title: Effects of Muscone on the Expression of P-gp, MMP-9 on Blood-Brain Barrier Model In Vitro.
abstract: Muscone is the main chemical ingredient in Musk which is main crude drug in Tongqiaohuoxue decoction (TQHXD), and TQHXD has a protective effect on damaged neurons, so we hypothesize that muscone can alter blood-brain barrier (BBB) permeability via the modulation of P-glycoprotein (P-gp) and matrix metalloproteinase-9 (MMP-9) expression. In this study, astrocytes (AC) and human umbilical vein endothelial cells (ECV304) were co-cultured to simulate the BBB model in vitro. Leak testing, transmembrane resistance experiments, and BBB-specific enzyme testing were used to test whether the model was successful. Different concentrations of muscone permeating the BBB were detected by gas chromatography (GC). The change of the transendothelial electrical resistance (TEER) on the BBB in vitro after treating with muscone was detected by Millicell-ERS. The protein expression of P-gp, MMP-9 in normal, and oxygen/glucose deprivation (OGD) BBB model was determined by western blotting to inquire that the mechanism of muscone penetrates the BBB model in vitro. The results show that muscone was detected in the lower medium of the BBB model by GC; the values of TEER were no significant difference before and after muscone (8 μM) was added to the BBB model; the expression of P-gp significantly decreased after the BBB model treatment with muscone (4, 8, and 16 μM) for 24 h; the expression of P-gp and MMP-9 in different concentrations of muscone groups had different degrees of reduction compared with the BBB in the state of OGD. In conclusion, muscone could permeate the BBB model, and it was associated with the inhibition of P-gp and MMP-9 expression. An understanding of the mechanisms of muscone across the BBB is crucial to the development of therapeutic modalities for cerebral vascular diseases.
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road, Hefei, 230012, China. wgyhefei@163.com.|Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China. wgyhefei@163.com.|Chinese Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei, 230012, China. wgyhefei@163.com.
authors.forename: Guang-Yun
authors.initials: GY
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road, Hefei, 230012, China. wnsci123@163.com.|Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China. wnsci123@163.com.|Chinese Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei, 230012, China. wnsci123@163.com.|Department of Pharmacy, Anhui University of Chinese Medicine, Xiang Shan Road, Hefei, China. wnsci123@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Anhui University of Chinese Medicine, Qian Jiang Road, Hefei, 230012, China.|Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China.|Chinese Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei, 230012, China.
authors.forename: Hua-Ning
authors.initials: HN
authors.lastname: Liao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D018920:Coculture Techniques; D003516:Cycloparaffins / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003516:Cycloparaffins; D020780:Matrix Metalloproteinase 9; C031021:muscone
keywords: Blood–brain barrier (BBB); Matrix metalloproteinase-9 (MMP-9); Muscone; P-glycoprotein (P-gp); Tight junction