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    Article

    Synergistic Effects of Guan-Xin-Er-Hao and Hydroxysafflor Yellow A on Atherosclerosis in ApoE-/- Mice: Unveiling Antioxidant and Anti-Inflammatory Mechanisms

    Wenya Huang1, Le Zhang1, Li Zhou1, Zhifang Cai1, Kaige Wu2, Yu Wang2, Runze Zhou1, Min Xu1, Jia Li1, Yunke Huang1,3, Ping Ren1, Xi Huang1★★ Corresponding author

    1. 1Institute of Depression and Comorbidity, Nanjing University of Chinese Medicine, Nanjing, CHINA.
    2. 2Xiangya Hospital of Central South University, Changsha, CHINA.
    3. 3Women’s Hospital School of Medicine, Zhejiang University, Hangzhou, CHINA.

    CORRESPONDENCE

    Xi Huang

    Institute of Depression and Comorbidity, Nanjing University of Chinese Medicine, Nanjing-210023, CHINA.

    290606@njucm.edu.cn

    Received: 18-10-2024; Revised: 07-01-1; Accepted: 04-03-2025.

    Volume 17, Issue 2 · pp. 665–678 · PUBLISHED 2025 · DOI: 10.5530/pres.20252095

    View on Pharmacogn. Res. original site ↗

    ABSTRACT

    Background The Guan-Xin-Er-Hao (GXII) decoction, a traditional Chinese medicine, contains hydroxysafflor yellow A (HSYA) as its main active compound for treating coronary heart disease. Objectives This study aimed to assess the therapeutic efficacy of HSYA compared to GXII and elucidate its molecular mechanisms in combating atherosclerosis. Materials and Methods Guan-Xin-Er-Hao (GXII) was analyzed using HPLC-MS, which identified three main absorbable components: Hydroxysafflor Yellow A (HSYA), Ferulic Acid and Tanshinol. Among them, HSYA demonstrated the most pronounced effects in the in vitro experiments, leading to its selection for subsequent in vivo studies due to its high content and superior bioavailability within GXII. ApoE−/− mice were fed a high-fat diet for eight weeks and treated orally with GXII or HSYA. Atherosclerotic plaque areas and plasma lipid levels served as indicators of anti-atherosclerotic activity. Oxidative stress markers (malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase) and inflammatory mediators (tumor necrosis factor-α, vascular cell adhesion molecule-1, interleukin-1β) were evaluated using enzyme-linked immunosorbent assays, western blotting and reverse transcription-polymerase chain reaction. Results The Contribution Rate (CR) analysis indicated that HSYA significantly influenced serum lipid levels, oxidative stress markers and inflammatory protein/mRNA levels, with HSYA demonstrating a CR exceeding 90% relative to GXII. These findings underscore HSYA's predominant role within GXII in exerting anti-atherosclerotic effects through mitigation of oxidative stress and inflammation. Conclusion The synergistic actions of GXII and HSYA reveal a promising therapeutic approach for atherosclerosis, offering valuable insights into their antioxidant and anti-inflammatory mechanisms in ApoE−/− mice.

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      Huang, W., Zhang, L., Zhou, L., Cai, Z., Wu, K., Wang, Y., Zhou, R., Xu, M., Li, J., Huang, Y., Ren, P., & Huang, X. (2025). Synergistic Effects of Guan-Xin-Er-Hao and Hydroxysafflor Yellow A on Atherosclerosis in ApoE-/- Mice: Unveiling Antioxidant and Anti-Inflammatory Mechanisms. Pharmacognosy Research, 17(2), 665–678. https://doi.org/10.5530/pres.20252095