ABSTRACT: MOMAST(®) HY100 and MOMAST(®) HP30 are polyphenolic liquid complexes from olive pressing juice with a total polyphenolic content of 100 g/kg (at least 50% as hydroxytyrosol) and 36 g/kg (at least 30% as hydroxytyrosol), respectively. We investigated the potential protective role of MOMAST(®) HY100 and MOMAST(®) HP30 on isolated rat colon, liver, heart, and prefrontal cortex specimens treated with Escherichia coli lipopolysaccharide (LPS), a validated ex vivo model of inflammation, by measuring the production of prostaglandin (PG)E2, 8-iso-PGF2α, lactate dehydrogenase (LDH), as well as cyclooxygenase (COX)-2, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA levels. MOMAST(®) HY100 decreased LPS-stimulated PGE2 and LDH levels in all tested tissues. Following treatment with MOMAST(®) HY100, we found a significant reduction in iNOS levels in prefrontal cortex and heart specimens, COX-2 and TNFα mRNA levels in heart specimens, and 8-iso-PGF2α levels in liver specimens. On the other hand, MOMAST(®) HP30 was found to blunt COX-2, TNFα, and iNOS mRNA levels, as well as 8-iso-PGF2α in cortex, liver, and colon specimens. MOMAST(®) HP30 was also found to decrease PGE2 levels in liver specimens, while it decreased iNOS mRNA, LDH, and 8-iso-PGF2α levels in heart specimens. Both MOMAST(®) HY100 and MOMAST(®) HP30 exhibited protective effects on multiple inflammatory and oxidative stress pathways.