nach oben

Erschienen in:

12.09.2019 | Original Paper

Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

verfasst von: Saif Ahmad, Shah Alam Khan, Adam Kindelin, Tasha Mohseni, Kanchan Bhatia, Md Nasrul Hoda, Andrew F. Ducruet

Erschienen in: NeuroMolecular Medicine | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Brain endothelial cells play an important role in maintaining blood flow homeostasis in the brain. Cerebral ischemia is a major cause of endothelial dysfunction which can disrupt the blood–brain barrier (BBB). Oxygen–glucose deprivation (OGD)/reperfusion promote cell death and BBB breakdown in brain endothelial cells. Acetyl-11-keto-β-boswellic acid (AKBA), a biologically active phytoconstituent of the medicinal plant Boswellia serrata, has been shown to be protective against various inflammatory diseases as well as ischemic brain injury. The molecular mechanisms underlying these beneficial characteristics of AKBA are poorly understood. We subjected bEND.3 cells to OGD/reperfusion to investigate the protective role of AKBA in this model. We found that AKBA treatment attenuated endothelial cell death and oxidative stress assessed by means of TUNEL assay, cleaved-caspase-3, and dihydroethidium (DHE) staining. Furthermore, OGD downregulated tight junction proteins ZO-1 and Occludin levels, and increased the expressions of inflammatory cytokines TNF-α, ICAM-1, and complement C3a receptor (C3aR). We also noticed the increased phosphorylation of ERK 1/2 in bEND.3 cells in OGD group. AKBA treatment significantly attenuated expression levels of these inflammatory proteins and prevented the degradation of ZO-1 and Occludin following OGD. In conclusion, AKBA treatment provides protection against endothelial cell dysfunction following OGD by attenuating oxidative stress and inflammation.

Ahmad, S., Fatteh, N., El-Sherbiny, N. M., Naime, M., Ibrahim, A. S., El-Sherbini, A. M., et al. (2013). Potential role of A2A adenosine receptor in traumatic optic neuropathy. Journal of Neuroimmunology,264(1–2), 54–64. https://doi.org/10.1016/j.jneuroim.2013.09.015.CrossRefPubMed

Ahmad, S., Kindelin, A., Khan, S. A., Ahmed, M., Hoda, M. N., Bhatia, K., et al. (2019). C3a receptor inhibition protects brain endothelial cells against oxygen-glucose deprivation/reperfusion. Experimental Neurobiology,28(2), 216–228. https://doi.org/10.5607/en.2019.28.2.216.CrossRefPubMedPubMedCentral

Alluri, H., Anasooya Shaji, C., Davis, M. L., & Tharakan, B. (2015). Oxygen-glucose deprivation and reoxygenation as an in vitro ischemia-reperfusion injury model for studying blood–brain barrier dysfunction. Journal of Visualized Experiments. https://doi.org/10.3791/52699.CrossRefPubMed

Alluri, H., Stagg, H. W., Wilson, R. L., Clayton, R. P., Sawant, D. A., Koneru, M., et al. (2014). Reactive oxygen species-caspase-3 relationship in mediating blood–brain barrier endothelial cell hyperpermeability following oxygen-glucose deprivation and reoxygenation. Microcirculation,21(2), 187–195. https://doi.org/10.1111/micc.12110.CrossRefPubMed

Arumugam, T. V., Woodruff, T. M., Lathia, J. D., Selvaraj, P. K., Mattson, M. P., & Taylor, S. M. (2009). Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience,158(3), 1074–1089. https://doi.org/10.1016/j.neuroscience.2008.07.015.CrossRefPubMed

Beghelli, D., Isani, G., Roncada, P., Andreani, G., Bistoni, O., Bertocchi, M., et al. (2017). Antioxidant and ex vivo immune system regulatory properties of Boswellia serrata extracts. Oxidative Medicine and Cellular Longevity,2017, 7468064. https://doi.org/10.1155/2017/7468064.CrossRefPubMedPubMedCentral

