Yang Zhen, Man Jingyuan, Liu Haoyu, Wu Di, Gu Qiangwen, Zhang Hongjuan, Liu Yu, Shao Dan, Hao Baocheng, Wang Shengyi
Key Laboratory of New Animal Drug Project, Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agriculture Sciences, Lanzhou 730050, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Antioxidants (Basel). 2025 Jan 1;14(1):41. doi: 10.3390/antiox14010041.
Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats' own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against HO-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.
氧化应激是指机体的氧化还原平衡在受到刺激后被打破，导致体内活性氧物种过度积累，进而引发多种疾病的现象。与安全性存在争议的人工抗氧化剂不同，天然抗氧化剂广泛存在、具有药理活性且毒副作用小，有望成为治疗氧化应激相关疾病的候选药物。藏药翼首草（L. (PV)）是一种具有抗氧化特性的天然草药，在青藏高原地区作为传统药物使用。然而，很少有研究关注其体外和体内的抗氧化活性及作用机制。因此，本研究首先通过体外实验证明，翼首草能够通过清除DPPH自由基和抑制羟自由基的产生发挥良好的体外抗氧化作用。其次，通过建立大鼠番泻叶致泻模型，证明翼首草可减轻氧化应激对体重增加和胸腺发育的影响，还能提高肠道内抗氧化酶的活性和非酶抗氧化剂的含量，增强大鼠自身的抗氧化防御能力，减轻腹泻引起的氧化损伤。随后，细胞氧化应激模型的应用证明，翼首草可通过抑制巨噬细胞中活性氧的过度积累对细胞氧化应激起到保护作用。此外，采用综合网络药理学方法分析和筛选了翼首草的候选抗氧化靶点，并在mRNA水平和蛋白质水平检测了它们的表达。我们的结果表明，翼首草可能通过激活BCL2L1并抑制ESR1、JAK2/STAT3和MMP2来保护巨噬细胞免受HO诱导的氧化损伤。这些发现为翼首草的抗氧化机制以及将其开发为新型天然抗氧化药物的前景开辟了新的视角。
