Anti-inflammatory and anti-apoptotic effects of the combination of <i>Ligusticum chuanxiong</i> and <i>Radix Paeoniae</i> against focal cerebral ischaemia via TLR4/MyD88/MAPK/NF-κB signalling pathway in MCAO rats

Gu, Junfei; Su, Shulan; Guo, Jianming; Zhu, Yue; Zhao, Ming; Duan, Jin Ao

doi:10.1111/jphp.12841

Cited by 47 publications

(32 citation statements)

References 42 publications

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“…It has been reported that the NF-κB and MAPK signaling pathways accelerate the inflammatory process in cerebral ischemia-reperfusion injury [32][33][34]. This process is consistent with the inflammatory response signaling pathway that is induced by LPS.…”

Section: Ala Alleviated Cerebral Ischemia-reperfusion Injury In the Msupporting

confidence: 78%

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Tan

Wang

et al. 2019

Cells

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Neuroinflammation is a major cause of central nervous system (CNS) damage and can result in long-term disability and mortality. Therefore, the development of effective anti-neuroinflammatory agents for neuroprotection is vital. To our surprise, the naturally occurring molecule alantolactone (Ala) was reported to significantly inhibit tumor growth and metastasis as a result of its excellent anti-inflammatory effects. Thus, we proposed that it could also act as an anti-neuroinflammatory agent. Thus, in this study, a coculture system of BV2 cells and PC12 cells were used as an in vitro neuroinflammatory model to investigate the anti-neuroinflammatory mechanism of Ala. The results indicated that Ala downregulated the expression of proinflammatory factors by suppressing the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.

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Section: Ala Alleviated Cerebral Ischemia-reperfusion Injury In the Msupporting

confidence: 78%

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Tan

Wang

et al. 2019

Cells

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“…The Lf-induced decrease in TLR-4 level, in the current study, could be attributed to the fact that Lf has anti-inflammatory as well as anti-oxidative properties [ 50 , 51 ], which was evident by the restoration of SOD and NrF2 levels towards normal values, with a statistically significant difference from the control group. The Lf-induced modulation of the TLR-4 pathway and the pro-inflammatory cascade, via inhibition of reactive oxygen species generation and through the direct use of anti-inflammatory agents, was previously reported [ 52 ]. Similarly, and at the cellular level, Lf was shown to modulate differentiation, activation, migration, proliferation, and functions of immune cells using the signaling pathways, NF-κB and MAPK [ 53 ].…”

Section: Discussionmentioning

confidence: 97%

Antidiabetic efficacy of lactoferrin in type 2 diabetic pediatrics; controlling impact on PPAR-γ, SIRT-1, and TLR4 downstream signaling pathway

Mohamed

Schaalan

2018

Diabetol Metab Syndr

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The current study aims to investigate the antidiabetic efficacy of camel milk-derived lactoferrin and potential involvement of PPAR-γ and SIRT-1 via TLR-4/NFκB signaling pathway in obese diabetic pediatric population. Sixty young obese patients with type 2 diabetes were selected from the Pediatric Endocrine Metabolic Unit, Cairo University and were randomly divided among two age and sex-matched groups so as to receive either standard therapy without lactoferrin in one arm or to be treated with oral lactoferrin capsules (250 mg/day, p.o) for 3 months in the other arm. Both groups were compared to 50 control healthy volunteers. Measurements of HbA1c, lipid profile, antioxidant capacity (SOD, Nrf2), proinflammatory interleukins; (IL-1β, IL-6, IL-18), Cyclin D-1, lipocalin-2, and PPAR-γ expression levels were done at the beginning and 3 months after daily consumption of lactoferrin. The mechanistic involvement of TLR4-SIRT-1-NFκB signaling cascade was also investigated. The antidiabetic efficacy of lactoferrin was confirmed by significant improvement of the baseline levels of HbA1c, BMI and lipid profile of the obese pediatric cohort, which is evidenced by increased PPAR-γ and SIRT-1 expression. Moreover, the anti-inflammatory effect was evident by the significant decrease in serum levels of IL-1β, IL-6, IL-18, TNF-α, lipocalin 2 in type 2 diabetic post-treatment group, which corresponded by decreased NFκB downstream signaling indicators. The antioxidant efficacy was evident by stimulated SOD levels and NrF2 expression; compared with the pre-treatment group (all at P ≤ 0.001). The consumption of high concentrations of lactoferrin explains its hypoglycemic efficacy and counts for its insulin-sensitizing, anti-inflammatory and immunomodulatory effects via TLR4-NFκB-SIRT-1 signaling cascade. Recommendations on regular intake of lactoferrin could ensure better glycemic control, compared to conventional antidiabetics alone.

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“…The data suggest that OMT administration may protect against LPS-induced ALI in vivo and in vitro by inhibiting the JNK signaling pathway. Toll-like receptor 4 (TLR4) can recognize and interact with LPS and subsequently activate the downstream MAPK pathways, eventually leading to an inflammatory response [ 12 , 15 ]. Previous studies reported that LPS-induced ALI can be attenuated by other drugs through the TLR4-mediated MAPK pathway [ 16 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Oxymatrine attenuates lipopolysaccharide-induced acute lung injury by activating the epithelial sodium channel and suppressing the JNK signaling pathway

Jin

2018

Exp. Anim.

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The epithelial sodium channel (ENaC) and mitogen-activated protein kinase (MAPK) pathway have been reported to be associated with the progression of acute lung injury (ALI). Oxymatrine (OMT) alone or combined with other drugs can ameliorate paraquat- or oleic acid-induced lung injury. However, the effect of OMT on lipopolysaccharide (LPS)-induced ALI remains unknown. The aim of the present study was to evaluate whether OMT can attenuate LPS-induced ALI through regulation of the ENaC and MAPK pathway using an ALI mouse model. Histological assessment of the lung and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were performed by H&E and Wright-Giemsa staining. The lung wet/dry (W/D) weight ratio and the levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), ENaC subunits, and the MAPK pathway members were determined. Isolated type II rat alveolar epithelial cells were incubated with OMT 30 min before LPS stimulation to investigate the activation of ENaC and the MAPK pathway. The results showed that OMT remarkably alleviated histopathologic changes in lung and pulmonary edema, reduced inflammatory cell counts in BALF, and decreased TNF-α and CRP levels in a dose-dependent manner. OMT significantly increased the three subunits of ENaC proteins in vivo and in vitro, while it decreased p-ERK/ERK, p-p38/p38, and p-JNK/JNK ratios in vivo. However, only the JNK pathway was markedly inhibited in vitro following pretreatment with OMT. Collectively, the results suggested that OMT might alleviate LPS-induced ALI by elevating ENaC proteins and inhibiting the JNK signaling pathway.

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Anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae against focal cerebral ischaemia via TLR4/MyD88/MAPK/NF-κB signalling pathway in MCAO rats

Abstract: XS could protect MCAO rats by anti-inflammation and anti-apoptosis through TLR4/MyD88/MAPK/NF-κB signalling pathway. Furthermore, the combination has a more meaningful improvement on focal cerebral ischaemic stroke.

Cited by 47 publications

References 42 publications

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Antidiabetic efficacy of lactoferrin in type 2 diabetic pediatrics; controlling impact on PPAR-γ, SIRT-1, and TLR4 downstream signaling pathway

Oxymatrine attenuates lipopolysaccharide-induced acute lung injury by activating the epithelial sodium channel and suppressing the JNK signaling pathway

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