Pharmacological Properties of CDBT in Hypoxia-induced Neuronal Cell Injury and Their Underlying Mechanisms
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives: This study aimed to reveal the pharmacological properties of the newly prescribed herbal mixture, Chenmadansam- gamibokhap-tang (CDBT), against hypoxia-induced neuronal cell injury (especially mouse hippocampal neuronal cell line, HT-22 cells) and their corresponding mechanisms. Methods: A cell-based in vitro experiment, in which a hypoxia condition induced neuronal cell death, was performed. Various concentrations of the CDBT were pre-treated to the HT-22 cells for 4 h before 18 h in the hypoxia chamber. The glial cell BV-2 cells were stimulated with IFNγ and LSP to produce inflammatory cytokines and reactive oxygen species. When the neuronal HT-22 cells were treated with this culture solution, the drug efficacy against neuronal cell death was examined. Results: CDBT showed cytotoxicity in the normal condition of HT-22 cells at a dose of 125 μg/mL and showed a protective effect against hypoxia-induced neuronal cell death at a dose of 31.3 μg/mL. CDBT prevented hypoxia-induced neuronal cell death in a dose-dependent manner in the HT-22 cells by regulating HIF1α and cell death signaling. CDBT prevented neuronal cell death signals and DNA fragmentation due to the hypoxia condition. CDBT significantly reduced cellular oxidation, cell death signals, and caspase-3 activities due to microglial cell activations. Moreover, CDBT significantly ameliorated LPS-induced BV-2 cell activation and evoked cellular oxidation through the recovery of redox homeostasis. Conclusions: CDBT cam be considered as a vital therapeutic agent against neuronal cell deaths. Further studies are required to reveal the other functions of CDBT in vivo or in the clinical field.
Abstract
Objectives: This study aimed to reveal the pharmacological properties of the newly prescribed herbal mixture, Chenmadansam- gamibokhap-tang (CDBT), against hypoxia-induced neuronal cell injury (especially mouse hippocampal neuronal cell line, HT-22 cells) and their corresponding mechanisms. Methods: A cell-based in vitro experiment, in which a hypoxia condition induced neuronal cell death, was performed. Various concentrations of the CDBT were pre-treated to the HT-22 cells for 4 h before 18 h in the hypoxia chamber. The glial cell BV-2 cells were stimulated with IFNγ and LSP to produce inflammatory cytokines and reactive oxygen species. When the neuronal HT-22 cells were treated with this culture solution, the drug efficacy against neuronal cell death was examined. Results: CDBT showed cytotoxicity in the normal condition of HT-22 cells at a dose of 125 μg/mL and showed a protective effect against hypoxia-induced neuronal cell death at a dose of 31.3 μg/mL. CDBT prevented hypoxia-induced neuronal cell death in a dose-dependent manner in the HT-22 cells by regulating HIF1α and cell death signaling. CDBT prevented neuronal cell death signals and DNA fragmentation due to the hypoxia condition. CDBT significantly reduced cellular oxidation, cell death signals, and caspase-3 activities due to microglial cell activations. Moreover, CDBT significantly ameliorated LPS-induced BV-2 cell activation and evoked cellular oxidation through the recovery of redox homeostasis. Conclusions: CDBT cam be considered as a vital therapeutic agent against neuronal cell deaths. Further studies are required to reveal the other functions of CDBT in vivo or in the clinical field.
참고문헌 (45)
- Winek K, "Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke", Stroke, 47(5), pp.1354~1363 (2016)
- Donnan GA, "Stroke", Lancet, 371(9624), pp.1612~1623 (2008)
- Paraskevas KI, "Secondary prevention of stroke", Lancet, 372(9643), pp.1036~ (2008)
- Lee JC, "Aging and Stroke", Kor J Gerontol, 16, pp.11~16 (2006)
- Li P, "An Antagomir to MicroRNA-106b-5p Ameliorates Cerebral Ischemia and Reperfusion Injury in Rats Via Inhibiting Apoptosis and Oxidative Stress", Mol Neurobiol, 54(4), pp.2901~2921 (2017)
- Genovese T, "Modulation of NADPH oxidase activation in cerebral ischemia", reperfusion injury in rats, 2011, pp.1372, 92~102
- Zhou L, "Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and-8", Neuroscience, 288, pp.105~111 (2015)
- Chen S, "Gasdermin Family:a Promising Therapeutic Target for Stroke", Transl Stroke Res, 9(6), pp.555~563 (2018)
- Puig B, "Molecular Communication of a Dying Neuron in Stroke", Int J Mol Sci, 19(9), pp.2834~ (2018)
- Mao XY, "Huperzine A Alleviates Oxidative Glutamate Toxicity in Hippocampal HT22 Cells via Activating BDNF", TrkB-Dependent PI3K, mTOR Signaling Pathway, pp.Cell Mol Neurobiol, 2016[DOI]
- Song J, "Glutathione suppresses cerebral infarct volume and cell death after ischemic injury : involvement of FOXO3 inactivation and Bcl2 expression", Oxid Med Cell Longev, 2015, pp.426069~ (2015)
- Xu Y, "YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCdelta", Drp1-Mediated Excessive Mitochondrial Fission, 2017, pp.2017, 1832093~
