Chrysophanol affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway
10.19405/j.cnki.issn1000-1492.2025.03.014
- Author:
Lele Wang
1
;
Caixia Tan
1
;
Wei Zhang
1
;
Ruihan Ge
1
;
Chen Li
1
;
Xinmin Wang
2
;
Le Zhang
3
Author Information
1. Medical College，Shihezi University，Shihezi 832002; Xinjiang Provincial and Ethnic High Incidence Key Laboratory of Ministry of Education，Shihezi 832002
2. The First Affiliated Hospital of Shihezi University，Shihezi 832003; State Key Laboratory of Pathogenesis， Prevention and Treatment of High Incidence Diseases in Central Asia，Shihezi 832000
3. Medical College，Shihezi University，Shihezi 832002; Xinjiang Provincial and Ethnic High Incidence Key Laboratory of Ministry of Education，Shihezi 832002; State Key Laboratory of Pathogenesis， Prevention and Treatment of High Incidence Diseases in Central Asia，Shihezi 832000
- Publication Type:Journal Article
- Keywords:
chrysophanol;
AMPK / PGC-1α signaling pathway;
mitochondrial biosynthesis;
macrophages;
polarization
- From:
Acta Universitatis Medicinalis Anhui
2025;60(3):488-494
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore whether chrysophanol(CHR) affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway.
Methods :The molecular docking and binding ability of CHR with AMPK and PGC-1α were predicted by Autodock vina software. Human monocytes(THP-1) were induced to M0 macrophages by phorbol myristate acetate(PMA), and to M1 macrophages by lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ), which were set as Control group. M1 macrophages treated with CHR were set as CHR group. M1 macrophages treated with CHR combined with AMPK inhibitor(Compound C) were set as CHR+Compound C group. The mRNA expression levels of M1 macrophage markers(iNOS, CD86) and mitochondrial biosynthesis related genes(PGC-1α, NFR-1, TFAM) were detected by Quantitative real time polymerase chain reaction(qRT-PCR). The expression level of M1 macrophage marker iNOS was detected by immunofluorescence. The protein expression levels of AMPK, p-AMPK and PGC-1α were detected by Western blot.
Results :The docking results showed that the binding energies of CHR with AMPK and PGC-1α were-8.4 kcal/mol and-7.4 kcal/mol, respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established. Compared with the Control group, CHR treatment significantly increased the mRNA expression of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.001). Compared with CHR treatment group, CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.05). Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group(P<0.001). Compared with CHR treatment group,CHR combined with Compound C treatment reversed the inhibitory effect of CHR on i NOS protein expression(P<0.05). Western blot results showed that compared with the Control group,the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1α(P<0.001).Compared with CHR treatment group,CHR combined with Compound C treatment significantly decreased the protein expression levels of p-AMPK and PGC-1α(P<0.05).
Conclusion :Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1α signaling pathway to promote mitochondrial biosynthesis.
- Full text:2026012318140931364大黄酚通过AMPK_PGC...体生物合成影响巨噬细胞极化_王乐乐.pdf
