Abstract
Relevance. This article presents an analytical review of current approaches aimed at improving the efficacy and safety of nonsteroidal anti-inflammatory drugs, which are widely used in clinical practice for inflammatory and pain syndromes. Despite their high therapeutic efficacy, nonsteroidal anti-inflammatory drugs are associated with adverse drug reactions, including gastro- and hepatotoxicity, which significantly limit their long-term use. In this context, particular attention is paid to glycyrrhizic acid as a natural anti-inflammatory and cytoprotective agent with antioxidant and membrane-stabilizing properties. Experimental evidence demonstrating the potential of combining nonsteroidal anti-inflammatory drugs with glycyrrhizic acid to reduce toxicity and enhance anti-inflammatory effects is presented. Objective. To systematize current literature data on modern approaches to reducing adverse effects of nonsteroidal anti-inflammatory drugs and to evaluate the potential of glycyrrhizic acid as a natural adaptogen for improving therapy safety. Materials and Methods. A literature analysis was conducted based on publications indexed in PubMed Central, Scopus, Web of Science, Google Scholar, as well as national scientific electronic libraries, covering the period from 2000 to 2025. Earlier studies were also included due to the relevance of key research on combinations of glycyrrhizic acid with synthetic drugs conducted prior to 2010. Inclusion criteria comprised experimental and clinical studies, as well as review articles addressing the pharmacological properties of nonsteroidal anti-inflammatory drugs, mechanisms of their adverse effects, and the biological activity of glycyrrhizic acid and its potential for combined use. Results. The analysis of the literature demonstrated that improving the safety profile of NSAIDs remains an important issue in modern pharmacotherapy. Glycyrrhizic acid, as a natural compound with pronounced anti-inflammatory, antioxidant, and cytoprotective properties, is considered a promising agent for the pharmacological correction of nonsteroidal anti-inflammatory drug-induced adverse effects. Conclusions. The combination of nonsteroidal anti-inflammatory drugs with glycyrrhizic acid represents a promising approach for developing safer and more effective anti-inflammatory therapies.