Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway

Cummins, Claire B.; Wang, Xiaofu; Lopez, Omar Nunez; Graham, Gabriel; Tie, Hong-Yan; Zhou, Jia; Radhakrishnan, Ravi S.

doi:10.3390/ijms19061567

Cited by 29 publications

(14 citation statements)

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“…After luteolin treatment, IL-6 affected either STAT3 phosphorylation or HO-1 expression was inhibited ( Figure 7B). A recent study indicated that luteolin treatment blocked STAT3 phosphorylation in hepatic stellate cells to attenuate the expression of STAT3-regulated proteins, which is in agreement with our study [57]. Similar results from the reporter assays confirmed that both AG490 and luteolin could downregulate IL-6-stimulated HO-1 expression in HepG2 cells (Figure 7).…”

Section: Discussionsupporting

confidence: 92%

Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells

et al. 2020

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Heme oxygenase-1 (HO-1) has several important roles in hepatocytes in terms of anti-inflammation, anti-apoptosis, and antioxidant properties. Interleukin-6 (IL-6) is a pleiotropic cytokine associated with liver regeneration and protection against injury. The aim of this study was to determine the potential crosstalk between HO-1 and IL-6, and to elucidate the signaling pathways involved in the induction of HO-1 by IL-6 in human hepatoma cells. Ectopic overexpression of HO-1 not only attenuated cell proliferation in vitro and in vivo, but also blocked the reactive oxygen species (ROS) induced by H2O2 and the pyocyanin in HepG2 or Hep3B cells. IL-6 expression was negatively regulated by HO-1, while IL-6 induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and HO-1 gene expression in HepG2 cells. The co-transfected HO-1 reporter vector and a protein inhibitor of the activated STAT3 (PIAS3) expression vector blocked the IL-6-induced HO-1 reporter activity. Both interferon γ and interleukin-1β treatments induced STAT1 but not STAT3 phosphorylation, which had no effects on the HO-1 expression. Treatments of AG490 and luteolin blocked the JAK/STAT3 signaling pathways which attenuated IL-6 activation on the HO-1 expression. Our results indicated that HO-1 is the antitumor gene induced by IL-6 through the IL-6/JAK/STAT3 pathways; moreover, a feedback circuit may exist between IL-6 and HO-1 in hepatoma cells.

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Section: Discussionsupporting

confidence: 92%

Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells

et al. 2020

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“…The sample that was not treated with luteolin was employed as the control. The mixture was incubated at 37 ºC at a speed of 150 rpm and the absorption of the bacterial suspension at 600 nm was measured after 2,4,8,12,16,20,24,28,32,36, and 40 h of incubation. The bacterial growth curve was plotted to analyse the effect of luteolin on T. pyogenes growth.…”

Section: Determination Of the Growth Curvementioning

confidence: 99%

“…Luteolin exerts its anti-inflammatory effects partly by regulating inflammatory mediators and different cytokines, which inhibit the signal transduction pathway. [19][20][21][22] Luteolin could hamper the progression of cancer through multiple mechanisms including the suppression of kinases, regulation of cell cycle, induction of apoptotic cell death, and reduction of transcription factors. [23][24][25][26] Many researchers have focused on the antiinflammatory and anti-tumour properties of luteolin; however, only minor attention has been paid to its good antibacterial activity.…”

Section: Introductionmentioning

confidence: 99%

<p>The Antibacterial Activity and Mechanism of Action of Luteolin Against <em>Trueperella pyogenes</em></p>

