Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis

Liu, Chang-Shun; Xia, Ting; Luo, Zhen-Ye; Wu, Yuanyuan; Hu, Yan-Nan; Chen, Feilong; Tang, Qinglian; Tan, Xiaomei

doi:10.1016/j.phymed.2020.153458

Cited by 63 publications

(27 citation statements)

References 25 publications

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“…The comparable binding scores of the compounds might be due to their similar molecular structures, which is consistent with a previous study. 24 According to the analysis based on AutoDock Tools when binding force scores are > 5.0, the tested compounds demonstrate similar molecular structures and exhibit a strong affinity for the target protein. Molecular docking results indicated that the active ingredients of HDC modulated the JAK2/STAT3 and IL-17 pathways mainly through suppressing the activities of JAK2, STAT3, and IL-17, which was in agreement with in vivo results, indicating the high reliability of the docking results.…”

Section: Molecular Docking Resultsmentioning

confidence: 99%

Investigation of the Active Ingredients and Mechanism of Hudi Enteric-Coated Capsules in DSS-Induced Ulcerative Colitis Mice Based on Network Pharmacology and Experimental Verification

Ding¹,

Liu²,

Li³

et al. 2021

DDDT

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Background: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification. Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by highperformance liquid chromatography. The relative expressions of HDC's core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins. Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β. Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/ STAT3 signaling pathway. Conclusion:The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/ JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.

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Section: Molecular Docking Resultsmentioning

confidence: 99%

Investigation of the Active Ingredients and Mechanism of Hudi Enteric-Coated Capsules in DSS-Induced Ulcerative Colitis Mice Based on Network Pharmacology and Experimental Verification

Ding¹,

Liu²,

Li³

et al. 2021

DDDT

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“…Baicalin, the active component of Radix Scutellariae, was found to play an antitumour role by regulating dozens of microRNAs [54]. Previous studies on Radix Scutellariae and Coptidis Rhizoma also found that the mechanism of alleviating UC is related to TNF-α, STAT3, and JAK-STAT signaling pathways [47,[55][56][57]. In Moreover, the molecular docking results revealed that the five abovementioned major compounds of GJHQHLRSD had a high binding affinity to the EGFR in the tyrosine kinase inhibitor signaling pathway (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

“…Because epithelial barrier repair in colitis is dependent on energy, EGFR tyrosine kinase inhibitors and mitochondrial autophagy regulation are particularly important. Xianglian pill reduced DSS-induced acute colitis in mice by inhibiting the secretion of proinflammatory cytokines and enhancing autophagy [ 47 ]. Moreover, a study on compound Sophorae decoction found that TCM can inhibit UC-associated carcinogenesis by fighting inflammation and regulating apoptosis and mitochondrial autophagy [ 48 ], which suggest that mitochondrial dysfunction is critical in UC-associated carcinogenesis [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Baicalin, the active component of Radix Scutellariae, was found to play an antitumour role by regulating dozens of microRNAs [ 54 ]. Previous studies on Radix Scutellariae and Coptidis Rhizoma also found that the mechanism of alleviating UC is related to TNF- α , STAT3, and JAK-STAT signaling pathways [ 47 , 55 – 57 ]. In conclusion, EGFR tyrosine kinase inhibitor and mitochondrial autophagy are key factors in the pathological progression and recovery of UC.…”

Section: Discussionmentioning

confidence: 99%

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Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study

