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<p><i>Salvia castanea</i> Diels f. <i>tomentosa</i> Stib. (SCD) is a traditional Tibetan herbal medicine that is frequently employed in the treatment of cardiovascular disease. However, the mechanism of its effect on plateau hypoxia-induced right ventricular hypertrophy remains unclear. In the present study, we evaluated the antihypoxic effect of the alcoholic extract of <i>Salvia castanea</i> Diels f.&#xa0;<i>tomentosa</i> Stib. (SCDA) through a normal pressure hypoxia tolerance experiment in mice, and investigated the effect and possible mechanism of SCDA on hypoxia-induced right ventricular hypertrophy in rats. 0.3 and 0.6 g/kg SCDA were used to treat Sugen5416 + hypoxia-induced right ventricular hypertrophy in SD rats for 3 weeks. The findings indicated that SCDA (0.6 g/kg) could inhibit right ventricular hypertrophy, as evidenced by a reduction in heart weight/body weight, Fulton’s index, mean pulmonary artery pressure and hypertrophic markers. Furthermore, through network pharmacology in conjunction with transcriptomics and molecular docking as well as experimental validation, it was demonstrated that SCDA reduced lipid peroxidation products, mainly through inhibiting hypoxia-induced activation of the tumour proteins p53 (P53), spermine/ spermine N1 acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15). Similarly, SCDA also increased levels of the antioxidant glutathione (GSH), which is associated with inhibition of P53 and promotion of the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), resulting in an improved balance between antioxidant and oxidant systems. This provides new drugs and targets for the treatment of right ventricular hypertrophy.</p> Graphical abstract <p></p>

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Alcoholic extract of Salvia castanea Diels f. tomentosa Stib. ameliorates hypobaric hypoxia-induced right ventricular hypertrophy by inhibiting the P53-SAT1-ALOX15 pathway and up-regulating the SLC7A11-GPX4 pathway

  • 期刊论文

  • 发表日期：

    2025年11月25日

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  • Jiajia Wu,
  • Qi Si,
  • Ruoxi Jia,
  • Zheng Tang,
  • Ruiping Li,
  • Kunpeng Mao,
  • Zihao Jia,
  • Xiaoying Zhang

摘要

Salvia castanea Diels f. tomentosa Stib. (SCD) is a traditional Tibetan herbal medicine that is frequently employed in the treatment of cardiovascular disease. However, the mechanism of its effect on plateau hypoxia-induced right ventricular hypertrophy remains unclear. In the present study, we evaluated the antihypoxic effect of the alcoholic extract of Salvia castanea Diels f. tomentosa Stib. (SCDA) through a normal pressure hypoxia tolerance experiment in mice, and investigated the effect and possible mechanism of SCDA on hypoxia-induced right ventricular hypertrophy in rats. 0.3 and 0.6 g/kg SCDA were used to treat Sugen5416 + hypoxia-induced right ventricular hypertrophy in SD rats for 3 weeks. The findings indicated that SCDA (0.6 g/kg) could inhibit right ventricular hypertrophy, as evidenced by a reduction in heart weight/body weight, Fulton’s index, mean pulmonary artery pressure and hypertrophic markers. Furthermore, through network pharmacology in conjunction with transcriptomics and molecular docking as well as experimental validation, it was demonstrated that SCDA reduced lipid peroxidation products, mainly through inhibiting hypoxia-induced activation of the tumour proteins p53 (P53), spermine/ spermine N1 acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15). Similarly, SCDA also increased levels of the antioxidant glutathione (GSH), which is associated with inhibition of P53 and promotion of the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), resulting in an improved balance between antioxidant and oxidant systems. This provides new drugs and targets for the treatment of right ventricular hypertrophy.

Graphical abstract