Xanthotoxin suppresses LPS-induced expression of iNOS, COX-2, TNF-α, and IL-6 via AP-1, NF-κB, and JAK-STAT inactivation in RAW 264.7 macrophages

Lee, Seung-Bin; Lee, Woo Seok; Shin, Ji‐Sun; Jang, Dae Sik; Lee, Kyung Tae

doi:10.1016/j.intimp.2017.05.021

Cited by 112 publications

(77 citation statements)

References 49 publications

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“…These results come in line with previous findings that treatment with sitagliptin downregulated the mRNA levels of IL-6, COX-2 and iNOS in lipopolysaccharide-stimulated cardiomyocytes in a dose-dependent manner (S.-B. Lee, Lee, Shin, Jang, & Lee, 2017;S.-H. Lee et al, 2016). Furthermore, sitagliptin inhibited the increased protein expression of IL-6, TNF-α and IL-1β.…”

Section: R a F Tsupporting

confidence: 92%

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF

Khodeer

Bilasy

Farag

et al. 2019

Can. J. Physiol. Pharmacol.

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Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.

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Section: R a F Tsupporting

confidence: 92%

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF

Khodeer

Bilasy

Farag

et al. 2019

Can. J. Physiol. Pharmacol.

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“…Alternatively, treatment with xanthotoxin or umbelliferone significantly reduced hippocampal TNF-α and IL-6 levels in STZtreated rats, signifying their anti-inflammatory effects, which may contribute to their neuroprotective activity. These data are consistent with previous reports on the anti-inflammatory properties of these coumarins (Lee et al, 2017;Qin et al, 2017).…”

Section: Discussionsupporting

confidence: 94%

“…According to a recent study, xanthotoxin also possesses neuroprotective activity against scopolamine-induced cognitive impairment in rats (Skalicka-wozniak, Budzynska, Biala, & Boguszewska-czubara, 2018). Moreover, a study by Lee, Bin Lee, Shin, Jang, and Lee (2017) showed that xanthotoxin exerts anti-inflammatory properties by suppressing cyclooxygenase II (COX II), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) expression in lipopolysaccharide-induced RAW macrophages via the inhibition of nuclear factor kappa-B (NF-κB) and the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling.…”

Section: Introductionmentioning

confidence: 99%

Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation

Hindam

Sayed

Skalicka‐Woźniak

et al. 2020

Phytotherapy Research

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The aim of the present study was to assess the neuroprotective effects of xanthotoxin and umbelliferone in streptozotocin (STZ)‐induced cognitive dysfunction in rats. Animals were injected intracerebroventricularly (ICV) with STZ (3 mg/kg) once to induce a sporadic Alzheimer's disease (SAD)‐like condition. Xanthotoxin or umbelliferone (15 mg/kg, i.p.) were administered 5 hr after ICV‐STZ and daily for 20 consecutive days. Xanthotoxin or umbelliferone prevented cognitive deficits in the Morris water maze and object recognition tests. In parallel, xanthotoxin or umbelliferone reduced hippocampal acetylcholinestrase activity and malondialdehyde level. Moreover, xanthotoxin or umbelliferone increased glutathione content. These coumarins also modulated neuronal cell death by reducing the level of proinflammatory cytokines (tumour necrosis factor‐alpha and interleukin‐6), inhibiting the overexpression of inflammatory markers (nuclear factor κB [NF‐κB] and cyclooxygenase II), and upregulating the expression of NF‐κB inhibitor (IκB‐α). Interestingly, xanthotoxin diminished phosphorylated JAK2 and phosphorylated STAT3 protein expression, while umbelliferone markedly replenished nuclear factor erythroid‐derived 2‐like 2 (Nrf2) and haem oxygenase‐1 (HO‐1) levels. The current study provides evidence for the protective effect of xanthotoxin and umbelliferone in STZ‐induced cognitive dysfunction in rats. This effect may be attributed, at least in part, to inhibiting acetylcholinestrase and attenuating oxidative stress, neuroinflammation and neuronal loss.

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“…Our results demonstrated that PRG1-1 significantly increased the production of NO in RAW264.7 macrophages compared to the untreated group. It is acknowledged that iNOS and COX-2 are crucial in the regulation of NO and are the key mediators in many inflammatory conditions (Lee, Lee, Shin, Jang, & Lee, 2017). PRG1-1 treatment increased the expression levels of iNOS and COX-2, both of which are associated with NO production.…”

Section: Discussionmentioning

confidence: 99%

Immune-enhancing effects of a polysaccharide PRG1-1 from Russula griseocarnosa on RAW264.7 macrophage cells via the MAPK and NF-κB signalling pathways

Chen

Gong

et al. 2018

Food and Agricultural Immunology

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Immune-enhancing effects of a polysaccharide PRG1-1 from Russulagriseocarnosa on RAW264.7 macrophage cells via the MAPK and NF-κB signalling pathways, Food and Agricultural Immunology, 29:1, 833-844, ABSTRACTPolysaccharides are one of many bioactive compounds found in edible mushrooms. Edible mushrooms have become attractive as "health foods" and as source materials for immunomodulators. The aim of this project was to study the immunoregulatory effects of a purified polysaccharide derived from wild Russula griseocarnosa (PRG1-1) on macrophages. Our data showed that in RAW264.7 macrophage cells, PRG1-1 increased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, PRG1-1 increased the production of nitric oxide (NO) and cytokines, including interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α). Western blotting demonstrated that the regulation of NO and cytokines was mediated through the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways. Therefore, PRG1-1 has the capacity to activate macrophages via the NF-κB and MAPK pathways. These findings helped to elucidate the immunemodulatory properties of the polysaccharide from R. griseocarnosa. ARTICLE HISTORY

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Xanthotoxin suppresses LPS-induced expression of iNOS, COX-2, TNF-α, and IL-6 via AP-1, NF-κB, and JAK-STAT inactivation in RAW 264.7 macrophages

Cited by 112 publications

References 49 publications

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF

Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF

Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation

Immune-enhancing effects of a polysaccharide PRG1-1 from Russula griseocarnosa on RAW264.7 macrophage cells via the MAPK and NF-κB signalling pathways

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