Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, PR China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, 832003, PR China.
Key Laboratory of Xinjiang Phytomedicine Resources and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, PR China.
Phytomedicine. 2024 Sep;132:155664. doi: 10.1016/j.phymed.2024.155664. Epub 2024 Apr 20.
Chronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited.
This study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy.
The present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD.
ULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK.
The combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.
慢性阻塞性肺疾病（COPD）是一种难治性呼吸系统疾病，主要归因于氧化应激、感染性炎症和特发性纤维化等多种病理因素数十年。药用植物甘草提取物（ULE）在中国被广泛用于控制呼吸系统疾病。然而，科学证据支持 ULE 在 COPD 管理中的治疗益处的监管机制受到极大限制。
本研究旨在通过多靶点策略发现 ULE 对 COPD 的潜在保护机制。
本研究旨在通过多靶点策略确定 ULE 对 COPD 的潜在保护作用。使用香烟烟雾和脂多糖建立 COPD 的体内和体外模型，以评估 ULE 的保护作用。通过测量炎症细胞因子并评估肺病理变化来评估。使用高效液相色谱法（HPLC）验证通过 HERB、文献工作和 ADME 工具收集和筛选的潜在化合物的活性化合物。使用转录组学、连接组学和网络药理学方法探讨 ULE 治疗 COPD 的机制。使用 RT-PCR、western blot 和免疫组织化学进一步研究 ULE 的相关靶点。使用 HCK 抑制剂（iHCK-37）评估 ULE 中活性化合物预防 COPD 的潜在机制。
ULE 有效保护 COPD 小鼠的肺部免受氧化应激、炎症和纤维化损伤。通过 ADME 特性和 HPLC 筛选和验证后，ULE 中鉴定出 4 种活性化合物：甘草素（LQ）、甘草查尔酮 B（LCB）、甘草查尔酮 A（LCA）和獐牙菜苦苷（ET）。网络药理学与转录组学分析相结合表明，ULE 通过抑制 HCK 减轻 COPD 中的氧化应激、炎症和纤维化。LCB 和 LQ 的组合优化了抗炎、抗氧化和抗纤维化活性。iHCK-37 通过抑制 HCK 进一步验证了 LCB 和 LQ 对 COPD 的预防治疗作用，从而发挥抗氧化、抗炎和抗纤维化作用。LCB 和 LQ 的组合以 1:1 的比例通过下调 HCK 发挥协同抗氧化、抗炎和抗纤维化作用，用于治疗 COPD。
LCB 和 LQ 的组合通过下调 HCK 对 COPD 具有显著的抗作用。
