Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1
Sparstolonin B (SsnB), which is found in <i>Sparganium stoloniferum,</i> prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammato...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/23/18/10213 |
_version_ | 1797487547643854848 |
---|---|
author | Nayeon Kim Chaeyeong Kim Soo Ho Ryu Go Oun Kim Jong-Sup Bae |
author_facet | Nayeon Kim Chaeyeong Kim Soo Ho Ryu Go Oun Kim Jong-Sup Bae |
author_sort | Nayeon Kim |
collection | DOAJ |
description | Sparstolonin B (SsnB), which is found in <i>Sparganium stoloniferum,</i> prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1β expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation. |
first_indexed | 2024-03-09T23:50:13Z |
format | Article |
id | doaj.art-f59825e1593c481b98176d772a5b855a |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T23:50:13Z |
publishDate | 2022-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-f59825e1593c481b98176d772a5b855a2023-11-23T16:37:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181021310.3390/ijms231810213Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1Nayeon Kim0Chaeyeong Kim1Soo Ho Ryu2Go Oun Kim3Jong-Sup Bae4College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, KoreaSparstolonin B (SsnB), which is found in <i>Sparganium stoloniferum,</i> prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1β expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation.https://www.mdpi.com/1422-0067/23/18/10213Sparstolonin BendotheliumiNOSp-STAT-1 |
spellingShingle | Nayeon Kim Chaeyeong Kim Soo Ho Ryu Go Oun Kim Jong-Sup Bae Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 International Journal of Molecular Sciences Sparstolonin B endothelium iNOS p-STAT-1 |
title | Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 |
title_full | Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 |
title_fullStr | Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 |
title_full_unstemmed | Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 |
title_short | Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1 |
title_sort | anti inflammatory effect of sparstolonin b through inhibiting expression of nf κb and stat 1 |
topic | Sparstolonin B endothelium iNOS p-STAT-1 |
url | https://www.mdpi.com/1422-0067/23/18/10213 |
work_keys_str_mv | AT nayeonkim antiinflammatoryeffectofsparstoloninbthroughinhibitingexpressionofnfkbandstat1 AT chaeyeongkim antiinflammatoryeffectofsparstoloninbthroughinhibitingexpressionofnfkbandstat1 AT soohoryu antiinflammatoryeffectofsparstoloninbthroughinhibitingexpressionofnfkbandstat1 AT goounkim antiinflammatoryeffectofsparstoloninbthroughinhibitingexpressionofnfkbandstat1 AT jongsupbae antiinflammatoryeffectofsparstoloninbthroughinhibitingexpressionofnfkbandstat1 |