PMID- 37634356 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20230911 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 235 DP - 2023 Oct 25 TI - In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus. PG - 115637 LID - S0731-7085(23)00406-5 [pii] LID - 10.1016/j.jpba.2023.115637 [doi] AB - The fruits of Alpinia oxyphylla Miq., a broadly utilized traditional Chinese medicine, have a number of effects on the central nervous system (CNS). The main active constituents of Alpiniae oxyphyllae fructus (AOF) were nootkatone, tectochrysin, chrysin and protocatechuic acid. An immortalized human brain microvascular endothelial cell (hCMEC/D3) and astrocyte (HA1800) coculture model was used to investigate the permeability of the blood-brain barrier (BBB). The validation of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods for the four compounds was conducted following industry guidelines. Calibration curves were generated with mean coefficients (R(2)) better than 0.99. The inter-day and intra-day precisions were less than 8.53% and 7.12%, respectively. The accuracies were lower than +/- 11.57%, and recoveries were greater than 86.07%. The samples of the transport experiment were examined, and the apparent permeability coefficients (P(app)) were calculated. The efflux ratios of the four compounds are all less than 2. The P(app) values of protocatechuic acid, chrysin, nootkatone, tectochrysin were at the level of 10(-5), 10(-6), 10(-6), and 10(-7) cm/s, respectively. All four compounds crossed the BBB by passive diffusion, with protocatechuic acid having high permeability, and tectochrysin having poor permeability. This research indicated the permeability of protocatechuic acid, chrysin, nootkatone and tectochrysin through the BBB and offered a foundation for related research on AOF in the treatment of CNS illnesses. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Xiao, Tongjie AU - Xiao T AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Pan, Mingyu AU - Pan M AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Wang, Yuanxiao AU - Wang Y AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Huang, Yanjiao AU - Huang Y AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Tsunoda, Makoto AU - Tsunoda M AD - Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. FAU - Zhang, Yingxia AU - Zhang Y AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Wang, Rong AU - Wang R AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Hu, Wenting AU - Hu W AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. FAU - Yang, Haimei AU - Yang H AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address: haimeiy@hainanu.edu.cn. FAU - Li, Lu-Shuang AU - Li LS AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address: lvylushuang@163.com. FAU - Song, Yanting AU - Song Y AD - Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. Electronic address: songyt@hainanu.edu.cn. LA - eng PT - Journal Article DEP - 20230811 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - IZ2Y119N4J (nootkatone) RN - 36R5QJ8L4B (protocatechuic acid) SB - IM MH - Humans MH - *Blood-Brain Barrier MH - *Fruit MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Alpiniae oxyphyllae fructus OT - Blood3brain barrier OT - Permeability COIS- Declaration of Competing Interest The authors declare that they have no conflicts of interest. EDAT- 2023/08/28 00:41 MHDA- 2023/09/11 06:42 CRDT- 2023/08/27 18:05 PHST- 2023/05/13 00:00 [received] PHST- 2023/07/15 00:00 [revised] PHST- 2023/08/04 00:00 [accepted] PHST- 2023/09/11 06:42 [medline] PHST- 2023/08/28 00:41 [pubmed] PHST- 2023/08/27 18:05 [entrez] AID - S0731-7085(23)00406-5 [pii] AID - 10.1016/j.jpba.2023.115637 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2023 Oct 25;235:115637. doi: 10.1016/j.jpba.2023.115637. Epub 2023 Aug 11.