Therapeutic targets of vitamin C on liver injury and associated biological mechanisms: A study of network pharmacology
Authors: Chao Guo
Bin Yang
Meizhen Liu
Xiaoliu Liang
Min Su
Journal: International Immunopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Inflammation; Liver injury; Network pharmacology; Target; Vitamin C.
Affiliations: Faculty of Basic Medicine, Guilin Medical University, Guilin 541004, PR China., Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang 537100, Guangxi, PR China., College of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR China., College of Pharmacy, Guangxi Medical University, Guangxi, Nanning 530021, PR China. Electronic address: .

Abstract:  In our previous studies, vitamin C (VC) exerts potent pharmacological activities against liver injury (LI). Therefore, this report was designed to use network pharmacology-based strategy to predict therapeutic targets of VC against LI, and further to investigate the pharmacological molecular mechanisms. Pathological targets of LI were identified, followed by acquisition of verified targets of VC. After constructing target-functional protein interaction network of VC against LI, the core therapeutic targets of VC against LI were obtained. Further, biological function and pathway enrichment analyses were performed on core therapeutic targets to evaluate the biological processes and key signaling pathways of VC against LI. As revealed in network pharmacology assays, 6 key therapeutic targets for VC against LI were identified, showing tumor necrosis factor (TNF), nuclear factor-kappa-B p65 (RELA), nuclear factor-kappa-B p105 (NFKB1), TNF receptor-associated factor 2 (TRAF2), interleukin 6 (IL-6) and interleukin 1 beta (IL1B). On the basis of data analyses from DAVID database and omicshare cloud platform, bio-functional enrichment assays showed that the therapeutic effects of VC against LI were closely associated with regulating inflammatory reaction and apoptosis. Further, pathway enrichment analysis indicated the anti-LI benefits of VC were principally implicated in regulating the top 20 signaling pathways, such as inflammation-associated TNF signaling pathway, NF-κB signaling pathway. Taken together, the bioinformatics data elucidate that anti-LI pharmacological activities of VC may be predominantly related to inhibition of inflammatory stress, contributing to suppression of LI development. These resultant findings highlight the predicted therapeutic targets may be potential biomarkers for anti-LI. 

Retracted: No

PubPeer comments:
 The network pharmacology approach of Su et al is not valid for vitamin C. For example, vitamin C is an important water soluble antioxidant and it is not reasonable to assume that effects on the genome could cover such effects. Criticism of an analogous paper has been published [1]. 1. https: doi.org 10.1039 d0fo02189j , 
 Dear Dr Harri Hemilu00e4, Thanks for your kind quote from a secondary source. As you know, bioinformatics analysis using network pharmacology may be used for identification of some core targe genes in bioactive compound against clinical disorders. Notably, all these bioinformatics findings collecting from online databases are not vaildated experimentally and clinically in our publication. However, It can be a significative thought for all clinician in clinical practice. As your mentioned Criticism of an analogous paper has been published [1], we can learn something for our future study in this issue and thanks for Drs Harri Hemilu00e4 andu00a0Anitra Carr. For some arguments, we contact the authors in this paper and know that they try to reply the comments presented but fail, as they said that some papers in Chinese version cited to support their standpoints can not be accepted. Anyway, we thank all helpful comments in our paper for better improving our future study. Thanks again. Best wishes. , 
 #2 You can publish a response to Hemilu00e4 and Carr in the same journal. Or you can post here a point-by-point rebuttal. ,