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Jatrorrhizine Hydrochloride alleviates tert-butyl hydroperoxide-induced endothelial cell injury through its anti-inflammatory activity and PPAR-γ activation
Corresponding Author(s) : Xiaolin Chen
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
The aim of this study was to investigate whether Jatrorrhizine hydrochloride (JAH) can attenuate oxidative damage of endothelial cells by regulating mitochondrial function and inflammatory response. It was found that JAH inhibited tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in mouse brain endothelial cells (MBECs) by increasing cell viability and inhibiting cell apoptosis. Moreover, JAH significantly inhibited the production of reactive oxygen species (ROS) and lipid peroxidation. It enhanced mitochondrial membrane potential (MMP) and maintained ATP synthesis. In addition, JAH regulated the expressions of inflammatory cytokines and increased the activation of endothelial nitric oxide synthase (eNOS). The protective effect of JAH was related to the protein expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) gene. In conclusion, these results suggest that JAH may have therapeutic potential for ischemic stroke associated with endothelial dysfunction through its antioxidant and anti-inflammatory properties.
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- Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. N Engl J Med 2015; 49: 1019-1030.
- Randolph SA. Ischemic Stroke. Workplace Health Saf 2016; 64: 444.
- Méloux A, Rigal E, Porcherot I, Mouhat B, Cottin Y, Rochette L, et al. Ischemic stroke induced myocardial dysfunction associated with nitro-oxidative stress and sympathetic overactivity. Arch Cardiovasc Dis Supplements 2018; 10: 227.
- Tuttolomondo A, Casuccio A, Della Corte V, Maida C, Pecoraro R, Di Raimondo D, et al. Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: Relationship with TOAST subtype. Atherosclerosis 2017; 256: 94.
- Pan Q, He C, Liu H, Liao X, Dai B, Chen Y, et al. Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow. Mol Brain 2016; 9: 63.
- Natalia MD, Fuentes CA, Castillo AE, González-Gómez LM, Vecchiola A, Fardella CE, et al. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension. Int J Mol Sci 2016; 17: 797.
- Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377: 2602-2603.
- Fujita T, Hirooka K, Nakamura T, Itano T, Nishiyama A, Nagai Y, et al. Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1-R) Blocker via Modulating AT1-R Signaling and Decreased Extracellular Glutamate Levels. Invest Ophthalmol Vis Sci 2012; 53: 4099-4110.
- Dahlof B. Prevention of stroke: new evidence. Eur Heart J Supplements 2009; 11: 33-38.
- Gu Y, Chen J, Shen J. Herbal Medicines for Ischemic Stroke: Combating Inflammation as Therapeutic Targets. J Neuroimmune Pharmacol 2014; 9: 313-339.
- Luo T, Shen XY, Li S, Ouyang T, Mai QA, Wang HQ. The Protective Effect of Jatrorrhizine against Oxidative Stress in Primary Rat Cortical Neurons. CNS Neurol Disord Drug Targets 2017; 16: 617-623.
- Hawkins BT, Gu YH, Izawa Y, del Zoppo GJ. DABIGATRAN ABROGATES BRAIN ENDOTHELIAL CELL PERMEABILITY IN RESPONSE TO THROMBIN. J Cereb Blood Flow Metab 2013; 61: 2043.
- Tao C, Zhu J, Zhang C, Huo K, Fei Z, Jiang XF. Protective Effects of SKF-96365, a Non-Specific Inhibitor of SOCE, against MPP+-Induced Cytotoxicity in PC12 Cells: Potential Role of Homer1. PLoS One 2013; 8: 55601.
- Saavedra JM. Angiotensin II AT1Receptor Blockers Ameliorate Inflammatory Stress: A Beneficial Effect for the Treatment of Brain Disorders. Cell Mol Neurobiol 2012; 32: 667-681.
- Geng YD, Zhang C, Shi YM, Xia YZ, Guo C, Yang L, et al. Icariside II-induced mitochondrion and lysosome mediated apoptosis is counterbalanced by an autophagic salvage response in hepatoblastoma. Cancer Lett 2015; 366: 19-31.
- Caprioli G, Maggi F, Bendif H, Miara MD, Cinque B , Lizzi AR, et al. Thymus lanceolatus ethanolic extract protects human cells from t-BHP induced oxidative damage. Food Funct 2018; 9: 3665-3672.
- Zhou L, Jiang L, Xu M, Liu Q, Gao N, Li P, et al. Miltirone exhibits antileukemic activity by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways. Sci Rep 2016; 6: 20585.
- Cardounel AJ, Cui H, Samouilov A, Johnson W, Kearns P, Tsai AL, et al. Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function. J Biol Chem 2007; 282: 879.
- Li H, Förstermann U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 2013; 13: 161-167.
- He D, Song X, Li L. Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved. Brain Res 2015; 1599: 150-157.
