کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1201170 1493513 2015 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes: Herbal medicines as a case study
ترجمه فارسی عنوان
توسعه یک روش اسپکترومتری کروماتوگرافی / کروماتوگرافی مایع مرکزی گریز از مرکز میتوکندری برای غربالگری مولکول های فعال زیست فعال از میتوکندری از ماتریس های پیچیده: داروهای گیاهی به عنوان یک مطالعه مورد
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
چکیده انگلیسی


• A method for screening mitochondrial ligands from complex matrixes was developed.
• 10 mitochondrial ligands were found from Polygoni Cuspidati Rhizoma et Radix.
• 9 mitochondrial ligands were found from Scutellariae Radix.
• 17 compounds were identified as new mitochondrial ligands.
• The direct mitochondria-bound activity of 9 compounds was confirmed.

Mitochondria are an important intracellular pharmacological target because damage to this organelle results in a variety of human disorders and because mitochondria are involved in complex processes such as energy generation, apoptosis and lipid metabolism. To expedite the search for natural bioactive compounds targeting mitochondria, we initially developed an efficient mitochondria-based screening method by combining centrifugal ultrafiltration (CU) with liquid chromatography/mass spectrometry (LC/MS), which is called screening method for mitochondria-targeted bioactive constituents (SM-MBC) and is compatible with the search of mitochondria-targeted compounds from complex matrixes such as herbal medicines extracts. Functionally active, structurally intact and pure mitochondria were obtained from rat myocardium using an optimized protocol for mitochondrial isolation comprising organelle release followed by differential and Nycodenz density gradient centrifugation. After evaluating the reliability of the method using thiabendazole (TZ), rotenone (RN), amiodarone (AR) and trimetazidine (TD) as positive controls, this method was successfully applied to screen bioactive constituents from extracts of Polygoni Cuspidati Rhizoma et Radix (PCRR) and Scutellariae Radix (SR). Nineteen active compounds were detected and identified by LC/MS, of which 17 were new mitochondria-targeted compounds. The activity of 9 of the 19 hit compounds was confirmed by in vitro pharmacological trials. These results demonstrate that SM-MBC can be used for the efficient screening of mitochondria-targeted constituents in complex preparations used to treat mitochondrial disorders, such as PCRR and SR. The results may be meaningful for an in-depth understanding of drug mechanism of action and drug discovery from medicinal herbs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1413, 25 September 2015, Pages 33–46
نویسندگان
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