Bertocchi, M., Isani, G., Medici, F., Andreani, G., Tubon Usca, I., Roncada, P., et al. (2018). Anti-inflammatory activity of Boswellia serrata extracts: An in vitro study on porcine aortic endothelial cells. Oxidative Medicine and Cellular Longevity,2018, 2504305. https://doi.org/10.1155/2018/2504305.CrossRefPubMedPubMedCentral

Chen, S. L., Deng, Y. Y., Wang, Q. S., Han, Y. L., Jiang, W. Q., Fang, M., et al. (2017). Hypertonic saline protects brain endothelial cells against hypoxia correlated to the levels of epidermal growth factor receptor and interleukin-1beta. Medicine (Baltimore),96(1), e5786. https://doi.org/10.1097/MD.0000000000005786.CrossRef

Cuaz-Perolin, C., Billiet, L., Bauge, E., Copin, C., Scott-Algara, D., Genze, F., et al. (2008). Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-β-boswellic acid in LPS-challenged ApoE-/- mice. Arteriosclerosis, Thrombosis, and Vascular Biology,28(2), 272–277. https://doi.org/10.1161/ATVBAHA.107.155606.CrossRefPubMed

Ding, Y., Chen, M., Wang, M., Wang, M., Zhang, T., Park, J., et al. (2014). Neuroprotection by acetyl-11-keto-β-boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Scientific Reports,4, 7002. https://doi.org/10.1038/srep07002.CrossRefPubMedPubMedCentral

Ding, Y., Qiao, Y., Wang, M., Zhang, H., Li, L., Zhang, Y., et al. (2016). Enhanced neuroprotection of acetyl-11-keto-β-boswellic acid (AKBA)-loaded O-carboxymethyl chitosan nanoparticles through antioxidant and anti-inflammatory pathways. Molecular Neurobiology,53(6), 3842–3853. https://doi.org/10.1007/s12035-015-9333-9.CrossRefPubMed

Ducruet, A. F., Zacharia, B. E., Sosunov, S. A., Gigante, P. R., Yeh, M. L., Gorski, J. W., et al. (2012). Complement inhibition promotes endogenous neurogenesis and sustained anti-inflammatory neuroprotection following reperfused stroke. PLoS ONE,7(6), e38664. https://doi.org/10.1371/journal.pone.0038664.CrossRefPubMedPubMedCentral

Eltzschig, H. K., & Eckle, T. (2011). Ischemia and reperfusion—From mechanism to translation. Nature Medicine,17(11), 1391–1401. https://doi.org/10.1038/nm.2507.CrossRefPubMed

Frey, R. S., Ushio-Fukai, M., & Malik, A. B. (2009). NADPH oxidase-dependent signaling in endothelial cells: Role in physiology and pathophysiology. Antioxidants & Redox Signaling,11(4), 791–810. https://doi.org/10.1089/ARS.2008.2220.CrossRef

Guo, S., Stins, M., Ning, M., & Lo, E. H. (2010). Amelioration of inflammation and cytotoxicity by dipyridamole in brain endothelial cells. Cerebrovascular Diseases,30(3), 290–296. https://doi.org/10.1159/000319072.CrossRefPubMed

Huang, S. H., Wang, L., Chi, F., Wu, C. H., Cao, H., Zhang, A., et al. (2013). Circulating brain microvascular endothelial cells (cBMECs) as potential biomarkers of the blood–brain barrier disorders caused by microbial and non-microbial factors. PLoS ONE,8(4), e62164. https://doi.org/10.1371/journal.pone.0062164.CrossRefPubMedPubMedCentral

Jiao, H., Wang, Z., Liu, Y., Wang, P., & Xue, Y. (2011). Specific role of tight junction proteins claudin-5, occludin, and ZO-1 of the blood–brain barrier in a focal cerebral ischemic insult. Journal of Molecular Neuroscience,44(2), 130–139. https://doi.org/10.1007/s12031-011-9496-4.CrossRefPubMed

Khatri, R., McKinney, A. M., Swenson, B., & Janardhan, V. (2012). Blood–brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke. Neurology,79(13 Suppl 1), S52–S57. https://doi.org/10.1212/WNL.0b013e3182697e70.CrossRefPubMed

