1、Damage of free radicals

Billions of free radicals attack every cell of the body about 3,000 times a day, according to leading scientists. It can lead to the oxidation of cell biofilm and cell mitochondria, resulting in the destruction of structure and function, thus accelerating the occurrence of human aging and diseases. And the free radicals themselves are objective, and for humans, whether in vivo or in vitro, free radicals are still being produced at an unprecedented rate. Numerous medical studies and clinical trials have confirmed that there are excessive free radicals in the body to develop tumors, the proportion of cardiovascular and cerebrovascular diseases, diabetes, arteriosclerosis, senile dementia and other diseases has increased significantly, and the aging speed has accelerated sharply.

Reactive Oxygen Species are also known as "free radicals". A series of internal and external causes can cause the body to produce too many free radicals. Every cell in the body USES a lot of energy to run every day. This energy is generated by tiny "power plants" inside individual cells, called mitochondria. In the process of normal human metabolism, mitochondrial oxygen combined with the related substances in the body can be converted to the energy needed to power a cell (ATP), as well as by-product - free radicals ROS, when the latter is accumulated to a certain degree may cause irreparable damage of mitochondria and cell, so as to weaken the function of mitochondria, triggering cell senescence and apoptosis.

Free radicals are everywhere in the body. They are free, active and aggressive. This is because free radicals are electron-deficient substances with a single unpaired group of electrons, always looking for opportunities to grab electrons from other substances in order to stabilize themselves. Therefore, free radicals attack the cell membranes, mitochondria and DNA of organs in the body, causing damage to target cells, which not only intensifies the aging process of human body but also causes a series of diseases.

2、Studies on the accumulation of SkQ1 into mitochondria

First, the ability of SkQ1 to accumulate in mitochondria has been test ed. For this test, a special electrode capable of measuring the SkQ1 concentration  in  the  medium  has  been  developed.  It  allowed  to demonstrate the ability of SkQ1 to accumulate in mitochondria. Also, the dependence of the accumulation of SkQ1 on the functional state of the mitochondria has been shown. Decreasing the membrane potential of the mitochondria with FCCP stimulated the release of SkQ1 from the  mitochondria.  However,  much  of  the  SkQ1  remained  bound  to mitochondrial membranes due to the high hydrophobicity of the compound (fig. 1).

     A key advantage of the synthesized SkQ1 antioxidants is their ability to be reduced by the respiratory chain of mitochondria. This special feature of SkQ1 compounds allows them to act as antioxidants repeatedly, in contrast to classical antioxidants which usually become inactive after interaction with a radical. Experiments have shown that SkQ1 is reduced by complex III of the respiratory chain. These data indicate that SkQ1,which is oxidized upon interaction with  radicals, is effectively regenerated by the respiratory chain of mitochondria. In other words,  SkQ1 is in fact recyclable antioxidant.

    Dose−dependency of SkQ1 activity indicates that SkQ1−based pharmaceuticals can have some unusual properties in comparison with traditional drugs. For the majority of usual pharmaceutical preparations (for example, inhibitors of various metabolic pathways), the efficiency increases proportionally to the increase of the dose. Selection of the optimum dose is usually limited by toxicity of the compound. In the case of mitochondrial antioxidants, the situation is expected to be completely different. Due to the strongest ability to accumulate inside cells and particularly in mitochondria they begin to work at very low concentrations.

3、Research on the effect of SKQ1 on human cells

     An unexpected result was obtained in the study of SkQ1 effect on cell cultures. It appeared that treatment of cells with SkQ1 increased their size (spreading) and number of places where the cells were attached to the substrate, (「strength− ening」 of the protein cytoskeleton). 

    This observation allowed us to make several assumptions. It is necessary to take into account that during in vitro cultivation, human fibroblasts are exposed to oxidative stress due to the increased content of oxygen in the envi− ronment in comparison with its level in a tissue in vivo. Theprevious experiments showed that SkQ1 was really able to modulate oxidative stress in cells . 

     Such protec- tion from oxidative stressprobably allows human fibroblasts to maintain their 「normal」 state even under in vitro cultivation. This leads to stronger attachment to the substrate, larger size, and 「strengthening」 of the cytoskeleton. 

     Such 「normaliza− tion」 of cells could be exploited in several ways. First, theincrease in the size of cells and their 「attach− ment」 could theoretically suppress ability of cancer cells for metastasis – the migration from a tumor to nearby tissues. 

     Hence, in certain cases SKQ1 might display an anti−carcinogenic effect (see 「Oncology」 section). Second, this activity of SkQ1 could be used to facilitate the process of wound healing since fibroblasts are active participants of it and oxidative stress was shown to play a sig− nificant role in this process (see 「Wound healing」 section).

4、Penetration of SKQ1

     SKQ1-the perfect anti oxidant，we  used  several  experimental  approaches  for  evaluating  the  activity  of  our compounds  as  in  vitro in  simple  non−biological  systems.  First  SkQ  mem− brane−penetrating ability was investigated in the  planar artificial bilayer lipid membranes (BLM) model. Experiments are conducted with a unique 「black membrane」 apparatus developed in the A.N. Belozersky Institute of Physico− Chemical Biology, Moscow State University.

    The 「black membrane」 experiments show that the synthesized compounds are indeed capable to penetrate through the lipid membrane. Severina's experiments on BLM have shown that SkQR1 and SkQ3 have the best penetrating ability. For SkQ1, MitoQ and DMQ the ability to pass through the "black membrane" appeared to be somewhat lower.The experiments showed that SkQ1 is the most effective antioxidant among the compounds tested.  

