2. Academic Validation
  3. An herbal formula Shenlian decoction upregulates M1/M2 macrophage proportion in hepatocellular carcinoma by suppressing complement cascade

An herbal formula Shenlian decoction upregulates M1/M2 macrophage proportion in hepatocellular carcinoma by suppressing complement cascade

  • Biomed Pharmacother. 2024 Jun 14:177:116943. doi: 10.1016/j.biopha.2024.116943.
Wenxuan Li 1,  Liping You 1,  Jiacheng Lin 2,  Jinghao Zhang 3,  Zhijia Zhou 1,  Tao Wang 1,  Yuelan Wu 1,  Chao Zheng 3,  Yueqiu Gao 4,  Xiaoni Kong 5,  Xuehua Sun 6
Affiliations

Affiliations

  • 1 Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 3 Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 4 Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: gaoyueqiu@hotmail.com.
  • 5 Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: xiaonikong@shutcm.edu.cn.
  • 6 Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: susan_sxh@shutcm.edu.cn.
PMID: 38878636 DOI: 10.1016/j.biopha.2024.116943
Abstract

The immunosuppressive microenvironment is a vital factor for the hepatocellular carcinoma (HCC) progression. However, effective treatment is lacking at current. Shenlian decoction (SLD) is a registered herbal therapy for the HCC treatment, but the underlying mechanism of SLD remains largely elusive. Here, we aimed to explore the anti-tumor effect of SLD in the treatment of HCC. SLD was intragastrically given after the tumor initiation in β-catenin/C-Met or DEN and CCl4 induced HCC mouse model. The tumor growth levels were evaluated by liver weight and histological staining. The tumor-infiltrating immune cells were detected by immunological staining and flow cytometry. The mechanism of the SLD was detected by non-targeted proteomics and verified by a cell co-culture system. The result showed that SLD significantly attenuated HCC progression. SLD promoted macrophage infiltration and increased the M1/M2 macrophage ratio within the tumor tissues. Non-targeted proteomics showed the inhibition of complement C5/C5a signaling is the key mechanism of SLD. Immunological staining showed SLD inhibited C5/C5a expression and C5aR1+ macrophage infiltration. The suggested mechanism was demonstrated by application of C5aR1 inhibitor, PMX-53 in mouse HCC model. Hepatoma cell-macrophage co-culture showed SLD targeted hepatoma cells and inhibited the supernatant-induced macrophage M2 polarization. SLD inhibited AMPK/p38 signaling which is an upstream mechanism of C5 transcription. In conclusion, we found SLD relieved immune-suppressive environment by inhibiting C5 expression. SLD could suppress the C5 secretion in hepatoma cells via inhibition of AMPK/p38 signaling. We suggested that SLD is a potential herbal therapy for the treatment of HCC by alleviating immune-suppressive status.

Keywords

Complement cascade; Hepatocellular carcinoma; SLD; Tumor-associated macrophages.

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