Modern possibilities of antioxidant therapy with saffron in ophthalmic practice: rationale for use and potential clinical efficacy
MODERN OPPORTUNITIES OF ANTIOXIDANT THERAPY WITH SAFFRAN IN OPHTHALMIC PRACTICE: RATIONALE FOR APPLICATION AND POTENTIAL CLINICAL EFFECTIVENESS
Petrenko O. V., Yakovets A. I.
National Medical Academy of Postgraduate Education named after P. L. Shupyk , Kiev, Ukraine
The article discusses common age-associated eye diseases, the pathogenesis of which is associated with oxidative stress. Saffron has pronounced antioxidant properties: it prevents the oxidation of polyunsaturated fatty acids, prevents membrane destructive processes in photoreceptors, increases the stability of the lipid layer of membranes. Glycosides and carotenoid zeaxanthin contained in saffron, create a depot of antioxidants and reactivate the depleted antioxidant system of the retina; bioflavonoids strengthen the walls of blood vessels, reduce the permeability of hematoparenchymal barriers, stimulate the process of protein biosynthesis, and accelerate regeneration processes. Currently, a large number of clinical studies have been conducted demonstrating the high efficacy and safety of saffron in the treatment of age-associated eye diseases.
Key words: age-associated eye diseases, saffron, antioxidant properties.
Today in the world there is a steady increase in visual disturbances and eye diseases, which is associated with the aging of the population and, accordingly, with an increase in age-related involutional changes in the visual analyzer. According to statistics presented by experts from the World Health Organization, about 314 million people have various vision pathologies, 45 million are blind . Among the main causes of blindness, age-associated eye diseases dominate: cataracts, age - related macular degeneration, glaucoma and diabetic retinopathy .
Cataract is a partial or complete opacity of the substance or capsule of the lens, leading to a decrease in its light transmission and decreased visual acuity . According to the WHO, it is responsible for up to 47.9 % of cases of blindness worldwide. In the age group 50-60 years old, it is detected in 15 % of the population, 70-80 years old - in 26-46 %, over 80 years old - in almost everyone [2; 4].
Age - related macular dystrophy (AMD), often resulting in disability [5; 6]. In economically developed countries, AMD as the cause of low vision ranks third in the structure of eye pathology after cataracts and glaucoma [7; 8]. The terminal stage of AMD (blindness) occurs in 1.7 % of the total population over 50 years old and about 18 % of the population over 85 years old [9; 36].
In 12.3 % of cases, vision loss is caused by glaucoma , characterized by a constant or periodic increase in intraocular pressure caused by impaired outflow of aqueous humor from the eye, followed by the development of specific visual field defects and optic nerve atrophy . The incidence of the disease is associated with age: in the group of 40–45-year-old people, it is found in 0.1 % of cases; in 50-60-year-olds - in 1.5 % of observations; after 75 years - in more than 3 % of cases . In 4.8 % of cases, chronic blindness is accompanied by the progression of diabetic retinopathy : from 5 to 20 % of patients with diabetes mellitus lose their vision every 5 years [2; 12].
It should be noted that all age-associated eye diseases, leading to visual impairment and blindness, significantly reduce the patient's ability to work, impair self-care and quality of life, and become a heavy burden for the close environment. This actualizes the problem and requires the search and development of new approaches in the treatment and prevention of this ophthalmic pathology.
Oxidative (oxidative) stress is an important link in the pathogenesis of age-associated eye diseases
It has now been established that oxidative stress plays an important role in the pathogenesis of age-associated eye diseases . The eye tissue is continuously exposed to the aggressive blue spectrum of sunlight. As a result of photooxidation, a singlet form of oxygen and its free radicals are formed, causing such damage to cells as lipid oxidation, protein breakdown and DNA damage [13; fourteen]. In addition, nutritional deficiencies due to impaired absorption, unfavorable environmental conditions, smoking, infections, and certain drugs are of no small importance in the development of oxidative stress .
It is known that normal body cells have a large number of defense mechanisms in the form of antioxidants and reducing enzymes, which successfully protect cells from oxidative damage caused by free radicals. Although oxidative stress is lifelong, its effects are especially noticeable with age. It is believed that as the body ages, the antioxidant defense system depletes and metabolism deteriorates. This leads to a condition in which the amount of free radicals far exceeds the capacity of the protective antioxidant systems, and the cells become vulnerable to destruction. The retina is especially sensitive to oxidative stress, since it needs a large amount of oxygen, is exposed to an extremely high level of exposure to light that can initiate the production of free radicals, and cell membranes contain many readily oxidizable polyunsaturated fatty acids [15; sixteen].
Free radicals also have an affinity for unsaturated fatty acids, a major component of photoreceptor cell membranes. As a result of this interaction, high molecular weight polymers with a high content of lipofuscin, the pigment of old age, are formed and deposited in the pigment epithelium. In turn, this leads to the expansion of the zones of atrophy of pigment epithelium cells and the death of photoreceptors .
