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黄芩苷脂质体通过抑制 TLR4/JNK/ERK/NF-B 通路缓解脂多糖诱导的小鼠急性肺损伤。

Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-B Pathway.

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Mediators Inflamm. 2020 Nov 11;2020:8414062. doi: 10.1155/2020/8414062. eCollection 2020.

DOI:10.1155/2020/8414062
PMID:33223957
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7673921/
Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are challenging diseases with the high mortality in a clinical setting. Baicalin (BA) is the main effective constituent isolated from the Chinese medical herb Georgi, and studies have proved that it has a protective effect on ALI induced by lipopolysaccharide (LPS) due to the anti-inflammatory efficacy. However, BA has low solubility which may limit its clinical application. Hence, we prepared a novel drug delivery system-Baicalin liposome (BA-LP) in previous research-which can improve some physical properties of BA. Therefore, we aimed to explore the effect of BA-LP on ALI mice induced by LPS. In pharmacokinetics study, the values of and AUC in the BA-LP group were significantly higher than that of the BA group in normal mice, indicating that BA-LP could prolong the duration time of BA. The BA-LP group also showed a higher concentration in lung tissues than the BA group. Pharmacodynamics studies showed that BA-LP had a better effect than the BA group at the same dosage on reducing the W/D ratio, alleviating the lung injury score, and decreasing the proinflammatory factors (TNF-, IL-1) and total proteins in bronchoalveolar lavage fluids (BALF). In addition, the therapeutic effects of BA-LP showed a dose-dependent manner. Western blot analysis indicated that the anti-inflammatory action of BA could be attributed to the inhibition of the TLR4-NFBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.

摘要

急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是临床治疗中具有高死亡率的挑战性疾病。黄芩苷（BA）是从中药黄芩中分离得到的主要有效成分，研究证明其具有抗炎作用，对脂多糖（LPS）诱导的 ALI 具有保护作用。然而，BA 的溶解度较低，可能限制了其临床应用。因此，我们在之前的研究中制备了一种新的药物传递系统-黄芩苷脂质体（BA-LP），可以改善 BA 的一些物理性质。因此，我们旨在探讨 BA-LP 对 LPS 诱导的 ALI 小鼠的作用。在药代动力学研究中，正常小鼠中 BA-LP 组的 和 AUC 值明显高于 BA 组，表明 BA-LP 可以延长 BA 的作用时间。BA-LP 组在肺组织中的浓度也高于 BA 组。药效学研究表明，在相同剂量下，BA-LP 组比 BA 组在降低 W/D 比、减轻肺损伤评分和降低支气管肺泡灌洗液（BALF）中促炎因子（TNF-、IL-1）和总蛋白方面具有更好的效果。此外，BA-LP 的治疗效果呈剂量依赖性。Western blot 分析表明，BA 的抗炎作用可能归因于 TLR4-NFBp65 和 JNK-ERK 信号通路的抑制。这些结果表明，BA-LP 可能是治疗 ALI 的有价值的治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/c9ce8fa2fdea/MI2020-8414062.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/9ae9b8312c43/MI2020-8414062.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/c9ce8fa2fdea/MI2020-8414062.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/9ae9b8312c43/MI2020-8414062.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/5fc657dc5d90/MI2020-8414062.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/9ff93f81fd4b/MI2020-8414062.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/f003e65e3510/MI2020-8414062.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d124/7673921/c9ce8fa2fdea/MI2020-8414062.006.jpg

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