Studies: ANTIOXIDANT & ANTI-INFLAMMATORY ACTIVITY OF CHIOS MASTIC
Chios Mastic has been used for ages as an antioxidant factor in fat and oil preservation 23 applications, such as in Egypt in 1970s. In recent years, there has been a constantly increased interest with regards to Chios Mastic and its antioxidant as well as its anti- inflammatory effects. Interestingly, it has been concluded in various studies that Chios Mastic inhibits LDL (Low Density Lipoprotein) oxidation in vitro. Precisely, this is essential since the resin can be utilized as a natural antioxidant, particularly for fatty substrates in food, cosmetic and pharmaceutical applications. In vivo human trials resulted in a remarkable decrease in cholesterol, showing its liver and heart protection characteristics. It is of vital importance to mention that Chios Mastic’s antioxidant activity may have direct impacts to its anti-inflammatory effects. Research has shown the in vivo anti- inflammatory activity of Chios Mastic in individuals suffering from inflammatory bowel disease, and the inhibition of inflammation in experimental models. Also, Chios Mastic presents a notable antiatherogenic activity, and thus comprising a potential novel treatment approach for atherosclerosis. It also improves the clinical course in patients with inflammatory Bowel Diseases. The research field of Chios Mastic in antioxidant and anti-inflammatory applications remains quite promising and challenging enough for even more sophisticated trials in the future.
In 2002, a study group investigated the biological activity of the saliva from different chewing gums, collected from healthy volunteers, on the inhibition of LDL oxidation in vitro. Interestingly, crude Chios Mastic was indicated as the most effective, followed by commercial Chios Mastic. Furthermore, in order to obtain the highest possible benefit, chewing time should be from over 15 minutes up to 1 hour 24.
Andrikopoulos et al (2003) studied various resins for their potential protective in vitro activity against copper-induced LDL oxidation. Chios Mastic has been proved to be the most effective in protecting human LDL from oxidation. The most effective extract of Chios Mastic was that of methanol/water, compared with other solvent combinations. The total Chios Mastic essential oil, collofonium-like residue and acidic fractions of the resin possessed also a high protective effect 25.
In 2004, Dedoussis et al explored the molecular mechanisms underlying the antiatherogenic effect of the total polar extract of Chios Mastic. Apoptosis and necrosis was induced to peripheral blood mononuclear cell (PBMC) exposed to oxLDL, based on the duration of exposure. The extract of Chios Mastic inhibited both apoptosis and necrosis, restored glutathione levels and downregulated CD36 expression, even at the mRNA level. Interestingly, the triterpenoid fraction of the resin rather than the phenolic one demonstrated remarkable increase in intracellular glutathione. The results comprise strong evidence of the resin’s antiatherogenic activity 26.
In 2005 a research team investigated Chios Mastic among other natural resins possessing biological properties and the bioactive triterpenes (oleanolic and ursolic acid) for their antioxidant action. Chios Mastic demonstrated high antioxidant effects in each of the oil substrates examined (lard, corn oil, olive oil and sunflower oil). The best concentration of the resin having the highest effect was substrate-depended. A synergistic effect in sunflower oil and corn oil was observed by the combination of Chios Mastic with citric acid. P. lentiscus showed satisfactory antioxidant action in lard. A significant antioxidant activity was presented by Chios Mastic and its essential oil, in virgin olive oil. To conclude, Chios Mastic resin and oil, can be used in pharmaceuticals, cosmetics and functional foods, because of their antioxidant activity in oil substrates 27.
In 2009, another research group studied whether Chios Mastic affects the function of activated macrophages. Solid and liquid types of the product were found to inhibit the production of pro-inflammatory compounds, like nitric oxide (NO) and prostaglandin (PG) e2 by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells. Moreover, there was a reduction on the number of viable cells. Chios Mastic additionally blocked the expression of specific proteins at the protein and at the mRNA levels 28. Chios Mastic was found to exhibit potent hydroxyl radical scavenging effects. Conclusively, Chios Mastic inhibits the production of both NO and PGe2 by activated macrophages mostly via its cytotoxic activity 29.
In 2010, the study of Mahmoudi et al had the objective of investigating Chios Mastic for its mineral components, anti-inflammatory and antioxidant effects in rats. It was indicated that the resin induced statistically significant inhibition of edema at all doses used, in comparison with the control groups. Inflammation was totally inhibited at 800 mg/kg i.p. and toxicity was absent up to 3 g/kg body weights i.p. in mice. Weak 1,1-diphenyl-2-picryl hydrazyl radical and nitric oxide scavenging activities were observed. However, it showed good Fe2+ chelating ability. Interestingly, the quantity of elements was reduced in the specific order Cu > Fe, Zn > Mn > Ni, Cd. The aforementioned information supports the use of Chios Mastic resin as an anti-inflammatory and antioxidant agent 30.
In 2011, a research group concluded that Chios Mastic may help in treating inflammatory diseases, by studying its anti-inflammatory activity in allergic asthma in mice, which is characterized by airway inflammation, eosinophilia, and airway hyperresponsiveness. The product significantly inhibited eosinophilia, while decreasing airway hyperresponsiveness and suppressing the production of inflammatory cytokines, as well as chemokines in bronchoalveolar lavage fluid. Additionally, Chios Mastic potently inhibited in vitro eotaxin-induced eosinophil chemotaxis, without affecting eotaxin receptor, chemokine receptor 3, expression 31.
