Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury
Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury...
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MDPI AG
2018-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/10/4/248 |
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| author | Liwei Tan Chen Liang Yeye Wang Yu Jiang Shengqiao Zeng Rui Tan |
| author_facet | Liwei Tan Chen Liang Yeye Wang Yu Jiang Shengqiao Zeng Rui Tan |
| author_sort | Liwei Tan |
| collection | DOAJ |
| description | Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (<i>w</i>/<i>w</i>) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T00:46:54Z |
| publishDate | 2018-11-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-1d925307062f4d6b8accfe5e51db0b482022-12-22T02:21:59ZengMDPI AGPharmaceutics1999-49232018-11-0110424810.3390/pharmaceutics10040248pharmaceutics10040248Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion InjuryLiwei Tan0Chen Liang1Yeye Wang2Yu Jiang3Shengqiao Zeng4Rui Tan5College of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu 610031, ChinaOxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (<i>w</i>/<i>w</i>) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy.https://www.mdpi.com/1999-4923/10/4/248nanomedicinesluteolin-loaded micellescerebral ischemia reperfusion injurybioavailabilityantioxidative stress |
| spellingShingle | Liwei Tan Chen Liang Yeye Wang Yu Jiang Shengqiao Zeng Rui Tan Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury Pharmaceutics nanomedicines luteolin-loaded micelles cerebral ischemia reperfusion injury bioavailability antioxidative stress |
| title | Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury |
| title_full | Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury |
| title_fullStr | Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury |
| title_full_unstemmed | Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury |
| title_short | Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia Reperfusion Injury |
| title_sort | pharmacodynamic effect of luteolin micelles on alleviating cerebral ischemia reperfusion injury |
| topic | nanomedicines luteolin-loaded micelles cerebral ischemia reperfusion injury bioavailability antioxidative stress |
| url | https://www.mdpi.com/1999-4923/10/4/248 |
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