Chuan WU, Anqi KONG, Ruxin XIE, et al. Naringin improves lipopolysaccharide-induced depression-like behaviors in mice[J]. Journal of Army Medical University, 2022, 44(23): 2368-2376.
DOI:
Chuan WU, Anqi KONG, Ruxin XIE, et al. Naringin improves lipopolysaccharide-induced depression-like behaviors in mice[J]. Journal of Army Medical University, 2022, 44(23): 2368-2376. DOI: 10.16016/j.2097-0927.202207029.
Naringin improves lipopolysaccharide-induced depression-like behaviors in mice
To investigate the effects of naringin (Nar) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice.
Methods
2
Thirty C57BL/6 male mice (8 weeks old
SPF grade
weighting 20~23 g) were randomly divided into 3 groups (
n
=10): control group
saline (Sal)+LPS group
and Nar+LPS group. The mice of the last group were pretreated with Nar (80 mg/kg
i.p.
once a day for 8 consecutive days). The exploratory behavior and anxiety-like behavior in mice were assessed by open field test
light and dark box experiment and elevated plus maze test. Sugar water preference test
hanging tail test and forced swimming test were used to evaluate the depression-like behaviors of the mice. Immunohistochemical assay for Iba1 was adopted to detect the effects of Nar and LPS treatments on the number of microglia in the hippocampus of mice. Western blotting and qRT-PCR were performed to determine the protein expression of NF-κB and the mRNA levels of IL-1β
TNF-α and NF-κB in mouse hippocampus
respectively.
Results
2
As compared with the control group
the mice in the Sal+LPS group showed decreased preference for sugar water (
P
<
0.05)
and increased immobile time in the forced swimming test (
P
<
0.01) as well as in the hanging tail test (
P
<
0.05). The number of microglia in the hippocampus was elevated (
P
<
0.01)
the protein level of NF-κB and the mRNA levels of IL-1β
TNF-α and NF-κB were also up-regulated (
P
<
0.05). When compared
with the Sal+LPS group
the mice in the Nar+LPS group presented increased preference for sugar water (
P
<
0.01)
and decreased immobility time in the forced swimming test (
P
<
0.01) and hanging tail test (
P
<
0.05)
with higher number of microglia in the hippocampus (
P
<
0.01)
and lower protein levels of NF-κB and mRNA levels of IL-1β
TNF-α and NF-κB (
P
<
0.01).
Conclusion
2
Nar may ameliorate LPS-induced depression-like behaviors in mice by inhibiting inflammation in the hippocampus.
关键词
Keywords
references
NANDEESH R, VIJAYAKUMAR S, MUNNOLLI A, et al . Bioactive phenolic fraction of Citrus maxima abate lipopolysaccharide-induced sickness behaviour and anorexia in mice: in-silico molecular docking and dynamic studies of biomarkers against NF-κB[J ] . Biomed Pharmacother, 2018, 108: 1535-1545. DOI:10.1016/j.biopha.2018.10.004..
ZHANG B, WANG P P, HU K L, et al . Antidepressant-like effect and mechanism of action of honokiol on the mouse lipopolysaccharide (LPS) depression model[J ] . Molecules, 2019, 24(11): 2035. DOI:10.3390/molecules24112035.
CHEN H F, MA Y N, CHEN M, et al . Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway[J ] . Ann Palliat Med, 2021, 10(7): 8015-8023. DOI:10.21037/apm-21-1728.
URYASH A, MIJARES A, FLORES V, et al . Effects of naringin on cardiomyocytes from a rodent model of type 2 diabetes[J ] . Front Pharmacol, 2021, 12: 719268. DOI:10.3389/fphar.2021.719268.
LIU K, WU L G, SHI X L, et al . Protective effect of naringin against ankylosing spondylitis via ossification, inflammation and oxidative stress in mice[J ] . Exp Ther Med, 2016, 12(2): 1153-1158. DOI:10.3892/etm.2016.3410.
BEN-AZU B, NWOKE E E, ADERIBIGBE A O, et al . Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice[J ] . Biomed Pharmacother, 2019, 109: 536-546. DOI:10.1016/j.biopha.2018.10.055.
ARIOZ B I, TASTAN B, TARAKCIOGLU E, et al . Melatonin attenuates LPS-induced acute depressive-like behaviors and microglial NLRP3 inflammasome activation through the SIRT1/Nrf2 pathway[J ] . Front Immunol, 2019, 10: 1511. DOI:10.3389/fimmu.2019.01511.
GIL M, KIM Y K, HONG S B, et al . Naringin decreases TNF-α and HMGB1 release from LPS-stimulated macrophages and improves survival in a CLP-induced Sepsis mice[J ] . PLoS One, 2016, 11(10): e0164186. DOI:10.1371/journal.pone.0164186..
DEVRAJ V M, VEMURI S K, BANALA R R, et al . Evaluation of anti-inflammatory and regenerative efficiency of naringin and naringenin in degenerated human nucleus pulposus cells: biological and molecular modeling studies[J ] . Asian Spine J, 2019, 13(6): 875-889. DOI:10.31616/asj.2019.0073.