Guo¹,

Liu²,

Zhang³

et al. 2020

IDR

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Purpose: This research aimed to investigate the antibacterial activity and potential mechanism of luteolin against T. pyogenes. Materials and Methods: The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of luteolin against various T. pyogenes strains. The potential mechanism of action of luteolin was elucidated through testing and analysing the luteolin-induced alterations of T. pyogenes in several aspects, including cell wall, cell membrane, protein expression, nucleic acid content, topoisomerase activity and energy metabolism. Results: The MIC values of luteolin against various T. pyogenes isolates and ATCC19411 were 78 µg/mL. The increased cell membrane permeability, destruction of cell wall integrity and TEM images after exposure to luteolin showed that the cell wall and membrane were damaged. The content of total protein and nucleic acid in T. pyogenes decreased significantly after treatment with luteolin (1/2 MIC) for 12, 24, and 36 h. Moreover, a hypochromic effect was observed in the absorption spectrum of luteolin when deoxyribonucleic acid (DNA) was added. In addition, after treatment with luteolin, a decrease in nicked or relaxed DNA content, which was catalysed by T. pyogenes-isolated DNA topoisomerase, was observed. In addition, the adenosine triphosphate (ATP) content in cells and the activity of succinate dehydrogenase (SDH) both decreased when T. pyogenes was exposed to different concentrations (1/4 MIC, 1/2 MIC, 1 MIC, 2 MIC) of luteolin for 1 h. Conclusion: Luteolin showed distinct antibacterial activity against T. pyogenes by multiple actions, which mainly include destroying the integrity of the cell wall and cell membrane, influencing the expression of proteins, inhibiting nucleic acid synthesis, and interfering with energy metabolism.

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“…It has been reported inhibiting STAT3 pathway could exerts anti-inflammatory and anti-oxidative effect [19]. Lut has the ability to inhibit hepatic fibrosis through suppression of the STAT3 pathway [12]. Besides, increasingly number of researches have demonstrated the STAT3 was the potential target of Lut [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Renal fibrosis is the basic pathological manifestation of many chronic kidney diseases(CKD) and delaying renal fibrosis is an effective treatment for CKD [11]. The action mechanism of Lut varies, but the nuclear factor (NF)-κB pathway, MAPK in the activator protein (AP)-1 pathway, and signal transducer and activator of transcription 3 (STAT3) pathway are its major target transcription factors [12,13]. In this study, we mainly focused on STAT3 pathway because it was significantly suppressed by Lut compared with NF-κB and AP-1 in our preliminary experiment.STAT3 is an important member of the STAT family and mediates cell survival and proliferation [14].…”

Section: Introductionmentioning

confidence: 99%

Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

Zhang

Liu

et al. 2020

Exp Clin Endocrinol Diabetes

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Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN has many pathological changes, but tubular injury is considered to be a crucial pathological feature and plays a key role in the progression of DN. Accumulating studies have confirmed that Luteolin (3,4,5,7-tetrahydroxyflavone, Lut) possesses anti-inflammatory and antioxidant activities, which may play a role in kidney protection in DN. Objectives This paper described the effects of Lut on appropriated tubular injury in the kidneys of db/db mice and searched the possible mechanisms underlying the kidney protection effect in DN. Methods Twelve-week-old male C57BL/6 J db/db and C57BL/6 J db/m mice were used for the animal experiments. They were organized into the following five groups for the animal experiments: a db/m group (control, n=6); a db/db group(n=8) ; a db/db group receiving Lut (10 mg/kg/day, n=8)treatment by oral gavage; a db/db group receiving stattic (a selective STAT3 inhibitor,50 mg/Kg/day, n=8) treatment by oral gavage and a db/db group receiving both stattic and Lut treatment by oral gavage. Results In this study, we found that Lut might ameliorate glomerular sclerosis and interstitial fibrosis in DN mouse models through inhibiting the inflammatory response and oxidative stress. And it might play its biological function mainly through repressing the STAT3 activation. Conclusions Lut attenuates DN mainly via suppression of inflammatory response and oxidative response. STAT3 pathway is the potential target, which ultimately reduces renal fibrosis and delays the progress of DN.

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Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway

Cited by 29 publications

References 50 publications

Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells

Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells

<p>The Antibacterial Activity and Mechanism of Action of Luteolin Against <em>Trueperella pyogenes</em></p>

Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

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