Taoren Honghua Drug Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and RAW264.7 Cells

Wang, Yiru; Jia, Qiang; Zhang, Yifan; Wei, Jing; Liu, Ping

doi:10.3389/fphar.2020.01070

Cited by 25 publications

(16 citation statements)

References 34 publications

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“…Recent studies have shown that MAPKs signaling pathway is activated to attenuate inflammation in AS ( Wang et al, 2020a ; Wang et al, 2020b ; Lu et al, 2020 ), making MAPKs an ideal target of drug therapy. NF-κB, a critical transcription factor in inflammatory responses, can be activated by ox-LDL to promote AS ( Chávez-Sánchez et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

et al. 2021

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Guanxinkang decoction (GXK), a traditional Chinese medicinal drug, is used to treat cardiovascular disease. The aim of the study was to investigate the effects of GXK on inflammation in LDLR−/− mice and RAW264.7 cells. Fed with high fat diet for 12 weeks, the mice were randomly divided into six groups, then administered with oral 0.9% saline or GXK (7.24, 14.48, and 28.96 g/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL or ox-LDL plus different concentrations of GXK (1.25, 2.5, and 5 μg/ml), or ox-LDL plus GXK plus MAPKs activators. Serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-qPCR, plaque sizes by Oil Red O, α-SMA, caspase 3, NF-κB p65 and TNF-α production by immunofluorescence staining, and protein expression by Western Blot. The phagocytic ability of cells was determined by neutral red uptake assay. Efferocytosis-related proteins (AML, MERTK, TYRO3 and MFGE8) and MAPKs pathways were detected by Western Blot. Compared to mice fed with high fat diet, the mice with GXK showed lower cholesterol, triglyceride, low-density lipoprotein cholesterol, IL-1β, IL-6, and TNF-α, smaller plaque sizes, higher α-SMA, and lower caspase 3 and NF-κB p65 in aortic roots. RAW264.7 cells treated with ox-LDL plus GXK had lower IL-1β, IL-6, and TNF-α. GXK also increased the phagocytic ability of cells. High levels of AML, MERTK, TYRO3 and MFGE8, and decreased levels of iNOS, VCAM-1, LOX-1 and MCP-1, and phosphorylation of ERK1/2, JNK, p38, and NF-κB were detected in GXK-treated group. MAPKs activators reversed the effects of GXK in repressing inflammation and promoting phagocytosis. These results suggested that GXK could attenuate atherosclerosis and resolve inflammation via efferocytosis and MAPKs signaling pathways in LDLR−/− mice and RAW264.7 cells.

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Section: Discussionmentioning

confidence: 99%

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

et al. 2021

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“…Assessment of Serum Lipid in the ApoE −/− Mice Blood samples collected under chloral hydrate anesthesia were kept still for 1 h at room temperature and then centrifuged for 15 min at 18 × g. The upper transparent serum was transferred into a new tube and diluted with double distilled H 2 O (2:3) for examinations. Total cholesterol (CHOL), triglyceride (TG), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) levels were detected as previously described (Wang et al, 2020).…”

Section: Measurement Of Nitric Oxide Synthasementioning

confidence: 99%

Amygdalin Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and Bone Marrow-Derived Macrophages

et al. 2020

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Amygdalin, the main component of Prunus persica (L.) Stokes, has been used to treat atherosclerosis in mouse model due to its anti-inflammatory role. However, the underlying mechanism remains poorly understood. This study aimed to evidence the influence of amygdalin on high-fat diet-induced atherosclerosis in ApoE knock-out (ApoE −/− ) mice, and unravel its anti-inflammatory mechanism. ApoE −/− mice fed with high-fat diet for eight weeks were randomly divided into four groups and injected with amygdalin at the concentration of 0.08 or 0.04 mg/kg for 12 weeks. Additionally, bone marrow-derived macrophages were intervened with oxidized low-density lipoprotein (oxLDL) or lipopolysaccharide plus various concentrations of amygdalin for further exploration. Body weight, serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-PCR, plaque sizes by Oil Red O, lymphatic vessels of heart atrium and Tnfα production by immunofluorescence staining. MAPKs, AP-1 and NF-κB p65 pathways were also explored. Amygdalin decreased body weight, serum lipids, plaque size, lymphatic vessels and inflammatory cytokines (Il-6, Tnfα), Nos1 and Nos2, and increased Il-10 expression in ApoE −/− mice. In oxLDL-induced bone marrow-derived macrophages, amygdalin reduced inflammatory cytokines (Il-6, Tnfα), Nos1 and Nos2, and increased Il-10 production. These effects were associated with the decreased phosphorylation of Mapk1, Mapk8, Mapk14, Fos and Jun, and the translocation of NF-κB p65 from nucleus to cytoplasm. The results suggested that amygdalin could attenuate atherosclerosis and play an anti-inflammatory role via MAPKs, AP-1 and NF-κB p65 signaling pathways in ApoE −/− mice and oxLDL-treated bone marrow-derived macrophages.

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“… 41 - 43 Repressing MAPKs pathway may attenuate inflammation and AS. 44 , 45 We thus investigated the effects of Sal B on MAPKs phosphorylation. As the results showed, the expression levels of phosphorylated ERK1/2, JNK, and p38 in the aorta of MOD group and ox-LDL-induced or LPS-induced RAW264.7 cells were higher than those in CON group.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B attenuates the inflammatory response in atherosclerosis by regulating MAPKs/ NF-κB signaling pathways in LDLR-/- mice and RAW264.7 cells

Zhang

Feng

et al. 2022

Int J Immunopathol Pharmacol

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Objectives: Salvianolic acid B (Sal B) is the main effective water-soluble component of Salvia miltiorrhiza. In this study, the anti-inflammatory effect of Sal B was explored in high-fat-diet (HFD)-induced LDLR-/- mice and oxidized low-density-lipoprotein (ox-LDL)-induced or lipopolysaccharide (LPS)-induced RAW264.7 cells. Methods: The LDLR-/- mice were randomly divided into four groups after 12 weeks of high-fat diet. Then, the mice were administrated with 0.9% saline or Sal B (25 mg/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL/LPS, or ox-LDL/LPS plus different concentrations of Sal B (1.25 μg/mL, 2.5 μg/mL, 5 μg/mL), or ox-LDL plus Sal B plus MAPKs activators. ELISA was used for detecting serum lipid profiles and inflammatory cytokines, RT-qPCR used for gene expression, Oil Red O used for plaque sizes, and immunofluorescence staining used for NF-κB p65 and TNF-α production. Inflammation-related proteins and MAPKs pathways were detected by Western Blot. Results: The results showed that Sal B decreased the levels of serum lipids (TC, TG, and LDL-C), attenuated inflammatory cytokines, and improved lipid accumulation in the aorta. Sal B also attenuated the elevation of inflammatory cytokines induced by ox-LDL or LPS in RAW264.7 cells, and the phosphorylation of MAPKs/NF-κB pathways in the aorta and RAW264.7 cells, resulting in a significant decrease in the contents of p-JNK, p-ERK 1/2, p-P38, p-IκB, and p-NF-κB p65. Conclusions: Sal B could exert anti-inflammatory effects on atherosclerosis via MAPKs/NF-κB signaling pathways in vivo and in vitro.

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Taoren Honghua Drug Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and RAW264.7 Cells

Cited by 25 publications

References 34 publications

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells

Amygdalin Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and Bone Marrow-Derived Macrophages

Salvianolic acid B attenuates the inflammatory response in atherosclerosis by regulating MAPKs/ NF-κB signaling pathways in LDLR-/- mice and RAW264.7 cells

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