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Abstract
Resistance-Modifying Agents: New Trends in the Utilization of Medicinal Plants
Sasitorn Chusri
Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, Songkhla 90112
Corresponding author: sasitorn.chu@psu.ac.th
Multidrug-resistant gram-positive and gram-negative bacteria are major causes for hospi-
tal-related infections and deaths. Moreover, the lack of effective antibiotics against such patho-
gens results in high mortality rates. Resistance-modifying agents (RMAs) can be co-administered
with antibiotics to treat bacterial infections. The advantages of the combinations are to decrease
the degree of drug resistance of the bacteria as well as reduce the emergence of drug-resistant
bacterial strains. It is rather difficult and expensive to develop new drugs; therefore, the applica-
tion of RMAs becomes important to find new approaches to reduce the increase in resistance to
antibiotics by pathogens. The aim of this review is to present an overview of the continuing
central role of medicinal plants and medicinal plant-derived compounds in the discovery and
development of RMAs. Selected examples of 28 medicinal plants and medicinal plant-derived
compounds are discussed. A brief overview of plant secondary metabolites as modifiers of
multidrug resistance mechanisms was additionally described including (i) inhibition of antibi-
otic-degrading enzymes, (ii) inhibition of antibiotic-bacterial receptor modifications, and (iii) in-
creasing drug accumulation. The review additionally reveals some promising medicinal plants
such as Alpinia officinarum, Camellia sinensis, and Quercus infectoria that have been proposed to
possess multiple resistance-modifying mechanisms. Interestingly, medicinal plants that inhibit
bacterial efflux pumps and increase bacterial membrane permeability can reduce the resistance
of gram-negative bacteria to a wide variety of antimicrobial agents. Effective RMAs that are
natural-derived compounds will be a new and alternative approach to using natural products
and a new method of suppressing resistance mechanisms of bacteria, particularly multidrug-
resistant strains.
Key words: medicinal plants, resistance-modifying agent, antibiotic resistance, synergism