Alpha-Mangostin Attenuation of Hyperglycemia-Induced Ocular Hypoperfusion and Blood Retinal Barrier Leakage in the Early Stage of Type 2 Diabetes Rats

The present study examined effects of alpha-mangostin ( -MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without -MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of -MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The -MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-, and VEGF than the untreated group. Interestingly, -MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, -MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities

Anticariogenic Activity of Garcinone B from Garcinia mangostana

AbstractObjectives: The aim of the present study was to evaluate anticariogenic activity of garcinoneB isolated from Garcinia mangostana Linn. pericarp extract.Materials and Methods: Garcinone B was evaluated for their antibacterial activity againstcariogenic bacteria by Kirby-Bauer disk diffusion method. Cariogenic bacteria tested in this studywere Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, Lacticaseibacillus caseiand standard strains (S. mutans ATCC 25175). Time-killed assay and hydrophobicitywere also determined.Results: We found that garcinone B was effective for all bacterial tests. It exhibited strongantibacterial activity against cariogenic bacteria with the range of MIC value of 0.25–0.5 μg/ml andzone of inhibition of 6-14 mm. The garcinone B exhibited strong antibacterial activity against mutans Streptococci and Lactobacillus with MIC value of 0.25 μg/ml and 0.5 μg/ml, respectively. In thetime-kill curve, garcinone B was bactericidal against S. mutans ATCC 25175 at the concentration of1 μg/ml, and completely killed the bacteria within 1 h at the concentration of 2 μg/ml. A decreasedcell surface hydrophobicity of S. mutans ATCC 25175 induced by garcinone B was found.Conclusions: These findings reveal that garcinone B has potential for antibacterial activityagainst cariogenic microorganisms. In addition, garcinone B has potential candidate for alternativechemotherapeutic approaches to dental caries.Keyword: Antibacteria, Garcinone B, Lactobacillus, Mangosteen, S. Mutans.SWU Dent J. 2021;14(2):25-34.

สารประกอบไตรเทอร์พีนจากรากพุทราไทย (TRITERPENES FROM THE ROOT OF THAI ZIZIPHUS MAURITIANA)

การศึกษาองค์ประกอบทางเคมีจากรากพุทราไทย สามารถแยกสารประกอบไตรเทอร์พีน 7 ชนิด โดยเป็นไตรเทอร์พีน ชนิด ceanothane 4 ชนิด : zizyberenalic acid, ceanothic acid, epiceanothic acid และ 24-hydroxyceanothic acid และเป็นไตรเทอร์พีน ชนิด lupane 3 ชนิด : lupeol, betulin และ betulinic acid โครงสร้างและสเตอริโอเคมีของสารทราบได้จากการวิเคราะห์ข้อมูลทางสเปกโทรสโคปี โดยใช้เทคนิค NMR เป็นส่วนใหญ่ และโดยการเปรียบเทียบข้อมูลกับสารประกอบอื่นที่มีรายงานไว้แล้ว งานวิจัยนี้เป็นครั้งแรกของรายงานการพบสารประกอบไตรเทอร์พีนชนิด ceanothane ในพุทราคำสำคัญ: พุทรา Ziziphus mauritiana Rhamnaceae ไตรเทอร์พีนFrom the dried root of Thai Ziziphus mauritiana Lam. (Rhamnaceae), four ceanothane-type: zizyberenalic acid, ceanothic acid, epiceanothic acid and 24-hydroxyceanothic acid, together with three lupane-type triterpenes: lupeol, betulin and betulinic acid were isolated. Their structures were elucidated and stereochemical assignments were performed by extensive NMR spectroscopic data analysis and by comparison of their physical data with the reported values. This is the first report on the isolation of the ceanothane-type triterpenes from this plant species.Keywords: Ziziphus mauritiana, Rhamnaceae, triterpen

Alpha-Mangostin Attenuation of Hyperglycemia-Induced Ocular Hypoperfusion and Blood Retinal Barrier Leakage in the Early Stage of Type 2 Diabetes Rats

The present study examined effects of alpha-mangostin (α-MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities

