HYPER-MASTIC project description

Chios Mastic consists one of the oldest, purely Greek herbal remedies and it has been registered by the EU as a product of Protected Designation of Origin. It is the resin of Pistacia lentiscus var. Chia, which grows exclusively in the southern territory of Chios island, Greece. Its action against helicobacter pylori is proven, while in 2015 it was recognized by the European Medicines Agency (EMA), as a phytotherapeutic with certain therapeutic indications.

Numerous new studies indicate the beneficial properties of Chios Mastic both for the liver and in auto-immune diseases of the intestine. New experimental studies of the researching network, support the possible beneficial effect of Chios mastic on the cardiovascular system, particularly on hypertension, which is one of the leading causes of cardiovascular death worldwide. This possible antihypertensive effect of Chios Mastic is the main reason for the commence of the HYPER-MASTIC research project.

HYPER-MASTIC’s subject is the research, development and commercial production of unique phytotherapeutic products with hypertensive action, based on Chios Mastic. The project will study both the raw material (resin) and new, innovative formulations that will be formed with the cooperation of Academic and Corporate Institutions. In fact, these institutions already have extensive cooperation, as well as preliminary results available, to support Chios Mastic’s possible antihypertensive action.

Within the HYPER-MASTIC project, "green" technologies for extraction and isolation of Chios Mastic will be used, to chemically determine its bioactive components. Furthermore, new, innovative quality control technologies will be developed, to reduce the spread of adulteration phenomena. During the project, both cellular and in vivo experimental models will be deployed, to determine the biological activity and safety of Chios Mastic products.

At the same time, a new phytotherapeutic product based on Chios Mastic will be developed, the antihypertensive action of which will be studied in a randomized clinical study. That study will be combined with both bioavailability studies and the application of modern approaches (metabolic, genomic), to investigate the acting mechanism of Chios Mastic components in humans.


HYPER-MASTIC project goals

HYPER-MASTIC’s ultimate goal is the global consolidation of Chios Mastic as a purely Greek, valuable phytotherapeutic product with antihypertensive action, which on top will be directly connected with both the Greek tradition and innovative entrepreneurship.

HYPER-MASTIC goals consist of:
• the use of "green" technologies for the extraction and isolation of Chios Mastic, to chemically determinate its bioactive components

  • the biological action and safety investigation of Chios mastic products, in cellular and in vivo experimental models
  • the reduction of widespread counterfeiting, through the development of quality control methods, adapted to the requirements of the European Pharmacopoeia
  • the development of a new, scientifically proven phytotherapeutic product, based on Chios Μastic
  • the clinical study of the created product, to prove its level of effectiveness against hypertension
  • the application of modern approaches (metabolic, genomic), to investigate the action mechanism of Chios Mastic components, as well as their bioavailability
  • the strengthening of Greek entrepreneurship and innovation in the global market in the field of herbal medicines, via the consolidation of cooperation networks, as well as the integration of knowledge derived from academic research
  • the adoption of a new culture in developing phytotherapeutics
  • the enhancing of the Greek pharmaceutical industry
  • the creation of new working positions and the strengthening of both the local economy of Chios and the Greek economy in general


Working Modules & Methods

In order to successfully complete the objectives of HYPER-MASTIC research project, all the planned actions have been organized into 5 Working Modules, each containing sub-working modules, lasting a total of 30 months. All modules are successive and complementary with specific sub-objectives.

The five Working Modules are as following:

1) Receiving and Quality Control of raw material (resin) and Chios Mastic products

HYPER-MASTIC’s first step is the receipt of Chios Mastic (the raw material will be supplied by Chios Gum Mastic Growers Association L.L.C.) and the development of certified, detailed quality control methodologies of the resin and its byproducts.

The development of detailed quality control methods that are in accordance with the principles of the European Pharmacopoeia, will be carried out by the Department of Pharmacy, Sector of Pharmacognosy and Chemistry of Natural Products, National and Kapodistrian University of Athens (UOA), along with IASIS PHARMA pharmaceutical company, using GC-MS, LC-HRMS, HPT and HPLC-DAD techniques. The best out of these methods will be validated and promoted for certification and industrial production.

2) Extraction, isolation and identification of Chios Mastic active ingredients

HYPER-MASTIC research project has three essential sides: extraction-isolation-identification. More specifically, the Sector of Pharmacognosy and Chemistry of Natural Products (UOA), in collaboration with Chios Gum Mastic Growers Association, will proceed to the application of "green" extraction techniques (ACE, SFE and CPE) and separation (CPC and SFC-UV), aiming to isolate all active ingredients and subsequently identifying them by LC-HRMS and NMR techniques.

3) Biological Evaluation of Chios Mastic in cellular and in vivo experimental models

Both the extracts and the isolated ingredients that will result from the second working module, will be evaluated for their potential cardioprotective / antihypertensive action and safety.

More specifically, the extracts will be evaluated at a genetic and cellular level, to study a series of parameters (antioxidant potential, protection against oxidative stress, activation of cytoprotective mechanisms).

This evaluation will be carried out by the Department of Biology, Sector of Cellular Biology and Biophysics, UOA. The 8 most bio-active extracts will also be studied in vivo in a rat experimental model, as well as with genomic and transcriptional approaches to further understand their action at a molecular level – study that will be carried out by the Department of Nutrition and Dietetics, Harokopio University.