- Nationwide College of Korean Medicine Faculty Council of Cardiology Internal Medicine, "Cardiovascular and Neurological Medicine in Korean Medicine I", pp.404~415 (2010), Goonja
- Chai L, "Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin injection, upregulate neurotrophins synthesis and release in hypoxia", reoxygenation rat astrocytes, 2013, pp.150(1), 100~107
- Tsai HD, "Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1", 6, 2016, pp.18(3), 274~282
- Zhang Q, "Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia", ischemia, 2012, pp.99(3), 311~323
- Jang JH, "Neuropharmacological potential of gastrodia elata blume and its components", Evid Based Complement Alternat Med, 2015, pp.309261~ (2015)
- 정래승, "Antioxidant, Antibiofilm, and Anticholinesterase Activities of Fermented Deodeok (Codonopsis lanceolata) Extracts", Food Science and Biotechnology, 21(5), pp.1413~1419 (2012), 한국식품과학회[DOI]
- Thiyagarajan M, "Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats", Life sci, 74(8), pp.969~985 (2004)
- Wang YJ, "Protective effect of tanshinone IIA on neurocyte apoptosis in rats with hypoxic ischemic brain damage and its mechanism", Chin Pharmaco Bull, 31(3), pp.443~444 (2015)
- Li Y, "Effect of astragalus injection on the expression of VEGF and VEGF2 in rats with cerebral ischemia reperfusion injury", Chin Integrat Med Cardio-, 2016, pp.14(1), 25~28
- Shin N, "Uncoupled Endothelial Nitric Oxide Synthase Enhances p-Tau in Chronic Traumatic Encephalopathy Mouse Model", Antioxid Redox Signal, 30(13), pp.1601~1620 (2019)
- nitrate in biological fluids, "Anal Biochem", 1982, 131~138
- Kamal AA, "Plasma lipid peroxides among workers exposed to silica or asbestos dusts", Environ Res, 49(2), pp.173~180 (1989)
- Ellman GL, "Tissue sulfhydryl groups", Arch Biochem Biophys, 82(1), pp.70~77 (1959)
- Wheeler CR, "Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity", Anal Biochem, 184(2), pp.193~199 (1990)
- Chhunchha B, "Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells(HT22)by controlling Prdx6 and NF-kappaB regulation", Am J Physiol Cell Physiol, 304(7), pp.636~655 (2013)
- O'Donnell MJ, "Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries(the INTERSTROKE study) : a case-control study", Lancet, 376(9735), pp.112~123 (2010)
- von Sarnowski B, "Lifestyle risk factors for ischemic stroke and transient ischemic attack in young adults in the Stroke in Young Fabry Patients study", Stroke, 44(1), pp.119~125 (2013)
- Alturkustani M, "Pathology of toxic leucoencephalopathy in drug abuse supports hypoxic-ischemic pathophysiology", etiology, 2017, pp.37(4), 321~328
- Galinsky R, "Complex interactions between hypoxia-ischemia and inflammation in preterm brain injury", Dev Med Child Neurol, 60(2), pp.126~133 (2018)
- Koh HS, "The HIF-1", glial TIM-3 axis controls inflammation-associated brain damage under hypoxia, 2015, pp.6, 6340~
- Skovira JW, "Cell cycle inhibition reduces inflammatory responses, neuronal loss, and cognitive deficits induced by hypobaria exposure following traumatic brain injury", J Neuroinflammation, 13(1), pp.299~ (2016)
- Liu Y, "Human Ischaemic Cascade Studies Using SH-SY5Y Cells : a Systematic Review and Meta-Analysis", Transl Stroke Res, 9(6), pp.564~574 (2018)
- Shi X, "Panax notoginseng saponins provide neuroprotection by regulating NgR1", RhoA, J Ethnopharmacol, pp.2016, 190[DOI]
- Wong SB, "The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures", Chin J Physiol, 59(3), pp.156~164 (2016)
- Braun S, "Dexamethasone-enhanced sensitivity of mouse hippocampal HT22 cells for oxidative stress is associated with the suppression of nuclear factor-kappaB", Neurosci Lett, 295(3), pp.101~104 (2000)
- Floyd RA, "Antioxidants, oxidative stress, and degenerative neurological disorders", Proc Soc Exp Biol Med, 222(3), pp.236~245 (1999)
- Herbert V, "Most free-radical injury is iron-related : it is promoted by iron, hemin, holoferritin and vitamin C, and inhibited by desferoxamine and apoferritin", Stem Cells, 12(3), pp.289~303 (1994)
- Fricker M, "Neuronal Cell Death", Physiol Rev, 98(2), pp.813~880 (2018)
- Zhang J, "Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously Hypertensive Rats", Cell Physiol Biochem, 40(1-2), pp.347~360 (2016)
- Zhang YJ, "Pharmacokinetics of phenolic compounds of Danshen extract in rat blood and brain by microdialysis sampling", J Ethnopharmacol, 136(1), pp.129~136 (2011)
- Kim HG, "Ethanolic extract of Astragali radix and Salviae radix prohibits oxidative brain injury by psycho-emotional stress in whisker removal rat model", PLoS One, 9(5), pp.e98329~ (2014)
- Kim HG, "Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal(HPA)axis in a chronic cold-stress mouse model", J Ethnopharmacol, 148(2), pp.505~514 (2013)
- Lee JS, "Myelophil ameliorates brain oxidative stress in mice subjected to restraint stress", Prog Neuropsychopharmacol Biol Psychiatry, 39(2), pp.339~347 (2012)