Effects of α-mangostin on apoptosis induction of human colon cancer

AIM: To investigate the effect of α-mangostin on the growth and apoptosis induction of human colon cancer cells

Stem Extract from Momordica cochinchinensis Induces Apoptosis in Chemoresistant Human Prostate Cancer Cells (PC-3)

Natural compounds have been recognized as valuable sources for anticancer drug development. In this work, different parts from Momordica cochinchinensis Spreng were selected to perform cytotoxic screening against human prostate cancer (PC-3) cells. Chromatographic separation and purification were performed for the main constituents of the most effective extract. The content of the fatty acids was determined by Gas Chromatography-Flame Ionization Detector (GC–FID). Chemical structural elucidation was performed by spectroscopic means. For the mechanism of the apoptotic induction of the most effective extract, the characteristics were evaluated by Hoechst 33342 staining, sub-G1 peak analysis, JC-1 staining, and Western blotting. As a result, extracts from different parts of M. cochinchinensis significantly inhibited cancer cell viability. The most effective stem extract induced apoptosis in PC-3 cells by causing nuclear fragmentation, increasing the sub-G1 peak, and changing the mitochondrial membrane potential. Additionally, the stem extract increased the pro-apoptotic (caspase-3 and Noxa) mediators while decreasing the anti-apoptotic (Bcl-xL and Mcl-1) mediators. The main constituents of the stem extract are α-spinasterol and ligballinol, as well as some fatty acids. Our results demonstrated that the stem extract of M. cochinchinensis has cytotoxic and apoptotic effects in PC-3 cells. These results provide basic knowledge for developing antiproliferative agents for prostate cancer in the future

Synthesis and preliminary evaluation of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones as angiogenesis inhibitors

Sunitinib (Sutent®) is a receptor tyrosine kinase (RTK) and angiogenesis inhibitor approved for the treatment of renal cell carcinomas, gastrointestinal stromal tumours and pancreatic neuroendocrine tumours. A key structural motif retained throughout medicinal chemistry efforts during sunitinib\u27s development was the indoline-2-one group. In the search for new anti-angiogenic scaffolds, we previously reported that non-indoline-2-one-based derivatives of semaxanib (SU5416, a structurally simpler sunitinib predecessor that underwent Phase III trials) are active as angiogenesis inhibitors, indicating that the group is not essential for activity. This Letter describes the synthesis and structure-activity relationships of another class of non-indoline-2-one angiogenesis inhibitors related to sunitinib/semaxanib; the 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones. A focussed library of 19 analogues was prepared using a simple novel process, wherein commercially available substituted arylacetic acids activated with an amide coupling reagent (HBTU) were reacted with the potassium salt of 3,5-dimethyl-1H-pyrrole-2-carbaldehyde in one-pot. Screening of the library using a cell-based endothelial tube formation assay identified 6 compounds with anti-angiogenesis activity. Two of the compounds were advanced to the more physiologically relevant rat aortic ring assay, where they showed similar inhibitory effects to semaxanib at 10 μg/mL, confirming that 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones represent a new class of angiogenesis inhibitors

Unexpected synthesis of 3-imino-2-(pyrrol-2-yl) isatogen derivatives affords facile access to a 2-pyrrolyl isatogen

2-Aryl isatogens and their 3-imino derivatives have been extensively studied but to date there have been no reported variants carrying pyrrolyl substituents at the 2-position. This study describes the unexpected synthesis of two novel 3-imino-2-(pyrrol-2-yl) isatogen derivatives upon attempted amide couplings with (E)- or (Z)-3-(3,5-dimethyl-1H-pyrrol-2-yl)-2-(2-nitrophenyl)acrylic acids and p-phenylenediamines in the presence of uronium-based coupling reagents. Imine hydrolysis of one derivative under mild acid conditions afforded a 2-pyrrolyl isatogen in high yield. The compound showed potent in vitro antiplasmodial activity against Plasmodium falciparumN. Kirk and G. Sansom acknowledge financial support from the Australian Government for Australian Postgraduate Awards. P. Sudta and S. Suksamrarn acknowledge financial support from the Thailand Research Fund through the Royal Golden Jubilee PhD Program. M. Kelso acknowledges partial financial support from the University of Wollongong