Zhou

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Ulcerative colitis (UC), a chronic and nonspecific inflammatory bowel disease, seriously affects the quality of patients’ life. Han Re Bing Yong Fa (treating diseases with both cool- and warm-natured herbs) is a classical therapeutic principle of traditional Chinese medicine (TCM), which is often used to treat chronic diseases, including UC. The Gan Jiang-Huang Qin-Huang Lian-Ren Shen decoction (GJHQHLRSD), a representative of Han Re Bing Yong Fa, is effective in alleviating inflammatory symptoms in UC. However, the pharmacological mechanism underlying its anti-inflammatory effect remains unclear. Methods. A network pharmacology strategy, including the construction and analysis of the drug–disease network, was used to explore the complex mechanism of GJHQHLRSD treatment of UC. In addition, molecular docking technology was used to preliminarily examine the binding ability of the potential active components and core therapeutic targets of GJHQHLRSD. Results. The network pharmacology results revealed 140 targets of GJHQHLRSD which are involved in UC. The PPI network analysis identified seven target genes: BCL2L1, NR3C1, ALOX5, S1PR5, NR1I2, CYP2D6, and LPAR6. The molecular docking results revealed that the following displayed strongest combined effects: EGFR with kaempferol, ERK1 with worenine, STAT3 with Palmidin A, BCL2L1 with diop and VEGFA with ginsenoside Rg3. The KEGG and gene ontology enrichment analyses results indicated that GJHQHLRSD functions by regulating the EGFR signaling pathway in UC treatment. Other effective biological processes involved in UC treatment included cancer-related as well as inflammation and viral infection signaling pathways, such as the “MicroRNAs in cancer,” “TNF signaling pathway,” and “JAK-STAT signaling pathway.” Conclusions. This study reflects the multicomponent, multitarget, and multipathway characteristics of the action mechanism of GJHQHLRSD in treating UC. Furthermore, it helps better understand the TCM therapeutic principle of Han Re Bing Yong Fa and explore novel candidate drug targets for UC treatment.

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“…Therefore, the mechanism of Shuangxia decoction is most likely to exert anti-insomnia effects by acting on classical inhibitory neuroreceptors. Molecular docking technology is a widely recognized technology for evaluating the interaction between drugs and targets, and the results can predict the potential mechanism of drug action (Li et al, 2020a), and more and more researchers are applying molecular docking technology to traditional Chinese medicine research, which is very suitable for preliminary exploration of the mechanism of action of complex herbs formula (Duan et al, 2020;Liu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Global Analysis the Potential Medicinal Substances of Shuangxia Decoction and the Process In Vivo via Mass Spectrometry Technology

Zhang

Liu

et al. 2021

Front. Pharmacol.

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Shuangxia decoction is an effective traditional Chinese medicine formula for treating insomnia. Up to now, there has not been any report about the effective substances. An omics data processing method based on mass spectrometry technology is used to explore the chemical composition changes of Shuangxia decoction, the components absorbed into the blood and brain, and to explore the anti-insomnia mechanism based on molecular docking technology. Forty-nine chemical components in Shuangxia decoction have been identified, and 51 new components generated by co-decoction have been discovered. It was found that 7,404 compounds of Shuangxia decoction were absorbed into the blood. Forty kinds of known compounds were quickly identified, and 15 new compounds generated by co-decoction were also found to be absorbed into the blood. By using UPLC-MS/MS method, it was confirmed that 10 compounds were absorbed into the blood and 9 compounds were absorbed into the brain. Furthermore, it is found that rosmarinic acid is mainly distributed in the hypothalamus and striatum, and caffeic acid is mainly distributed in the hypothalamus, striatum, and hippocampus. Molecular docking results showed rosmarinic acid, danshensu, and HMLA with GABAA receptor have excellent binding characteristics, even surpassing the proligand. Danshensu and HMLA with dopamine D2 receptor also showed good binding energy. Our findings will help to further confirm the mechanism of Shuangxia decoction for relieving insomnia, and we also establish a novel data processing method for supplementing the mechanism of the efficacy of other traditional Chinese medicine formula.

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Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis

Cited by 63 publications

References 25 publications

Investigation of the Active Ingredients and Mechanism of Hudi Enteric-Coated Capsules in DSS-Induced Ulcerative Colitis Mice Based on Network Pharmacology and Experimental Verification

Investigation of the Active Ingredients and Mechanism of Hudi Enteric-Coated Capsules in DSS-Induced Ulcerative Colitis Mice Based on Network Pharmacology and Experimental Verification

Active Ingredients and Potential Mechanisms of the Gan Jiang-Huang Qin-Huang Lian-Ren Shen Decoction against Ulcerative Colitis: A Network Pharmacology and Molecular Docking-Based Study

Global Analysis the Potential Medicinal Substances of Shuangxia Decoction and the Process In Vivo via Mass Spectrometry Technology

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