Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs

Shalini, V.; Pushpan, Chithra K.; Sindhu, Ganapathy; Jayalekshmy, A.; Helen, A.

doi:10.1016/j.imbio.2015.09.016

Cited by 41 publications

(38 citation statements)

References 43 publications

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“…Notably, the effect of CD74 and CD44-specific siRNAs in LPS-treated hepatocytes was much weaker than that in rMIF-treated hepatocytes. LPS affects a lot of inflammatory cytokines expression directly through inflammatory signaling pathways, such as NF-κB and MAPK signaling pathway4243. Although our results showed that MIF induced by LPS can mediate MCP-1 expression, but LPS itself has an ability to increase MCP-1 expression as well44.…”

Section: Discussionmentioning

confidence: 50%

Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

Xie

Yang

Tian

et al. 2016

Sci Rep

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Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation.

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Section: Discussionmentioning

confidence: 50%

Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

Xie

Yang

Tian

et al. 2016

Sci Rep

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“…shown to modulate the inflammatory reaction and the activation of inflammatory pathway (NF-kB/COX-2/ TNF-a/IL-1b). 26,35 Propofol was demonstrated to reduce inflammation through suppressing reactive oxygen species (ROS)-regulated Akt/IKKb/NF-kB signaling pathway. 36 Our previous study showed that propofol reduces brain inflammation and the expression of NF-kB, COX-2, TNF-a, and IL-1b in rats of SAH.…”

Section: Discussionmentioning

confidence: 99%

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Zhang

Chen

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

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Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor-kappa B (NF-kB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-kB p65, COX-2, TNF-a, and IL-1b, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

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“…In addition, compound 8 used in this study and PI3K/Akt inhibitor (LY294002) both inhibited the production of TNF- α [26]. Moreover, kolaviron (a tetramer of 4 ) inhibited inflammatory responses, including the production of IL-6, by inhibiting the activation of ERK1/2, NF κ B, p38MAPK, Akt, phospho-c-Jun, and JNK [44].…”

Section: Discussionmentioning

confidence: 99%

5,7‐Dihydroxyflavone Analogues May Regulate Lipopolysaccharide‐Induced Inflammatory Responses by Suppressing IκBα‐Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages

Nishina

Shimizu

Koketsu

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4′-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB. Phosphorylation of Akt and ERK5 (upstream of NFκB) by LPS stimulation was significantly regulated by 1 and 9, as well as by BIX 02189 and LY 294002, which are phosphorylation inhibitors of ERK5 and Akt, respectively. The results suggest that compounds 1 and 9 may suppress the levels of iNOS and COX2 by regulating phosphorylation of Akt, ERK5, and IκBα and thus NFκB-related signaling pathways, resulting in anti-inflammatory effects in the cells. Because 1 and 9 showed low cytotoxicity and regulated both PGE2 and NO production caused by inflammatory responses, they may hold promise as natural anti-inflammatory agents.

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Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs

Cited by 41 publications

References 43 publications

Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

5,7‐Dihydroxyflavone Analogues May Regulate Lipopolysaccharide‐Induced Inflammatory Responses by Suppressing IκBα‐Linked Akt and ERK5 Phosphorylation in RAW 264.7 Macrophages

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