PMID- 30501051
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 10
IP  - 4
DP  - 2018 Nov 29
TI  - Pharmacodynamic Effect of Luteolin Micelles on Alleviating Cerebral Ischemia 
      Reperfusion Injury.
LID - 10.3390/pharmaceutics10040248 [doi]
LID - 248
AB  - 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% 
      (w/w) 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-kappa-gene 
      binding kappa (NF-kappaB) 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)-alpha, interleukin (IL)-1beta, 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.
FAU - Tan, Liwei
AU  - Tan L
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      rafael0927@163.com.
AD  - College of Life Science and Engineering, Southwest Jiaotong University, Chengdu 
      610031, China. rafael0927@163.com.
FAU - Liang, Chen
AU  - Liang C
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      18780163811@163.com.
FAU - Wang, Yeye
AU  - Wang Y
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      yezi_1317@163.com.
FAU - Jiang, Yu
AU  - Jiang Y
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      jiangyu950704@163.com.
FAU - Zeng, Shengqiao
AU  - Zeng S
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      zzshqiao@gmail.com.
FAU - Tan, Rui
AU  - Tan R
AD  - College of Medicine, Southwest Jiaotong University, Chengdu 610031, China. 
      tanrui@swjtu.edu.cn.
AD  - College of Life Science and Engineering, Southwest Jiaotong University, Chengdu 
      610031, China. tanrui@swjtu.edu.cn.
LA  - eng
GR  - 81274184/National Natural Science Foundation of China/
GR  - 81473337/National Natural Science Foundation of China/
GR  - 81573563/National Natural Science Foundation of China/
GR  - 2018M631098/China Postdoctoral Science Foundation/
GR  - [2017]66/the National Special Fund for the traditional Chinese medicine resources 
      Research in the Public Interest of China/
GR  - 2016C051/Sichuan Special Funds of Traditional Chinese medicine/
GR  - 2014SZ0212/Sichuan Project of Science and Technology/
PT  - Journal Article
DEP - 20181129
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC6320772
OTO - NOTNLM
OT  - antioxidative stress
OT  - bioavailability
OT  - cerebral ischemia reperfusion injury
OT  - luteolin-loaded micelles
OT  - nanomedicines
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, and in the decision to publish the results.
EDAT- 2018/12/07 06:00
MHDA- 2018/12/07 06:01
PMCR- 2018/12/01
CRDT- 2018/12/02 06:00
PHST- 2018/10/29 00:00 [received]
PHST- 2018/11/13 00:00 [revised]
PHST- 2018/11/14 00:00 [accepted]
PHST- 2018/12/02 06:00 [entrez]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2018/12/07 06:01 [medline]
PHST- 2018/12/01 00:00 [pmc-release]
AID - pharmaceutics10040248 [pii]
AID - pharmaceutics-10-00248 [pii]
AID - 10.3390/pharmaceutics10040248 [doi]
PST - epublish
SO  - Pharmaceutics. 2018 Nov 29;10(4):248. doi: 10.3390/pharmaceutics10040248.