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Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage.
Biomed Pharmacother. 2019 Sep; 117:109102.BP

Abstract

Ischemic stroke is a cerebrovascular disease with high morbidity, high mortality, and high disability, representing a serious threat to human life and health. Clinically, the extensive injury caused by ischemic stroke results from ischemia-reperfusion (I/R) injury thrombolytic treatment. However, there are few reports on the use of medications in the subacute stage of cerebral I/R. Baicalein (5,6,7-trihydroxyflavone) is a biologically active ingredient extracted from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the therapeutic effect of baicalein administered in the subacute phase of cerebral I/R injury in a rat model of ischemia induced by occlusion of the middle cerebral artery (MCA). Rats were treated daily with baicalein (200 mg/kg, i.g.) in the subacute phase (24 h after reperfusion) for 7 days. The results showed that baicalein significantly reduced neurobehavioral deficits and decreased brain infarct volume from 18.99% to 7.41%. Immunofluorescence analysis of the ischemic penumbra showed that baicalein significantly reduced expression of the M1 marker, cluster of differentiation (CD) 16 and CD86, and increased expression of the M2 marker, CD 163 and CD206, indicating that baicalein inhibited M1 transformation and promoted M2 transformation of microglia/macrophage to inhibit neuroinflammation. Moreover, baicalein suppressed NF-κB signaling by reducing IκBα phosphorylation and nuclear translocation of NF-κB/p65, which decreased the release of the pro-inflammatory factors IL-6, IL-18, and TNF-α. In addition, baicalein reduced phosphorylation of JNK, ERK and p38, which are involved modulation of microglia/macrophage M1/M2 polarization. Western blot analysis of apoptosis- and autophagy-related proteins showed that baicalein increased the Bcl-2/Bax ratio and reduced caspase-3 expression to decrease neuronal apoptosis and ameliorate neuronal loss. Baicalein also decreased the LC3-II/LC3-I ratio and promoted phosphorylation of the PI3K/Akt/mTOR signaling pathway which implied inhibition of autophagy. These observations suggest that baicalein exerts neuroprotective effects by reducing neuroinflammation, apoptosis and autophagy, and protects against cerebral I/R injury in the subacute phase in vivo.

Authors+Show Affiliations

School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China; Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.2 Nanwei Road, Beijing, 100050, China.Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.2 Nanwei Road, Beijing, 100050, China.Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.2 Nanwei Road, Beijing, 100050, China.School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, No.280, Waihuan East Road, Guangzhou, 510006, China.Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.2 Nanwei Road, Beijing, 100050, China.School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China. Electronic address: wucf@syphu.edu.cn.School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China; Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, NO.2 Nanwei Road, Beijing, 100050, China. Electronic address: dugh@imm.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31228802

Citation

Yang, Shilun, et al. "Baicalein Administered in the Subacute Phase Ameliorates Ischemia-reperfusion-induced Brain Injury By Reducing Neuroinflammation and Neuronal Damage." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 117, 2019, p. 109102.
Yang S, Wang H, Yang Y, et al. Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage. Biomed Pharmacother. 2019;117:109102.
Yang, S., Wang, H., Yang, Y., Wang, R., Wang, Y., Wu, C., & Du, G. (2019). Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 117, 109102. https://doi.org/10.1016/j.biopha.2019.109102
Yang S, et al. Baicalein Administered in the Subacute Phase Ameliorates Ischemia-reperfusion-induced Brain Injury By Reducing Neuroinflammation and Neuronal Damage. Biomed Pharmacother. 2019;117:109102. PubMed PMID: 31228802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage. AU - Yang,Shilun, AU - Wang,Haigang, AU - Yang,Yinglin, AU - Wang,Rui, AU - Wang,Yuehua, AU - Wu,Chunfu, AU - Du,Guanhua, Y1 - 2019/06/19/ PY - 2019/02/23/received PY - 2019/05/24/revised PY - 2019/06/06/accepted PY - 2019/6/23/pubmed PY - 2020/1/9/medline PY - 2019/6/23/entrez KW - Baicalein KW - Cerebral ischemia-reperfusion injury KW - Ischemic stroke KW - NF-κB signaling KW - Neuroinflammation SP - 109102 EP - 109102 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 117 N2 - Ischemic stroke is a cerebrovascular disease with high morbidity, high mortality, and high disability, representing a serious threat to human life and health. Clinically, the extensive injury caused by ischemic stroke results from ischemia-reperfusion (I/R) injury thrombolytic treatment. However, there are few reports on the use of medications in the subacute stage of cerebral I/R. Baicalein (5,6,7-trihydroxyflavone) is a biologically active ingredient extracted from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the therapeutic effect of baicalein administered in the subacute phase of cerebral I/R injury in a rat model of ischemia induced by occlusion of the middle cerebral artery (MCA). Rats were treated daily with baicalein (200 mg/kg, i.g.) in the subacute phase (24 h after reperfusion) for 7 days. The results showed that baicalein significantly reduced neurobehavioral deficits and decreased brain infarct volume from 18.99% to 7.41%. Immunofluorescence analysis of the ischemic penumbra showed that baicalein significantly reduced expression of the M1 marker, cluster of differentiation (CD) 16 and CD86, and increased expression of the M2 marker, CD 163 and CD206, indicating that baicalein inhibited M1 transformation and promoted M2 transformation of microglia/macrophage to inhibit neuroinflammation. Moreover, baicalein suppressed NF-κB signaling by reducing IκBα phosphorylation and nuclear translocation of NF-κB/p65, which decreased the release of the pro-inflammatory factors IL-6, IL-18, and TNF-α. In addition, baicalein reduced phosphorylation of JNK, ERK and p38, which are involved modulation of microglia/macrophage M1/M2 polarization. Western blot analysis of apoptosis- and autophagy-related proteins showed that baicalein increased the Bcl-2/Bax ratio and reduced caspase-3 expression to decrease neuronal apoptosis and ameliorate neuronal loss. Baicalein also decreased the LC3-II/LC3-I ratio and promoted phosphorylation of the PI3K/Akt/mTOR signaling pathway which implied inhibition of autophagy. These observations suggest that baicalein exerts neuroprotective effects by reducing neuroinflammation, apoptosis and autophagy, and protects against cerebral I/R injury in the subacute phase in vivo. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/31228802/Baicalein_administered_in_the_subacute_phase_ameliorates_ischemia_reperfusion_induced_brain_injury_by_reducing_neuroinflammation_and_neuronal_damage_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(19)30755-3 DB - PRIME DP - Unbound Medicine ER -