Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages
Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of <i>Salvia miltiorrhiza</i> Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide...
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MDPI AG
2024-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/1/236 |
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| author | Shian Hu Zehua Yang Ling Li Qinwen Yan Yutong Hu Feng Zhou Yang Tan Gang Pei |
| author_facet | Shian Hu Zehua Yang Ling Li Qinwen Yan Yutong Hu Feng Zhou Yang Tan Gang Pei |
| author_sort | Shian Hu |
| collection | DOAJ |
| description | Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of <i>Salvia miltiorrhiza</i> Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B’s effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl<sub>4</sub>-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury. |
| first_indexed | 2024-03-08T15:01:34Z |
| format | Article |
| id | doaj.art-a38783f4a8764f21ab3f4c3abadfd1f1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T15:01:34Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-a38783f4a8764f21ab3f4c3abadfd1f12024-01-10T15:04:35ZengMDPI AGMolecules1420-30492024-01-0129123610.3390/molecules29010236Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in MacrophagesShian Hu0Zehua Yang1Ling Li2Qinwen Yan3Yutong Hu4Feng Zhou5Yang Tan6Gang Pei7College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaHunan Drug Inspection Center, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaCollege of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, ChinaSalvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of <i>Salvia miltiorrhiza</i> Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B’s effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl<sub>4</sub>-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.https://www.mdpi.com/1420-3049/29/1/236macrophagessalvianolic acid BLDHAhistone lactylationH3K18laliver injury |
| spellingShingle | Shian Hu Zehua Yang Ling Li Qinwen Yan Yutong Hu Feng Zhou Yang Tan Gang Pei Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages Molecules macrophages salvianolic acid B LDHA histone lactylation H3K18la liver injury |
| title | Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages |
| title_full | Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages |
| title_fullStr | Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages |
| title_full_unstemmed | Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages |
| title_short | Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages |
| title_sort | salvianolic acid b alleviates liver injury by regulating lactate mediated histone lactylation in macrophages |
| topic | macrophages salvianolic acid B LDHA histone lactylation H3K18la liver injury |
| url | https://www.mdpi.com/1420-3049/29/1/236 |
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