Osthole, a Natural Coumarin Improves Cognitive Impairments and BBB Dysfunction After Transient Global Brain Ischemia in C57 BL/6J Mice: Involvement of Nrf2 Pathway

Chen, ZiWei; Mao, Xuexuan; Liu, AnMin; Gao, Xiaoyun; Chen, Xiaohong; Ye, MinZhong; Ye, JianTao; Liu, Peiqing; Xu, Suowen; Liu, Jianxin; He, Weichun; Lian, Qishen; Pi, Rongbiao

doi:10.1007/s11064-014-1483-z

Cited by 46 publications

(21 citation statements)

References 41 publications

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“…In another study, osthole protected against LPS-induced inflammation in BV2 cells via NF-κB suppression and upregulation of the Nrf2/HO-1 pathway dose dependently [245]. Additionally, osthole exerted neuroprotective effects against global cerebral I/R injury by reducing oxidative stress via the upregulation of the Nrf2/HO-1 signaling pathway [246]. The renoprotective effect of osthole against accelerated focal segmental glomerulosclerosis was mediated via Nrf2 activation and subsequently downregulation of the NF-κB-mediated COX-2 expression [247].…”

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

confidence: 95%

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

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

158

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

confidence: 95%

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

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

158

106

View full text Add to dashboard Cite

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“…The effective component, 7‐methoxy‐8‐(3‐methyl‐2‐butenyl)‐2H‐1‐benzopyran‐2‐one, is a natural coumarin first derived from the plant Cnidium monnieri (L.) Cusson (Figure A) . Recently, its potential antioxidant, immunomodulation, anti‐inflammatory, and anticancer effects have been explored . Osthole exerts neuroprotective effects against neurodegeneration, alleviating brain injury and decline in neurobehavioral function caused by both chronic and acute ischemia .…”

Section: Introductionmentioning

confidence: 99%

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas–Fas ligand and mitochondrial pathway

Liu

Chang

et al. 2018

Environmental Toxicology

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Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC.

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“…The mechanism of emodin has been extensively researched, and osthole, as an emerging Chinese medicine, has been widely investigated in recent years. Hao et al (25) demonstrated that osthole exhibited a therapeutic effect on pulmonary fibrosis, while Chen et al (26) reported beneficial effects of osthole on cognitive impairment in animals, which may occur via the Nrf2 pathway. These results indicate that osthole may act on the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of osthole against inflammation induced by lipopolysaccharide in BV2 cells

et al. 2018

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Inflammation and oxidative stress are implicated in the development of neurodegenerative diseases. Osthole is a compound that is extracted from She Chuang Zi, which is a type of traditional Chinese medicine. Osthole has previously been demonstrated to exhibit anticancer activities and has a low toxicity. However, to the best of our knowledge, the anti‑inflammatory effects of osthole in microglial cells have not been investigated extensively. The aim of the present study was to investigate the potential protective effects of osthole against inflammation induced by lipopolysaccharide (LPS) in microglial cells. The present study employed LPS‑stimulated BV2 mouse microglia to establish an inflammatory cell model and to investigate the anti‑inflammatory effects of osthole. Cells were pretreated with osthole for 1 h prior to LPS (10 µg/ml) stimulation. At 6 h after the addition of LPS, alterations in the levels of inflammatory factors, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β, were determined by ELISA. Furthermore, at 24 h after the addition of LPS, western blot analysis was performed to analyze the alterations in the protein expression of nuclear factor‑κB (NF‑κB) p65, phosphorylated‑NF‑κB p65, nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase (HO)‑1. The results demonstrated that the secretion of the inflammatory cytokines TNF‑α, IL‑6 and IL‑1β by LPS‑stimulated BV2 cells was significantly reduced by osthole treatment. Simultaneously, osthole treatment inhibited the LPS‑induced activation of the NF‑κB signaling pathway. In addition, osthole upregulated the expression of Nrf2 and HO‑1 in a dose‑dependent manner. Based on these results, osthole may exhibit anti‑inflammatory effects via the NF‑κB and Nrf2 pathways, indicating that osthole has the potential to be developed into an effective anti-inflammatory drug.

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Osthole, a Natural Coumarin Improves Cognitive Impairments and BBB Dysfunction After Transient Global Brain Ischemia in C57 BL/6J Mice: Involvement of Nrf2 Pathway

Cited by 46 publications

References 41 publications

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

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

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas–Fas ligand and mitochondrial pathway

Protective effects of osthole against inflammation induced by lipopolysaccharide in BV2 cells

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