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Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanism...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570789/ https://www.ncbi.nlm.nih.gov/pubmed/36234758 http://dx.doi.org/10.3390/molecules27196220 |
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author | Khalid, Hafiz Rameez Aamir, Muhammad Tabassum, Sana Alghamdi, Youssef Saeed Alzamami, Ahmad Ashfaq, Usman Ali |
author_facet | Khalid, Hafiz Rameez Aamir, Muhammad Tabassum, Sana Alghamdi, Youssef Saeed Alzamami, Ahmad Ashfaq, Usman Ali |
author_sort | Khalid, Hafiz Rameez |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active “constituent–target–pathway” networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense. |
format | Online Article Text |
id | pubmed-9570789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95707892022-10-17 Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma Khalid, Hafiz Rameez Aamir, Muhammad Tabassum, Sana Alghamdi, Youssef Saeed Alzamami, Ahmad Ashfaq, Usman Ali Molecules Article Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active “constituent–target–pathway” networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense. MDPI 2022-09-21 /pmc/articles/PMC9570789/ /pubmed/36234758 http://dx.doi.org/10.3390/molecules27196220 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khalid, Hafiz Rameez Aamir, Muhammad Tabassum, Sana Alghamdi, Youssef Saeed Alzamami, Ahmad Ashfaq, Usman Ali Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title | Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title_full | Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title_fullStr | Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title_full_unstemmed | Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title_short | Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma |
title_sort | integrated system pharmacology approaches to elucidate multi-target mechanism of solanum surattense against hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570789/ https://www.ncbi.nlm.nih.gov/pubmed/36234758 http://dx.doi.org/10.3390/molecules27196220 |
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