School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Phytomedicine. 2022 Jul;101:154143. doi: 10.1016/j.phymed.2022.154143. Epub 2022 May 3.
Acute lung injury (ALI) is a complex pulmonary destructive disease with limited therapeutic approaches. Hydnocarpin D (HD) is a flavonolignan isolated from Hydnocarpus wightiana which possesses antioxidant and anti-inflammatory properties. However, whether HD has beneficial effects on ALI as well as its underlying mechanism remains to be elucidated.
This study evaluated the protective effect of HD in ALI and the underlying molecular mechanisms.
In vivo, the role of HD on lipopolysaccharide (LPS)-induced ALI in mice was tested by determination of neutrophil infiltration, levels of inflammatory cytokines, lung histology and edema, vascular and alveolar barrier disruption. In vitro, murine macrophage RAW 264.7 cells were used to investigate the molecular mechanisms RESULTS: Administration of HD protected mice against LPS-induced ALI, including ameliorating the histological alterations in the lung tissues, and decreasing lung edema, protein content of bronchoalveolar lavage fluid, infiltration of inflammatory cell and secretion of cytokines. Moreover, HD blocked the phosphorylation of TLR-4, NF-κB, and ERK in LPS-induced lung injury. In vitro, HD inhibited LPS-induced oxidative stress and inflammation in RAW 264.7 cells, which largely depend upon the upregulation of antioxidant defensive Nrf2 pathway, thereby suppressing LPS-activated proinflammatory mediator secretion, NLRP3 inflammasome, and MAPK/NF-κB signaling pathway.
HD attenuates oxidative stress and inflammation against LPS-induced ALI via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.
急性肺损伤（ALI）是一种复杂的肺部破坏性疾病，治疗方法有限。Hydnocarpin D（HD）是从滇榄中分离得到的一种类黄酮木脂素，具有抗氧化和抗炎特性。然而，HD 是否对 ALI 有有益作用以及其潜在机制仍有待阐明。
本研究评估了 HD 在 ALI 中的保护作用及其潜在的分子机制。
在体内，通过测定中性粒细胞浸润、炎症细胞因子水平、肺组织学和水肿、血管和肺泡屏障破坏来测试 HD 对脂多糖（LPS）诱导的 ALI 小鼠的作用。在体外，使用鼠巨噬细胞 RAW 264.7 细胞来研究分子机制。
HD 可保护小鼠免受 LPS 诱导的 ALI，包括改善肺组织的组织学改变，减少肺水肿、肺泡灌洗液蛋白含量、炎症细胞浸润和细胞因子分泌。此外，HD 阻断了 LPS 诱导的肺损伤中 TLR-4、NF-κB 和 ERK 的磷酸化。在体外，HD 抑制了 LPS 诱导的 RAW 264.7 细胞中的氧化应激和炎症，这在很大程度上依赖于抗氧化防御 Nrf2 途径的上调，从而抑制 LPS 激活的促炎介质分泌、NLRP3 炎性体和 MAPK/NF-κB 信号通路。
HD 通过 MAPK/NF-κB 和 Keap1/Nrf2/HO-1 途径减轻 LPS 诱导的 ALI 中的氧化应激和炎症，是治疗 ALI 的一种有前途的新型治疗候选物。
