Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line

Kordulewska, Natalia; Topa, Justyna; Rozmus, Dominika; Jarmołowska, Beata

doi:10.3390/ijms222413634

Cited by 7 publications

(4 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 65 A similar relationship to this manuscript was found in the studies of Kordulewska et al, where OST decreased H4R expression in the Caco-2 line at each concentration tested. 35 Surprisingly, we found that H4R expression was higher under the influence of LPS than under that of histamine. The answer to these differences could be the fact that the skin of people with AD faces constant fluctuations and higher concentrations of histamine, which can desensitize the receptor to histamine even in vitro.…”

Section: Discussionmentioning

confidence: 69%

“…Osthole (OST) (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one) is a natural coumarin and a major chemical constituent of the plant Cnidium monnieri (L) Cusson and is considered a promising natural product that could be used pharmacologically in the future. These include anti-cancer [24][25][26] anti-inflammatory, [27][28][29][30] antioxidant, 31 anti-angiogenic, 32 anti-allergic 27,33,34 immunomodulatory 33,35 and hepatoprotective [36][37][38] activities. In our previous publications, we found that OST is immunosuppressive in peripheral blood mononuclear cells (PBMCs) isolated from children with allergies or asthma 27,30,[39][40][41][42][43] and autism spectrum disorders (ASD), in keratinocytes and fibroblast cell lines 28, and in a 3D skin model.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis

Kordulewska,

Król-Grzymała

2024

JIR

Self Cite

View full text Add to dashboard Cite

Introduction Chronic recurrent skin inflammation and severe itching in patients with atopic dermatitis (AD) significantly impair their quality of life. The H4 histamine receptor plays a key role in histamine-induced itching. During the skin inflammation associated with AD, pro-inflammatory mediators (interleukins, cytokines) are released from neurons. Ultimately, a cascade of reactions leads to the activation and sensitization of transient receptor potential channels (TRP), which exacerbate the inflammation and itching associated with AD. Osthole (OST) is a natural coumarin with a proven versatile pharmacological effect: anti-cancer, anti-inflammatory and immunomodulatory. However, the molecular mechanism of OST in relieving inflammation in histamine-mediated itching is not yet clear. Purpose In the studies presented, the possible effect of the OST action on the inhibition of the gene expression of the histamine H4 receptor and the key genes of the TRP channels as well as on the concentration of proinflammatory interleukins was analyzed. Methods Inflammation was induced in a 3D skin model and a keratinocyte cell line Normal Human Epidermal Keratinocytes (NHEK) identical to that of AD, and then OST was administered at various doses. The concentrations of IL-4/-13 were determined by ELISA. RNA was isolated from the 3D skin cells and the NHEK cell line, and the qPCR method was used to determine the expression of: IL-4α, H4R, TRPV1, TRPV4, TRPM8 analyzed. Results The study showed that OST significantly reduced the secretion of IL-4/-13 in a keratinocyte cell line and in a 3D skin model. In addition, OST was found to significantly decrease the gene expression of IL-4α, H4R, TRPV1, TRPV4 and increase TRPM8 in both the NHEK cell line and the organotypic 3D skin model. Conclusion The data obtained provide the first in vitro evidence of itch relief following the application of OST to atopic skin. Research on the use of OST as an active component of emollients in the treatment of AD should be continued in the future.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis

Kordulewska,

Król-Grzymała

2024

JIR

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, in animal models of colitis, isoliquiritigenin, paeoniflorin, resveratrol, quercetin, shikonin, piperine, imperatorin, roxithromycin, α‐linolenic acid, genistein and osthole independently exert anti‐inflammatory activity, typically via NF‐κB inhibition or a reduction in pro‐inflammatory cytokine secretion (i.e. TNF‐α, interleukin‐6, interleukin‐1β, interleukin‐8) (Abron et al, 2018; Andújar et al, 2012; Choi et al, 2015, 2016; Cui et al, 2010; Gu et al, 2017; Guo et al, 2020; Kordulewska et al, 2021; Luo & Luo, 2021; Reifen et al, 2015; Sotnikova et al, 2013). Interestingly, each of these substances has an inhibitory effect on MRGPRX2‐mediated mast cell degranulation (Callahan et al, 2020; Ding et al, 2021; Hou et al, 2018; Kumar et al, 2020; Ogasawara & Noguchi, 2021; Qiao et al, 2020; Wang, Wang, et al, 2021a; Wang, Zhang, et al, 2021b; Wang, Zhang, Li, et al, 2020b; Wang, Zhang, Wang, et al, 2020a; Zhang et al, 2020).…”

