title: Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain injury via gp91phoxsubunit of NADPH oxidase/ROS/ERK/MMP-9 signaling pathway.
abstract: Oxidative stress chiefly contributes to the disruption of the BBB following traumatic brain injury (TBI). The Chinese herbal medicine rhubarb is a promising antioxidant in treating TBI. Here we performed in vivo and in vitro experiments to determine whether rhubarb and its absorbed bioactive compound protected the BBB after TBI by increasing ZO-1 expression through inhibition of gp91phoxsubunit of NADPH oxidase/ROS/ERK/MMP-9 pathway. Rats were subjected to the controlled cortical impact (CCI) model, and primary rat cortical astrocytes were exposed to scratch-wound model. The liquid chromatography with tandem mass spectrometry method showed that rhein was the compound absorbed in the brains of CCI rats after rhubarb administration. The wet-dry weights and Evans blue measurements revealed that rhubarb and rhein ameliorated BBB damage and brain edema in CCI rats. Western blots showed that rhubarb and rhein downregulated GFAP in vitro. RT-PCR, immunohistochemistry, Western blot and dichlorodihydrofluorescein diacetate analysis indicated that rhubarb prevented activation of gp91phoxsubunit of NADPH oxidase induced ROS production, subsequently inhibited ERK/MMP-9 pathway in vivo and in vitro. Interestingly, rhein and rhubarb similarly protected the BBB by inhibiting this signaling cascade. The results provide a novel herbal medicine to protect BBB following TBI via an antioxidative molecular mechanism.
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.|Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Xuegong
authors.initials: X
authors.lastname: Fan
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Chunhu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Zebing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, 2nd Xiangya Hospital, Central South University, 410011 Changsha, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Gan
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Xingui
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 410008 Changsha, China.|Institute of TCM-related Depressive Comorbidity, Nanjing University of Chinese medicine, 210046 Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D020780:Matrix Metalloproteinase 9; C020491:rhein