In diabetes mellitus, hyperglycemia plays a central role in the development of oxidative stress. Glucose autooxidation , non-enzymatic glycosylation, and activation of sorbitol metabolism are sources of free radicals or reactive oxygen species in this disease. In conditions of normal metabolism, they are also formed, but are quickly inactivated. Under conditions of imbalance between production and inactivation , oxidative stress develops . In addition, prolonged hyperglycemia leads to impaired capillary permeability, loss of pericytes, the formation of microaneurysms and retinal hypoxia .
Thus, taking into account the important role of oxidative stress in the development and progression of age-associated eye diseases, the use of antioxidant therapy is an effective and pathogenetically substantiated method for their prevention and treatment. Back in 1992-2001. The Age Related Eye Disease Study ( AREDS ), a large study of 11 US centers and 4,757 patients aged 55–88 with AMD and cataracts, established the efficacy and safety of antioxidant therapy. The results of AREDS showed that its administration reduces the risk of progression of AMD and cataracts by 17 % compared with placebo control, with a combination of antioxidants and minerals - by 25 % .
Biochemical composition, antioxidant and metabolic properties of saffron, mechanisms of retinoprotection
Recent studies show that antioxidants of plant origin have an undoubted advantage in the treatment and prevention of age-associated eye diseases [21; 22]. This is due to their ability to synthesize physiologically active compounds in an assimilable form, the ability to adapt to transport systems across the cell membrane, efficiency and high safety, multifunctionality , low toxicity, minimal side effects, and the absence of drug dependence. In this respect, saffron is of particular interest, the diversity and uniqueness of its chemical composition ensure the versatility of its biological action on the metabolic and structural systems of the body.
The basis of the chemical composition of saffron is formed by such components as the carotenoids lycopene , α -, β - and γ -carotenes, zeaxanthin ; glycosides - crocetin , safronal , picrocrocin ; flavonoids - isorhamnetin , kaempferol ; essential and fatty oils; B vitamins (thiamine, riboflavin); minerals - copper, potassium, calcium, manganese, iron, selenium, phosphorus, zinc and magnesium .
It has been established that one of the mechanisms of the retinoprotective action of saffron is the realization of its antioxidant properties. Saffron as an antioxidant [27; 28] prevents the oxidation of polyunsaturated fatty acids, prevents membrane-destructive processes in photoreceptors and inactivation of membrane-bound enzyme complexes, increases the stability of the lipid layer of membranes. Against the background of these processes, stabilization of other biochemical parameters in the eye also occurs. So, in the study of Azerbaijani scientists H. V. Babayev et al . (2016) showed that the administration of saffron prevents the suppression of the activity of antioxidant enzymes (catalase, superoxide dismutase and glutatin peroxidase ) in degenerative processes in the retina. This is facilitated by the fact that saffron stabilizes the redox balance by mobilizing natural antioxidant systems .
The second mechanism of saffron's retinoprotective activity is associated with maintaining the balance of pro- and antioxidant systems. The presence of glycosides and the carotenoid zeaxanthin in the saffron extract allows creating a depot of antioxidants and reactivating the depleted own antioxidant system of the retina. The α- and β- carotene constituents of saffron , lycopene are the main precursors of vitamin A, contributing to the formation of retinol in the body (the main retinal pigment - rhodopsin and the cone pigment - iodopsin ), which, in turn, improves the work of the visual analyzer, triggering the mechanisms of perception Sveta. In addition to carotenoids from the group of natural polyphenols, the saffron extract contains bioflavonoids ( isorhamnetin , kaempferol ), which help to strengthen the walls of blood vessels, reduce the permeability of hematoparenchymal barriers, stimulate the process of protein biosynthesis, and accelerate regeneration processes [24; 25; 36].
Potassium, which is part of saffron, is an important component of cells and body fluids, manganese and copper are used as cofactors for the antioxidant enzyme superoxide dismutase , iron as a cofactor for cytochrome oxidase enzymes , selenium and zinc protect cell membranes and prevent the generation of free radicals, calcium and magnesium play an important role in cellular metabolism. B vitamins are involved in the conduction of nerve impulses along the visual fibers, are part of the visual pigment, and also participate in the synthesis of an enzyme that lowers intraocular pressure .
In the complex, all components of saffron have a normalizing and stimulating effect on biochemical processes in the visual analyzer. They reduce the severity of oxidative stress, normalize metabolic processes, strengthen the walls of blood vessels, which, in turn, leads to the restoration and improvement of the functional and structural state of the eyes.
Evidence base for the use of saffron in age-associated eye diseases
To date, the use of saffron in age-associated eye diseases has a sufficient evidence base, which demonstrates the effectiveness and safety of its use in the treatment of these pathologies.
For example, in a study conducted Falsini Bed and . et al . (2010), studied the effect of the dietary supplement saffron on the sensitivity of the retina to light in patients with early age - related macular degeneration. It involved 25 patients who were randomly assigned to 2 groups. The first group ( n = 13) received saffron 20 mg / day daily, the second ( n = 12) - placebo for 6 months. Evaluation of treatment results was carried out after 3 and 6 months according to the results of an electroretinogram .
