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

Long, Yu; Yan, Xiang; Liu, Songyu; Zhang, Haoyang; Wan, Jinyan; Yang, Qian; Cui, Mingquan; Ci, Zhimin; Li, Nan; Peng, Wei

doi:10.1155/2020/8414062

Cited by 39 publications

(15 citation statements)

References 30 publications

(30 reference statements)

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“…In influenza A-infected A549 and MDCK cells, baicalin also could increase IFN levels, resulting in a reduction of pro-inflammatory cytokines production ( Nayak et al, 2014 ). Meanwhile, baicalin greatly attenuated inflammatory cell infiltration and decreased the levels of pro-inflammatory cytokines tumor necrosis factor α (TNF-α), IL-6, and IL-1β by regulating a variety of molecular mechanisms including Nuclear erythroid factor 2 (Nrf2)/heme oxygenase 1 (HO-1), CX3CL1-CX3CR1 axis and TLR4/MAPKs/NF-κB, to defend against lipopolysaccharide-induced severe lung injury ( Ding et al, 2016 ; Meng et al, 2019 ; Long et al, 2020 ). Baicalin also boosted the differentiation and modulatory activity of Foxp3 + Treg cells, promoted TGF-β secretion, and significantly inhibited the production of inflammatory cytokines ( Yang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

You

Fan

et al. 2022

Front. Pharmacol.

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Background: Cytokine storm (CS) is a systemic inflammatory syndrome and a major cause of multi-organ failure and even death in COVID-19 patients. With the increasing number of COVID-19 patients, there is an urgent need to develop effective therapeutic strategies for CS. Baicalin is an anti-inflammatory and antiviral traditional Chinese medicine. In the present study, we aimed to evaluate the therapeutic mechanism of baicalin against CS through network analysis and experimental validation, and to detect key targets of CS that may bind closely to baicalin through molecular docking.Method: Access to potential targets of baicalin and CS in public databases. We constructed the protein-protein interaction (PPI) network of baicalin and CS by Cytoscape 9.0 software and performed network topology analysis of the potential targets. Then, the hub target was identified by molecular docking technique and validated in the CS model. Finally, GO and KEGG pathway functional enrichment analysis of common targets were confirmed using R language, and the location of overlapping targets in key pathways was queried via KEGG Mapper.Result: A total of 86 overlapping targets of baicalin and CS were identified, among which MAPK14, IL2, FGF2, CASP3, PTGS2, PIK3CA, EGFR, and TNF were the core targets. Moreover, it was found that baicalin bound most closely to TNF through molecular docking, and demonstrated that baicalin can effectively inhibit the elevation of TNF-α in vitro and in vivo. Furthermore, bioenrichment analysis revealed that the TNF signaling pathway and IL-17 signaling pathway may be potential key pathways for baicalin to treat CS.Conclusion: Based on this study, baicalin was identified as a potential drug for the alleviation of CS, and the possible key targets and pathways of baicalin for the treatment of CS were elucidated to reveal the main pharmacological mechanisms.

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Section: Introductionmentioning

confidence: 99%

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

You

Fan

et al. 2022

Front. Pharmacol.

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“…However, the complexity of components of formula and ambiguity of mechanisms prevent their widespread use. In the previous literature, almost all studies about ARDS treatment by TCM have focused on the single component or bioactive molecules extracted from TCM ( Li et al, 2018 ; Long et al, 2020 ). The appearance of network pharmacology analysis and high throughput sequencing break the barriers and greatly promote the development of TCM theory.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, apparent side effects were not observed in mice after 1 wk of HNFPX administration. Reportedly, as the main components of NFPX, Carthami Clos and Scutellariae Radix play an essential role in treating LPS-induced ARDS ( Zhang et al, 2017 ; Long et al, 2020 ; Davis et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology, Transcriptome and Artificial Intelligence for Investigating Into the Effect and Mechanism of Ning Fei Ping Xue Decoction Against the Acute Respiratory Distress Syndrome

Fan

et al. 2021

Front. Pharmacol.

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Acute respiratory distress syndrome (ARDS) is a high-mortality disease and lacks effective pharmacotherapy. A traditional Chinese medicine (TCM) formula, Ning Fei Ping Xue (NFPX) decoction, was demonstrated to play a critical role in alleviating inflammatory responses of the lung. However, its therapeutic effectiveness in ARDS and active compounds, targets, and molecular mechanisms remain to be elucidated. The present study investigates the effects of NFPX decoction on ARDS mice induced by lipopolysaccharides (LPS). The results revealed that NFPX alleviated lung edema evaluated by lung ultrasound, decreased lung wet/Dry ratio, the total cell numbers of bronchoalveolar lavage fluid (BALF), and IL-1β, IL-6, and TNF-α levels in BALF and serum, and ameliorated lung pathology in a dose-dependent manner. Subsequently, UPLC-HRMS was performed to establish the compounds of NFPX. A total of 150 compounds in NFPX were characterized. Moreover, integrating network pharmacology approach and transcriptional profiling of lung tissues were performed to predict the underlying mechanism. 37 active components and 77 targets were screened out, and a herbs-compounds-targets network was constructed. Differentially expressed genes (DEGs) were identified from LPS-treated mice compared with LPS combined with NFPX mice. GO, KEGG, and artificial intelligence analysis indicated that NFPX might act on various drug targets. At last, potential targets, HRAS, SMAD4, and AMPK, were validated by qRT-PCR in ARDS murine model. In conclusion, we prove the efficacy of NFPX decoction in the treatment of ARDS. Furthermore, integrating network pharmacology, transcriptome, and artificial intelligence analysis contributes to illustrating the molecular mechanism of NFPX decoction on ARDS.

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“…falcatum Linne polysaccharides, a major herb of SSHT, suppressed LPS-induced proinflammatory cytokines production including IL-6, IL-1 β , IFN- β , and TNF- α in peritoneal macrophages of mice [ 26 ]. Additionally, baicalin derived from S. baicalensis Georgi consisting of SSHT has been studied to decrease TNF- α and IL-1 β levels in bronchoalveolar lavage fluids of LPS-induced ALI mice [ 27 ]. Total saponin from Ginseng as another major herb of SSHT was reported to inhibit LPS-induced increase of serum TNF- α level [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Sosiho-Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells

Choi

Kim

Jung

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Acute lung injury (ALI) is a series of syndromes with persistent inflammation and abnormally increased vascular permeability. Sosiho-tang (SSHT), a traditional herbal formula consisting of a mixture of seven herbs, has been used to treat allergic reactions and chronic hepatitis disease in East Asia. In this study, we determined whether SSHT has an inhibitory effect against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. 0.05, 0.55, and 5.55 mg/kg of SSHT were orally administered to C57BL/6J mice for 7 days prior to the administration of LPS. After 2 h of LPS sensitization, lung tissues were collected to confirm the lung histology and ALI-related inflammatory factors. SSHT ameliorated the LPS-induced alveolar hemorrhage, alveolar wall thickening, and the shrinkage of the alveolar spaces in the ALI mice model. Proinflammatory cytokines including IL-6, TNF-α, and IFN-γ in the lung tissue were significantly regulated in the SSHT-treated groups compared to the LPS only-treated group. Also, increases of IL-6 and TNF-α and decrease of IFN-γ expressions were dose-dependently modulated by SSHT treatment in LPS-induced raw 264.7 cells. Additionally, the translocation of NF-κB into nucleus and phosphorylation of mitogen-activated protein (MAP) kinase were significantly attenuated by the treatment of SSHT in LPS-sensitized ALI mice. SSHT showed anti-inflammatory activities by inhibiting proinflammatory cytokines and NF-κB signaling in LPS-induced ALI. This study demonstrates that SSHT has preventive effects on LPS-induced ALI by regulating inflammatory responses as an alternative for treating lung diseases.

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

Cited by 39 publications

References 30 publications

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

Inspiration for COVID-19 Treatment: Network Analysis and Experimental Validation of Baicalin for Cytokine Storm

Integrating Network Pharmacology, Transcriptome and Artificial Intelligence for Investigating Into the Effect and Mechanism of Ning Fei Ping Xue Decoction Against the Acute Respiratory Distress Syndrome

Anti-Inflammatory Effects of Sosiho-Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells

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