Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway

Ye, Yinyin; Wang, Yuwei; Yang, Yanlang; Tao, Liangfei

doi:10.1007/s00011-019-01313-0

Cited by 37 publications

(20 citation statements)

References 25 publications

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“…LPS stimulation is mediated by TLR4. The transcription of proinflammatory cytokines such as TNF- α and IL-6 is activated by LPS [ 58 ]. For TNF- α synthesis, LPS strikingly promotes the activity of the nuclear factor- κ B (NF- κ B), which directly enhances the transcription of the TNF- α gene [ 59 ].…”

Section: Itaconate Regulates the Activating Transcription Factor 3mentioning

confidence: 99%

Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Metabolic products can lead to crucial biological function alterations. Itaconate is probably the best example of how a metabolic process can be diverted to generate an immunomodulator effect in macrophages. Through inflammatory stimuli, such as lipopolysaccharide, the immune response gene 1 is activated and promotes the production of itaconate from the tricarboxylic acid cycle by decarboxylating cis-aconitate. Itaconate has been reported to have multiple immunoregulatory and antioxidative effects. In addition, reports have described its antibacterial and protumor effects. The involved mechanism in these effects includes the activation of nuclear factor E2-related factor 2 by alkylation of Kelch-like ECH-associated protein 1, inhibition of aerobic glycolysis by targeting glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase A, inhibition of succinate dehydrogenase, and blockade of IκBζ translation. All of these discoveries elucidated the transformation of the pro- into anti-inflammatory status in macrophages, which is crucial in innate immunity and set the ground for the emerging therapeutic implications of itaconate. In this review, we point out that itaconate is a novel and pivotal metabolic determinant of the immunoregulatory response in macrophages and highlight studies that have improved our understanding of the connection between the immune response and metabolism. In addition, we shed light on the therapeutic potential of itaconate and its derivatives to treat inflammatory diseases.

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Section: Itaconate Regulates the Activating Transcription Factor 3mentioning

confidence: 99%

Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Based on our macrophage research experience ( 1 ) and other previous studies ( 19 , 20 ), we treated RAW264.7 macrophages with 1 μg/mL LPS for 24 h to induce the expression of inflammatory factors. We determined the iNOS expression levels using quantitative real time PCR, Western blot, and ELISA analyses, and evaluated TNF-α and IL-1β expression levels with ELISAs.…”

Section: Methodsmentioning

confidence: 99%

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

et al. 2021

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Macrophages play a critical role in innate and adaptive immunity, and the regulation of macrophage function in inflammatory disease treatment has been widely studied. Litsea cubeba is an important Chinese medicinal plant used for the treatment of inflammatory diseases. However, the inflammatory bioactive ingredients in L. cubeba and underlying molecular mechanisms are poorly understood. Herein, we first obtained and elucidated a novel isoquinoline alkaloid, Litcubanine A (LA), from L. cubeba. An in vitro study indicated that LA could significantly inhibit LPS-induced activation of inflammatory macrophages via the NF-κB pathway, leading to the decrease of inflammatory factors including iNOS, TNF-α, and IL-1β. Moreover, LA showed an inhibiting effect on the expression of NO in macrophages by directly binding to iNOS protein. Molecular simulation docking also demonstrated that active LA created an interaction with GLU 371 residue of iNOS via attractive charge derived from the N→O group, revealing its highly selective inhibition toward iNOS. By using the IκK inhibitor and iNOS inhibitor, these two regulatory targets of LA on inflammatory macrophages were verified in vitro. Finally, by using a caudal fin resection model in zebrafish larvae, and the skin wound healing model in mice, we proved in vivo that LA down-regulated the secretion of local inflammatory factors by inhibiting macrophage recruitment and activation at the early stage of the injury. Collectively, our study demonstrated that the novel isoquinoline alkaloid LA suppresses LPS-induced activation of inflammatory macrophages by modulating the NF-κB pathway, suggesting that inflammatory macrophage activation pathway is an effective target for inflammation treatment, and LA is a new pharmacophore for the development of novel and effective anti-inflammatory agents to regulate local macrophages.

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“…Tanga et al demonstrated for the first time that upon nerve injury (L5 nerve transection), behavioral hypersensitivity is induced via TLR4/NF-κB pathway, suggesting that TLR4 activation is a critical cause of the pathogenesis of neuropathic and chronic pain (Tanga et al, 2005). In this context, targeting TLR4/NF-κB pathway can be recommended as a decisive therapeutic strategy to relieve nerve injury-induced neuroinflammation and pain (Yadav and Surolia, 2019;Ye et al, 2020). Interestingly, TLR4 is much involved in iNOS activation (Deng et al, 2015).…”

Section: The Mb-induced Interruption Of Inos/no-nf-κb Signalingmentioning

confidence: 99%

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

Lee

Han

2021

Front. Neurosci.

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Methylene blue (MB) is a cationic thiazine dye, widely used as a biological stain and chemical indicator. Growing evidence have revealed that MB functions to restore abnormal vasodilation and notably it is implicated even in pain relief. Physicians began to inject MB into degenerated disks to relieve pain in patients with chronic discogenic low back pain (CDLBP), and some of them achieved remarkable outcomes. For osteoarthritis and colitis, MB abates inflammation by suppressing nitric oxide production, and ultimately relieves pain. However, despite this clinical efficacy, MB has not attracted much public attention in terms of pain relief. Accordingly, this review focuses on how MB lessens pain, noting three major actions of this dye: anti-inflammation, sodium current reduction, and denervation. Moreover, we showed controversies over the efficacy of MB on CDLBP and raised also toxicity issues to look into the limitation of MB application. This analysis is the first attempt to illustrate its analgesic effects, which may offer a novel insight into MB as a pain-relief dye.

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Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway

Cited by 37 publications

References 25 publications

Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress

Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress

Novel Isoquinoline Alkaloid Litcubanine A - A Potential Anti-Inflammatory Candidate

Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

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