5、SKQ1  Gerontology

     A set of experiments have been carried out with OXYS rats suffering  from  progeria  caused by constant oxidative stress. The remarkable feature of these rats is a number of senile diseases developing within a few months after birth. Such diseases include cataract, retinal dystrophy, osteoporosis, thymus involution, reduction of sexual motivation of males, and impaired memory. Experiments made by N.G. Kolosova and her colleagues (Institute of Cytology and Genetics, Siberian  Division of Russian Academy of Sciences) have shown that the development of all  above listed features of ageing was significantly slowed down by the administration  of 50−250 nmol SkQ1/kg/day with food.

     Another  set  of  long−term  experiments  was performed  by  the  group  of  V.N.  Anisimov (N.  N.Petrov  Institute  of  Oncology,  St. Petersburg). The effect of SkQ1 on ageing of normal outbreed mice was investigated. Lifetime  administration of SkQ1 with drinking water in 5 nmol/kg dose considerably reduced age−related mortality of normal animals. The effect on the death rate for the first 20% of deceased animals was especially significant resulting in 2.5−fold increase of life span. For 50 % of deceased animals a 30% effect was documented. Finally for long− lived mice (the last 20 % of the cohort) there was approximately 10 % extension of lifespan. In other words, SkQ1 caused so−called rec− tangularization of the mortality curve of mice. The same trend was revealed in experiments with fungi  (podospora,  Fig.  3)  and inverte− brates (insect − drosophila, Fig. 4; crustacean − daphnia Fig. 5) whose lifespans were also increased by the lifetime SkQ1 treatment.

 Lifetime SkQ1 treatment not only prolonged the lifespan of animals but also resulted in an improvement in the 「quality of life」. For example, normally the  majority of aged female mice have irregular estrous cycles by the age of 22 months.  In V.N. Anisimov experiments SkQ1 treated mice, but not control animals, retained regular cycles similar to young animals.

 The antioxidant also dramatically changed the causes of death. SkQ1 strongly reduced mortality caused by infections, which usually increases with age due to impaired immunity. Table  1  summarizes  most  important  results  of studies on SkQ1 and SkQR1 effects on animals in vivo. The table shows that 20 different traits of  ageing  can  be  positively  affected  (slowed down, stopped or even reversed) by SkQ therapy. Thefore SkQ compounds can be regarded as powerful geroprotectors. Remarkably SkQ does not  increase the maximum  lifespan as much as the quality of life in its second half. In other words, SkQ prolongs youth.

6、the perfect anti oxidant

      It has been hypothesized that age-dependent accumulation of oxidative damages in living organisms may be the main cause of ageing process. It might be possible to control this damage accumulation through controlling the level of ROS (Reactive Oxygen Species) production in mitochondria. It is important to stress that ROS production should be controlled, not stopped, so that ROS can still fulfill a number of crucial biological functions. For instance they fight bacteria and viruses, both directly – via elimination of pathogens, – and indirectly – via regulation of the immunological response to infection through triggering apoptosis (cell death).

SKQ1- The 「ideal」 antioxidant should be specifically targeted to mitochondria where ROS are produced and it should effectively remove not all the ROS but just their excess. It is also important for an antioxidant not to be toxic and not to be recognized and eliminated by cell enzymes.

       Extremely low concentrations of SkQ1 have shown pharmacological effect in our experiments. Such low-dose effect of SkQ1 can be attributed to two important properties of the compound:

•  high effectiveness in targeting mitochondria and

• being a 「recyclable antioxidant」.

      SkQ1 being able to target the inner leaflet of the inner mitochondrial membrane with high precision is why only very low amounts of the compound are needed in order to affect the cell at the first place. But our experiments also showed that once inside mitochondria, SkQ1, which is oxidized upon interaction with radicals, is effectively regenerated by the respiratory chain. This valuable property provides SkQ1 with an ability to act on a cell for an extended period of time in low doses.The combination of highly targeted action and being able to achieve effect in extremely low concentrations are probably the major reason why SkQ1 has not shown any adverse effects in therapeutic doses we have been studying in our pre-clinical and clinical experiments.

       With these criteria fulfilled, a successful anti-oxidant compound should be able to prevent/repair oxidative damage in organism and prevent/treat many age-related disorders across various therapeutic areas.

       Preclinical studies of SkQ1 toxicity were done in a State certified facility in accordance with the standard protocol approved by Health Ministry of Russian Federation.

      It was shown that the SkQ1 preparation does not possess anaphylactogenic, allergic, embryotoxic or teratogenic effects, it did not influence the major immunity barriers and reproductive function of animals. The SkQ1 preparation did not show mutagenic and carcinogenic effects. 

      The injection of the preparation did not result in a change of the animal behavior, biochemical or clinical indicators, or diuresis. SkQ1 preparation in both studied doses produced an increase of QT interval in ECG.

      Fifteen daily oral injections of the SkQ1 preparation in a total dose equal to LD10 had no influence on the pathomorphological structure of internal organs.

SKQ1 by PURECELL

SKQ1  - " Your shield against Free Radical Damage"

Mitochondria are the cell's energy production powerhouses, producing free radicals as a byproduct of their energy production cycle. Free Radicals are known to cause severe aging damage and death to cells.

SKQ1 by PURECELL is the only antioxidant in the world scientifically proven to stop free radical production in the mitochondria of every cell in the body.

Usage 

Use SKQ1 on the soft skin inside your arm. Once every two days with 3 drops in the morning.

Within a few weeks all the cells of your body will begin to regenerate and repair.  You will feel and look younger as the days pass. While others suffer the daily damage of free radical attack inside each cell, you will have SKQ1 to act as your shield against the ravages of time."

Storage

Use in 3 months.

Keep refrigerated or at room temperature less than 25°C.