Exploration of the Potential Mechanism of Calculus Bovis in Treatment of Primary Liver Cancer by Network Pharmacology

Aim and Objective: Calculus Bovis (CB) has been employed to treat diseases for a long time. It has been identified to play significant anti-inflammatory and anti-tumor roles. However, the mechanism of treating primary liver cancer (PLC) remains to be revealed. This study aims to clarify the molecules and mechanisms of CB in treating PLC. Materials and Methods: After oral bioavailability (OB) and drug-likeness (DL) screening, 15 small molecules were identified as the potential ingredients against PLC. Following this, related targets network constructions and pathways were applied to clarify the mechanism of CB in treating PLC. An in vitro experiment was carried out to identify the function of CB in treating PLC. Results: Eleven compounds of CB were identified that play an anti-PLC role, including oleanolic acid, ergosterol, ursolic acid, etc. The potential targets which were observed include: IL6, MAPK-8, VEGFA, Caspase-3, etc. Further analysis showed that the mechanism of CB in the treatment of PLC involved apoptosis-related pathways and immune- related pathways. Conclusion: In summary, the current study combines network pharmacology and in vitro experiments to reveal the mechanism of CB against PLC. We concluded that 11 ingredients of CB have an anti-PLC effect. Furthermore, CB plays a key role in treating PLC mainly by apoptosis-related pathways and immune-related pathways. Our experiment verifies that CB promotes the apoptosis of SMMC-7721.

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Uncovering the Pharmacology of Xiaochaihu Decoction in the Treatment of Acute Pancreatitis Based on the Network Pharmacology

BioMed Research International ◽

10.1155/2021/6621682 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Lianghui Zhan ◽

Jinbao Pu ◽

Yijuan Hu ◽

Pan Xu ◽

Weiqing Liang ◽

...

Keyword(s):

Acute Pancreatitis ◽

Molecular Docking ◽

Pancreatic Neoplasm ◽

Mapk Signaling ◽

Network Pharmacology ◽

Ppi Network ◽

Vitro Experiment ◽

In Vitro Experiment ◽

Tnf Α

Background. Xiaochaihu decoction (XD) has demonstrated the pharmacodynamics on acute pancreatitis. This study was aimed at investigating the material and molecular basis of Xiaochaihu decoction. Methods. Firstly, compounds of seven herbs containing XD were collected from the TCMSP, ETCM, and BATMAN-TCM databases, and the putative targets of pancreatitis were obtained from the OMIM, TTD, and GeneCards databases. Then, the PPI network was constructed according to the matching results between XD potential targets and pancreatic neoplasm targets. Furthermore, enrichment analysis on GO and KEGG by DAVID utilized bioinformatics resources. Finally, molecular docking was performed to simulate the interaction between the active compound of XD and putative targets. In an in vitro experiment, AR42J cells were induced by LPS and then treated with Quercetin (25, 50, and 100 μM) or XCHD. The IL-6, TNF-α, and IL-1β levels were detected by ELISA kit, MAPK3 and TP53 mRNA expressions were measured by qRT-PCR, and the proteins of MAPK3 and TP53 expressions were measured by WB. Results. A total of 196 active ingredients and 91 putative targets were selected. The PPI network analysis demonstrated that Quercetin was the candidate agent and MAPK3, IL-6, and TP53 were the potential targets for the XD treatment of acute pancreatitis. The KEGG analysis revealed that pathways in cancers, TNF signaling way, and MAPK signaling way might play an important role in pancreatitis therapy. And molecular docking results showed that Quercetin combined well with MAPK3, IL-6, and TP53. An in vitro experiment indicated that XCHD and Quercetin inhibited the IL-6, TNF-α, and IL-1β levels and MAPK3 and TP53. Conclusion. This study illustrated that XCHD and Quercetin contained in XD played an important role in the treatment of acute pancreatitis by acting on the key genes of MPAK3, IL-6, and TP53 which were associated with inflammation and apoptosis.

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In Silico and in Vitro Evaluation of Deamidation Effects on the Stability of the Fusion Toxin DAB389IL-2

Current Proteomics ◽

10.2174/1570164616666190131150033 ◽

2019 ◽

Vol 16 (4) ◽

pp. 307-313 ◽

Cited By ~ 2

Author(s):

Nasrin Zarkar ◽

Mohammad Ali Nasiri Khalili ◽

Fathollah Ahmadpour ◽

Sirus Khodadadi ◽

Mehdi Zeinoddini

Keyword(s):

In Silico ◽

Catalytic Domain ◽

Md Simulations ◽

Special Importance ◽

Native Form ◽

Vitro Experiment ◽

In Vitro Experiment ◽

Pharmaceutical Protein ◽

The Stability

Background: DAB389IL-2 (Denileukin diftitox) as an immunotoxin is a targeted pharmaceutical protein and is the first immunotoxin approved by FDA. It is used for the treatment of various kinds of cancer such as CTCL lymphoma, melanoma, and Leukemia but among all of these, treatment of CTCL has special importance. DAB389IL-2 consists of two distinct parts; the catalytic domain of Diphtheria Toxin (DT) that genetically fused to the whole IL-2. Deamidation is the most important reaction for chemical instability of proteins occurs during manufacture and storage. Deamidation of asparagine residues occurs at a higher rate than glutamine residues. The structure of proteins, temperature and pH are the most important factors that influence the rate of deamidation. Methods: Since there is not any information about deamidation of DAB389IL-2, we studied in silico deamidation by Molecular Dynamic (MD) simulations using GROMACS software. The 3D model of fusion protein DAB389IL-2 was used as a template for deamidation. Then, the stability of deamidated and native form of the drug was calculated. Results: The results of MD simulations were showed that the deamidated form of DAB389IL-2 is more unstable than the normal form. Also, deamidation was carried by incubating DAB389IL-2, 0.3 mg/ml in ammonium hydrogen carbonate for 24 h at 37o C in order to in vitro experiment. Conclusion: The results of in vitro experiment were confirmed outcomes of in silico study. In silico and in vitro experiments were demonstrated that DAB389IL-2 is unstable in deamidated form.

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