The in vitro and in vivo anti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, via the blocking of the activation of the NF-κB and MAPK/p38 pathways

Fan, Hui; Gao, Zhenfang; Ji, Kai; Li, Xin; Wu, Jingbao; Liu, Yue; Wang, Xuekai; Liang, Haiyue; Liu, Yanan; Li, Xiaoting; Liu, Pan; Chen, Daquan; Zhao, Feng

doi:10.1016/j.phymed.2019.152864

Cited by 91 publications

(61 citation statements)

References 39 publications

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“…Osthole exhibited various pharmacological activities, including antioxidant [229][230][231], anticancer [232,233], and antiinflammatory properties [231,234,235].…”

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

“…Several reports of underlying molecular mechanisms reported that osthole displays a strong anti-inflammatory activity. Fan et al reported that osthole effectively and safely protected against ulcerative colitis (UC) via marked inhibition of TNF-α expression in the colon and markedly reduced MPO activity via suppression of NF-κB p65 and p-IκBα [234]. In an in vitro study, osthole inhibited the production of TNF-α, NO, PGE2, and IL-6 in LPS-induced macrophages [234].…”

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

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Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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“…Osthole exhibited various pharmacological activities, including antioxidant [229][230][231], anticancer [232,233], and antiinflammatory properties [231,234,235].…”

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

Section: Fraxin Fraxin (7-hydroxy-6-methoxy-8-[(2s3r4s5s 6rmentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

View full text Add to dashboard Cite

show abstract

“…Experiment data reveals that DSS triggers the degradation of IκBα and increases the protein expression of NF-κBp65 and p-IκBα in UC mice, but after treatment with osthole (10, 20, 40 mg/ kg), the expressions of NF-κBp65 and p-IκBα decrease, and expression of IκBα increases. Therefore, osthole treatment can relieve the symptoms of UC by inhibiting weight loss, colon shortening, and the DAI score, and blocking the up-regulation of TNF-α in serum and colon tissues by inhibiting the activation of NF-κB pathway [132].…”

Section: Astringent Medicinementioning

confidence: 99%

“…Attenuate NF-κB expression [127] Macrophages Inhibit NF-κB activation [129] Rubus coreanus RAW264.7 macrophages Attenuate the nuclear translocations of NF-κBp65 [130] RAW 264.7 cells Reduce NF-κB activity [131] Osthole DSS-induced colonic tissue Reduce the expression of NF-κBp65 [132] Tonifying Qi and activating blood category Tou Nong San TNBS-induced colon tissue Reduce the activation of the NF-κBp65 [134] Heat-clearing and drying dampness category…”

Section: Aom/dss-induced Colon Tissuementioning

confidence: 99%

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

Zhao

2020

Chin Med

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Nuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines' compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines' ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines' category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.

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“…Osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, exerts anti-inflammatory effects by blocking of the activation of the NF-κB and MAPK/p38 pathways [222]. Osthole (20 µM) can suppress HGF-induced EMT via repression of the c-Met/Akt/mTOR pathway in human breast cancer cells [223].…”

Section: Reversal Of Emt By Anti-inflammatory Natural Compoundsmentioning

confidence: 99%

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

Lee

2019

Cancers

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Epithelial mesenchymal transition (EMT) is a key process in the progression of malignant cancer. Therefore, blocking the EMT can be a critical fast track for the development of anticancer drugs. In this paper, we update recent research output of EMT and we explore suppression of EMT by natural anti-inflammatory compounds and pro-resolving lipids.A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the m ajor signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2) belongs to the runt-related transcription factor family [19]. Runx2 plays a key role in EMT of hepatocellular carcinoma (HCC) [20]. GATA transcription factors are also implicated in the EMT of cancer cells [21].A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the major signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2...

show abstract

The in vitro and in vivo anti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, via the blocking of the activation of the NF-κB and MAPK/p38 pathways

Cited by 91 publications

References 39 publications

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

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