Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach
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Published:2023-12-21
Issue:1
Volume:25
Page:156
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Muthamil Subramanian1ORCID, Muthuramalingam Pandiyan2ORCID, Kim Hyun-Yong1ORCID, Jang Hyun-Jun1ORCID, Lyu Ji-Hyo1, Shin Ung Cheol1, Go Younghoon3ORCID, Park Seong-Hoon4ORCID, Lee Hee Gu5, Shin Hyunsuk2ORCID, Park Jun Hong16ORCID
Affiliation:
1. Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju 58245, Republic of Korea 2. Division of Horticultural Science, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju 52725, Republic of Korea 3. Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea 4. Genetic and Epigenetic Toxicology Research Group, Korea Institute of Toxicology, Daejeon 34141, Republic of Korea 5. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea 6. Korean Convergence Medicine Major, University of Science & Technology (UST), KIOM Campus, Daejeon 34054, Republic of Korea
Abstract
Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.
Funder
National Research Council of Science & Technology Korea institute of Oriental medicine
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference108 articles.
1. Cancer cachexia: Mediators, signaling, and metabolic pathways;Fearon;Cell Metab.,2012 2. Effects of whole-body vibration training in a cachectic C26 mouse model;Plas;Sci. Rep.,2021 3. An integrative transcriptome study reveals Ddit4/Redd1 as a key regulator of cancer cachexia in rodent models;Niu;Cell Death Dis.,2021 4. Muthamil, S., Kim, H.Y., Jang, H.J., Lyu, J.H., Shin, U.C., Go, Y., Park, S.-H., Lee, H.G., and Park, J.H. (2023). Understanding the relationship between cancer associated cachexia and hypoxia-inducible factor-1. Biomed. Pharmacother., 163. 5. Cancer-associated cachexia—Understanding the tumour macroenvironment and microenvironment to improve management;Stemmler;Nat. Rev. Clin. Oncol.,2023
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