Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action.

Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function.

Chios mastic gum inhibits influenza A virus replication and viral pathogenicity.

Chios mastic gum (CMG), a resin of the mastic tree (Pistacia lentiscus var. chia), has been used to treat multiple disorders caused by gastrointestinal malfunctions and bacterial infections for more than 2500 years. However, little is known about CMG's antiviral activity. CMG is known to influence multiple cellular processes such as cell proliferation, differentiation and apoptosis. As virus replication is largely dependent on the host cellular metabolism, it is conceivable that CMG regulates virus infectivity. Therefore, in this study, we evaluated CMG's potential as an antiviral drug to treat influenza A virus (IAV) infection. CMG treatment dramatically reduced the cytopathogenic effect and production of RNAs, proteins and infectious particles of IAV. Interestingly, CMG interfered with the early stage of the virus life cycle after viral attachment. Importantly, the administration of CMG greatly ameliorated morbidity and mortality in IAV-infected mice. The results suggest that CMG displays a potent anti-IAV activity by blocking the early stage of viral replication. Thus, mastic gum could be exploited as a novel therapeutic agent against IAV infection.

Traditional uses, phytochemistry and pharmacology of Chios mastic gum (Pistacia lentiscus var. Chia, Anacardiaceae): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Chios mastic gum constitutes a unique Greek product, produced exclusively in the southern part of the island of Chios. References about its use from local populations for the treatment of gastrointestinal disorders or as a cosmetic agent can even be encountered in ancient texts of Galen, Theophrastus and Dioscorides. Nowadays, this versatile resin has been rediscovered, not only as a traditional remedy and aromatic agent, but as a potent phytotherapeutic product with various biological properties. AIM OF THE STUDY: The aim of this study is to quote the summation of the ethnopharmacology, phytochemical profile and pharmacological properties of the resin of Pistacia lentiscus var. Chia and thus provide the scientific community with a summary of the research conducted so far. Furthermore, perspectives and uses are being discussed and studied so as to broaden the field of its applications. MATERIALS AND METHODS: A comprehensive review of the literature on Pistacia lentiscus var. Chia was performed using as resources scientific databases such as Scopus, Sciencedirect, Pubmed and Web of science, studies and traditional books provided by the Chios Mastiha Growers Association as well as PhD and Master' s theses. RESULTS: Chios mastic gum has been used as a traditional medicine over the last 2500 years. More than 120 chemical compounds have been identified in the resin and the major components are a natural polymer, acidic and neutral triterpenes and volatile secondary metabolites. Several plant extracts and compounds have been studied for their antibacterial, anti-inflammatory, antioxidant, anti-ulcer, anti-diabetic, cardioprotective and anti-cancer properties in vitro and in vivo. Clinical interventions and trials have also showed the therapeutic potential of Chios mastic gum. In 2015 Pistacia lentiscus L., resin (mastic) was recognized as a herbal medicinal product with traditional use by the European Medicines Agency (EMA) with two therapeutic indications (mild dyspeptic disorders & skin inflammation/healing of minor wounds). Over the last years, Chios mastic gum is widely involved in medicinal products, food supplements and cosmetics and has become object of study, also in the field of Pharmacotechnology. CONCLUSIONS: Chios mastic's beneficial properties have been demonstrated in the treatment of gastrointestinal disorders, wound healing, skin inflammations, plasma lipid and blood sugar reduction and oral care. These properties are attributed to triterpenes and volatile compounds. However, because of the resin's chemical complexity and the lack of commercial standards for its main compounds, there is a notable gap in literature concerning the biological evaluation of CMG's isolated components. Therefore, future research should focus on the development of efficient extraction, isolation and analysis techniques in order to unravel CMG's full pharmacological potential.

Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase. OBJECTIVE: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION. DESIGN AND SETTING: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212). MAIN OUTCOMES MEASURES: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out ("off-drug") period; and safety. STUDY POPULATION: Twenty-two participants aged 18 years or older with previous NAION. INTERVENTION(S): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site. RESULTS: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values. CONCLUSIONS: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.

