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Study M1024

Study name

Fan L 2023

Title

Brain regional pharmacokinetics of hydroxytyrosol and its molecular mechanism against depression assessed by multi-omics approaches

Overall design

The aim of this study was to reveal the specific antidepressive mechanism of hydroxytyrosol in chronic unpredictable mild stress (CUMS) induced depressive mice. ICR mice were divided into the following 3 groups (n = 9 in each group): (1) control group, (2) CUMS group, and (3) CUMS + hydroxytyrosol group (stressor plus hydroxytyrosol treatment at the dose of 70 mg/kg). The CUMS stress procedure lasted for 4 weeks, and drugs were administered via intragastric once per day during the model building period. Serum samples were used for untargeted metabonomic analysis (n = 8/group), and metabolic profiles in the different micro-regions (CA1, CA3 and DG regions) of the hippocampus were investigated using spatial-resolved metabolomics (n = 3/group).

Study Type

Type1;

Type2;

Data available

Unavailable

Organism

Mouse; ICR mouse;

Categories of depression

Animal model; Chronic mild stress model; Chronic mild stress model;

Criteria for depression

Sucrose preference test, forced swimming test, tail suspension test

Sample size

24

Tissue

Central; Brain; CA3 region of hippocampus;

Peripheral; Blood; Serum;

Central; Brain; CA1 region of hippocampus;

Central; Brain; DG region of hippocampus;

Platform

MS-based; LC-MS: Dionex U3000 UPLC system with QE plus high-resolution mass spectrometer (Thermo Fisher Scientific, USA);

MS-based; AFADESI-MSI: Airflow-assisted desorption electrospray ionization mass spectrometry imaging;

PMID

36774845

DOI

10.1016/j.phymed.2023.154712

Citation

Fan L, Peng Y, Li X. Brain regional pharmacokinetics of hydroxytyrosol and its molecular mechanism against depression assessed by multi-omics approaches. Phytomedicine. 2023 Apr;112:154712.

Metabolite

Citric acid;

Linoleic acid;

Stearic acid;

Myristic acid;

Palmitoleic acid;

Palmitic acid;

N-Acetyl-L-aspartic acid;

L-Tryptophan;

Arachidonic acid;

D-Glucose;

L-Arginine;

Sebacic acid;

Bilirubin;

Cholic acid;

Propionylcarnitine;

Oxoglutaric acid;

Indoxyl sulfate;

Ascorbic acid;

Taurine;

Betaine;

Creatine;

Histamine;

Docosahexaenoic acid;

Adenosine;

L-Acetylcarnitine;

Glycerophosphocholine;

L-Carnitine;

LysoPC(18:1);

LysoPC(18:2);

LysoPC(20:1);

Oleoylcarnitine;

Stearoylcarnitine;

D-Galactose;

LysoPC(16:1/0:0);

Dodecanoylcarnitine;

Benzoic acid;

4-Trimethylammoniobutanoic acid;

Spermidine;

PE(18:1/0:0);

Corticosterone;

Hydroxybutyrylcarnitine;

L-Palmitoylcarnitine;

Proline betaine;

LysoPC(20:4);

LysoPC(20:5);

LysoPC(22:6);

Alpha-Linolenic acid;

LysoPE(0:0/20:1);

Cer(d18:1/16:0);

Monoethylhexyl phthalic acid;

LysoPC(22:5);

LysoPC(20:3);

Sphinganine;

LysoPE(16:0/0:0);

PC(15:0/0:0);

PC(18:1/0:0);

PC(20:5/0:0);

Dodecanoic acid;

Eicosapentaenoic acid;

LysoPC(22:1);

LysoPC(14:0/0:0);

LysoPE(0:0/18:2);

LysoPE(18:1/0:0);

LysoPE(0:0/22:4);

LysoPC(20:2);

Myristoleic acid;

LysoPC(18:3);

LysoPC(0:0/16:0);

PS(10:0/10:0);

Isovaleraldehyde;

N-Undecanoylglycine;

12,13-DHOME;

LysoPE(22:6/0:0);

LysoPE(18:2/0:0);

SM(d17:1/17:0);

Tetracosahexaenoic acid;

Galactaric acid;

PC(22:4/0:0);

PC(22:6/0:0);

PC(0:0/20:4);

PC(22:5/0:0);

PC(19:1/0:0);

PC(20:3/0:0);

LysoPE(0:0/20:3);

LysoPE(23:0/0:0);

PE(20:2/0:0);

MIPPC(t18:0/22:0(2OH));

OHHdiA-PE;

PE(20:1/0:0);

PC(20:1/0:0);

PC(O-18:2/2:0);

PC(20:2/0:0);

PC(10:0/9:0);

PC(P-18:0/0:0);

LysoPE(0:0/22:6);

LysoPE(0:0/22:5);

PIM1(19:0/16:0);

LysoPE(22:5/0:0);

LysoPE(16:1/0:0);

LysoPE(0:0/16:1);

PIM1(19:1/18:1);

LysoPE(0:0/20:4);

LysoPE(20:4/0:0);

PIM1(19:2/18:0);

PA(21:4/0:0);

PE(0:0/22:4);

PIM1(17:0/18:0);

PC(16:0/0:0);

PE(18:0/0:0);

PC(O-14:0/2:0);

PE(0:0/18:0);

PC(16:1/0:0);

PC(17:1/0:0);

PC(18:3/0:0);

PC(0:0/14:0);

PI(20:4/0:0);

PHOHA-PA;

PI(18:2/0:0);

9-Oxo-nonanoic acid;

Dimethylurea;

Tridecanoic acid;

2-Hydroxystearic acid;

PKHdiA-PG;

PC(20:4/0:0);

TG(15:0/16:0/20:2);

2-Hydroxymyristoylcarnitine;

3-Hydroxyhexadecanoylcarnitine;

3-Hydroxypalmitoleoylcarnitine;

OHOOA-PE;

PC(17:2/0:0);

PS(10:0/0:0);

MIPC(t18:0/22:0);

(9R,10S)-dihydroxystearate;

PC(O-18:0/0:0);