Yi-Qi-Jian-Pi formula modulates the PI3K/AKT signaling pathway to attenuate acute-on-chronic liver failure by suppressing hypoxic injury and apoptosis in vivo and in vitro

Tang, Li; Wang, Feixia; Xiao, Lingyan; Shen, Min; Xia, Siwei; Zhang, Zili; Zhang, Feng; Zheng, Shizhong; Tan, Shanzhong

doi:10.1016/j.jep.2021.114411

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…Then, Western blot was used to detect the changes of the top 2 pathways predicted by KEGG analysis. On account of that PI3K/AKT and HIF-1 pathway were the top 2 pathways in the KEGG analysis, and the current literature suggested 44 , 45 that PI3K/AKT was the upstream pathway of HIF-1. The results demonstrated that mGSLJZ restrained the protein expression of p-PI3K/AKT and p-AKT/AKT and HIF-1α, which indicated that mGSLJZ can inhibit the activation of the PI3K/AKT/HIF-1 pathway ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer

Huang

Fang

Ruan

et al. 2023

Journal of Traditional and Complementary Medicine

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Section: Resultsmentioning

confidence: 99%

Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer

Huang

Fang

Ruan

et al. 2023

Journal of Traditional and Complementary Medicine

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“…Excessive reactive oxygen species (ROS) can directly lead to oxidative stress, which plays an important role in liver damage [55]. Activation of the PI3K/Akt signaling can alleviate liver injury by reducing ROS levels, inhibiting apoptosis, and accelerating hyoxia-inducible factor-1α [56].…”

Section: Discussionmentioning

confidence: 99%

Identifying the Mechanism of Polygoni Cuspidati Rhizoma et Radix in Treating Acute Liver Failure Based on Network Pharmacology and Molecular Docking

Hong

Ding

Hong³

et al. 2022

Gastroenterology Research and Practice

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Background and Objective. Acute liver failure (ALF) is a rare clinical syndrome with a poor prognosis and leads to multiple organ failure. Polygoni Cuspidati Rhizoma et Radix (PCRR) is a commonly used Chinese medicine, which is recognized as a potential therapeutic herb against ALF. This study aimed to explore the pharmacological mechanisms of the therapeutic effect of PCRR in ALF via network pharmacology and molecular docking. Materials and Methods. The potential bioactive compounds of PCRR and their targets were collected from TCMSP, TCMID, and BATMAN-TCM databases with absorption, distribution, metabolism, and excretion protocols (oral bioavailability ≥30% and drug-likeness ≥0.18). The ALF-related target genes were identified using the GeneCards and OMIM databases. A protein-protein interaction (PPI) network among these targets was constructed using the Cytoscape software to obtain the core targets. The genes associated with ALF were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify the signaling pathways related to the therapeutic effect of PCRR in ALF. Results. In total, 10 bioactive compounds of PCRR and 200 targets related to them were obtained, and 2913 ALF-related target genes were identified. PPI network analysis pinpointed 15 core targets, namely, TP53, AKT1, JUN, HSP90AA1, MAPK1, RELA, TNF, ESR1, IL6, MYC, MAPK14, FOS, RB1, CDKN1A, and EGFR. GO enrichment and KEGG pathway analyses revealed that the therapeutic mechanisms of PCRR in ALF are related to cell metabolism, oxidative stress, inflammation, and hepatocyte apoptosis. Conclusion. This is the first study to explore the therapeutic mechanisms of PCRR in ALF via network pharmacology and molecular docking. This study provides a research platform with candidate ALF-related targets of PRCC for the development of therapeutics against ALF.

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“…The liver damage in this model was easy to control via different doses of CCl 4 +LPS/D−GalN. Therefore, the CCl 4 +LPS/D−GalN-induced ACLF mouse model has also been used to test the potential therapeutic effects of drugs on ACLF [ 39 ]. We replicated murine models of ACLF and ALF with mortality by LPS+D−GalN and CCl 4 , as previously described [ 36 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling

Lin

Ling

Yan

et al. 2022

Cells

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Background: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases. Methods: The LPS/D−GalN-induced ALF mice model and the CCl4+LPS/D−GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses. Results: MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment. Conclusions: Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.

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Yi-Qi-Jian-Pi formula modulates the PI3K/AKT signaling pathway to attenuate acute-on-chronic liver failure by suppressing hypoxic injury and apoptosis in vivo and in vitro

Cited by 16 publications

References 29 publications

Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer

Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer

Identifying the Mechanism of Polygoni Cuspidati Rhizoma et Radix in Treating Acute Liver Failure Based on Network Pharmacology and Molecular Docking

Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling

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