Seven New Noroleanane Triterpenoids from Mastic and their NO Inhibitory and Cytotoxic Activities.

Mastic is a natural resin produced by Pistacia lentiscus L. (Anacardiaceae) with high medicinal value and have been traditionally used as Uighur imported medicine for centuries. In this study, 16 triterpenoids including seven new norleanane triterpenoids (1-7), along with nine known oleanane triterpenoids (8-16), were isolated from the mastic. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, UV, ESI-HR-MS and NMR spectroscopy) and single-crystal X-ray diffraction. Compounds 4-7, 11, 14 and 16 showed strong inhibitory NO production in LPS-induced RAW264.7 cells with IC50 values 7.44-9.76 µM, respectively (positive control dexamethasone, 9.93 ± 1.17 µM). Furthermore, compounds 3 and 12 significantly inhibited the growth of SW480 cells, compound 3 showed the most pronounced inhibitory effect with an  IC50 of 2.30 ± 0.38 µM.

Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota.

BACKGROUND: Chios mastic gum (CMG) is a traditional Greek medicine used to treat a variety of gastrointestinal disorders, including inflammatory bowel disease (IBD). However, the bioactive compounds of CMG and the mechanisms of action for controlling of IBD remain unknown. PURPOSE: Masticadienonic acid (MDA) is one of the most abundant constituents isolated from CMG. This study aims to investigate the potential effects and underlying mechanisms of MDA in the pathogenesis of colitis. METHODS: The effects of MDA were evaluated using a dextran sulphate sodium (DSS)-induced acute colitis mouse model. The body and spleen weight and colon length and weight were measured and the clinical symptoms were analysed. Blood samples were collected to analyse the level of serum inflammatory markers. Colon tissues were processed for histopathological examination, evaluation of the epithelial barrier function, and investigation of the probable mechanisms of action. The gut microbiota composition was also studied to determine the mechanism for the beneficial effects of MDA on IBD. RESULTS: MDA could ameliorate the severity of IBD by increasing the body weight and colon length, reducing spleen weight, disease activity index, and histological score. MDA treatments reduce the release of serum inflammatory cytokines tumour necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) via inhibiting the MAPK and NF-κB signalling pathways. MDA supplementation could also improve the intestinal barrier function by activating the NF-E2-related factor-2 (Nrf2) signalling pathway and restoring the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. In addition, MDA administration modulates the gut microbiota composition in DSS-induced colitis mice. CONCLUSION: The results indicate that MDA attenuated experimental colitis by restoring intestinal barrier integrity, reducing inflammation, and modulating the gut microbiota. The present study provides novel insights into CMG-mediated remission of IBD and may facilitate the development of preventive and therapeutic strategies for IBD.