Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive‐like behaviors by suppressing neuroinflammation in hypothalamus of mice

Feng, Rui; He, Ming-Chao; Li, Qiang; Liang, Xiaoqiang; Tang, Dezhi; Zhang, Jiali; Liu, Shufen; Lin, Fu-Hui; Zhang, Yan

doi:10.1002/ptr.6777

Cited by 15 publications

(11 citation statements)

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“…Furthermore, it has been reported and summarized that TLR4/ MyD88/NF-κB signaling plays an important role in the aberrantly activated microglia (Feng et al, 2020). Peroxiredoxin 2 (a DAMP) interacts with TLR4 on microglia and then activates microglia through the TLR4/MyD88/NF-κB signaling pathway (Lu et al, 2018a).…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling

et al. 2022

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Depression is a prevalent psychiatric disorder. Microglial state transition has been found in many neurological disorders including depression. Gypenosides (Gypenosides I-LXXVIII, Gps) are saponin extracts isolated from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino that exert anti-inflammatory and neuroprotective activities and regulate depression-like behaviors. However, its effect on microglial state transition in depression remains unknown. We aimed to evaluate the potential relationship between Gps and TLR4/MyD88/NF-κB signaling in microglial state transition in vitro and in vivo. First, BV-2 cells (microglial cell line) were exposed to lipopolysaccharides (LPS) and treated with 10 or 5 μg/ml Gps. Second, the chronic unpredictable mild stress (CUMS)-induced depression mouse model was used to investigate the antidepressant-like behaviors effects of Gps (100 or 50 mg/kg). We determined depression-like behaviors using the open-field test (OFT), forced swim test (FST), and sucrose preference test (SPT). Proteins and inflammatory factors in the TLR4/MyD88/NF-κB signaling pathway and the different microglial reaction states markers were subsequently conducted using enzyme-linked immunosorbent assay, immunocytochemistry, immunofluorescence, qPCR, or Western blotting analyses to evaluate the anti-inflammatory and antidepressant properties of Gps and the underlying molecular mechanisms. We found that Gps regulated the microglial cell line state transition in LPS-exposed BV-2 cells, as evidenced by the significantly decreased expression of inflammatory parameters iNOS, IL-1β, IL-6, and TNF-α and significantly promoted anti-inflammatory microglial phenotypes markers CD206 (Mrc1) and IL-10. More importantly, Gps protected against the loss of monoamine neurotransmitters and depression-like behavior in a mouse model of depression, which was accompanied by a regulation of the microglial state transition. Mechanistically, Gps inhibited TLR4/MyD88/NF-κB signaling, which reduced the release of downstream inflammatory cytokines (IL-1β, IL-6, and TNF-α) and promoted microglial phenotype transition, which all together contributed to the antidepressant effect. Our results suggest that Gps prevents depression-like behaviors by regulating the microglial state transition and inhibiting the TLR4/MyD88/NF-κB signaling pathway. Thus, Gps could be a promising therapeutic strategy to prevent and treat depression-like behaviors and other psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling

et al. 2022

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“…TLR4 can activate nuclear factor kappa-B (NF-κB) through a cascade of reactions and induce the NLRP3 inflammasome pathway, leading to the maturation of IL-1β ( 8 ). Some terrestrial plant extracts rich in phenol, flavonoids, and pyrazine compounds ( 9 – 11 ) and probiotics, such as Lactobacillus delbrueckii ( 12 ) can alleviate depression/anxiety-like behavior in the IBD mice by inhibiting the TLR4-NLRP3 signaling pathways. Nevertheless, the mechanism of marine algae extracts rich in phlorotannins and fucoxanthin on depression/anxiety-like behavior in the IBD mice was not reported.…”

Section: Introductionmentioning

confidence: 99%

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice

Dong

Lin

et al. 2021

Front. Nutr.