Liao, L. X., Zhao, M. B., Dong, X., Jiang, Y., Zeng, K. W., & Tu, P. F. (2016). TDB protects vascular endothelial cells against oxygen-glucose deprivation/reperfusion-induced injury by targeting miR-34a to increase Bcl-2 expression. Scientific Reports,6, 37959. https://doi.org/10.1038/srep37959.CrossRefPubMedPubMedCentral

Ma, X., Zhang, H., Pan, Q., Zhao, Y., Chen, J., Zhao, B., et al. (2013). Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline. PLoS ONE,8(12), e82604. https://doi.org/10.1371/journal.pone.0082604.CrossRefPubMedPubMedCentral

Narasimhan, P., Liu, J., Song, Y. S., Massengale, J. L., & Chan, P. H. (2009). VEGF Stimulates the ERK 1/2 signaling pathway and apoptosis in cerebral endothelial cells after ischemic conditions. Stroke,40(4), 1467–1473. https://doi.org/10.1161/STROKEAHA.108.534644.CrossRefPubMedPubMedCentral

Ni, Y., Teng, T., Li, R., Simonyi, A., Sun, G. Y., & Lee, J. C. (2017). TNFalpha alters occludin and cerebral endothelial permeability: Role of p38MAPK. PLoS ONE,12(2), e0170346. https://doi.org/10.1371/journal.pone.0170346.CrossRefPubMedPubMedCentral

Pan, R., Yu, K., Weatherwax, T., Zheng, H., Liu, W., & Liu, K. J. (2017). Blood occludin level as a potential biomarker for early blood brain barrier damage following ischemic stroke. Scientific Reports,7, 40331. https://doi.org/10.1038/srep40331.CrossRefPubMedPubMedCentral

Park, Y. S., Lee, J. H., Bondar, J., Harwalkar, J. A., Safayhi, H., & Golubic, M. (2002). Cytotoxic action of acetyl-11-keto-beta-boswellic acid (AKBA) on meningioma cells. Planta Medica,68(5), 397–401. https://doi.org/10.1055/s-2002-32090.CrossRefPubMed

Roy, S., Khanna, S., Krishnaraju, A. V., Subbaraju, G. V., Yasmin, T., Bagchi, D., et al. (2006). Regulation of vascular responses to inflammation: inducible matrix metalloproteinase-3 expression in human microvascular endothelial cells is sensitive to antiinflammatory Boswellia. Antioxidants & Redox Signaling,8(3–4), 653–660. https://doi.org/10.1089/ars.2006.8.653.CrossRef

Sadeghnia, H. R., Arjmand, F., & Ghorbani, A. (2017). Neuroprotective effect of Boswellia serrata and its active constituent acetyl-11-keto-β-boswellic acid against oxygen-glucose-serum deprivation-induced cell injury. Acta Poloniae Pharmaceutica,74(3), 911–920.PubMed

Salvador, E., Burek, M., & Forster, C. Y. (2015). Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade. Frontiers in Cellular Neuroscience,9, 323. https://doi.org/10.3389/fncel.2015.00323.CrossRefPubMedPubMedCentral

Shang, P., Liu, W., Liu, T., Zhang, Y., Mu, F., Zhu, Z., et al. (2016). Acetyl-11-keto-beta-boswellic acid attenuates prooxidant and profibrotic mechanisms involving transforming growth factor-beta1, and improves vascular remodeling in spontaneously hypertensive rats. Scientific Reports,6, 39809. https://doi.org/10.1038/srep39809.CrossRefPubMedPubMedCentral

Sidney, S., Sorel, M. E., Quesenberry, C. P., Jaffe, M. G., Solomon, M. D., Nguyen-Huynh, M. N., et al. (2018). Comparative trends in heart disease, stroke, and all-cause mortality in the United States and a large integrated healthcare delivery system. American Journal of Medicine. https://doi.org/10.1016/j.amjmed.2018.02.014.CrossRefPubMed

Strazielle, N., & Ghersi-Egea, J. F. (2013). Physiology of blood–brain interfaces in relation to brain disposition of small compounds and macromolecules. Molecular Pharmaceutics,10(5), 1473–1491. https://doi.org/10.1021/mp300518e.CrossRefPubMed

