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Molecules (Basel, Switzerland)
Jan 01, 2024;29 (1):

Salvianolic Acid B Alleviates Liver Injury by Regulating Lactate-Mediated Histone Lactylation in Macrophages.

Shian Hu, Zehua Yang, Ling Li, Qinwen Yan, Yutong Hu, Feng Zhou, Yang Tan, Gang Pei
Author Information
  1. Shian Hu: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
  2. Zehua Yang: Hunan Drug Inspection Center, Changsha 410000, China.
  3. Ling Li: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
  4. Qinwen Yan: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
  5. Yutong Hu: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
  6. Feng Zhou: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
  7. Yang Tan: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China. ORCID
  8. Gang Pei: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410000, China.
PMID: 38202819 DOI: 10.3390/molecules29010236

Abstract

Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of 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-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.

Keywords

H3K18la LDHA histone lactylation liver injury macrophages salvianolic acid B

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Grants

  1. 82174271/National Natural Science Foundation of China
  2. 202302/Key Discipline Project on Chinese Parmacology of Hunan University of Chinese Medicine

MeSH Term

Lactic Acid
Histones
Liver
Macrophages
Lactate Dehydrogenase 5
Benzofurans
Depsides

Chemicals

Lactic Acid
Histones
salvianolic acid B
Lactate Dehydrogenase 5
Benzofurans
Depsides
Journal Article

Word Cloud

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