In vitro and in vivo evaluation of the genotoxic and antigenotoxic potential of the major Chios mastic water constituents.

Chios mastic products are well-known for their broad applications in food industry, cosmetics, and healthcare since the antiquity. Given our recent finding that Chios mastic water (CMW) exerts antigenotoxic action, in the present study, we evaluated the genotoxic as well as the antigenotoxic potential of the four major compounds of CMW, namely, verbenone, α-terpineol, linalool, and trans-pinocarveol. The cytokinesis block micronucleus (CBMN) assay in cultured human lymphocytes and the Drosophila Somatic Mutation And Recombination Test (SMART), also known as the wing spot test, were employed. None of the four major CMW's constituents or their mixtures showed genotoxic or recombinogenic activity in either of the assays used. Co-treatment of each of the constituents with MMC revealed that all except trans-pinocarveol exerted antigenotoxic potential. Moreover, co-administration of verbenone with linalool or α-terpineol presented statistically significant reduction of MMC-induced mutagenicity. In conclusion, the major CMW constituents were shown to be free of genotoxic effects, while some exerted antigenotoxic activity either alone or in combinations, suggesting synergistic phenomena. Our results provide evidence on the key antigenotoxicity effectors of the plant extract CMW.

Chios mastic gum decreases renin levels and ameliorates vascular remodeling in renovascular hypertensive rats.

Chios mastic gum (CMG) exerts robust anti-inflammatory and antioxidant properties and it affects pathways that are implicated in the pathophysiology of endothelial and vascular inflammation. Aim of this study was to test the hypothesis that CMG administration lowers blood pressure (BP) and improves hypertension-induced target organ damage. 2-kidney, 1-clip (2K1C) hypertensive rats were treated with CMG (40 mg/kg body weight/day) for 2-weeks after the establishment of hypertension. Acute CMG administration lowered systolic, diastolic and mean arterial BP, while these hemodynamic effects were sustained throughout the 2-week administration period. CMG group also exhibited alleviated target organ damage as proposed by amelioration of biomechanical properties of the aorta -including cross-sectional area (CSA), aortic wall stiffness and thickness-, reversal of myocardial small vessel hypertrophy and maintenance of serum albumin levels. The anti-hypertensive effects of CMG are likely to be mediated by the decrease in renin serum levels. Regression analysis indicated that the effect of CMG on organ damage was BP-lowering dependent and was not associated with direct effects of renin or with its anti-inflammatory properties. We suggest a BP lowering effect of CMG via down-regulation of renin excretion associated with attenuation of target organ damage and inflammatory status. These observations provide profound evidence for the beneficial role of CMG in hypertension, which could possibly translate to further clinical research.

Evaluation of Biological Activity of Mastic Extracts Based on Chemotherapeutic Indices.

BACKGROUND: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. MATERIALS AND METHODS: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells. Antibacterial activity was determined by their cytotoxicity against bacteria and normal oral cells. Antiviral activity was determined by their protection of viral infection and cytotoxic activity. Cytochrome P-450 (CYP) 3A4 activity was measured by ß-hydroxylation of testosterone. RESULTS: Ethyl acetate extract showed slightly higher tumor specificity (TS=2.6) and one order higher antibacterial activity (selectivity index (SI)=0.813) than other extracts (TS=1.4-2.5; SI=0.030-0.063). All extracts showed no anti-human immunodeficiency virus (HIV) activity, but some anti-herpes simplex virus (HSV) activity, which was masked by potent cytotoxicity. They showed strong inhibitory activity against CYP3A4. CONCLUSION: Ethyl acetate extraction following the removal of cytotoxic and CYP3A4 inhibitory substances by n-hexane can enhance antitumor and antibacterial activity of mastic.