Takada, Y., Ichikawa, H., Badmaev, V., & Aggarwal, B. B. (2006). Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression. The Journal of Immunology,176(5), 3127–3140.CrossRef

Tornabene, E., & Brodin, B. (2016). Stroke and drug delivery—In vitro models of the ischemic blood–brain barrier. Journal of Pharmaceutical Sciences,105(2), 398–405. https://doi.org/10.1016/j.xphs.2015.11.041.CrossRefPubMed

Van Beek, J., Bernaudin, M., Petit, E., Gasque, P., Nouvelot, A., MacKenzie, E. T., et al. (2000). Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal cerebral ischemia in the mouse. Experimental Neurology,161(1), 373–382. https://doi.org/10.1006/exnr.1999.7273.CrossRefPubMed

Wang, M., Chen, M., Ding, Y., Zhu, Z., Zhang, Y., Wei, P., et al. (2015). Pretreatment with beta-boswellic acid improves blood stasis induced endothelial dysfunction: Role of eNOS activation. Scientific Reports,5, 15357. https://doi.org/10.1038/srep15357.CrossRefPubMedPubMedCentral

Watters, O., & O’Connor, J. J. (2011). A role for tumor necrosis factor-alpha in ischemia and ischemic preconditioning. Journal of Neuroinflammation,8, 87. https://doi.org/10.1186/1742-2094-8-87.CrossRefPubMedPubMedCentral

Writing Group, M, Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., et al. (2016). Executive summary: Heart disease and stroke statistics—2016 update: A report from the American Heart Association. Circulation,133(4), 447–454. https://doi.org/10.1161/CIR.0000000000000366.CrossRef

Wu, F., Zou, Q., Ding, X., Shi, D., Zhu, X., Hu, W., et al. (2016). Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. Journal of Neuroinflammation,13, 23. https://doi.org/10.1186/s12974-016-0485-y.CrossRefPubMedPubMedCentral

Yin, K. J., Chen, S. D., Lee, J. M., Xu, J., & Hsu, C. Y. (2002). ATM gene regulates oxygen-glucose deprivation-induced nuclear factor-kappaB DNA-binding activity and downstream apoptotic cascade in mouse cerebrovascular endothelial cells. Stroke,33(10), 2471–2477.CrossRef

Zhao, X. J., Larkin, T. M., Lauver, M. A., Ahmad, S., & Ducruet, A. F. (2017). Tissue plasminogen activator mediates deleterious complement cascade activation in stroke. PLoS ONE,12(7), e0180822. https://doi.org/10.1371/journal.pone.0180822.CrossRefPubMedPubMedCentral

Zhou, P., Lu, S., Luo, Y., Wang, S., Yang, K., Zhai, Y., et al. (2017). Attenuation of TNF-alpha-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-kappaB, JNK and p38 signaling pathways. Frontiers in Pharmacology,8, 464. https://doi.org/10.3389/fphar.2017.00464.CrossRefPubMedPubMedCentral

Titel: Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion
verfasst von: Saif Ahmad
Shah Alam Khan
Adam Kindelin
Tasha Mohseni
Kanchan Bhatia
Md Nasrul Hoda
Andrew F. Ducruet
Publikationsdatum: 12.09.2019
Verlag: Springer US
Erschienen in: NeuroMolecular Medicine / Ausgabe 4/2019
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-019-08569-z

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

25.04.2024 | Hypotonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2019

Measuring Respiration in Isolated Murine Brain Mitochondria: Implications for Mechanistic Stroke Studies

Blockade of Acid-Sensing Ion Channels Attenuates Recurrent Hypoglycemia-Induced Potentiation of Ischemic Brain Damage in Treated Diabetic Rats

The Role of Complement C3a Receptor in Stroke

Blood Biomarkers for Stroke Diagnosis and Management

Cerebral Amyloid Angiopathy, Alzheimer’s Disease and MicroRNA: miRNA as Diagnostic Biomarkers and Potential Therapeutic Targets

High-Mobility Group Box-1-Induced Angiogenesis After Indirect Bypass Surgery in a Chronic Cerebral Hypoperfusion Model

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie