Anti-inflammatory effect of the hexane fraction from Orostachys japonicus in RAW 264.7 cells by suppression of NF-κB and PI3K-Akt signaling

Lee, Hyeong-Seon; Bilehal, Dinesh; Lee, Gyeong-Seon; Ryu, Deok‐Seon; Kim, Hyun-Kyung; Suk, Dong-Hee; Lee, Dong‐Seok

doi:10.1016/j.jff.2013.04.004

Cited by 19 publications

(20 citation statements)

References 31 publications

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“…Studies has been reported that LPS was able to trigger the PI3K/Akt signal transducing pathway, which subsequently stimulated the NF‐κB signaling pathway in immune cells (Lee et al, ). To evaluate whether phyllanthin suppresses LPS‐induced NF‐κB activation via this pathway in macrophages, we investigated the effect of phyllanthin on the LPS‐induced phosphorylation of Akt via immunoblot.…”

Section: Resultsmentioning

confidence: 99%

Phyllanthin from Phyllanthus amarus inhibits LPS‐induced proinflammatory responses in U937 macrophages via downregulation of NF‐κB/MAPK/PI3K‐Akt signaling pathways

Harikrishnan

Jantan

Haque

et al. 2018

Phytotherapy Research

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Phyllanthin, a lignan from Phyllanthus species, has been reported to possess potent immunosuppressive properties on immune cells and on adaptive and innate immune responses in animal models. Herein, we investigated the inhibitory effects of phyllanthin isolated from Phyllanthus amarus on nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and PI3K-Akt signal transducing pathways in LPS-activated U937 cells. The lipopolysaccharide-stimulated excess production of prostaglandin was significantly suppressed by phyllanthin via the mechanisms linked to the modulatory effects of cyclooxygenase 2 protein and gene expression.Phyllanthin also significantly inhibited the release and mRNA expression of proinflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha). Phyllanthin also significantly downregulated the phosphorylation of IκBα, NF-κB (p65), and IKKα/β and suppressed the activation of JNK, ERK, p38MAPK, and Akt in a concentration-dependent manner. Additionally, phyllanthin downregulated the expression of upstream signaling molecules including MyD88 and toll-like receptor 4 that are essential for the activation of NF-κB, MAPKs, and PI3K-Akt signal transducing pathways.Based on these observations, phyllanthin may exert their suppressive effects on inflammatory process by mediating the release of inflammatory signaling molecules via the NF-κB, MAPKs, and PI3K-Akt signal transducing pathways. Thus, phyllanthin holds a great promise as a potential anti-inflammatory agent to treat various inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Phyllanthin from Phyllanthus amarus inhibits LPS‐induced proinflammatory responses in U937 macrophages via downregulation of NF‐κB/MAPK/PI3K‐Akt signaling pathways

Harikrishnan

Jantan

Haque

et al. 2018

Phytotherapy Research

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“…The anti-oxidant properties of HO-1 are related to the inhibition of formation of adhesion molecules, such as NO, and reduction of oxidative stress CO produced through the degradation of heme decreases the production of inflammatory mediators, such as cytokines and NO (18). Previous studies have shown that OJD and OJH effectively decreased NO production in LPS-stimulated RAW 264.7 cells (10,12). In the present study, OJD and OJH significantly induced HO-1 expression in LPS-stimulated RAW 264.7 cells in a dose- and time-dependent manner (Figs.…”

Section: Discussionmentioning

confidence: 99%

Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway

Lee

Kim

et al. 2014

BMB Reports

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Orostachys japonicus shows various biological activities. However, the molecular mechanisms remain unknown in LPS-stimulated macrophages. Here, we investigated the anti-oxidizing effect of the dichloromethane (DCM) and hexane fractions from O. japonicus (OJD and OJH) against oxidative stress in RAW 264.7 cells stimulated by LPS. OJD and OJH significantly increased the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Additionally, it was found that the expression of HO-1 was stimulated by Nrf2 activated via degradation of Keap1. ERK and p38 inhibitors repressed HO-1 induced by OJD and OJH in LPS-stimulated cells, respectively. In conclusion, these results suggest that OJD and OJH may block oxidative damage stimulated by LPS, via increasing the expression of HO-1 and Nrf2, and MAPK signaling pathway. [BMB Reports 2014; 47(2): 98-103]

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“…Cell line and reagents. The EtOAc fraction was prepared from O. japonicas in our laboratory using methods described previously (5,8,19,20). After analyzing the EtOAc fraction by GC-MS system, 12 peaks were identified.…”

Section: Methodsmentioning

confidence: 99%

Orostachys japonicus induces apoptosis and cell cycle arrest through the mitochondria-dependent apoptotic pathway in AGS human gastric cancer cells

Ryu

Kim

Kwon

et al. 2014

International Journal of Oncology

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We investigated the anticancer mechanisms of the ethylacetate (EtOAc) fraction from Orostachys japonicus in human gastric cancer (AGS) cells. Flow cytometric analysis revealed that the number of total apoptotic cells following treatment with the EtOAc fraction increased in a dose-dependent manner. In the cell cycle analyses, the EtOAc fraction increased the peak in the sub-G1, indicating apoptosis, and in the G₂/M phases in a dose-dependent manner. In the RT-PCR analysis, the expression of cyclin-dependent kinase 1 (CDK 1) and cyclin B1 decreased in a dose- and time-dependent manner. The results of western blotting revealed that the protein levels of p53, cytochrome c, and cleaved caspase-3, -8 and -9 proteins increased and those of B cell lymphoma-2 (bcl-2) and pro-caspase-3, -8 and -9 proteins decreased in a dose- and time-dependent manner, whereas the levels of bcl-2-associated x protein (bax) remained unchanged. Furthermore, the changes in the levels of pro-caspase-3, -8 and -9 and cleaved caspase-3, -8 and -9 were abolished by the pan-caspase inhibitor Z-VAD-FMK. In addition, phosphorylation of p38 and JNK increased in a time-dependent manner. These results, for the first time, provide an understanding of the potential anticancer activity of the O. japonicus, which functions through the induction of apoptosis and cell cycle arrest.

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Anti-inflammatory effect of the hexane fraction from Orostachys japonicus in RAW 264.7 cells by suppression of NF-κB and PI3K-Akt signaling

Cited by 19 publications

References 31 publications

Phyllanthin from Phyllanthus amarus inhibits LPS‐induced proinflammatory responses in U937 macrophages via downregulation of NF‐κB/MAPK/PI3K‐Akt signaling pathways

Phyllanthin from Phyllanthus amarus inhibits LPS‐induced proinflammatory responses in U937 macrophages via downregulation of NF‐κB/MAPK/PI3K‐Akt signaling pathways

Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway

Orostachys japonicus induces apoptosis and cell cycle arrest through the mitochondria-dependent apoptotic pathway in AGS human gastric cancer cells

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