Du Hongxu, Li Zhangxun, Su Lijuan, He Zhengke, Tan Xiaoyan, Hou Fengzhi, He Tanjie, Pan Yu, Xu Shuang, Cao Liting, Dong Shiqi, Ma Yue
Department of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Southwest University, Chongqing, China.
Immunology Research Center, Medical Research Institute, Southwest University, Chongqing, China.
Front Pharmacol. 2024 Jul 22;15:1417372. doi: 10.3389/fphar.2024.1417372. eCollection 2024.
To investigate the anti-inflammatory activity and mechanism of Baicalin derivative (Baicalin butyl ester, BE).
BE was synthesized and identified using UV-Vis spectroscopy, FT-IR spectroscopy, mass spectrometry (MS) and high-performance liquid chromatography (HPLC) methods. Its anti-inflammatory potential was explored by an inflammation model. Network pharmacology was employed to predict the anti-inflammatory targets of BE, construct protein-protein interaction (PPI) networks, and analysis topological features and KEGG pathway enrichment. Additionally, molecular docking was conducted to evaluate the binding affinity between BE and its core targets. qRT-PCR analysis was conducted to validate the network pharmacology results. The organizational efficiency was further evaluated through octanol-water partition coefficient and transmembrane activity analysis.
UV-Vis, FT-IR, MS, and HPLC analyses confirmed the successfully synthesis of BE with a high purity of 93.75%. anti-inflammatory research showed that BE could more effectively suppress the expression of NO, COX-2, IL-6, IL-1β, and iNOS. Network pharmacology and experiments validated that BE's anti-inflammatory effects was mediated through the suppression of SRC, HSP90AA1, PIK3CA, JAK2, AKT1, and NF-κB via PI3K-AKT pathway. Molecular docking results revealed that the binding affinities of BA to the core targets were lower than those of BE. The Log -value of BE (1.7) was markedly higher than that of BA (-0.5). Furthermore, BE accumulated in cells at a level approximately 200 times greater than BA.
BE exhibits stronger anti-inflammatory activity relative to BA, possibly attributed to its better lipid solubility and cellular penetration capabilities. The anti-inflammatory mechanism of BE may be mediated through the PI3K-AKT pathway.
研究黄芩苷衍生物（黄芩苷丁酯，BE）的抗炎活性及作用机制。
采用紫外可见光谱、傅里叶变换红外光谱、质谱（MS）和高效液相色谱（HPLC）方法合成并鉴定BE。通过炎症模型探究其抗炎潜力。运用网络药理学预测BE的抗炎靶点，构建蛋白质-蛋白质相互作用（PPI）网络，并分析拓扑特征和KEGG通路富集情况。此外，进行分子对接以评估BE与其核心靶点之间的结合亲和力。采用qRT-PCR分析验证网络药理学结果。通过正辛醇-水分配系数和跨膜活性分析进一步评估其组织效率。
紫外可见光谱、傅里叶变换红外光谱、质谱和HPLC分析证实成功合成了BE，纯度高达93.75%。抗炎研究表明，BE能更有效地抑制NO、COX-2、IL-6、IL-1β和iNOS的表达。网络药理学和实验验证，BE的抗炎作用是通过PI3K-AKT通路抑制SRC、HSP90AA1、PIK3CA、JAK2、AKT1和NF-κB介导的。分子对接结果显示，BA与核心靶点的结合亲和力低于BE。BE的Log 值（1.7）明显高于BA（-0.5）。此外，BE在细胞中的积累水平约为BA的200倍。
与BA相比，BE具有更强的抗炎活性，这可能归因于其更好的脂溶性和细胞穿透能力。BE的抗炎机制可能通过PI3K-AKT通路介导。