Triantafyllou et al (2011) explored the potential role of antioxidant activity of Chios Mastic. Significant scavenging activity of superoxide by Chios Mastic itself was not shown. The results indicated that Chios Mastic inhibits PKC, which substantially weakens the production of superoxide and H2O2 by NADPH oxidases, an antioxidant characteristic which may have direct implication to the anti-inflammatory properties of the studied compound 32.
In 2012, Quartu et al evaluated the effect of the administration of Chios Mastic essential oil on changes of fatty acid profile and endocannabinoid congener concentrations, caused by transient bilateral common carotid artery occlusion in the rat frontal cortex and plasma. It is worth mentioning that ischemia/reperfusion results in inflammation and oxidative stress, damaging membrane highly polyunsaturated fatty acids and subsequently leads to neuronal death. The results showed that acute treatment with Chios Mastic oil before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-caused deruction of DHA is apparently prevented and COX-2 expression lowers, and in plasma, where PeA and OeA levels and DHA biosynthesis increase. The increase of palmytoylethanolamide and oleoylethanolamide plasma levels may cause DHA biosynthesis via peroxisome proliferator-activated receptor alpha activation, protecting brain tissue from ischemia/ reperfusion injury 33.
Gortzi et al (2014) used a total Chios Mastic extract after the removal of the contained insoluble polymer to improve solubility and in vivo activity. Conclusively, the encapsulated fractions of Chios Mastic, and specifically the acidic one, showed higher antioxidant activity compared to the non-encapsulated fractions 34.
Most recently, in 2018, focusing on the bioavailability of terpenes in human plasma and their effect on oxidative stress biomarkers, an open-label and single arm postprandial trial was carried out. In this acute experiment in healthy adult males, blood samples were collected on time points 0 h (before ingestion) and on subsequent time points after ingestion of Chios Mastic. Ultra-high-pressure liquid chromatography high-resolution MS (UHPLC-HRMS/MS) was applied for high throughput analysis of plasma. Serum resistance to oxidation and oxidized LDL (oxLDL) levels were measured. In this firstly ever reported study on the bioavailability of Chios Mastic’s compounds in human blood, major terpenes were found bioavailable since 0.5 h after administration, reaching a peak between 2 h and 4 h. Serum resistance to oxidation, expressed as difference of tLAG started to increase from 0.5 h. This increase reached statistical significance at 4 h, peaked at 6 h, and remained statistically significant until 24 h. oxLDL levels, the most reliable marker of oxidative stress expressed as % change from 0 h, was reduced significantly from time point-1 h until time point-6 h. Results demonstrated the terpene bioavailability pattern after oral administration of Chios Mastic, on the one hand, and on the other the potential of terpenes to mediate antioxidant defense in vivo 35.
Additionally, a total of 24 free amino acids were quantified after Mastic ingestion in plasma. Interestingly, amino acids were modulated in response to Mastic intake, an indicatively potential key role of this natural product in human metabolism 36.
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- Inducible NO synthase (iNOS) and cyclooxygenase (COX)-2.
- Zhou L., Satoh K., Takahashi K., Watanabe S., Nakamura W., Maki J., Hatano H., Takekawa F., Shimada C., Sakagami H. : Re-evaluation of anti-inflammatory activity of mastic using activated macrophages. In vivo, 23: 583-590.
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- Qiao J., Li A., Jin X., Wang J. : Mastic alleviates allergic inflammation in asthmatic model mice by inhibiting recruitment of eosinophils. Am. J. Respir. Cell Mol. Biol., 45: 95–100.
- Triantafyllou A., Bikineyeva A., Dikalova A., Nazarewicz R., Lerakis S., Dikalov S. : Anti-inflammatory activity of Chios mastic gum is associated with inhibition of TNF-alpha induced oxidative stress. Nutrition J., 10: 64-72.
- Quartu M., Serra M.P., Boi M., Pillolla G., Melis T., Poddighe L., Del Fiacco M., Falconieri D., Carta G., Murru E., Cordeddu L., Piras A., Collu M., Banni S. : Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion. Lipids Health Dis., 11(8).
- Gortzi O., Athanasiadis V., Lalas S., Chinou I., Tsaknis J. : Study of antioxidant and antimicrobial activity of chios mastic gum fractions (neutral, acidic) before and after encapsulation in liposomes. J. Food Process. Technol., 5 (8): 355-359.
- Papada E, Gioxari A, Brieudes V, Amerikanou C, Halabalaki M, Skaltsounis AL, Smyrnioudis I, Kaliora AC. Bioavailability of Terpenes and Postprandial Effect on Human Antioxidant Potential. An Open-Label Study in Healthy Subjects. Mol Nutr Food Res. 2018; 62(3). doi: 10.1002/mnfr.201700751.
- Papada E, Torović L, Amerikanou C, Kalogeropoulos N, Smyrnioudis I, Kaliora AC. Modulation of Free Amino Acid Profile in Healthy Humans Administered with Mastic Terpenes. An Open-Label Trial. Nutrients. 2018 Jun 3;10(6). pii: E715. doi: 10.3390/nu10060715.