Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K/Akt/NF-κB pathway: In vivo and in vitro studies

Yan, Zunxiang; Zhang, Kai; Zhang, Kang; Wang, Guibo; Wang, Lei; Zhang, Jingyan; Qiu, Zhengying; Guo, Zhuang; Kang, Yandong; Song, Xiaoping; Li, Jianxi

doi:10.1016/j.jep.2022.115212

Cited by 11 publications

(7 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been previously demonstrated that activated EGFR recruits the downstream signal PI3K/Akt to play a key role in physiological processes such as cell proliferation, differentiation, and apoptosis. It has also been reported that PI3K/Akt is activated when diarrhea occurs . In this study, we found that diarrhea can activate the PI3K/Akt signaling pathway, and PSNB can significantly reduce the mRNA expression of PI3K and Akt.…”

Section: Discussionsupporting

confidence: 67%

“…The causes of diarrhea are complex and can be caused by viruses, bacteria, parasites, and drugs. Studies have shown that diarrhea is accompanied by a certain inflammatory response, 1 so antibiotics are currently used for treatment, including gentamicin, enrofloxacin, penicillin, streptomycin, etc., 2 but problems such as antibiotic residues and some bacterial resistances are becoming more and more serious, and antibiotic therapy is found to cause diarrhea, that is, antibiotic-associated diarrhea, when antibiotics are used to treat other diseases. 3 Therefore, there is a need to develop safe and effective alternative treatment strategies for diarrhea.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology

Guo

Liu

et al. 2023

ACS Omega

View full text Add to dashboard Cite

Paederia scandens is a natural medicinal plant that is widely used for its various pharmacological effects including antiviral, antitumor, anti-inflammatory, and antibacterial activities. However, there is no scientific evidence to support its antidiarrheal effect. In this study, the antidiarrheal activity of P. scandens was evaluated using several validated models. By using HPLC-ESI-MS in conjunction with a network pharmacology approach, the possible antidiarrheal mechanisms of P. scandens active fragments were studied, and they were subsequently verified in a mouse model of diarrhea. Finally, utilizing molecular docking, active compounds that might have antidiarrheal properties were hypothesized. The results show that the main antidiarrheal part of P. scandens has 10 chemical components in the n-butanol fraction (PSNB). The key targets of PSNB and diarrhea, EGFR, AKT1, and PIK3CA, were screened by network pharmacology analysis. And the mechanism of PSNB in the treatment of diarrhea may be highly related to the EGFR tyrosine kinase inhibitor resistance and PI3K/AKT signaling pathway. Besides, through the qRT-PCR and western-blot experiments, it was found that PSNB could inhibit the gene expression of proinflammatory factors by reducing the protein expression of AKT1 and PI3K and regulating the NF-κB signaling pathway in mice. In addition, asperuloside, paederosidic acid, paederoside, paederosidic acid methyl ester, and 6′-O-E-feruloylmonotropein have better docking energies than other chemical components in PSNB with EGFR, AKT1, and PIK3CA. In conclusion, the main antidiarrheal active site of P. scandens is the n-butanol site. PSNB may exert an antidiarrheal effect by regulating the PI3K/Akt/NF-κB signaling pathway. Among them, asperuloside, paederosidic acid, paederoside, paederosidic acid methyl ester, and 6′-O-E-feruloylmonotropein may be the active ingredients that exert an antidiarrheal effect.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology

Guo

Liu

et al. 2023

ACS Omega

View full text Add to dashboard Cite

show abstract

“… Fang et al (2018) showed that berberine ameliorates necrotizing enterocolitis through the PI3K-Akt signaling pathway. Yan et al (2022) showed that Huang Bai Jian Pi decoction relieves diarrhea and regulates the expression of inflammatory factors through the PI3K-Akt signaling pathway. These results suggest that the PI3K-Akt signaling pathway plays a regulatory role in enteritis, which is consistent with our network pharmacological prediction.…”

