Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways
Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of <i>Psoralea corylifolia</i> L. (PC). Although other constitu...
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MDPI AG
2023-02-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/2/103 |
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| author | You Chul Chung Ami Lee Jin Ah Ryuk Youn-Hwan Hwang |
| author_facet | You Chul Chung Ami Lee Jin Ah Ryuk Youn-Hwan Hwang |
| author_sort | You Chul Chung |
| collection | DOAJ |
| description | Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of <i>Psoralea corylifolia</i> L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E<sub>2</sub> [PGE<sub>2</sub>]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells’ inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells’ (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses. |
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| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-11T08:59:24Z |
| publishDate | 2023-02-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-e2a85e46015644b6ad721541faedc3362023-11-16T19:51:10ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-02-014521601161210.3390/cimb45020103Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling PathwaysYou Chul Chung0Ami Lee1Jin Ah Ryuk2Youn-Hwan Hwang3Herbal Medicine Research Division, Korea Institution of Oriental Medicine, Daejeon 34054, Republic of KoreaHerbal Medicine Research Division, Korea Institution of Oriental Medicine, Daejeon 34054, Republic of KoreaHerbal Medicine Research Division, Korea Institution of Oriental Medicine, Daejeon 34054, Republic of KoreaHerbal Medicine Research Division, Korea Institution of Oriental Medicine, Daejeon 34054, Republic of KoreaNatural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of <i>Psoralea corylifolia</i> L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E<sub>2</sub> [PGE<sub>2</sub>]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells’ inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells’ (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses.https://www.mdpi.com/1467-3045/45/2/103inflammationNF-κBchalconemacrophagesisodorsmanin ARAW 264.7 |
| spellingShingle | You Chul Chung Ami Lee Jin Ah Ryuk Youn-Hwan Hwang Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways Current Issues in Molecular Biology inflammation NF-κB chalcone macrophages isodorsmanin A RAW 264.7 |
| title | Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways |
| title_full | Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways |
| title_fullStr | Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways |
| title_full_unstemmed | Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways |
| title_short | Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways |
| title_sort | isodorsmanin a prevents inflammatory response in lps stimulated macrophages by inhibiting the jnk and nf κb signaling pathways |
| topic | inflammation NF-κB chalcone macrophages isodorsmanin A RAW 264.7 |
| url | https://www.mdpi.com/1467-3045/45/2/103 |
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