The clinical application of polymyxin B (PMB) is limited by its nephrotoxic effects, making the reduction of PMB‐induced nephrotoxicity has become a pressing concern for clinicians. Tetrahydrocurcumin (THC), known for its beneficial characteristics in biological functions, presents an attractive option for intervention therapy to mitigate PMB‐induced nephrotoxicity. However, the underlying mechanism of how THC mitigates PMB‐induced nephrotoxicity is still poorly understood. Here, we first evaluated the potential of THC intervention therapy to mitigate PMB‐induced nephrotoxicity in an in vitro model of PMB‐induced cell injury. Moreover, we demonstrated that THC effectively protected HK‐2 cells from PMB‐induced apoptosis by using cell counting kit‐8 and flow cytometry assay. THC could also suppress PMB‐induced endoplasmic reticulum (ER) stress via PERK/eIF2α/ATF4/CHOP pathway. In addition, using PERK inhibitor GSK2606414 to inhibit ER stress also alleviated PMB‐induced apoptosis. Taken together, these findings provide novel insights that THC possesses the ability to alleviate PMB‐induced nephrotoxicity by inhibiting the ER stress‐mediated PERK/eIF2α/ATF4/CHOP axis, which sheds light on the benefits of THC as an intervention strategy to reduce PMB‐induced nephrotoxicity, thus providing a potential avenue for improved clinical outcomes in patients receiving PMB treatment.

中文翻译：

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四氢姜黄素通过抑制内质网应激介导的 PERK/eIF2α/ATF4/CHOP 信号通路轴来减弱硫酸多粘菌素 B 诱导的 HK-2 细胞凋亡


多粘菌素B（PMB）的肾毒性作用限制了其临床应用，使得减少PMB引起的肾毒性已成为临床医生迫切​​关注的问题。四氢姜黄素 (THC) 以其生物功能方面的有益特性而闻名，为减轻 PMB 引起的肾毒性的干预治疗提供了一个有吸引力的选择。然而，THC 如何减轻 PMB 引起的肾毒性的潜在机制仍知之甚少。在这里，我们首先评估了 THC 干预疗法在 PMB 诱导的细胞损伤体外模型中减轻 PMB 诱导的肾毒性的潜力。此外，我们通过使用细胞计数试剂盒-8和流式细胞术检测证明，THC有效保护HK-2细胞免受PMB诱导的细胞凋亡。 THC 还可以通过 PERK/eIF2α/ATF4/CHOP 途径抑制 PMB 诱导的内质网 (ER) 应激。此外，使用PERK抑制剂GSK2606414抑制ER应激也减轻了PMB诱导的细胞凋亡。总而言之，这些发现提供了新的见解，即 THC 具有通过抑制 ER 应激介导的 PERK/eIF2α/ATF4/CHOP 轴来减轻 PMB 诱导的肾毒性的能力，这揭示了 THC 作为减少 PMB 干预策略的好处‐诱导的肾毒性，从而为改善接受 PMB 治疗的患者的临床结果提供了潜在途径。