LIU L, ZHANG Q, CAI Y L, et al . Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviors via enhanced hippocampal neurogenesis[J ] . Oncotarget, 2016, 7(35): 56045-56059. DOI:10.18632/oncotarget.11178.
SI L, WANG Y Y, LIU M, et al . Expression and role of microRNA-212/nuclear factor I-A in depressive mice[J ] . Bioengineered, 2021, 12(2): 11520-11532. DOI:10.1080/21655979.2021.2009964.
LIU S B, XU S L, WANG Z J, et al . Anti-depressant-like effect of sinomenine on chronic unpredictable mild stress-induced depression in a mouse model[J ] . Med Sci Monit, 2018, 24: 76467653. DOI:10.12659/MSM.908422.
ZHANG B, WANG P P, HU K L, et al . Antidepressant-like effect and mechanism of action of honokiol on the mouse lipopolysaccharide (LPS) depression model[J ] . Molecules, 2019, 24(11): 2035. DOI:10.3390/molecules24112035.
DANG R Z, WANG M Y, LI X H, et al . Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway[J ] . J Neuroinflammation, 2022, 19(1): 41. DOI:10.1186/s12974-022-02400-6.
SONG A Q, GAO B, FAN J J, et al . NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice[J ] . J Neuroinflammation, 2020, 17(1): 178. DOI:10.1186/s12974-020-01848-8.
KWON H S, KOH S H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes[J]. Transl Neurodegener, 2020, 9(1): 42. DOI:10.1186/s40035-020-00221-2.
HICKMAN S, IZZY S, SEN P, et al . Microglia in neurodegeneration[J ] . Nat Neurosci, 2018, 21(10): 1359-1369. DOI:10.1038/s41593-018-0242-x.
LI Z L, YANG B C, GAO M, et al . Naringin improves Sepsis -induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis[J ] . Mol Ther Nucleic Acids, 2021, 25: 502-514. DOI:10.1016/j.omtn.2021.07.005..
MENG X D, FU M M, WANG S F, et al . Naringin ameliorates memory deficitsand exerts neuroprotective effects in a mouse model of Alzheimer's disease by regulating multiple metabolic pathways[J ] . Mol Med Rep, 2021, 23(5): 332. DOI:10.3892/mmr.2021.11971.
GOPINATH K, SUDHANDIRAN G. Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway[J]. Neuroscience, 2012, 227: 134-143. DOI:10.1016/j.neuroscience.2012.07.060.
DAYARATHNE L A, RANAWEERA S S, NATRAJ P, et al . The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells[J ] . J Vet Sci, 2021, 22(6): e92. DOI:10.4142/jvs.2021.22.e92.
BEN-AZU B, NWOKE E E, ADERIBIGBE A O, et al . Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice[J ] . Biomed Pharmacother, 2019, 109: 536-546. DOI:10.1016/j.biopha.2018.10.055.
GAO C, WU M L, DU Q H, et al . Naringin mediates adult hippocampal neurogenesis for antidepression via activating CREB signaling[J ] . Front Cell Dev Biol, 2022, 10: 731831. DOI:10.3389/fcell.2022.731831.
FANG K, LI H R, CHEN X X, et al . Quercetin alleviates LPS-induced depression-like behavior in rats via regulating BDNF-related imbalance of copine 6 and TREM1/2 in the Hippocampus and PFC[J ] . Front Pharmacol, 2020, 10: 1544. DOI:10.3389/fphar.2019.01544..
LI M M, LI C L, YU H J, et al . Lentivirus -mediated interleukin-1β (IL-1β) knock-down in the Hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice[J ] . J Neuroinflammation, 2017, 14(1): 190. DOI:10.1186/s12974-017-0964-9..
ZHOU H C, WANG X H, ZHANG B. Depression of lncRNA NEAT1 antagonizes LPS-evoked acute injury and inflammatory response in alveolar epithelial cells via HMGB1-RAGE signaling[J]. Mediators Inflamm, 2020, 2020: 8019467. DOI:10.1155/2020/8019467.
TAO X, YAN M Z, WANG L S, et al . Homeostasis imbalance of microglia and astrocytes leads to alteration in the metabolites of the kynurenine pathway in LPS-induced depressive-like mice[J ] . Int J Mol Sci, 2020, 21(4): 1460. DOI:10.3390/ijms21041460.
HUANG X, FEI G Q, LIU W J, et al . Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways[J ] . Acta Pharmacol Sin, 2020, 41(5): 612-619. DOI:10.1038/s41401-019-0317-6.
WANG L, YANG J W, LIN L T, et al . Acupuncture attenuates inflammation in microglia of vascular dementia rats by inhibiting miR-93-mediated TLR4/MyD88/NF- κ B signaling pathway[J ] . Oxid Med Cell Longev, 2020, 2020: 8253904. DOI:10.1155/2020/8253904.
NAKAMOTO C, KAWAMURA M, NAKATSUKASA E, et al . GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior[J ] . PLoS One, 2020, 15(2): e0229288. DOI:10.1371/journal.pone.0229288.
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