Overview of Chios Mastic Gum (Pistacia lentiscus) Effects on Human Health

2. Anti-Inflammatory Properties

Inflammation constitutes the common pathogenetic substrate for many acute and chronic diseases. It represents the human’s immune system response to various stimuli, such as pathogens, toxic compounds and damaged cells, regulated by a variety of endogenous factors, including cytokines, growth factors and activated cells [6]. There are two types of inflammation, acute and chronic. While acute inflammation usually refers to a short-term activation of the immune system as a response to an external trigger, chronic inflammation may occur in the absence of any specific stimuli, resulting in the development of many chronic diseases. It is now well established that several chronic disorders, such as connective tissue and inflammatory bowel diseases, diabetes mellitus, cancer and cardiovascular disorders share, to a lesser or greater degree, common pathogenetic mechanisms involving inflammation [7].

There is now an emerging body of evidence to support the anti-inflammatory activity of Chios mastiha. This anti-inflammatory action seems to be performed via the inhibition of the production of pro-inflammatory substances. In particular, administration of both solid and liquid types of mastiha seems to inhibit prostaglandin secretion along with inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression by macrophages at both protein and mRNA level in animal experimental models [8]. In vitro, mastiha blocks the expression of the adhesion molecules VCAM-1 and ICAM-1 by TNF-alpha-stimulated human aortic endothelial cells, thereby interfering in endothelial activation that is recognized as the primary event of the atherosclerotic process [9].

Data derived by human studies are also in the same direction (Table 2). In a small clinical study including 10 patients with mild or moderately active Crohn’s disease recruited to treatment with mastic caps for 4 weeks (2.2 g/day), a significant decrease in the activity index of the disease and the plasma levels of interleukin-6 and CRP compared to baseline was observed, while no significant side effects were reported [10]. In the same patient cohort, a remarkable reduction in TNF-a secretion following treatment with mastic caps was later reported, suggesting an additional inhibitory mechanism of monocyte chemotaxis, thus providing more support to the role of mastiha as immune system regulator [11].

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Based on the findings of this pilot study, in 2019, Papada et al. designed and performed a randomized controlled trial to further investigate the impact of mastiha on patients with inflammatory bowel disease. A total of 60 patients were randomly assigned to receive either mastiha (2.8 g/day) or placebo for 3 months adjunct to standard medication. Patients treated with mastiha had a significant decrease in faecal lysozyme compared to patients on placebo, indicative of lower disease activity. In addition to this, a significant improvement in Inflammatory Bowel Disease Questionnaire scores reflecting a beneficial effect on patients’ quality of life was observed in the mastiha arm compared to the baseline [12]. When the same protocol was applied to 68 patients with inactive inflammatory bowel disease for 6 months, in contrast to controls, patients allocated to mastiha as add-on treatment to standard medication presented no increase in interleukin-6 or in faecal biomarkers calprotectin and lactoferrin, which are neutrophil-derived proteins whose concentrations typically rise in patients with gastrointestinal mucosal inflammation [14]. Recent data support that mastiha treatment interferes in the regulation of Th17 cell function and differentiation, resulting in increased serum levels of interleukin-17A that is considered to play a protective role in the development and relapse of inflammatory bowel disease [15]. Figure 1 summarizes the most important pathogenetic and clinical effects of mastic.

Chios mastic exerts anti-inflammatory and antioxidative properties (central frame). Anti-inflammatory action is attributed to the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression by macrophages and the blockage of the expression of the adhesion molecules VCAM-1 and ICAM-1 by TNF-alpha stimulated endothelial cells, ultimately resulting in reduced Tumor Necrosis-alpha (TNA-a) and inflammatory interleukins (ILs) production. The antioxidative properties are mainly driven by a downregulation of CD36 expression in macrophages along with an increase in the intracellular antioxidant glutathione levels. The clinical effects of mastic (outer frames) represent the result of anti-inflammatory and anti-oxidant action and include a hypolipidemic action with a decrease in oxidized-LDL (ox-LDL) particles and foam cell formation, beneficial effects in inflammatory bowel disease, dermatitis and periodontal inflammation, antimicrobial and anticancer properties.

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Mastic demonstrates a protective effect on intestinal epithelial cells, largely determined by its anti-inflammatory and antioxidant properties [25]. This action has been more thoroughly investigated in inflammatory bowel diseases, where mastic has been found to decrease the cytokines tumor necrosis factor-a, malonaldehyde, intercellular adhesion molecule-1 (ICAM-1) and interleukin -6, -8 and -10, both in preclinical and clinical studies; thus, efficiently inhibiting intestinal damage [26,27]. In addition, mastiha supplementation promotes a partial but respectable recovery of microbial diversity, acting as a natural probiotic factor [28]. A randomized controlled trial including 148 subjects showed that mastic, at a dose of 350 mg three times daily, significantly improved symptoms related with functional dyspepsia after 3 weeks of treatment [16].

It has also been found that mastic reduces liver enzymes and improves hepatic steatosis and collagen content in experimental models with non-alcoholic fatty liver disease (NAFLD) [28]. Considering that oxidation and inflammation dominate the pathogenetic substrate of NAFLD, the MAST4HEALTH randomized clinical trial reported a significant improvement in total antioxidant status of obese patients with NAFLD treated with mastiha for a 6 month period [17]. Several mastic compounds, including oleanonic acid, oleanolic acid and gallic acid act as modulators of peroxisome proliferator-activated receptors (PPARs), which are recognized as regulators of glucose and lipid metabolism, inflammation and fibrosis progression in the liver, playing a crucial role in the development of NAFLD [29].

There is an accumulating body of evidence suggesting that the topical application of mastic ointment attenuates inflammatory and/or pruritic responses in animal experimental models of allergic dermatitis [30]. This action is once again attributed to the anti-inflammatory properties of mastic and, particularly, to the drastic reduction of cytokine production. Clinical data derived from randomized controlled trials also suggest that mastic exhibits a beneficial effect on wound healing. Higher healing rates of episiotomy wound healing were observed in 73 women who were treated for three days postpartum with mastic oleoresin, which was administered through smoking of the wound [18]. These data are consistent with findings provided by animal studies that demonstrate a favorable action of mastic oil on the healing of wounds caused by laser burns [31].

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The aforementioned data undoubtedly support that mastic possesses anti-inflammatory properties. On the other hand, with the exception of inflammatory bowel disorders, data regarding the potential anti-inflammatory effect of mastiha on other systemic inflammatory disorders are scarce. In these terms, large-scale, well-designed clinical trials involving patients with common inflammatory disorders are yet to be performed in order to establish the anti-inflammatory function of mastiha.

References

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About the Author: Tung Chi