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Two Balkan Peninsula endemics,  Nepeta rtanjensis  and  N. argolica  subsp.  argolica , both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of antimicrobial and immunomodulating activities of the two  Nepeta  species and their major iridoids isolated from natural sources— cis,trans -NL,  trans,cis -NL, and 1,5,9-epideoxyloganic acid (1,5,9- e DLA), as well as of phenolic acid rosmarinic acid (RA). Methanol extracts and pure iridoids displayed excellent antimicrobial activity against eight strains of bacteria and seven strains of fungi. They were especially potent against food-borne pathogens such as  L. monocytogenes ,  E. coli ,  S. aureus ,  Penicillium  sp., and  Aspergillus  sp. Targeted iridoids were efficient agents in preventing biofilm formation of resistant  P. aeruginosa  strain, and they displayed additive antimicrobial interaction. Iridoids are, to a great extent, responsible for the prominent antimicrobial activities of the two  Nepeta  species, although are probably minor contributors to the moderate immunomodulatory effects. The analyzed iridoids and RA, individually or in mixtures, have the potential to be used in the pharmaceutical industry as potent antimicrobials, and in the food industry to increase the shelf life and safety of food products.

Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources