Pulmonary fibrosis (PF) is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2–3 years. The inhibition of transforming growth factor-β receptor type-I (TGF-β RI) by an appropriate drug may provide a promising strategy for the treatment of this disease. Polygonum cuspidatum (PC) is a well-known traditional Chinese herbal medicine which has an anti-PF effect. Accordingly, a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI. Based on this strategy, a total of 24 ingredients were identified. Then, absorption, distribution, metabolism, and excretion (ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour. Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors. Eventually, a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI, with an IC₅₀ of 2.211 μM in vitro. Furthermore, the complex formed through molecular docking was tested via molecular dynamics simulations, which revealed that resveratrol had strong interactions with residues of TGF-β RI. This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI. In addition, this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

肺纤维化 (PF) 是一种不可逆的肺部疾病，其特征是瘢痕组织过多，中位生存率较差，仅为 2-3 年。通过适当的药物抑制转化生长因子-β受体-I (TGF-β RI) 可能为该病的治疗提供一种有前途的策略。虎杖(Polygonum cuspidatum, PC) 是一种著名的中草药，具有抗 PF 作用。因此，开发了高分辨率质谱与计算机策略相结合的新方法，以寻找靶向 TGF-β RI 的 PC 潜在化学成分。基于这一策略，总共确定了 24 种成分。然后，随后预测吸收、分布、代谢和排泄 (ADME) 相关特性可排除具有潜在不良药代动力学行为的化合物。通过对TGF-β RI的分子对接研究发现新的PF抑制剂。最终，PC 中存在的一种称为白藜芦醇的化合物被证明对 TGF-β RI 具有出色的生物活性，IC_{为 50}体外 2.211 μM。此外，通过分子动力学模拟测试了通过分子对接形成的复合物，结果表明白藜芦醇与 TGF-β RI 的残基具有强烈的相互作用。该研究表明，白藜芦醇具有靶向 TGF-β RI 的能力，因此具有治疗 PF 的巨大潜力。此外，这项研究表明，通过高分辨率质谱结合计算机技术探索对特定靶标具有优异生物活性的天然产物是发现新药的有前途的策略。