〔Abstract〕 Abstract Objective To explore whether chrysophanol (CHR) affects macrophage polarization by promoting mito- chondrial biosynthesis through AMPK/PGC-1 αpathway. Methods The molecular docking and binding ability of CHR with AMPK and PGC-1 αwere predicted by Autodock vina software . Human monocytes ( THP-1) were in- duced 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 mi- tochondrial biosynthesis related genes (PGC-1 α, NFR-1 , TFAM) were detected by Quantitative real time polymer- ase chain reaction (qRT-PCR) . The expression level of M1 macrophage marker iNOS was detected by immunofluo- rescence . The protein expression levels of AMPK , p-AMPK and PGC-1 αwere detected by Western blot. Results The docking results showed that the binding energies of CHR with AMPK and PGC-1 αwere - 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 mito- chondrial biosynthesis-related genes PGC-1 α, 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 mitochon- drial biosynthesis-related genes PGC-1 α, 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 iN- OS 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-1 α ( P < 0. 001) . Compared with CHR treatment group , CHR combined with Compound C treatment significantly decreased the pro- tein expression levels of p-AMPK and PGC-1 α ( P < 0. 05) . Conclusion Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1 αsignaling pathway to promote mitochondrial biosynthesis .