Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Zou, Tong; Gao, Shan; Yu, Zhaolan; Zhang, Fuyong; Yao, Lan; Xu, Mengyao; Li, Junxin; Wu, Zhigui; Huang, Yilan; Wang, Shurong

doi:10.1038/s41598-022-18246-0

Cited by 12 publications

(6 citation statements)

References 62 publications

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“…Previous literature has reported that Sal B inhibits M1 macrophage polarization by suppressing NF-κB pathway activation and reducing Akt/mTOR activation [ 22 ]. In this paper, we revealed the potential mechanism by which Sal B inhibits macrophages trend toward M1 type from the perspective of the regulation of glycolysis and histone lactylation.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Hu,

Yang,

et al. 2024

Molecules

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Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B’s effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl4-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.

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Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Hu,

Yang,

et al. 2024

Molecules

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“…Its increased expression induces NF‐κB p65 translocation into the nucleus, promoting the transcription of proinflammatory factors IL‐6, IL‐1β, and TNF‐α. Furthermore, activation of NF‐κB and AKT/mTOR pathways results in the M1 phenotype polarization of RAW264.7 macrophages (Zou et al., 2022). Therefore, the quantitative expression of proinflammatory factors can determine the degree of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the anti‐inflammatory mechanism of quercetin 3,7‐dirhamnoside using an integrated pharmacology strategy

He,

Sun,

et al. 2023

Chem Biol Drug Des

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Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti‐inflammatory and pus‐removal properties. To explore its potential anti‐inflammatory mechanism, quercetin 3,7‐dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti‐inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti‐inflammatory QDR targets were identified. By analyzing the intersection between the protein–protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC‐alpha serine/threonine‐protein kinase (AKT1), Ras‐related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine‐protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor‐bound protein 2 (GRB2), and endothelin‐1 receptor (EDNRA). QDR has anti‐inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3‐kinase 3(PI3K)/AKT, cAMP, T‐cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein–ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein–ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)‐induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL‐6, IL‐1β, and TNF‐α. QDR downregulated the expression of p‐AKT1(Ser473)/AKT1 and p‐mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti‐inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti‐inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.

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“…Frontiers in Pharmacology frontiersin.org the LPS + IFN-γ-activated AKT/mTOR pathway and enhanced autophagy, while insulin activation of the mTOR signaling pathway counteracted the inhibitory effect of Sal B on M1 macrophage polarization, suggesting that Sal B can inhibit M1 macrophage polarization and reduce the release of inflammatory factors through the mTOR signaling pathway, thus exerting an anti-atherogenic effect (Zou et al, 2022). Tanshinone I and Tanshinone IIA are also important active substances extracted from Salvia miltiorrhiza Bunge.…”

Section: Othersmentioning

confidence: 99%

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review

Liu

et al. 2023

Front. Pharmacol.

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Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

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Salvianolic acid B inhibits RAW264.7 cell polarization towards the M1 phenotype by inhibiting NF-κB and Akt/mTOR pathway activation

Cited by 12 publications

References 62 publications

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages

Assessment of the anti‐inflammatory mechanism of quercetin 3,7‐dirhamnoside using an integrated pharmacology strategy

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review

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