Department of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Pharmacy, Jiamusi University, Jiamusi 154000, China.
Phytomedicine. 2022 Dec;107:154469. doi: 10.1016/j.phymed.2022.154469. Epub 2022 Sep 20.
Acute lung injury (ALI) is a serious health issue which causes significant morbidity and mortality. Inflammation is an important factor in the pathogenesis of ALI. Even though ALI has been successfully managed using a traditiomal Chinese medicine (TCM), Huanglian Jiedu Decoction (HLD), its mechanism of action remains unknown.
This study explored the therapeutic potential of HLD in lipopolysaccharide (LPS)-induced ALI rats by utilizing integrative pharmacology.
Here, the therapeutic efficacy of HLD was evaluated using lung wet/dry weight ratio (W/D), myeloperoxide (MPO) activity, and levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6. Network pharmacology predictd the active components of HLD in ALI. Lung tissues were subjected to perform Hematoxylin-eosin (H&E) staining, metabolomics, and transcriptomics. The acid ceramidase (ASAH1) inhibitor, carmofur, was employedto suppress the sphingolipid signaling pathway.
HLD reduced pulmonary edema and vascular permeability, and suppressed the levels of TNF-α, IL-6, and IL-1β in lung tissue, Bronchoalveolar lavage fluid (BALF), and serum. Network pharmacology combined with transcriptomics and metabolomics showed that sphingolipid signaling was the main regulatory pathway for HLD to ameliorate ALI, as confirmed by immunohistochemical analysis. Then, we reverse verified that the sphingolipid signaling pathway was the main pathway involed in ALI. Finally, berberine, baicalein, obacunone, and geniposide were docked with acid ceramidase to further explore the mechanisms of interaction between the compound and protein.
HLD does have a better therapeutic effect on ALI, and its molecular mechanism is better elucidated from the whole, which is to balance lipid metabolism, energy metabolism and amino acid metabolism, and inhibit NLRP3 inflammasome activation by regulating the sphingolipid pathway. Therefore, HLD and its active components can be used to develop new therapies for ALI and provide a new model for exploring complex TCM systems for treating ALI.
急性肺损伤（ALI）是一种严重的健康问题，可导致高发病率和死亡率。炎症是 ALI 发病机制中的一个重要因素。尽管使用传统中药（TCM）黄连解毒汤（HLD）成功地治疗了 ALI，但它的作用机制尚不清楚。
本研究通过整合药理学探讨 HLD 在脂多糖（LPS）诱导的 ALI 大鼠中的治疗潜力。
在这里，通过肺湿/干重比（W/D）、髓过氧化物酶（MPO）活性以及肿瘤坏死因子（TNF-α）、白细胞介素（IL）-1β 和 IL-6 的水平来评估 HLD 的治疗效果。网络药理学预测了 HLD 在 ALI 中的活性成分。对肺组织进行苏木精-伊红（H&E）染色、代谢组学和转录组学分析。使用酸神经酰胺酶（ASAH1）抑制剂卡莫氟抑制鞘脂信号通路。
HLD 减轻了肺水肿和血管通透性，并抑制了肺组织、支气管肺泡灌洗液（BALF）和血清中 TNF-α、IL-6 和 IL-1β 的水平。网络药理学结合转录组学和代谢组学表明，鞘脂信号是 HLD 改善 ALI 的主要调节途径，免疫组化分析也证实了这一点。然后，我们反向验证了鞘脂信号通路是 ALI 涉及的主要途径。最后，小檗碱、黄芩素、obacunone 和栀子苷与酸神经酰胺酶对接，进一步探讨了化合物与蛋白质相互作用的机制。
HLD 对 ALI 确实有更好的治疗效果，并且从整体上更好地阐明了其分子机制，即通过调节鞘脂途径来平衡脂质代谢、能量代谢和氨基酸代谢，并抑制 NLRP3 炎性体的激活。因此，HLD 及其活性成分可用于开发 ALI 的新疗法，并为探索治疗 ALI 的复杂 TCM 系统提供新的模型。
