Lan-Qin oral liquid alleviates influenza A virus-induced acute lung injury by regulating monocyte-derived macrophages and TLR4-PI3K-AKT-NF-κB signal pathways

Article

Author: Xie, Tian-Yun ; Chen, De-Jian ; Chen, Zhen-Feng ; Li, Jin-Jin ; Shi, Wei ; Yang, Xia ; Chen, Zi-Hao ; Zhang, Feng-Xiang ; Liu, Cheng-Jun ; Tu, Xin-Pu ; Yang, Yue-Dan ; Liang, Wan-Ting

ETHNOPHARMACOLOGICAL RELEVANCELan-Qin oral liquid (LQ), a combined traditional Chinese medicine preparation originated from Huang-Lian-Jie-Du decoction recorded in classical book of "The Handbook of Prescriptions for Emergencies", possesses remarkable efficacy in treating influenza. However, its pharmacological mechanism against influenza is still unclear, restricting its clinical applications.AIM OF THE STUDYThis work aimed to explore the effects and mechanism of LQ against influenza virus-induced acute lung injury (ALI).MATERIALS AND METHODSThe influenza virus A/PR/8/34 (PR8)-induced ALI mouse model was used to investigate the effects of LQ. The survival rate, lung index, lung pathological changes, cytokines in the bronchoalveolar lavage fluid (BALF), and monocyte levels in the blood, spleen, and BALF were detected and analyzed. Meanwhile, alveolar macrophages (AMs) and monocyte-derived macrophages (MDMs) in BALF were also detected by flow cytometry. An AMs-eliminated coupled PR8 infection model was established by using clodronate liposomes (CL) and utilized to evaluate the effects of LQ. The potential anti-ALI mechanism of LQ was explored by in vivo chemical profiling and network pharmacology. Furthermore, western blotting was used to verify the mechanism of action of LQ against influenza.RESULTSLQ (66 g crude drug/kg/day) treatment significantly improved the survival rate and lifespan of PR8 infected mice and reduced lung index, lung pathological damage, levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ, and MCP-1) in BALF and viral titers in the lung. Meanwhile, LQ treatment significantly reduced monocytes in blood and lung. Subsequent results indicate that MDMs levels were significantly reduced while there was no appreciable impact on AM levels after LQ treatment. In addition, chemical profiling indicated that a total of 241 compounds were identified or tentatively characterized in LQ, and 99 prototypes were presented in the host circle system. Network pharmacology analysis revealed that TNF, IL-6, AKT1, etc. Might be the core targets of LQ in treating ALI, involving in PI3K-AKT signaling pathway, MAPK signaling pathway, TNF signaling pathway, etc. Further, it was found that LQ exerts its anti-PR8-induced ALI effects by reducing MDMs and regulating the TLR4-PI3K-AKT-NF-κB signaling pathway.CONCLUSIONSLQ could treat PR8-induced ALI by reducing MDMs and regulating the TLR4-PI3K-AKT-NF-κB signaling pathway. Meanwhile, the chemical information of LQ in vitro and in vivo was also supplied for further pharmacological substance exploration.

01 Mar 2023·Computers in Biology and Medicine

Exploration of the anti-inflammatory mechanism of Lanqin oral solution based on the network pharmacology analysis optimized by Q-markers selection

Article

Author: Wu, Yongjiang ; Fu, Weiliang ; Xu, Youdong ; Liu, Xuesong ; Yu, Hengyuan ; Zhang, Yiwei ; Ma, Hui ; Xiao, Lulu ; Chen, Yong ; Xu, Tengfei

Network pharmacology is widely used to predict the mechanism of traditional Chinese medicines (TCM), but the framework in traditional network pharmacology analysis ignores the relationship between the concentration of components and drug efficacy. Lanqin oral solution (LOS) is a TCM formulation that widely used in the clinical treatment of pharyngitis, but its pharmacodynamic mechanism is still unknown. The present study was designed to elaborate the anti-inflammatory mechanism of LOS based on the quality markers (Q-markers). The efficacy of LOS was correlated with the fingerprint common peaks by chemometrics to select key peaks, and the Q-markers were further confirmed by mass spectrometry. Network pharmacology analysis was performed based on the chosen Q-markers to elaborate the potential pharmacodynamic mechanisms. Four efficacy-related chromatographic peaks were screened by the novel competitive adaptive reweighted sampling (CARS) spectrum-effect relationship analysis and series of other chemometrics methods. Four peaks were further characterized as the Q-markers in the LOS by mass spectrometry, i.e., geniposide, berberine, palmatine and baicalin. The ingredient-target network demonstrated that the LOS showed more impact on the NF-κB signaling pathway to elicit anti-inflammatory ability. Overall, the present study has introduced CARS into the spectrum-effect relationship analysis for the first time, which complemented the commonly applied chemometric methods. The network established based on the screened Q-markers was highly interpretable and successfully achieved the prediction of the anti-inflammatory mechanism of LOS. The proposed workflow provides a systematic method for exploring the mechanism of TCM based on identifying efficacy indicators. More importantly, it offers a reference for clarifying the mechanisms for other TCM formulations.

01 Jul 2022·Journal of Chromatography AQ2 · CHEMISTRY

A database-guided integrated strategy for comprehensive chemical profiling of traditional Chinese medicine

Q2 · CHEMISTRY

Article

Author: Liu, Run-Zhou ; Yang, Hua ; Tan, Qin ; Li, Ping ; Song, Min ; Zhao, Heng-Li ; Fan, Ya-Liu ; Wang, Rui

A comprehensive chemical profiling of traditional Chinese medicine is the basic issue for further pharmacological research and quality assessment. To facilitate chemical identification and potential components discovery, the present study proposed an integrated identification strategy guided by a self-built component database constructed from literatures to carry out the global profiling of complex matrixes. Lanqin Oral Liquid was applied as example to validate the feasibility of this strategy. Based on LQL Component Database containing 710 compounds, modified MDF windows was established to extract the interested analogues, isoquinoline alkaloids, flavonoids and iridoid glycosides, according to their regular integral masses and mass defect. For compounds with characteristic substructures, such as quinic acids, crocins and some glycoside derivatives, the associated neutral losses and diagnostic fragment ions were collected to assist in profiling. Directly matching the m/z or formulas in database was proposed to components with limited regularity of accurate masses and substructures, like indole alkaloids, sesquiterpenes and some nucleosides. Eventually, 170 ions of 1038 precursor ions were identified or temporarily deduced, including 59 alkaloids, 36 flavonoids, 48 terpenoids, 24 organic acids and their derivatives, 2 oligosaccharides, and 1 lignans. Among them, 52 putative compounds were confirmed by chemical standards. The results indicated that the database-oriented identification strategy could locate potential components quickly and eliminate interfering ions, which have the potential for in-depth analysis of compounds.

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Indication	Country/Location	Organization	Date
Pharyngitis	China	Jiangsu Yangtze River Pharmaceutical Group Co., Ltd.	01 Jan 1999

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