Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway
Abstract Background Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in li...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-023-00739-3 |
| _version_ | 1797849810793922560 |
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| author | Hongling Zhou Tangjia Yang Zibin Lu Xuemei He Jingyu Quan Shanhong Liu Yuyao Chen Kangtai Wu Huihui Cao Junshan Liu Linzhong Yu |
| author_facet | Hongling Zhou Tangjia Yang Zibin Lu Xuemei He Jingyu Quan Shanhong Liu Yuyao Chen Kangtai Wu Huihui Cao Junshan Liu Linzhong Yu |
| author_sort | Hongling Zhou |
| collection | DOAJ |
| description | Abstract Background Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. Methods Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. Results LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. Conclusion Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders. |
| first_indexed | 2024-04-09T18:51:16Z |
| format | Article |
| id | doaj.art-0b2930528f804c9698bcac0092c774b7 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-04-09T18:51:16Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-0b2930528f804c9698bcac0092c774b72023-04-09T11:26:51ZengBMCChinese Medicine1749-85462023-04-0118111210.1186/s13020-023-00739-3Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathwayHongling Zhou0Tangjia Yang1Zibin Lu2Xuemei He3Jingyu Quan4Shanhong Liu5Yuyao Chen6Kangtai Wu7Huihui Cao8Junshan Liu9Linzhong Yu10Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityThird Level Research Laboratory of State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical UniversityAbstract Background Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. Methods Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. Results LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. Conclusion Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders.https://doi.org/10.1186/s13020-023-00739-3LiquiritinLipopolysaccharideAcute lung injuryJNKNur77c-Jun |
| spellingShingle | Hongling Zhou Tangjia Yang Zibin Lu Xuemei He Jingyu Quan Shanhong Liu Yuyao Chen Kangtai Wu Huihui Cao Junshan Liu Linzhong Yu Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway Chinese Medicine Liquiritin Lipopolysaccharide Acute lung injury JNK Nur77 c-Jun |
| title | Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway |
| title_full | Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway |
| title_fullStr | Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway |
| title_full_unstemmed | Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway |
| title_short | Liquiritin exhibits anti-acute lung injury activities through suppressing the JNK/Nur77/c-Jun pathway |
| title_sort | liquiritin exhibits anti acute lung injury activities through suppressing the jnk nur77 c jun pathway |
| topic | Liquiritin Lipopolysaccharide Acute lung injury JNK Nur77 c-Jun |
| url | https://doi.org/10.1186/s13020-023-00739-3 |
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