The results of the study showed an increase in electrical activity and wave amplitude, indicating an improvement in the sensitivity of the retina to light in patients taking saffron, both compared to baseline and placebo. This allowed the authors to conclude that it is advisable to prescribe saffron to patients suffering from retinal macular degeneration in order to improve the functional state of the retina and the prognosis of the disease.
The study Italian researchers Marangoni D . et al . (2013) also studied the effect of a dietary supplement saffron on the photosensitivity of the retina in age - related macular degeneration. For 6–12 months, 33 patients with this eye disease received 20 mg / day of saffron daily .
To assess the effectiveness, the macular focal electroretinogram was compared before the study and after treatment every 3 months. In the course of the study, it was found that the use of saffron provides an improvement in the photosensitive function of the retina: after 3 months of its daily intake, an increase in the amplitude of the waves on the electroretinogram was noted , and these indicators were stable throughout the entire observation period.
A similar study was conducted Piccardi M . et al . (2012) with the participation of 29 patients aged 55–85 years with AMD, receiving a dietary supplement saffron at a dose of 20 mg / day for 14 months . Efficiency control was carried out every 3 months using an electroretinographic study of retinal photosensitivity and visual acuity determination .
The results of the study showed the effectiveness of saffron after 3 months of admission: there was an improvement in photosensitivity by 0.3 logarithmic units compared to the initial data, and visual acuity according to the Snellen table - by 0.2 units.
Australian scientists Stone D . et al . (2013) conducted a double-blind study with a control group, which examined the efficacy and safety of the biological additive saffron for visual acuity in patients with age - related macular dystrophy. All patients were divided into 2 groups: the first received saffron at 20 mg / day , the second - placebo for 3 months. After 3 months, without informing the patients, the groups were swapped. Therefore, each patient who participated in the study took both saffron and placebo .
Patients who received saffron in the first 3 months reported a significant improvement in vision, which was noted as early as the second week of its intake and persisted over 3 months of follow-up. Patients receiving placebo did not notice any visual changes. After the groups were swapped, the patients receiving the placebo reported that their vision had deteriorated again, while those receiving the saffron showed a significant improvement, as evidenced by the results of macular retinography . At the same time, the authors of the study noted that saffron is an absolutely safe nutraceutical , which is well tolerated by patients and does not cause side effects.
In a pilot study Bonyadi M . et al . (2014) studied the effect of a dietary supplement saffron on intraocular pressure in patients with open-angle glaucoma. It involved 34 patients with this pathology, randomized into 2 equal groups, who for a month, in addition to treatment with eye drops timolol and dorzolamide, received saffron at a dose of 20 mg / day or placebo.
After four weeks of therapy, intraocular pressure in the group of patients receiving saffron was 10.6 ± 3.0 versus 13.8 ± 2.2 mm Hg. Art. in the control group, which allowed the authors to conclude about its effectiveness in the treatment of glaucoma .
1. Today, there is an increase in age-associated eye pathologies, which is explained by an aging population around the world. Cataracts, glaucoma, age - related macular degeneration of the retina, diabetic retinopathy are widespread diseases that often lead to blindness.
2. In the pathogenesis of age-related ophthalmic pathology, oxidative stress is the key to the formation of free radicals that cause cell damage. An important role belongs to the depletion of the body's own antioxidant systems caused by aging.
3. Saffron consists of carotenoids , flavonoids , glycosides, vitamins and minerals that provide antioxidant and metabolic properties necessary for the prevention and treatment of age-associated eye pathology.
4. Saffron as an antioxidant prevents the oxidation of polyunsaturated fatty acids, prevents membrane-destructive processes in photoreceptors and inactivation of membrane-bound enzyme complexes, increases the stability of the lipid layer of membranes. It also maintains the balance of pro- and antioxidant systems, creates a depot of antioxidants and reactivates the depleted antioxidant system of the retina.
5. Dietary supplement saffron has a sufficient evidence base demonstrating the efficacy and safety of its use in age-associated eye diseases.
6. Given the powerful antioxidant properties of saffron, its use can be recommended for the treatment and prevention of not only age-related eye diseases, but also any ophthalmic pathology, in the pathogenesis of which oxidative stress plays a key role .
To date, the pharma tsevticheskom market of Ukraine appeared dietary supplement " MakuloVit ", the product I in accordance with the standards of GMP . This guarantees a high level of purification and quality of raw materials, the absence of GMOs. Manufacturing standards for both pharmaceuticals and an affordable price make the therapy effective, safe and affordable for a wide range of patients in need of improving and maintaining vision.
List of references
1. Visual impairment and blindness // WHO Information Bulletin. 2009. - No. 282 ( https : // www . Who . Int / mediacentre / factsheets / fs 282 / ru / index . Html ).
2. Problems of blindness and low vision // KBU RO “KB im. NASemashko »( https : // old . Xn --62-6 kct 0 akqt 0 e . Xn - p 1 ai / novosti / problemy - slepoty - i - slabovidenia ).
3. Shilnikov LV Eye diseases: lecture notes ( https : // med . Wikireading . Ru / 7016 ).
4. Cataract ( https : // www&n