Section: Discussionmentioning

confidence: 99%

Potential pharmacological mechanisms of four active compounds of Macleaya cordata extract against enteritis based on network pharmacology and molecular docking technology

et al. 2023

View full text Add to dashboard Cite

Background:Macleaya cordata extract (MCE) is effective in the treatment of enteritis, but its mechanism has not been fully elucidated. Therefore, this study combined network pharmacology and molecular docking technologies to investigate the potential pharmacological mechanism of MCE in the treatment of enteritis.Methods: The information of active compounds in MCE was accessed through the literature. Furthermore, PubChem, PharmMapper, UniProt, and GeneCards databases were used to analyze the targets of MCE and enteritis. The intersection of drug and disease targets was imported into the STRING database, and the analysis results were imported into Cytoscape 3.7.1 software to construct a protein–protein interaction (PPI) network and to screen core targets. The Metascape database was used for conducting Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. AutoDock Tools software was used for the molecular docking of active compounds with the core targets.Results: MCE has four active compounds, namely, sanguinarine, chelerythrine, protopine, and allocryptopine, and a total of 269 targets after de-duplication. Furthermore, a total of 1,237 targets were associated with enteritis, 70 of which were obtained by aiding the drug–disease intersection with the aforementioned four active compound targets of MCE. Five core targets including mitogen-activated protein kinase 1 (MAPK1) and AKT serine/threonine kinase 1 (AKT1) were obtained using the PPI network, which are considered the potential targets for the four active compounds of MCE in the treatment of enteritis. The GO enrichment analysis involved 749 biological processes, 47 cellular components, and 64 molecular functions. The KEGG pathway enrichment analysis revealed 142 pathways involved in the treatment of enteritis by the four active compounds of MCE, among which PI3K-Akt and MAPK signaling pathways were the most important pathways. The results of molecular docking showed that the four active compounds demonstrated good binding properties at the five core targets.Conclusion: The pharmacological effects of the four active compounds of MCE in the treatment of enteritis involve acting on signaling pathways such as PI3K-Akt and MAPK through key targets such as AKT1 and MAPK1, thus providing new indications for further research to verify its mechanisms.

show abstract

“…The NF-κB transcription factor is a typical pro-inflammatory signaling factor, and the activation of NF-κB can promote the occurrence and development of downstream inflammatory reactions ( 27 ). Abnormal regulation of these pathways has been found in several diseases presenting with diarrhea ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Differential proteomic of plasma provides a new perspective on scientific diagnosis and drug screening for dampness heat diarrhea in calves

Yan

Zhang²,

Wang³

et al. 2022

Front. Vet. Sci.

Self Cite

View full text Add to dashboard Cite

Dampness heat diarrhea (DHD) is one of the most common syndromes of calf diarrhea. Its complex etiology and lack of objective diagnostic criteria bring great challenges to the diagnosis and treatment of this disease. This study aims to screen some prospective diagnostic biomarkers or therapeutic targets for calves with DHD by investigating the differential protein profiles of plasma between DHD calves and clinically healthy calves by mass spectrometry-based proteomic. A total of 120 DHD calves and 90 clinically healthy calves were divided into two groups randomly, 30 DHD calves and 30 clinically healthy calves in the test group, and 90 DHD calves and 60 clinically healthy calves in the validation group. In the test group, a total of 52 proteins were differentially expressed between calves with DHD and clinically healthy calves, 13 proteins were significantly increased and 39 proteins were significantly decreased. The differentially expressed proteins were associated with the intestinal immune network of IgA production, caffeine metabolism, purine metabolism, and PI3K signaling pathway. In the validation group, 13 proteins were selected from 52 differential expression proteins for parallel reaction monitoring validation to verify their associations with DHD calves. The targeted proteomic results showed that fibronectin precursor (FN1) and apolipoprotein C-IV precursor (APOC4) were significantly associated with DHD in calves, and they were downregulated in sick calves. In conclusion, the differential expression of plasma proteins was associated with DHD pathogenesis in calves, and the FN1 and APOC4 might be the potential clinical biomarkers for diagnosis of DHD in calves, and the intestinal immune network of IgA production, caffeine metabolism, purine metabolism, and PI3K signaling pathway are the candidate targets to treat DHD in calves. Our finding provides a reference for further investigating the pathogenesis, developing techniques of diagnosis, and screening treatment drugs for DHD in calves.

show abstract

Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K/Akt/NF-κB pathway: In vivo and in vitro studies

Cited by 11 publications

References 51 publications

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology

Potential pharmacological mechanisms of four active compounds of Macleaya cordata extract against enteritis based on network pharmacology and molecular docking technology

Differential proteomic of plasma provides a new perspective on scientific diagnosis and drug screening for dampness heat diarrhea in calves

Contact Info

Product

Resources

About