Du-moxibustion ameliorates depression-like behavior and neuroinflammation in chronic unpredictable mild stress-induced mice.
Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice.
C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay.
We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1β and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM.
A shortage of this study is that only CUMS model of depression were used, while other depression model were not included.
Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.
Jia Z
，Yu W
，Li X
，Dong T
，Wang X
，Li J
，Yang J
，Liu Y
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Alpinia oxyphylla Miq. volatile oil ameliorates depressive behaviors and inhibits neuroinflammation in CUMS-exposed mice by inhibiting the TLR4-medicated MyD88/NF-κB signaling pathway.
This study aimed to explore the antidepressant effect and underlying mechanism of the Alpinia oxyphylla Miq. volatile oil (AOVO) in mice exposed to chronic unpredictable mild stress (CUMS). C57BL/6 mice were grouped and administered with different dosages of AOVO (0.25, 0.50, 1.00, or 2.00 mL/kg body weight, i.g.), TAK242 (a TLR4 inhibitor, 0.75 mg/kg body weight, i.p.), or TAK242 (0.75 mg/kg body weight, i.p.) + AOVO (0.50 mL/kg body weight, i.g.) for 21 days. Depression-like symptoms in the mice were then evaluated through their body weight gain (BW), the open field test (OFT), the sucrose preference test (SPT), the novelty-suppressed feeding test (NSFT), and forced swimming test (FST). The concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and 5-hydroxytyrptamine (5-HT) in the mice were determined using ELISA kits. Hematoxylin and eosin (HE) dying were performed for histopathological examination. The expression of inflammatory proteins was assessed through western blotting (WB) and immunofluorescence staining. AOVO was found to improve the behavioral indexes of CUMS-exposed mice behavioral and synergize TAK242 to mitigate both their depressive symptoms and neuroinflammation. Moreover, AOVO was found to inhibit the hippocampal damage, decrease inflammatory cytokines (Reduced IL-1β, IL-6, and TNF-α by 19.97 %, 22.87 %, and 24.13 %, respectively), and downregulate the expression of TLR4/MyD88/NF-κB signaling pathway-related proteins in the hippocampus of CUMS-exposed mice (Reduced TLR4, MyD88, and NF-κB by 46.14 %, 42.48 %, and 38.08 %, respectively). These findings demonstrate that AOVO can ameliorate depressive behaviors and mitigate neuroinflammation in the CUMS-exposed mice via suppressing the TLR4-medicated MyD88/NF-κB signaling pathway.
Wu B
，Gan A
，Wang R
，Lin F
，Yan T
，Jia Y
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Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4/NF-κB pathway.
Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment.
Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation.
RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes.
Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
Zhang D
，Jing B
，Chen ZN
，Li X
，Shi HM
，Zheng YC
，Chang SQ
，Gao L
，Zhao GP
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ResearchGate
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