Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

Kim, Eun Jeong; Kim, Jeeho; Lee, Min Young; Sudhanva, Muddenahalli Srinivasa; Sundaravinayagam, Devakumar; Jeon, Young Jin

doi:10.4062/biomolther.2014.072

Cited by 20 publications

(11 citation statements)

References 37 publications

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“…Macrophages play an important role in inflammation and in the pathogenesis of autoimmune diseases, and the inhibition of morphological and functional changes of macrophages by silymarin therefore indicated its potential to act as an anti-inflammatory agent. Our data, and those of others, have demonstrated that silymarin protected pancreatic beta cells from destruction induced by proinflammatory cytokines [ 25 , 28 ]. Proinflammatory cytokines are known to induce the expression of iNOS mRNA and the production of NO, resulting in beta cell death [ 29 , 30 ] An in vivo study using a rat model further showed that silymarin increased insulin gene expression and beta cell proliferation [ 31 ].…”

Section: Discussionsupporting

confidence: 87%

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Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway

Kim

Lee

Jeon

2015

Korean J Physiol Pharmacol

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The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-κB), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-κB inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-κB activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-κB in mediating inflammatory responses in macrophages.

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Section: Discussionsupporting

confidence: 87%

“…RAW264.7 cells were treated with the indicated concentrations of silymarin in the presence of LPS (200 ng/ml) for 18 h. Culture supernatants were collected, and the accumulation of nitrite in culture supernatants was measured as an indicator of NO production in the medium, as previously described [ 23 , 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway

Kim

Lee

Jeon

2015

Korean J Physiol Pharmacol

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“…Silymarin is antiapoptotic in cytokine-induced MIN6 cell death. Treatment with 50 μ g/mL of silymarin reduced cytokine mixture-induced NF- κ B-activated NO production; the effect was mediated by ERK-1 and ERK-2 phosphorylation [ 114 ]. It has been reported that silymarin rescued pancreatic beta cell function in diabetic animals.…”

Section: Natural Bioactive Compounds For the Regulation Of Pancreamentioning

confidence: 99%

Plant-Derived Compounds Targeting Pancreatic Beta Cells for the Treatment of Diabetes

2015

Evidence-Based Complementary and Alternative Medicine

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Diabetes is a global health problem and a national economic burden. Although several antidiabetic drugs are available, the need for novel therapeutic agents with improved efficacy and few side effects remains. Drugs derived from natural compounds are more attractive than synthetic drugs because of their diversity and minimal side effects. This review summarizes the most relevant effects of various plant-derived natural compounds on the functionality of pancreatic beta cells. Published data suggest that natural compounds directly enhance insulin secretion, prevent pancreatic beta cell apoptosis, and modulate pancreatic beta cell differentiation and proliferation. It is essential to continuously investigate natural compounds as sources of novel pharmaceuticals. Therefore, more studies into these compounds' mechanisms of action are warranted for their development as potential anti-diabetics.

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“…The anti-inflammatory effects of silymarin is mediated through the inhibition of NF-κB regulated gene products including COX-2 and Prostaglandin E2 (PGE2), as well as inflammatory cytokines 57 , through suppressing the degradation of Inhibitory kappa B (IκB) degradation, preventing both the translocation of NF-κB into the nucleus and the activation of gene transcription associated with inflammation 58 .…”

Section: Discussionmentioning

confidence: 99%

A randomized trial assessing the efficacy of Silymarin on endometrioma-related manifestations

Mirzaei

Sadatmahalleh

Rouholamin

et al. 2022

Sci Rep

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To study the effect of silymarin on the Interleukin-6 (IL-6) level, size of endometrioma lesion, pain, sexual function, and Quality of Life (QoL) in women diagnosed with endometriosis. This randomized, double-blind placebo-controlled clinical trial was performed on 70 women with endometriosis which was divided into two groups of intervention and control. The intervention was 140 mg silymarin (or matching placebo) administered twice daily for 12 weeks. The volume of endometrioma lesions, the level of IL-6 concentration in serum, pain, sexual function, and QoL were analyzed before and after the intervention. The means of endometrioma volume (P = 0.04), IL-6 (P = 0.002), and pain (P < 0.001) were reduced significantly in the silymarin group after intervention. However, the QoL and female sexual function did not improve substantially in the two groups (P > 0.05). Silymarin significantly reduced interleukin-6 levels, sizes of endometrioma lesions, and pain-related symptoms. The trial has been registered in the Iranian Registry of Clinical Trials (IRCT20150905023897N5) on 4th February 2020 (04/02/2020) (https://en.irct.ir/trial/42215) and the date of initial participant enrollment was 2nd March 2020 (02/03/2020).

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Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

Cited by 20 publications

References 37 publications

Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway

Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway

Plant-Derived Compounds Targeting Pancreatic Beta Cells for the Treatment of Diabetes

A randomized trial assessing the efficacy of Silymarin on endometrioma-related manifestations

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