Section: Mrgprs In Mast‐cell Induced Gastrointestinal Inflammationmentioning

confidence: 99%

Mas‐related G protein‐coupled receptors in gastrointestinal dysfunction and inflammatory bowel disease: A review

Hawker

Zhang

Liu

2023

British J Pharmacology

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic debilitating condition, hallmarked by persistent inflammation of the gastrointestinal tract. Despite recent advances in clinical treatments, the aetiology of IBD is unknown, and a large proportion of patients are refractory to pharmacotherapy. Understanding IBD immunopathogenesis is crucial to discern the cause of IBD and optimise treatments. Mas‐related G protein‐coupled receptors (Mrgprs) are a family of approximately 50 G protein‐coupled receptors that were first identified over 20 years ago. Originally known for their expression in skin nociceptors and their role in transmitting the sensation of itch in the periphery, new reports have described the presence of Mrgprs in the gastrointestinal tract. In this review, we consider the impact of these findings and assess the evidence that suggests that Mrgprs may be involved in the disrupted homeostatic processes that contribute to gastrointestinal disorders and IBD.

show abstract

“… 9 Our previous studies also demonstrated several natural compounds, such as sarsasapogenin, 5 shikonin, 10 and celastrol, 11 that served as potential anti‐RA drugs. Osthole (OS) is an active ingredient that could be extracted from Cnidium , Angelica , and Citrus plants with low cost and presented anti‐inflammatory 12 , 13 , 14 and immunosuppressive activities 15 , 16 in human diseases. Nevertheless, the therapeutical effect of OS on RA and RA‐ILD is not fully understood, and the potential role of OS in improving the sensitivity of traditional anti‐RA drugs is yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Lin

Chen

Tao

et al. 2023

MedComm

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and RA interstitial lung disease (ILD) is a severe complication of RA. This investigation aims to determine the effect and underlying mechanism of osthole (OS), which could be extracted from Cnidium , Angelica , and Citrus plants and evaluate the role of transglutaminase 2 (TGM2) in RA and RA‐ILD. In this work, OS downregulated TGM2 to exert its additive effect with methotrexate and suppress the proliferation, migration, and invasion of RA‐fibroblast‐like synoviocytes (FLS) by attenuating NF‐κB signaling, resulting in the suppression of RA progression. Interestingly, WTAP‐mediated N6‐methyladenosine modification of TGM2 and Myc‐mediated WTAP transcription cooperatively contributed to the formation of a TGM2/Myc/WTAP‐positive feedback loop through upregulating NF‐κB signaling. Moreover, OS could downregulate the activation of the TGM2/Myc/WTAP‐positive feedback circuit. Furthermore, OS restrained the proliferation and polarization of M2 macrophages to inhibit the aggregation of lung interstitial CD11b + macrophages, and the effectiveness and non‐toxicity of OS in suppressing RA and RA‐ILD progression were verified in vivo. Finally, bioinformatics analyses validated the importance and the clinical significance of the OS‐regulated molecular network. Taken together, our work emphasized OS as an effective drug candidate and TGM2 as a promising target for RA and RA‐ILD treatment.

show abstract

Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line

Cited by 7 publications

References 83 publications

The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis

The Effect of Osthole on Transient Receptor Potential Channels: A Possible Alternative Therapy for Atopic Dermatitis

Mas‐related G protein‐coupled receptors in gastrointestinal dysfunction and inflammatory bowel disease: A review

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Contact Info

Product

Resources

About