Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-κB Pathway
Yu Long, Xiang Yan, Songyu Liu, Yulu Zhang, Jinyan Wan, Qiyue Yang, Mingquan Cui, Zhimin Ci, Nan Li, Wei Peng
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 Scutellaria baicalensis 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 <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:msub> <a:mrow> <a:mi>t</a:mi> </a:mrow> <a:mrow> <a:mn>1</a:mn> <a:mo>/</a:mo> <a:mn>2</a:mn> </a:mrow> </a:msub> </a:math> and AUC0- <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:msub> <c:mrow/> <c:mrow> <c:mi>t</c:mi> </c:mrow> </c:msub> </c:math> 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 in vivo 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-α, IL-1β) 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-NFκBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.