concentration in DPPH assay, among them 13 were from roots and aerial parts of E. wallichii, 5 from B. ciliata, 6 from A. oblongifolium and one from A. thomsonii. QR1 is measured as overall representative of the phase II enzymes. Phase xiii Abstract II enzymes are primarily responsible for the metabolic detoxification of chemical carcinogens and other harmful oxidants, leading to the protection of cells against redox cycling, oxidative stress, and carcinogenesis. Therefore, induction of QR1 at the tumor initiation stage is suggestive for cancer prevention potential. A total of 10 extracts/fractions demonstrated potent induction of QR1 in a cell-based assay with CD (concentration required to double the enzyme activity) <10 μg/ml among them one is from A. oblongifolium and 9 from W. coagulans. A total of 8 extracts and fractions showed cytotoxicity in an SRB assay against MCF-7, LU-1 and MDA-MB 231 cancer cell lines, among them 3 are from E. waliichii and 5 from the W. coagulans. The overall results suggested that W. coagulans might be the most promising plant for further studies as the extracts/fractions from this plant showed highest and significant activity in most of the assays. After the initial screening, W. coagulans was selected to pursue further for isolation and purification of the pharmacologically relevant compounds. For this purpose, total 10 kg dry weight of the W. coagulans aerial part was extracted, fractionated and subjected to biological evaluation in the above described assays to confirm the biological activities and to find the most active fractions. Active fractions were further processed through sequential bioactivity guided fractionation utilizing various chromatographic techniques, which led to isolation of 9 biologically active pure compounds. Structure elucidation of these compounds was carried by utilizing mass spectrometry (MS), one dimensional nuclear magnetic resonance (1D-NMR), and two dimensional nuclear magnetic resonance (2D-NMR) techniques. Structural elucidation showed that these compounds belong to a very important, biologically active and chemically distinct class of natural products known as “withanolides”. On the basis of existing reports and spectroscopic results it is concluded that out of these 9 compounds 3 are new and 6 are already known withanolides. This study is a contribution towards the exploration of new withanolides as well as their potential use in cancer chemopreventive and anticancer drug discovery.