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<p>Environmental exposure to heavy metals poses significant threats to human health. In view of side effects and limitations of present&#xa0;chelation therapy, further search for the potential agents counteracting metal toxicity is warranted. Salidroside, the main active ingredient of <i>Rhodiola rosea</i>, has shown potential as a natural agent for alleviating heavy metal toxicity.&#xa0;Our aim is to review the mechanisms by which salidroside mitigates toxicity induced by various heavy metals, providing a basis for developing protective strategies and offering a new perspective for future research. Research has shown that salidroside exerts protections against metal-induced toxicity through multiple mechanisms, including: (1) Regulating the HIF-1α/mTOR pathway to alleviate hypoxic injury; (2) Activating Nrf2/ARE antioxidant pathway; (3) Inhibiting mitochondrial pathway of apoptosis (Bcl-2/Bax/caspase-3); (4) Enhancing gap junctional intercellular communication (GJIC);(5) Down-regulating pro-inflammatory signaling through targeting MAPK and NF-κB pathways.Modulation of these signaling pathways, as well as certain other mechanisms, are involved in the protective effects of salidroside against metal toxicity in liver, brain, heart, kidneys and other organs, as evidenced from <i>in vivo</i> and <i>in vitro</i> studies. Compared with traditional chelating agents, salidroside has low toxicity and promising efficacy in alleviating cobalt, cadmium, lead, manganese, methylmercury, cisplatin, arsenic and iron toxicity. Therefore, salidroside holds promise as a new natural product for mitigating metal-induced toxicity and further studies are needed to clarify its clinical applicability.</p>

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Salidroside in heavy metal toxicity: a mechanistic review of antioxidant, anti-inflammatory, and anti-apoptotic pathways

  • 期刊论文

  • 发表日期：

    2026年4月22日

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  • Wenjie Sun,
  • Chenxu Hu,
  • Zhao Xiao,
  • Zehua Tao,
  • Chongyang Guo,
  • Yubin Zhang,
  • Soha M. Atya,
  • Anatoly V. Skalny,
  • Michael Aschner,
  • Bobo Yang,
  • Hongbin Zhou,
  • Alexey A. Tinkov,
  • Rongzhu Lu

摘要

Environmental exposure to heavy metals poses significant threats to human health. In view of side effects and limitations of present chelation therapy, further search for the potential agents counteracting metal toxicity is warranted. Salidroside, the main active ingredient of Rhodiola rosea, has shown potential as a natural agent for alleviating heavy metal toxicity. Our aim is to review the mechanisms by which salidroside mitigates toxicity induced by various heavy metals, providing a basis for developing protective strategies and offering a new perspective for future research. Research has shown that salidroside exerts protections against metal-induced toxicity through multiple mechanisms, including: (1) Regulating the HIF-1α/mTOR pathway to alleviate hypoxic injury; (2) Activating Nrf2/ARE antioxidant pathway; (3) Inhibiting mitochondrial pathway of apoptosis (Bcl-2/Bax/caspase-3); (4) Enhancing gap junctional intercellular communication (GJIC);(5) Down-regulating pro-inflammatory signaling through targeting MAPK and NF-κB pathways.Modulation of these signaling pathways, as well as certain other mechanisms, are involved in the protective effects of salidroside against metal toxicity in liver, brain, heart, kidneys and other organs, as evidenced from in vivo and in vitro studies. Compared with traditional chelating agents, salidroside has low toxicity and promising efficacy in alleviating cobalt, cadmium, lead, manganese, methylmercury, cisplatin, arsenic and iron toxicity. Therefore, salidroside holds promise as a new natural product for mitigating metal-induced toxicity and further studies are needed to clarify its clinical applicability.