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World J Hepatol. Jun 27, 2026; 18(6): 118215
Published online Jun 27, 2026. doi: 10.4254/wjh.118215
Discussion on the effect of Honghua Qinggan Shisanwei Wan on regulating macrophage polarization and alleviating liver injury
Chun-Li Ma, Xin Zhang, Xu Bao, Lin-Yun Zhao, Li-Li Cao, Cheng-You Ma, Ting Zhang, Mei Hong, Rui-Ping Hu, Yu-Long Bao
Chun-Li Ma, Xin Zhang, Xu Bao, Lin-Yun Zhao, Li-Li Cao, Mei Hong, Rui-Ping Hu, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010100, Inner Mongolia Autonomous Region, China
Cheng-You Ma, College of Geo-Exploration Science and Technology, Jilin University, Changchun 130026, Jilin Province, China
Ting Zhang, School of Basic Medical Sciences, Inner Mongolia Minzu University, Tongliao 028000, Inner Mongolia Autonomous Region, China
Yu-Long Bao, State Key Laboratory, Oncology Collaborative Innovation Center, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010100, Inner Mongolia Autonomous Region, China
Co-first authors: Chun-Li Ma and Xin Zhang.
Co-corresponding authors: Yu-Long Bao and Rui-Ping Hu.
Author contributions: Ma CL, Hong M, and Bao YL contributed to conceptualization, draft the original manuscript; Ma CL and Zhang X contributed equally to this manuscript as co-first authors; Ma CY, Bao YL, and Hu RP reviewed and edited the manuscript; Ma CL and Bao YL contributed to funding acquisition; Zhang X, Bao X, Zhao LY, Cao LL, and Zhang T contributed to methodology; Zhang X contributed to software; Hu RP contributed to supervision; Bao YL and Hu RP contributed equally to this manuscript as co-corresponding authors. All authors approved final revision of the paper.
Supported by Program for Innovative Research Team in Universities of Inner Mongolia Autonomous Region, No. NMGIRT2418; Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region, No. NJYT23052; the Natural Science Foundation of Inner Mongolia, No. 2024MS08054, No. 2024LHMS08024, No. 2023QN08059, and No. 2025YQ037; the General Project of Inner Mongolia Medical University, No. YKD2022MS006; the Key Project of Inner Mongolia Medical University, No. YKD2022ZD008; Science and Technology Plan of the Inner Mongolia Automous Region, No. 2021GG0098; Inner Mongolia Medical University 2025 Maker Cultivation Project, No. 101322025138 and No. 101322025102; the Duxue Talent Program of Inner Mongolia Medical University, No. ZY20243102; the Shanxue Talent Program of Inner Mongolia Medical University, No. ZY20242109; and Research Fund for Post-doctoral Fellows to Stay in Mongolia after Completing Their Post-doctoral Programs.
Institutional animal care and use committee statement: The experimental mice have obtained permission from Inner Mongolia Medical University (approval No. YKD202405027).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
Corresponding author: Yu-Long Bao, State Key Laboratory, Oncology Collaborative Innovation Center, School of Basic Medical Sciences, Inner Mongolia Medical University, No. 5 Xinhua Street, Hohhot 010100, Inner Mongolia Autonomous Region, China.
yulongbao@immu.edu.cn
Received: December 29, 2025
Revised: January 23, 2026
Accepted: April 24, 2026
Published online: June 27, 2026
Processing time: 173 Days and 19.5 Hours
BACKGROUND
Chronic liver injury is a significant global health concern, necessitating the development of effective therapeutic strategies. Honghua Qinggan Shisanwei Wan (HHQG), a traditional Mongolian medicinal formula comprising 13 herbal components, is reputed for its efficacy in clearing liver heat, detoxifying the liver, and treating “Yama” disease. However, the precise mechanisms by which HHQG regulates macrophage polarization - a critical process in liver inflammation and repair - remain inadequately defined.
AIM
To elucidate the effects of HHQG on macrophage polarization and to clarify the underlying molecular mechanisms using in vitro and in vivo experimental models.
METHODS
A carbon tetrachloride (CCL4)-induced liver injury mouse model and the RAW264.7 macrophage cell line were employed. The effects of HHQG on macrophage polarization were assessed through reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and cell counting kit-8 assays. This study employed the molecular docking method to simulate the interactions between the key compounds of HHQG (Apigenin, Emodin, Genistein, Kaempferol, Quercetin) and the nuclear receptor subfamily 4 group A member 1 (NR4A1) and NR4A2.
RESULTS
Toxicity experiments demonstrated that HHQG showed no significant hepatotoxicity at the tested doses. In the CCL4-induced liver injury model, HHQG significantly alleviated weight loss, reduced serum alanine aminotransferase and aspartate aminotransferase levels, ameliorated liver tissue necrosis, inflammatory infiltration and collagen deposition, and effectively inhibited the expression of inflammatory factors [tumor necrosis factor-α, CCL2, interleukin (IL)-1β, IL-6]. Transcriptome analysis indicated that HHQG activated peroxisome proliferator-activated receptor and lipid metabolism-related pathways, inhibited mitogen-activated protein kinase and other inflammation-related pathways, and regulated the expression of genes related to macrophage polarization (such as upregulating Nr4a1/2, Ppargc1a, and downregulating CCR2, Ly6C1/2). Quantitative real-time polymerase chain reaction and immunohistochemical assays showed that HHQG could reduce the infiltration of pro-inflammatory macrophages (decreased F4/80, CD11b, T-cell immunoglobulin and mucin domain-containing protein 4), promote the expression of M2-related anti-inflammatory factors (C-X3-C motif chemokine receptor 1, YM-1, transforming growth factor-β, IL-10), and upregulate the expression of transcription factors NR4A1/NR4A2 in a dose-dependent manner. In vitro RAW264.7 cell experiments further confirmed that 50 μg/mL and 100 μg/mL HHQG inhibited M1 pro-inflammatory genes and enhanced the expression of M2 genes and NR4A1/NR4A2. Molecular docking results showed that in terms of binding affinity, apigenin exhibited the lowest Vina score (-8.2) in the NR4A1 system, while quercetin showed the lowest Vina score (-8.2) in the NR4A2 system.
CONCLUSION
HHQG exhibits significant hepatoprotective effects by regulating macrophage polarization.
Core Tip: Honghua Qinggan Shisanwei Wan (HHQG), a traditional Mongolian medicinal formula, shows hepatoprotective potential. This study reveals HHQG inhibits M1 macrophage polarization and promotes M2 polarization, regulating the peroxisome proliferator-activated receptor signaling pathway by upregulating nuclear receptors nuclear receptor subfamily 4 group A member 1 and nuclear receptor subfamily 4 group A member 2. Molecular docking confirms key compounds’ stable binding with these receptors, highlighting HHQG’s promise for treating liver-related disorders.