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Saccharina japonica is a common marine vegetable in East Asian markets and has a variety of health benefits. This study was focused on the anti-depressant/anxiety effects of Saccharina japonica ethanol extract (SJE) on dextran sodium sulfate (DSS)-induced mice and its potential mechanism in their brain. Male C57BL/6 mice were treated with mesalazine and various doses of SJE (1, 2, and 4 g/kg body weight) for 2 weeks, followed by DSS treatment at the second week. The DSS-induced mice showed depression/anxiety-like behavior, which included shorter path length in the open field test and longer immobility time in the tail suspension test. L-SJE alleviated the depression-like behaviors. In the DSS-induced mice, reduced synaptic plasticity activated microglia, increased proinflammatory cytokines, decreased anti-inflammatory cytokine, and increased expression levels of Toll-like receptors-4, nuclear factor kappa-B, NOD-like receptors 3, apoptosis-associated speck-like protein, and Caspase-1 were observed, most of which were alleviated by SJE treatment. Furthermore, all the SJE groups could significantly enhance superoxide dismutase activity, while the L-SJE treatment decreased the contents of malondialdehyde, and the H-SJE treatment inhibited apoptosis. All these results showed that the SJE might serve as a nutritional agent for protecting the brain in ulcerative colitis mice.

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“…Modern research supports the usefulness of FLL for the treatment of backache, blurred vision, insomnia, menopausal symptoms, palpitations, rheumatic pains, and tinnitus and for alleviating age-related symptoms [ 18 , 19 ]. Furthermore, FLL has been shown to have anti-inflammatory effects in mouse peritoneal macrophages [ 20 ], and recently, a phenol glycosides extract of FLL was reported to alleviate depressive-like behavior by inhibiting neuroinflammation in mouse hypothalamus [ 21 ]. However, evidence-based medicinal proof of therapeutic efficacy of FLL in neuroinflammation is lacking.…”

Section: Introductionmentioning

confidence: 99%

Anti-Neuroinflammatory Effects and Mechanism of Action of Fructus ligustri lucidi Extract in BV2 Microglia

Kim

Park

Koh

et al. 2021

Plants

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For centuries, Fructus ligustri lucidi (FLL; the fruit of Ligustrum lucidum Aiton or Ligustrum japonicum Thunb.) has been commonly used in traditional Chinese medicine for treating hepatitis and aging-related symptoms and in traditional Korean medicine to detoxify kidneys and the liver. Pharmacological research has shown FLL has antioxidant, anti-inflammatory, anticancer, anti-osteoporosis, and hepatoprotective activities. This study was undertaken to investigate the effects of FLL extract (FLLE) on neuroinflammation. After setting a non-toxic concentration using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay data, we investigated the effects of FLLE using Western blotting, cell migration, enzyme-linked immunosorbent assay, a nitric oxide (NO) assay, and immunofluorescence staining in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. FLLE was non-toxic to BV2 cells up to a concentration of 500 μg/mL and concentration-dependently inhibited the production of NO and prostaglandin E2 and the protein levels of inducible nitric oxide synthase and cyclooxygenase-2 under LPS-induced inflammatory conditions. It also inhibited the secretion of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Furthermore, FLLE pretreatment attenuated LPS-induced increases of CD68 (a marker of microglia activation) and suppressed the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-stimulated BV2 cells, and significantly increased heme oxygenase (HO)-1 levels. FLLE also reduced the LPS-induced increase in the migratory ability of BV2 cells and the phosphorylation of vascular endothelial growth factor receptor 1. Collectively, FLLE effectively inhibited inflammatory response by suppressing the MAPK and NF-κB signaling pathways and inducing HO-1 in LPS-stimulated BV2 microglial cells. Our findings provide a scientific basis for further study of FLL as a candidate for preventing or alleviating neuroinflammation.

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Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive‐like behaviors by suppressing neuroinflammation in hypothalamus of mice

Cited by 15 publications

References 50 publications

Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling

Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice

Anti-Neuroinflammatory Effects and Mechanism of Action of Fructus ligustri lucidi Extract in BV2 Microglia

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