buy AMI5 inhibitor br Materials and methods br Results br Di

Materials and methods
Results
Discussion Free radical damage can be considered as one of the major causative factors involved in many diseases such as inflammation and dementia. It is well established that anti-oxidants are capable of preventing injury to blood vessel membranes, thereby optimizing blood flow to the heart and brain, defending against cancer-causing DNA damage and thus help lowering the risk of cancer, cardiovascular and various mental illnesses including Alzheimer\'s diseases [31,32]. Xanthones are closely related to the polyphenol family. Therefore, screening natural antioxidants from xanthones should be an effective pathway to discover lead compounds. In the present study, antioxidant capacity of all the isolated xanthones (1–6) was evaluated using the radical DPPH, ABTS+, O2−, OH, NO, FRAP, metal chelating activity and the inhibition of lipid peroxidation assay. IC50 and equivalents (TE) per microliter of sample (mmol/L TE) was used for the evaluation of the activity. Of these tested compounds, buy AMI5 inhibitor 6 exhibited very strong antioxidant activity in a structural-dependent manner (Table 1). The second most active compound is 3. The great radical scavenging activity of this compound is quite self-evident that it has a catechol moiety. Compound 6 is a dioxygenated xanthone with two free hydroxyls located at C-1 and C-2, and C-diglycoside at C-8; while compound 3 is also a trioxygenated xanthone with three free hydroxyls located at C-1, C-2 and C-8. Generally, xanthones with higher oxygenation display better activity than those with less oxygenation. Glycosylated xanthones (6) is more active than those that are not (1–5). 6 is more active than 3 and 2 is more active than 5. Antioxidant capacity of xanthones does not benefit from free hydroxyl group(s) located only at either C-1 or C-8 alone. Interestingly, 6 and 3 of the isolated compounds showed highest radical scavenging activities, which can be explained by the present of ortho-dihydroxy groups in their molecular structure [33–35]. The present study revealed that the hydroxyl group has strongest influence antioxidant activities, while methoxyl group has a weak influence (Fig. 1B and C). Cancer diseases are one of the main causes of death worldwide. The discovery of new molecules from natural origin is a global trending currently for the less toxicity of natural products [36]. The anticancer properties of aerial parts methanol extract of S. corymbosa on HeLa (human cervical cancer), HepG2 cells (Liver-Human hepatocellular carcinoma) and Neuroblastoma (IMR32) cell lines have already been reported by Mahendran and Narmatha Bai [7]. MTT assay is most widely used to determine the cytotoxic potential of medicinal agents and other toxic materials. The reduction of yellow MTT to purple colored formazan takes place only when mitochondrial reductase enzymes are active and therefore the conversion can be directly related to number of viable cells. The cytotoxic effect of xanthone compounds after 48h of treatment in HeLa, HepG2, IMR32 and NIH 3T3 cells was observed. The results are presented in Table 2. Among these compounds, 1,2-dihydroxy-6-methoxyxanthone-8-O-β-d-xylopyranosyl (6) was found to have significant anti-proliferative activity. The presence of ortho-dihydroxy groups as well as hydroxyl groups in their basic skeleton of xnathones is responsible of their wide range of activities [37,38]. It was shown that their cytotoxic activity could increase with the number and position of these groups in their structure [39,40]. This can explain to a certain degree the interesting antiproliferative activity of the ortho-dihydroxy groups (3, 6) (Fig. 1b) and non ortho-dihydroxy group (1, 2, 4 and 5) reported in the present work. Different responses of xanthones by different cell lines have also been reported by Matsumoto et al. [41] who found that α-mangostin induced caspase-independent apoptosis via the mitochondrial pathway in colon cancer cells. In addition, gaudichaudione A, a cytotoxic xanthone, induced mitochondrial destabilization [42]. Therefore, although xanthones induced apoptosis via different pathways in different cancer cell types, in the present study, support that xanthones preferentially target the mitochondria for apoptosis induction.