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Canthin-6-one (CO) from Picrasma quassioides (D.Don) Benn. ameliorates lipopolysaccharide (LPS)-induced astrocyte activation and associated brain endothelial disruption
Yue, Qian1,2; Xu, Yunshao1,2; Lin, Ligen1,2; Hoi, Maggie Pui Man1,2
2022-07-01
Source PublicationPhytomedicine
ISSN0944-7113
Volume101
Abstract

Background: Canthin-6-one (CO) is an active ingredient found in Picrasma quassioides (D.Don) Benn. (PQ) that displays various biological activities including anti-inflammatory properties. Several studies reported PQ displayed neuroprotective activities, but its effects on astrocytes have not yet been investigated. Astrocytes are crucial regulators of neuroinflammatory responses under pathological conditions in the central nervous system (CNS). Proinflammatory astrocytes can induce the blood-brain barrier (BBB) breakdown, which plays a key role in the progression of neurodegenerative disorder (ND). Purpose: This study aims to investigate the anti-neuroinflammatory effects of CO in LPS-induced astrocyte activation and its underlying mechanisms in protecting the blood-brain barrier (BBB) in vitro. Methods: Mouse astrocytes (C8-D1A) were activated with lipopolysaccharide (LPS) with or without CO pretreatment. Effects of CO on astrocyte cell viability, secretions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nitric oxide (NO) were determined. Intracellular transcriptions and translations of proinflammatory mediators, molecular signaling, [Ca] and the levels of reactive oxygen species (ROS) were evaluated by RT-PCR, western blotting, and flow cytometry, respectively. Astrocyte-conditioned medium (ACM) was further prepared for incubating endothelial monolayer (bEnd.3) grown on transwell. Endothelial disruptions were evaluated by transendothelial electrical resistance (TEER), FITC-dextran permeability and monocyte adhesion assays. Endothelial tight junctions (TJs) and molecular signaling pathways were evaluated by immunofluorescence staining and western blotting. Results: CO attenuated LPS-induced expression of astrocytic proinflammatory mediators (TNF-α, IL-1β, IL-6, NO) and inhibited deleterious molecular activities including inducible nitric oxide synthase (iNOS), p-NFκB and p-STAT3 in astrocytes. Incubation of ACM collected from CO-treated astrocytes significantly ameliorated endothelial disruptions, reduced expressions of endothelial cytokine receptors (IL-6R, gp130 (IL-6RB), TNFR and IL-1R), suppressed proinflammatory pathways, MAPKs (p-AKT, p-MEK, p-ERK, p-p38, p-JNK) and p-STAT3, restored endothelial stabilizing pathways (p-Rac 1) and upregulated beneficial endothelial nitric oxide synthase (eNOS). Conclusion: Our study demonstrates for the first time CO exhibited potent protective effects against astrocyte-mediated proinflammatory responses and associated endothelial barrier disruptions.

KeywordAstrocyte Blood-brain Barrier (Bbb) Brain Endothelial Cell Canthin-6-one (Co) Endothelial Integrity Neuroinflammation
DOI10.1016/j.phymed.2022.154108
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPlant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
WOS SubjectPlant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000794996800001
Scopus ID2-s2.0-85129293825
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorHoi, Maggie Pui Man
Affiliation1.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, N22-7012, Avenida da Universidade, Taipa, Macau, SAR, China
2.DPS, Faculty of Health Sciences, University of Macau, Macau, SAR, China
First Author AffilicationInstitute of Chinese Medical Sciences;  Faculty of Health Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Yue, Qian,Xu, Yunshao,Lin, Ligen,et al. Canthin-6-one (CO) from Picrasma quassioides (D.Don) Benn. ameliorates lipopolysaccharide (LPS)-induced astrocyte activation and associated brain endothelial disruption[J]. Phytomedicine,2022,101.
APA Yue, Qian,Xu, Yunshao,Lin, Ligen,&Hoi, Maggie Pui Man.(2022).Canthin-6-one (CO) from Picrasma quassioides (D.Don) Benn. ameliorates lipopolysaccharide (LPS)-induced astrocyte activation and associated brain endothelial disruption.Phytomedicine,101.
MLA Yue, Qian,et al."Canthin-6-one (CO) from Picrasma quassioides (D.Don) Benn. ameliorates lipopolysaccharide (LPS)-induced astrocyte activation and associated brain endothelial disruption".Phytomedicine 101(2022).
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