Last, but not least, development and application of metabolic approaches using mass spectrometry will take place, for the detection of the components of Chios mastic in cellular systems and / or biological fluids. These approaches will be performed by the Department of Pharmacy, Sector of Pharmacognosy and Chemistry of Natural Products (UOA).

4) Clinical study in hypertensive volunteers with Chios mastic product (in tablet form)

Following the above results’ evaluation, production of a specific Chios mastic formulation will take place, which will be used to conduct a clinical study in hypertensive volunteers.

This new pharmaceutical product -with Chios mastic as its active ingredient- will be produced by IASIS PHARMA. IASIS PHARMA, in cooperation with the Therapeutical Clinic of Medical School, UOA, will conduct a double-blind, randomized study, which will include 3 groups (35 people per group) of hypertensive patients. Volunteer selection and monitoring protocols will be followed in accordance with international regulations, while the number and dosage regimen will be calculated based on pilot preliminary studies carried out by the research network.

Blood and urine samples will be taken from the volunteers (420 blood samples) at specific periods (0, 1, 2 and 3 months). Documented examinations will be performed in all patients, to evaluate multiple parameters of the function and structure of the cardiovascular system, before and after the administration of the Chios mastic pharmaceutical product.

5) Clinical study’s biological samples analysis

The final stage of HYPER-MASTIC scientific study includes the volunteers’ biological samples (blood) analysis. More specifically, a bioavailability study will be conducted, regarding the components of Chios mastic (210 per biological fluid, multiplied by 4 points), as well as metabolic studies, aiming to highlight bio-indicators - molecules. In this task, Department of Pharmacy, Sector of Pharmacognosy and Chemistry of Natural Products (UOA) will be cooperating with IASIS PHARMA.

Furthermore, the pharmaceutical product in use will be tested regarding the activation of cell-protective mechanisms (such as antioxidant activity, proteasome activation) both at molecular and cellular level. That will be examined by the Department of Biology, Sector of Cellular Biology and Biophysics, UOA.

Finally, the Department of Nutrition and Dietetics, Harokopio University will conduct extensive genomic and transcriptomic analyzes, to record the molecular basis of Chios mastic products’ action mechanism.


Expected Results

The main goal of the HYPER-MASTIC research project is the promotion of Chios mastic and its products, as phytotherapeutic products with antihypertensive action, based on reliable scientific documentation. The expected results of the project can be distinguished in purely scientific knowledge, innovation and economic development, while special emphasis is given to the beneficial effects of the project on society.

  • For the Chios mastic resin: modern, validated and certified quality control methodologies will be developed, in accordance with the European Pharmacopoeia and international quality and safety standards. The application of these methodologies is expected to contribute to consumer protection, in response to the widespread phenomena of Chios mastic counterfeiting and fraud worldwide, which ultimately degrade Chios mastic products.
  • Significant results are expected to emerge from the methodologies of extraction, separation, isolation and identification of the Chios mastic components. Until today, their isolation in pure form has not been possible, their availability by the HYPER-MASTIC network is a milestone for the success of the project. It will also allow further investigation of their biological properties in other pharmacological targets, as well as the implementation of quality control procedures in the future. Particular emphasis will be put on the use of "green methodology techniques", with obvious benefits for the environment and the health of the population, but also a significant cost reduction.
  • During the project, the bioavailability study of Chios mastic components through the analysis of biological fluids of the patients of the clinical study, is expected to provide important information on the safety and effectiveness of the Chios mastic components, all for the benefit of the consumers.
  • Based on data from a pilot clinical study carried out by the HYPER-MASTIC network, the administration of Chios mastic is expected to drastically reduce blood pressure, to act protectively at the sites of damage to organs targeting hypertension, as well as against vascular aging. This effect is expected to be observed either autonomously, or in parallel and cumulatively with that of antihypertensive drugs that patients may receive.
    The findings are significant, as hypertension is one of the leading causes of cardiovascular death and the most common chronic disease leading to primary care facilities, with huge medical and financial costs. The possible finding of a beneficial effect of the phytotherapeutic preparations of Chios mastic on the levels of blood pressure and its complications, would be extremely beneficial both from a medical and from an economic point of view.
  • The combined and complementary application of modern approaches (genomic, metabolic) and modern bioassays in endothelial cells and in vivo in rat hypertension model, is expected to lead to the finding of correlations, indicating new signaling and pathogenic pathogens.
  • Thanks to the long experience of the participants in the HYPER-MASTIC project in research and development focusing on Chios mastic, but also in the detailed project design, we aspire that the new product to be developed will be a national development model in the field of phytotherapy.
  • The research institutes participating in the project will gain new knowledge, while the participating companies will gain significant benefits, through the comparative advantages provided by the integrated scientific documentation. This will lead to faster and more stable market penetration.
  • Through the scientific project, the creation of working positions is sought and expected, along with the formation of a new philosophy for young scientists and workers in the field of phytotherapeutic products. A different culture is expected to be formed, giving alternative solutions to the development of the country.
  • Finally, the successful completion of the project will contribute to the development of the local community of Chios, to the support of the Greek economy but also to the protection of the overall society, by contributing to consumer safety.