Pseudomonas aeruginosa is capable to deploy a collection of virulence factors that are not only essential for host infection and persistence, but also to escape from the host immune system and to become more resistant to drug therapies. Thus, developing anti-virulence agents that may directly counteract with specific virulence factors or disturb higher regulatory pathways controlling the production of virulence armories are urgently needed. In this regard, this study reports that Pistacia lentiscus L. fruit cyclohexane extract (PLFE1) thwarts P. aeruginosa virulence by targeting mainly the pyocyanin pigment production by interfering with 4-hydroxy-2-alkylquinolines molecules production. Importantly, the anti-virulence activity of PLFE1 appears to be associated with membrane homeostasis alteration through the modulation of SigX, an extracytoplasmic function sigma factor involved in cell wall stress response. A thorough chemical analysis of PLFE1 allowed us to identify the ginkgolic acid (C17:1) and hydroginkgolic acid (C15:0) as the main bioactive membrane-interactive compounds responsible for the observed increased membrane stiffness and anti-virulence activity against P. aeruginosa. This study delivers a promising perspective for the potential future use of PLFE1 or ginkgolic acid molecules as an adjuvant therapy to fight against P. aeruginosa infections.
Pistacia lentiscus L. (Anacardiaceae) is widely distributed in the Mediterranean basin. Its fruit oil is used in traditional medicine to treat burns, skin impairments as well as inflammatory diseases as soothing massage or internal use. An increased interest is spotted lately with several commercial brands are spun portraying the benefits of this oil but with no stringent regulations to ascertain its safe use as an edible or cosmeceutical product. This work concerned the investigation of secondary metabolites presents in Pistacia lentiscus fruits oil using both GC-MS and HPLC-DAD-MS technics, and the evaluation of cytotoxicity on human normal dermal fibroblasts to assess safety of use as cosmetic ingredient. This study stands as the first one to report the identification of alkylsalicylic acids in fruits oil and unsaponifiable fraction of Pistacia lentiscus fruit oil which calls for therefore, quantification of alkylsalicylic acids, known as skin irritants, in Pistacia lentiscus oil, used as nutraceuticals or cosmeceuticals by manufacturers.
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