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<p>Liver regeneration (LR) is crucial for liver function recovery, but there is still no effective treatment to promote LR. Chlorogenic acid (CGA) is the main active compound of <i>Eucommia ulmoides</i> Oliv., which is traditionally recorded to possess liver tonifying function. Our results revealed that CGA promoted LR in mice performed with 90% and 70% partial hepatectomy (PHx). CGA activated nuclear factor erythroid 2-related factor 2 (Nrf2) through interacting with kelch-like ECH-associated protein 1 (Keap1) during LR process. Nrf2 activation initiated the mRNA expression of E2 promoter binding factor 1 (E2F1) to accelerate cell cycle progression. Moreover, Nrf2 activation also initiated the mRNA expression of peroxisome proliferative-activated receptor, gamma, coactivator 1-alpha (PGC-1<i>α</i>) to promote ATP production, which supplied the sufficient energy to support LR. The importance of Nrf2 was further validated in Nrf2 knockout and liver specific <i>Keap1</i> genetic depletion mice. Moreover, Arg415 residue in the kelch domain of Keap1 was proved to be pivotal for the binding of CGA with Keap1. Our findings not only highlighted the critical role of Nrf2 during LR process, but also provided a solid research foundation for exploring CGA as a promising therapeutic candidate to promote LR.</p>

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Chlorogenic acid promotes liver regeneration after partial hepatectomy through activating Nrf2 via directly targeting Keap1

  • 期刊论文

  • 发表日期：

    2026年3月20日

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  • Hao-yu Xue,
  • Xin-nan Gu,
  • Zhuang Huang,
  • Ze Zhang,
  • Kun-yu Zhang,
  • Zhen-lin Huang,
  • Bin Lu,
  • Jian-gao Fan,
  • Meng-juan Wei,
  • Li-li Ji

摘要

Liver regeneration (LR) is crucial for liver function recovery, but there is still no effective treatment to promote LR. Chlorogenic acid (CGA) is the main active compound of Eucommia ulmoides Oliv., which is traditionally recorded to possess liver tonifying function. Our results revealed that CGA promoted LR in mice performed with 90% and 70% partial hepatectomy (PHx). CGA activated nuclear factor erythroid 2-related factor 2 (Nrf2) through interacting with kelch-like ECH-associated protein 1 (Keap1) during LR process. Nrf2 activation initiated the mRNA expression of E2 promoter binding factor 1 (E2F1) to accelerate cell cycle progression. Moreover, Nrf2 activation also initiated the mRNA expression of peroxisome proliferative-activated receptor, gamma, coactivator 1-alpha (PGC-1α) to promote ATP production, which supplied the sufficient energy to support LR. The importance of Nrf2 was further validated in Nrf2 knockout and liver specific Keap1 genetic depletion mice. Moreover, Arg415 residue in the kelch domain of Keap1 was proved to be pivotal for the binding of CGA with Keap1. Our findings not only highlighted the critical role of Nrf2 during LR process, but also provided a solid research foundation for exploring CGA as a promising therapeutic candidate to promote LR.