Drug discovery strategies for modulating oxidative stress in gastrointestinal disorders

ABSTRACT

Introduction

Due to the ever-growing incidence of gastrointestinal disorders accompanied by substantial economic impact, it is of great importance to manage these conditions globally. Since the significant role of oxidative stress has been proved in the initiation and propagation of most of the gastrointestinal disorders, medical science is now moving toward fusing traditional knowledge with advanced technology, aiming to promote the use of antioxidants in gastrointestinal disorders.

Areas covered

Through PubMed, the Cochrane library, the WHO, Clinicaltrials.gov and Google Scholar, the US FDA, and EMA, the authors collated and reviewed the appropriate literature published between the 1 January 2015 and 31 March 2020 and provided their expert perspectives on the drug discovery strategies for modulating oxidative stress in gastrointestinal disorders.

Expert opinion

As with other pharmaceuticals, antioxidants have been generally developed following the basic principles of drug discovery; the recent focus of which is designing multi-potent natural antioxidants mainly through using rational design and target-based drug discovery strategies. Although there have been encouraging in-vivo studies on the use of antioxidants in gastrointestinal disorders, especially inflammatory bowel disease and gastritis, there have been considerable deficits regarding in-vitro and clinical applications that should be immediately addressed.

KEYWORDS:

• Oxidative stress
• antioxidants
• gastrointestinal diseases
• drug discovery
• efficacy
• preclinical tests
• safety
• traditional and complementary medicines
• herbal medicines

Article Highlights

• Use of antioxidants, mainly natural sourced compounds, has been recently considered as promising approach in improving gastrointestinal disorders, gastritis, and IBD in particular.

• Following the basic principles of drug discovery and using rational-design strategy, antioxidants are mainly developed by target-based drug discovery strategies, whereby multi-potent antioxidants have become the focus of recent studies.

• Key promising targets in this regard are free radicals, endogenous antioxidants, transition metal ions, gut microbiota, mitochondria, transcription factors (mainly NF-κB and Nrf-2) as well as inflammatory cells, genes, and cytokines.

• There are plethora of experimental candidates studied in the past 5 years, whereas no careful attention has been dedicated to clinical phases, pharmacokinetics, and safety profile of these compounds.

• There has been a dramatic rise in antioxidants market whilst there is no firm assurance on their efficacy and safety regarding considerable deficits in regulation, registration, and pharmacovigilance of these products.

Acknowledgements

Iran National Science Foundation (INSF) is acknowledged for the General Seat Award directed to the corresponding author.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.