Dataset Information

Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.

ABSTRACT: Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell-cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6"'-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.

SUBMITTER: Liu H

PROVIDER: S-EPMC9163036 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.

Liu Huayan H Zhang Xin X Liu Yujiao Y Xin Nian N Deng Yulin Y Li Yujuan Y

NPJ science of food 20220602 1

Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins ...[more]

PMID: 35655066

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Project description:BackgroundEthanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways.MethodsMale Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays.ResultsMESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS.ConclusionsThese results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.

Dataset Information

Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.

Publications

Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.

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