Benzoylaconine Modulates LPS-Induced Responses Through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells

Zhou, Changkai; Gao, Jing; Ji, Hongyan; Li, Wenjing; Liu, Donghua; Guo, Qie; Zhou, Ling; Jing, Fanbo

doi:10.1007/s10753-021-01478-z

Cited by 17 publications

(11 citation statements)

References 35 publications

(35 reference statements)

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“…Both of these are crucial topics for further research in the future. Similar to our previous findings [ 35 ], results from other current research suggest that monoester-diterpenoid alkaloids in Aconitum plants like BMA, BAC, and BHA can attenuate inflammatory responses, probably through the same mechanism.…”

Section: Discussionsupporting

confidence: 92%

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells

Zhou

Gao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Benzoylmesaconine (BMA), the most abundant monoester alkaloid in Aconitum plants, has some biological activities and is a potential therapeutic agent for inflammation-related diseases. However, the potential anti-inflammatory mechanisms of BMA have not been clarified. Purpose. This study aimed to investigate the underlying molecular mechanisms of the anti-inflammatory action of this compound using lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Methods. The release of pro-inflammatory cytokines and mediators were detected by nitric oxide (NO) assays, reactive oxygen species (ROS) assays, and enzyme-linked immunosorbent assays (ELISA) in LPS-activated RAW264.7 macrophage cells. Quantitative real-time PCR was used to measure the gene expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cell viability was determined using a cell counting kit-8 (CCK-8) assay. The expression of iNOS, COX-2, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB)-related proteins were detected by western blot, and nuclear translocation of p65 was observed by immunofluorescence. Results. BMA significantly decreased the production of IL-1β, IL-6, TNF-α, PGE2, NO, and ROS and inhibited the protein and mRNA levels of COX-2 and iNOS in LPS-activated RAW264.7 macrophages. Moreover, LPS-induced phosphorylation of IκBα, JNK, p38, and ERK; degradation of IκBα; and nuclear translocation of p65 were significantly suppressed by BMA treatment. Conclusion. These findings demonstrate that the anti-inflammatory effect of BMA was through the suppression of the NF-κB and MAPK signaling pathways and that it may be a therapeutic agent targeting specific signal transduction events required for inflammation-related diseases.

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Section: Discussionsupporting

confidence: 92%

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells

Zhou

Gao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The development of doxorubicin-mediated chronic HF is attenuated by Salsolinol via improving the mitochondrial function in cardiomyocytes [ 21 ]. Although BAC has been verified to play a part in the mitochondrial biogenesis [ 11 ], RAW264.7 cell responses [ 12 ], whether BAC has an effect on HF through modulating the mitochondrial function was unknown. In the current study, different concentrations of BAC were used to treat H9C2 cells, which enhanced H9C2 cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, BAC increased the cell viability and oxygen consumption rate and induced mitochondrial biogenesis in mice through the activation of AMPK signaling [ 11 ]. BAC regulated lipopolysaccharide-triggered RAW264.7 cell responses via modulating the toll-like receptor-mediated NF-κB and MAPK signaling pathways [ 12 ]. BAC exerted biological activities and pharmacological effect in rats [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Benzoylaconine improves mitochondrial function in oxygen-glucose deprivation and reperfusion-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis

Chen¹,

Yan

Zhang³

2022

Korean J Physiol Pharmacol

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Heart failure (HF) has become one of the severe public health problems. The detailed role of mitochondrial function in HF was still unclear. Benzoylaconine (BAC) is a traditional Chinese medicine, but its role in HF still needs to be explored. In this study, oxygen-glucose deprivation and reperfusion (OGD/R) was executed to mimic the injury of H9C2 cells in HF. The viability of H9C2 cells was assessed via MTT assay. OGD/R treatment markedly decreased the viability of H9C2 cells, but BAC treatment evidently increased the viability of OGD/R-treated H9C2 cells. The apoptosis of H9C2 was enhanced by OGD/R treatment but suppressed by BAC treatment. The mitochondrial membrane potential was evaluated via JC-1 assay. BAC improved the mitochondrial function and suppressed oxidative stress in OGD/R-treated H9C2 cells. Moreover, Western blot analysis revealed that the protein expression of p-AMPK and PGC-1α were reduced in OGD/R-treated H9C2 cells, which was reversed by BAC. Rescue assays indicated that AMPK attenuation reversed the BAC-mediated protective effect on OGD/R-treated cardiomyocytes. Moreover, BAC alleviated myocardial injury in vivo . In a word, BAC modulated the mitochondrial function in OGD/R-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis. The findings might provide support for the application of BAC in the treatment of HF.

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“…LPS binds to Tolllike receptor 4 (TLR4) on the plasma membranes of macrophage RAW264.7 cells, and the signaling with LPS/TLR4 pathway is transmitted into the cells [30][31][32]. Notably, TLR4 signaling activates NF-κB and MAPK signaling in RAW264.7 cells [33][34][35]. Also, there is growing evidence that LPS internalizes and binds intracellular proteins and receptors [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

“…Also, there is growing evidence that LPS internalizes and binds intracellular proteins and receptors [30][31][32]. The production of TNF-α, IL-6, IL-1β, or PGE 2 with LPS treatment may be implicated in intracellular signaling NF-κB p65, and/or MAPK in RAW264.7 cells [33][34][35]. COX-1 and COX-2 may be implicated in the production of PGE2 in RAW264.7 cells [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol expresses the anti-inflammatory effects in mouse macrophages RAW264.7 cells in vitro

Yamaguchi

Yoshiike²,

Watanabe³

et al. 2022

Preprint

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Background: Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines are produced in macrophages with stimulation of lipopolysaccharide (LPS) and are used as biomarkers participating in diverse disease conditions. The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) was initially identified in the Pacific oyster Crassostrea Gigas. DHMBA has properties to reduce oxidative stress as radical scavenging and increase the production of antioxidant proteins. The pharmacologic role of DHMBA, however, has been poorly understood.Methods and Results: This study has been undertaken to investigate whether DHMBA attenuates growth, cytokine production, and osteoclastogenesis in inflammatory mouse macrophage RAW264.7 cells. Culturing with DHMBA (1-1000 µM) suppressed the growth and stimulated the death of RAW264.7 cells in vitro, leading to decrease in cell number. Mechanistically, DHMBA treatment decreased the levels of Ras, PI3K, Akt, MAPK, phospho-MAPK, and mTOR of signaling factors to promote the proliferation, and it raised the levels of p53, p21, Rb, and regucalcin, which are cell growth suppressors. The levels of caspase-3 and cleaved caspase-3 were increased by DHMBA treatment. Culturing with DHMBA suppressed productions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1β, or prostaglandin E2, were enhanced by LPS stimulation. Notably, the levels of NF-κB p65 were increased by LPS treatment, and this increase was repressed by DHMBA treatment. LPS treatment stimulated osteoclastogenesis of RAW264.7 cells. This stimulation was blocked by DHMBA treatment.Conclusion: DHMBA was found to potentially suppress the activity of inflammatory macrophages in vitro, suggesting therapeutic usefulness in inflammatory conditions.

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Benzoylaconine Modulates LPS-Induced Responses Through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells

Cited by 17 publications

References 35 publications

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells

Benzoylaconine improves mitochondrial function in oxygen-glucose deprivation and reperfusion-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis

The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol expresses the anti-inflammatory effects in mouse macrophages RAW264.7 cells in vitro

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