Investigations on Wild Allium Species. Part I: Cysteine Sulfoxides of Flowers. Part 2: Anticancer Activity of Bulb Extracts.

Since ancient times, onions, garlic and some other species of the genus Allium L. (onions) have been used as phyto-pharmaceutics, seasonings, and vegetables. Most prominent are common onion (A. cepa L.) and garlic (A. sativum L.). The medicinal benefits of these two species were intensely investigat...

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Bibliographic Details
Main Author: Jivishov, Emil
Contributors: Keusgen, Michael (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:English
Published: Philipps-Universität Marburg 2018
Pharmazeutische Chemie
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Summary:Since ancient times, onions, garlic and some other species of the genus Allium L. (onions) have been used as phyto-pharmaceutics, seasonings, and vegetables. Most prominent are common onion (A. cepa L.) and garlic (A. sativum L.). The medicinal benefits of these two species were intensely investigated during the last decades and lipid lowering, antibiotic, anti-atherosclerotic and anti-diabetic effects were described. In addition, a number of ethnic studies proved their canceroprotective effect. The health benefits of Allium vegetables are mainly related to sulfur containing compounds as well as saponins. The so-called cysteine sulfoxides of these plants are believed to be mainly responsible for these health benefits. These compounds are converted to thiosulfinates like allicin, when plant material is disrupted. This reaction is catalyzed by the action of the enzyme alliinase. Flowers of Allium species of subgenus Melanocrommyum, most of them for the first time, were analyzed for their cysteine sulfoxide(CSO) content. While all of the flowers carried methiin, only a few of flowers carried any of the following CSOs: isoalliin, alliin, marasmin, S-(2-pyrrolyl)-cysteine sulfoxide, S-(2-pyridyl)-cysteine N-oxide and butiin. Total CSO content of analyzed flowers varied from 0.12% to 7.05%, relatively to fresh material weight. Bulbs of several Allium species were extracted using ethyl acetate and screened for their cytotoxic activity against bladder cancer cell lines (T24 and UMUC3). Four most cytotoxic extracts were investigated further for their mechanism of action using flow cytometry assay, real-time PCR and Western blot analysis. Same four extracts were also investigated for their bioactive compounds. It was found that A.aflatunense, A. stipitatum, A.rosenorum and A. pallens acted as cancer cell killers. Mechanisms of action of the extracts were apoptosis, antioxidant response and cell cycle arrest. Bioactive compounds of A. stipitatum were found to be 2-(methyldithio)pyridine-N-oxide and as 2-[(methylthiomethyl)dithio]pyridine-N-oxide which were responsible for cell cycle arrest and inducting antioxidant response via Nrf2/HO-1 system. Tentatively identified bioactive compounds in A.aflatunense are 2,2′-dithio-bis-pyridine-N-oxide and 2-[(methylthiomethyl)dithio]pyridine-N-oxide.
Physical Description:138 Pages
DOI:https://doi.org/10.17192/z2018.0125