Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation
It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenoli...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/22/12128 |
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| author | Xingyu Liu Jie Su Geng Wang Lihua Zheng Guannan Wang Ying Sun Yongli Bao Shuyue Wang Yanxin Huang |
| author_facet | Xingyu Liu Jie Su Geng Wang Lihua Zheng Guannan Wang Ying Sun Yongli Bao Shuyue Wang Yanxin Huang |
| author_sort | Xingyu Liu |
| collection | DOAJ |
| description | It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from <i>Hyssopus cuspidatus</i> (<i>H. cuspidatus</i>), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases. |
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| language | English |
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| publishDate | 2021-11-01 |
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| spelling | doaj.art-a57da4c3b3d841feb224df8d95350b322023-11-22T23:37:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221212810.3390/ijms222212128Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB ActivationXingyu Liu0Jie Su1Geng Wang2Lihua Zheng3Guannan Wang4Ying Sun5Yongli Bao6Shuyue Wang7Yanxin Huang8National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun 130117, ChinaNMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun 130117, ChinaNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNational Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, ChinaNMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun 130117, ChinaIt seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from <i>Hyssopus cuspidatus</i> (<i>H. cuspidatus</i>), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.https://www.mdpi.com/1422-0067/22/22/12128anti-inflammation<i>Hyssopus cuspidatus</i>hyssopusidemacrophagesNF-κBphenolic glycoside |
| spellingShingle | Xingyu Liu Jie Su Geng Wang Lihua Zheng Guannan Wang Ying Sun Yongli Bao Shuyue Wang Yanxin Huang Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation International Journal of Molecular Sciences anti-inflammation <i>Hyssopus cuspidatus</i> hyssopuside macrophages NF-κB phenolic glycoside |
| title | Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation |
| title_full | Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation |
| title_fullStr | Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation |
| title_full_unstemmed | Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation |
| title_short | Discovery of Phenolic Glycoside from <i>Hyssopus cuspidatus</i> Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation |
| title_sort | discovery of phenolic glycoside from i hyssopus cuspidatus i attenuates lps induced inflammatory responses by inhibition of inos and cox 2 expression through suppression of nf κb activation |
| topic | anti-inflammation <i>Hyssopus cuspidatus</i> hyssopuside macrophages NF-κB phenolic glycoside |
| url | https://www.mdpi.com/1422-0067/22/22/12128 |
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