- Abdelrahman M, Sivarajah A, Thiemermann C. Beneficial effects of PPAR-γ ligands in ischemia–reperfusion injury, inflammation and shock. Cardiovasc Res 2005; 65: 772-781.
- Iwai M, Chen R, Imura Y, Horiuchi M. TAK-536, a New AT1 Receptor Blocker, Improves Glucose Intolerance and Adipocyte Differentiation. Am J Hypertens 2007; 20: 579-586.
References
Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, et al. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. N Engl J Med 2015; 49: 1019-1030.
Randolph SA. Ischemic Stroke. Workplace Health Saf 2016; 64: 444.
Méloux A, Rigal E, Porcherot I, Mouhat B, Cottin Y, Rochette L, et al. Ischemic stroke induced myocardial dysfunction associated with nitro-oxidative stress and sympathetic overactivity. Arch Cardiovasc Dis Supplements 2018; 10: 227.
Tuttolomondo A, Casuccio A, Della Corte V, Maida C, Pecoraro R, Di Raimondo D, et al. Endothelial function and arterial stiffness indexes in subjects with acute ischemic stroke: Relationship with TOAST subtype. Atherosclerosis 2017; 256: 94.
Pan Q, He C, Liu H, Liao X, Dai B, Chen Y, et al. Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow. Mol Brain 2016; 9: 63.
Natalia MD, Fuentes CA, Castillo AE, González-Gómez LM, Vecchiola A, Fardella CE, et al. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension. Int J Mol Sci 2016; 17: 797.
Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med 2017; 377: 2602-2603.
Fujita T, Hirooka K, Nakamura T, Itano T, Nishiyama A, Nagai Y, et al. Neuroprotective Effects of Angiotensin II Type 1 Receptor (AT1-R) Blocker via Modulating AT1-R Signaling and Decreased Extracellular Glutamate Levels. Invest Ophthalmol Vis Sci 2012; 53: 4099-4110.
Dahlof B. Prevention of stroke: new evidence. Eur Heart J Supplements 2009; 11: 33-38.
Gu Y, Chen J, Shen J. Herbal Medicines for Ischemic Stroke: Combating Inflammation as Therapeutic Targets. J Neuroimmune Pharmacol 2014; 9: 313-339.
Luo T, Shen XY, Li S, Ouyang T, Mai QA, Wang HQ. The Protective Effect of Jatrorrhizine against Oxidative Stress in Primary Rat Cortical Neurons. CNS Neurol Disord Drug Targets 2017; 16: 617-623.
Hawkins BT, Gu YH, Izawa Y, del Zoppo GJ. DABIGATRAN ABROGATES BRAIN ENDOTHELIAL CELL PERMEABILITY IN RESPONSE TO THROMBIN. J Cereb Blood Flow Metab 2013; 61: 2043.
Tao C, Zhu J, Zhang C, Huo K, Fei Z, Jiang XF. Protective Effects of SKF-96365, a Non-Specific Inhibitor of SOCE, against MPP+-Induced Cytotoxicity in PC12 Cells: Potential Role of Homer1. PLoS One 2013; 8: 55601.
Saavedra JM. Angiotensin II AT1Receptor Blockers Ameliorate Inflammatory Stress: A Beneficial Effect for the Treatment of Brain Disorders. Cell Mol Neurobiol 2012; 32: 667-681.
Geng YD, Zhang C, Shi YM, Xia YZ, Guo C, Yang L, et al. Icariside II-induced mitochondrion and lysosome mediated apoptosis is counterbalanced by an autophagic salvage response in hepatoblastoma. Cancer Lett 2015; 366: 19-31.
Caprioli G, Maggi F, Bendif H, Miara MD, Cinque B , Lizzi AR, et al. Thymus lanceolatus ethanolic extract protects human cells from t-BHP induced oxidative damage. Food Funct 2018; 9: 3665-3672.
Zhou L, Jiang L, Xu M, Liu Q, Gao N, Li P, et al. Miltirone exhibits antileukemic activity by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways. Sci Rep 2016; 6: 20585.
Cardounel AJ, Cui H, Samouilov A, Johnson W, Kearns P, Tsai AL, et al. Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function. J Biol Chem 2007; 282: 879.
Li H, Förstermann U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 2013; 13: 161-167.
He D, Song X, Li L. Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved. Brain Res 2015; 1599: 150-157.
Abdelrahman M, Sivarajah A, Thiemermann C. Beneficial effects of PPAR-γ ligands in ischemia–reperfusion injury, inflammation and shock. Cardiovasc Res 2005; 65: 772-781.
Iwai M, Chen R, Imura Y, Horiuchi M. TAK-536, a New AT1 Receptor Blocker, Improves Glucose Intolerance and Adipocyte Differentiation. Am J Hypertens 2007; 20: 579-586.