Umbelliferone Ameliorates Complete Freund Adjuvant–Induced Arthritis via Reduction of NF-κB Signaling Pathway in Osteoclast Differentiation

Guo-juan, WU; Nie, Wenbo; Qiu, Wang; Hao, Youguo; Gong, Sitang; Zheng, Yuxin; Lv, Hao

doi:10.1007/s10753-021-01418-x

Cited by 20 publications

(10 citation statements)

References 42 publications

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“…Our results suggest that the regulation of miR27a by the p38 pathway may occur at the transcriptional level, but the direct regulatory factors have not been found yet, and we will further explore it in future studies. However, although NF-κB has been reported to be involved in many biological processes in many literatures, 47,48 our results show that NFκB inhibitors only increase the expression of the precursor miR27a, but have no significant effect on miR27a, this may be due to the shear and degradation of the precursor miR27a. Interestingly, TNFα is an important factor in disc degeneration 49,50 ; thus, these results suggest that TNFα induces apoptosis, the inflammatory response and extracellular matrix degradation and promotes FSTL1 expression when IDD occurs.…”

Section: Discussioncontrasting

confidence: 62%

TNF‐α induces up‐regulation of MicroRNA‐27a via the P38 signalling pathway, which inhibits intervertebral disc degeneration by targeting FSTL1

Shi

Wang

et al. 2021

J Cellular Molecular Medi

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The mechanism of intervertebral disc degeneration is still unclear, and there are no effective therapeutic strategies for treating this condition. miRNAs are naturally occurring macromolecules in the human body and have many biological functions. Therefore, we hope to elucidate whether miRNAs are associated with intervertebral disc degeneration and the underlying mechanisms involved. In our study, differentially expressed miRNAs were predicted by the GEO database and then confirmed by qPCR and in situ hybridization. Apoptosis of nucleus pulposus cells was detected by flow cytometry and Bcl2, Bax and caspase 3. Deposition of extracellular matrix was assessed by Alcian blue staining, and the expression of COX2 and MMP13 was detected by immunofluorescence, Western blot and qPCR. Moreover, qPCR was used to detect the expression of miR27a and its precursors. The results showed that miR27a was rarely expressed in healthy intervertebral discs but showed increased expression in degenerated intervertebral discs. Ectopic miR27a expression inhibited apoptosis, suppressed the inflammatory response and attenuated the catabolism of the extracellular matrix by targeting FSTL1. Furthermore, it seems that the expression of miR27a was up‐regulated by TNF‐α via the P38 signalling pathway. So we conclude that TNF‐α and FSTL1 engage in a positive feedback loop to promote intervertebral disc degeneration. At the same time, miR27a is up‐regulated by TNF‐α via the P38 signalling pathway, which ameliorates inflammation, apoptosis and matrix degradation by targeting FSTL1. Thus, this negative feedback mechanism might contribute to the maintenance of a low degeneration load and would be beneficial to maintain a persistent chronic disc degeneration.

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Section: Discussioncontrasting

confidence: 62%

TNF‐α induces up‐regulation of MicroRNA‐27a via the P38 signalling pathway, which inhibits intervertebral disc degeneration by targeting FSTL1

Shi

Wang

et al. 2021

J Cellular Molecular Medi

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“…Such suppressed NF-κB canonical signaling can decrease the expression of inflammatory cytokines, adhesion molecules, and other promoters in the inflammatory cascade ( Liu et al, 2017 ). The conclusion of the two compounds suppressing NF-κB signaling can be supported by other studies showing that umbelliferone ( Ouyang et al, 2019 ; Wu G et al, 2021 ) and scopoletin ( Li et al, 2009 ; Chen et al, 2021 ) can effectively suppress phosphorylation of specific NF-κB subunits (e.g. p65 and IĸBα) and expression of downstream genes (e.g.…”

Section: Resultsmentioning

confidence: 67%

“…There have been reports on anti-rheumatic performances of umbelliferone and scopoletin. On a rat model with Freund’s complete adjuvant (FCA)-induced arthritis, umbelliferone was found to reduce pro-inflammatory cytokines, such as TNF-α and IL-1β ( Ouyang et al, 2019 ; Wu G et al, 2021 ), and osteoclastogenesis biomarkers, such as MMP-3 and MMP-9 ( Wu G et al, 2021 ); according to the authors, such reduced gene expressions were due to suppressed NF-κB signaling upon umbelliferone administration. On the same rat model, scopoletin significantly alleviated clinical symptoms, immune responses, and joint pathological conditions ( Chen et al, 2021 ); scopoletin was also proved to induce RA FLS apoptosis by inhibiting NF-κB activation ( Li et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Umbelliferone and scopoletin target tyrosine kinases on fibroblast-like synoviocytes to block NF-κB signaling to combat rheumatoid arthritis

et al. 2022

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Rheumatoid arthritis (RA) is a complex autoimmune condition primarily affecting synovial joints, which targeted synthetic drugs have damaging safety issues. Saussurea laniceps, a reputed anti-rheumatic medicinal herb, is an excellent place to start looking for natural products as safe, effective, targeted therapeutics for RA. Via biomimetic ultrafiltration, umbelliferone and scopoletin were screened as two anti-rheumatic candidates with the highest specific affinities towards the membrane proteomes of rheumatic fibroblast-like synoviocytes (FLS), the pivotal effector cells in RA. In vitro assays confirmed that the two compounds, to varying extents, inhibited RA-FLS proliferation, migration, invasion, and NF-κB signaling. Network pharmacology analysis and molecular docking analysis jointly revealed that umbelliferone and scopoletin act on multiple targets, mostly tyrosine kinases, in combating RA. Taken together, our present study identified umbelliferone and scopoletin as two major anti-rheumatic components from SL that may bind and inhibit tyrosine kinases and subsequently inactivate NF-κB in RA-FLSs. Our integrated drug discovery strategy could be valuable in finding other multi-target bioactive compounds from complex matrices for treating multifactorial diseases.

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“…The contribution of natural products to the treatment of immune mediated diseases is evidenced by the identification of several NFκB inhibitors. 11 , 12 Although East Asian countries have a vast history of medicinal achievements, that keeps growing until today; in Argentina, the study of products obtained from regional plants is emerging and has been proclaimed a national scientific priority. 13 In particular, there are several species of native plants in Mendoza (Argentina) with folkloric reports of anti-inflammatory uses but none of them has been thoroughly studied with respect to its suppressive properties over lymphocytes proliferation or function.…”

Section: Introductionmentioning

confidence: 99%

Prosopis strombulifera aqueous extract reduces T cell response and ameliorates type I diabetes in NOD mice

Persia

Abba

Pascual

et al. 2023

Journal of Traditional and Complementary Medicine

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Umbelliferone Ameliorates Complete Freund Adjuvant–Induced Arthritis via Reduction of NF-κB Signaling Pathway in Osteoclast Differentiation

Cited by 20 publications

References 42 publications

TNF‐α induces up‐regulation of MicroRNA‐27a via the P38 signalling pathway, which inhibits intervertebral disc degeneration by targeting FSTL1

TNF‐α induces up‐regulation of MicroRNA‐27a via the P38 signalling pathway, which inhibits intervertebral disc degeneration by targeting FSTL1

Umbelliferone and scopoletin target tyrosine kinases on fibroblast-like synoviocytes to block NF-κB signaling to combat rheumatoid arthritis

Prosopis strombulifera aqueous extract reduces T cell response and ameliorates type I diabetes in NOD mice

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