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Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.

Xiao AJ, Chen W, Xu B, Liu R, Turlova E, Barszczyk A, Sun CL, Liu L, Deurloo M, Wang GL, Feng ZP, Sun HS - Mar Drugs (2014)

Bottom Line: Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects.Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult.In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. xaj527@163.com.

ABSTRACT
Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.

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Effects of xyloketal B on apoptosis in neonatal HI brain injury. (A) Mouse brain coronal section model image. Blue box: TUNEL staining area; (B) Apoptotic cells detected by the TUNEL assay. Images showed representative TUNEL-positive cells (red) of sham, HI only and xyloketal B treated brains. Scale bar corresponds to 50 µm; (C) Quantitative analysis of TUNEL-positive cells of sham, HI only and xyloketal B treated brains. The TUNEL positive cells were counted per ×10 field in the penumbra area. Xyloketal B pretreatment reduced the number of TUNEL-positive cells in comparison to the HI only group in 3 days after HI. *: p < 0.05, n = 3. Sham: Sham-surgery group; HI: Hypoxic-ischemic injury group; Xyl B + HI: hypoxic-ischemic injury plus pretreatment with xyloketal B group.
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marinedrugs-13-00029-f005: Effects of xyloketal B on apoptosis in neonatal HI brain injury. (A) Mouse brain coronal section model image. Blue box: TUNEL staining area; (B) Apoptotic cells detected by the TUNEL assay. Images showed representative TUNEL-positive cells (red) of sham, HI only and xyloketal B treated brains. Scale bar corresponds to 50 µm; (C) Quantitative analysis of TUNEL-positive cells of sham, HI only and xyloketal B treated brains. The TUNEL positive cells were counted per ×10 field in the penumbra area. Xyloketal B pretreatment reduced the number of TUNEL-positive cells in comparison to the HI only group in 3 days after HI. *: p < 0.05, n = 3. Sham: Sham-surgery group; HI: Hypoxic-ischemic injury group; Xyl B + HI: hypoxic-ischemic injury plus pretreatment with xyloketal B group.

Mentions: We next investigated the potential mechanisms underlying the neuroprotective effects of xyloketal B. We first asked whether xyloketal B reduced HI-induced apoptosis. Fragmentation of nuclear DNA in the penumbral area in the ipsilateral brain (Figure 5A) was measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining 3 days after HI insult (Figure 5B). A count of TUNEL-positive cells from the ipsilateral hemisphere showed that the xyloketal B pre-treatment significantly decreased the number of TUNEL-positive cells (Xyl B + HI group: 35.50 ± 3.80 TUNEL positive cells per × 10 field. p < 0.05), compared to the vehicle-treated HI group (189.17 ± 8.99 TUNEL positive cells per × 10 field.), while the sham group had 16.67 ± 2.59 TUNEL positive cells per × 10 field (Figure 5C). This result indicates that xyloketal B pre-treatment inhibited HI-induced apoptosis.


Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.

Xiao AJ, Chen W, Xu B, Liu R, Turlova E, Barszczyk A, Sun CL, Liu L, Deurloo M, Wang GL, Feng ZP, Sun HS - Mar Drugs (2014)

Effects of xyloketal B on apoptosis in neonatal HI brain injury. (A) Mouse brain coronal section model image. Blue box: TUNEL staining area; (B) Apoptotic cells detected by the TUNEL assay. Images showed representative TUNEL-positive cells (red) of sham, HI only and xyloketal B treated brains. Scale bar corresponds to 50 µm; (C) Quantitative analysis of TUNEL-positive cells of sham, HI only and xyloketal B treated brains. The TUNEL positive cells were counted per ×10 field in the penumbra area. Xyloketal B pretreatment reduced the number of TUNEL-positive cells in comparison to the HI only group in 3 days after HI. *: p < 0.05, n = 3. Sham: Sham-surgery group; HI: Hypoxic-ischemic injury group; Xyl B + HI: hypoxic-ischemic injury plus pretreatment with xyloketal B group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4306923&req=5

marinedrugs-13-00029-f005: Effects of xyloketal B on apoptosis in neonatal HI brain injury. (A) Mouse brain coronal section model image. Blue box: TUNEL staining area; (B) Apoptotic cells detected by the TUNEL assay. Images showed representative TUNEL-positive cells (red) of sham, HI only and xyloketal B treated brains. Scale bar corresponds to 50 µm; (C) Quantitative analysis of TUNEL-positive cells of sham, HI only and xyloketal B treated brains. The TUNEL positive cells were counted per ×10 field in the penumbra area. Xyloketal B pretreatment reduced the number of TUNEL-positive cells in comparison to the HI only group in 3 days after HI. *: p < 0.05, n = 3. Sham: Sham-surgery group; HI: Hypoxic-ischemic injury group; Xyl B + HI: hypoxic-ischemic injury plus pretreatment with xyloketal B group.
Mentions: We next investigated the potential mechanisms underlying the neuroprotective effects of xyloketal B. We first asked whether xyloketal B reduced HI-induced apoptosis. Fragmentation of nuclear DNA in the penumbral area in the ipsilateral brain (Figure 5A) was measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining 3 days after HI insult (Figure 5B). A count of TUNEL-positive cells from the ipsilateral hemisphere showed that the xyloketal B pre-treatment significantly decreased the number of TUNEL-positive cells (Xyl B + HI group: 35.50 ± 3.80 TUNEL positive cells per × 10 field. p < 0.05), compared to the vehicle-treated HI group (189.17 ± 8.99 TUNEL positive cells per × 10 field.), while the sham group had 16.67 ± 2.59 TUNEL positive cells per × 10 field (Figure 5C). This result indicates that xyloketal B pre-treatment inhibited HI-induced apoptosis.

Bottom Line: Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects.Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult.In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. xaj527@163.com.

ABSTRACT
Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.

Show MeSH
Related in: MedlinePlus