Biological effects and potential mechanisms

of action of Pistacia lentiscus Chios mastic

extract in Caco-2 cell model

Maira Zorzan1,2, Daniela Collazuol1, Giovanni Ribaudo3, Alberto Ongaro3, Carla Scaroni1, Giuseppe Zagotto3, Decio Armanini1, Susi Barollo1, Fabio Galeotti4, Nicola Volpi4, Marco Redaelli2,5, Raffaele Pezzani1,5

1 O.U. Endocrinology, Department of Medicine (DIMED), University of Padova, via Ospedale 105, Padova, 35128, Italy2 Venetian Institute for Molecular Science and Experimental Technologies, VIMSET. Piazza Milani 4, Campolongo Maggiore, 30010, Italy

3 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo, 5, Padova, 35131, Italy4 Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, Modena, 41121, Italy

5 AIROB, Associazione Italiana per la Ricerca Oncologica di Base, Borgo Veneto (PD), Italy

INTRODUCTION: Pistacia lentiscus L. (PL) is an evergreen shrub of the family Anacardiaceae commonly present in the Mediterranean area especially in the Greek island ofChios where it is cultivated for its fragrant and aromatic resin. This resin is called mastic gum or mastic (known as the “tears of Chios”). In ethnomedicine, PL mastic has beenused for more than 2500 years in Mediterranean basin to treat gastrointestinal diseases, such as gastralgia, peptic ulcer, dyspepsia, diarrhoea, stomach upsets, nausea (1).More recently PL has been reported to possess antimicrobial, anti-inflammatory, antioxidative, wound-healing, neuroprotective, antidiarrheal, anti-atheroscletic,hypotensive, hypoglycemic, diuretic, anti-urolithiasis and anticancer effects (2-4).

AIM: to investigate Pistacia lentiscus extract effects at cellular level in a colon cell model (Caco-2)

We used a Pistacia lentiscus extract obtained from a patented extraction procedure that permits to have a raw material named “Supermastic” rich in triterpenes and with elimination of polyterpene polymers

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Piazza Milani 4, 30010

Campolongo Maggiore (VE) ITALY

VIMSETVenetian Institute for Molecular Sciences and

Experimental Technologies

.

HPLC-ESI-MS chromatogram of the Supermastic PL extract.

Caco-2 cells treated with Supermastic PLextract at different concentrations. A) MTTtest at 6h. Experiments performed intriplicate. B) Clonogenic assay at 24h.Experiments performed in quadruplicate. C)Histogram of wound healing assay.Experiments performed in quadruplicates.Treatment vs control: t test, * p<0.05, **p<0.01, *** p<0.001.

Inflammation and disaccharidase in Caco-2 cells. A-C) Interleukinsquantification analysis in Caco-2 cells treated or untreated withdifferent concentrations of Supermastic PL extract. Experimentsperformed in triplicates. D-E) Quantitative Real-time PCR for IL-1αand IL-6. Experiments performed in triplicates. F) Disaccharidaseactivity expressed as glucose generation in cells treated or untreatedwith different concentrations of Supermastic PL extract. W/O: nodisaccharidase added. Experiments performed in duplicates. G)Quantitative Real-time PCR for sucrase-isomaltase. Experimentsperformed in triplicates. Treatment vs control: t-test, * p<0.05, ***p<0.001.

Paracellular permeability assay in Caco-2 cells treated oruntreated with different concentrations of Supermastic PLextract. All results (treatments vs control) are significantlydifferent, p<0.01. Experiments performed in triplicates.

The most beautiful thing we can experience is the mysterious. It is the source of all true art and science. Albert Einstein

REFERENCES:[1] Dimas, K. S., et al. (2012). Review: Chios mastic gum: a plant-produced resin exhibiting numerous diverse pharmaceutical and biomedical properties. In Vivo, 26(5), 777-785. [2] Benhammou, N., et al. (2008). Antioxidant and antimicrobial activities of the Pistacia lentiscus and Pistacia atlantica extracts. African Journal of Pharmacy and Pharmacology, 2, 22-28. doi: 10.5897/AJPP[3] Paraschos, S.,et al. (2012). Chios gum mastic: A review of its biological activities. Curr Med Chem, 19(14), 2292-2302. [4] Rauf, A., et al. (2017). Phytochemical, ethnomedicinal uses and pharmacological profile of genus Pistacia. Biomed Pharmacother, 86, 393-404. doi: 10.1016/j.biopha.2016.12.017

Conflict of interestThe authors declare no conflict of interest

1. Supermastic PL extract showed no toxic effect

2. Pro-inflammatory cytokines did not increased

CONCLUSIONSSupermastic Pistacia

lentiscus extractBiochemical and biological assays

to study themechanism of action

3. Potential role in glycaemic control

4. Barrier effect for protecting against biochemical and biological insults