BIOLOGICAL SIGNIFICANCE OF PHYTO-CONSTITUENTS OF MEDICINAL PLANTS IN MAINTAINING VISION & HEALTHY EYE SIGHT

BIOLOGICAL SIGNIFICANCE OF PHYTO-CONSTITUENTS OF MEDICINAL PLANTS IN MAINTAINING VISION & HEALTHY EYE SIGHT

Teja Rangu, Santhosh Suddagoni *, Ganesh Akula and Santikari Sesha Phanindra

Mansarovar Global University, Bilkisganj, Sehore, Bhopal, Madhya Pradesh, India.

ABSTRACT: The eye is one of the most sensitive organs of human body and is continuously exposed to different environmental agents so it is very important to take care of eyes. Poor vision makes it harder to read, drive, and cook. Many eye problems and diseases can be treated if caught early. Ophthalmologists will examine eyes for signs of vision problems or eye diseases. It's the best way to find out if glasses or contacts are needed in the early stages of a serious but treatable eye disease. Wearing protective eyewear when playing sports or doing activities around the home, smoking cessation, wearing UV radiation-blocking sunglasses, Cleaning hands and contact lenses properly to avoid the risk of infection, etc., are the steps to protect vision.

Keywords: Eye diseases, Ophthalmologist, Omega-3 fatty acids, Contact lenses

INTRODUCTION: People with vision problems are more likely than those with good vision to have diabetes, poor hearing, heart problems, high blood pressure, lower back pain and stroke, as well as have increased risk for falls, injury and depression ¹. Zinc, Vitamin-C (Ascorbic acid), Vitamin-E (α-tocopherol, β-tocopherol, δ-tocopherol and γ-tocopherol), Selenium, Carotenoids, Vit- B1 (Thiamine), Vit- B2 (Riboflavin), Vit-B3 (Niacin), Vit-B6 (pyridoxine), Vit-B9 (folate or folic acid)&Vit-B12 (cyanocobalamin), Omega-6-fatty acids like gamma Linolenic acid (GLA), Vit- A (converted beta carotene) and Omega-3-fatty acids like ALA (alpha- Linoleic acid), EPA (Eicosapentaenoic acid) & DHA (Docosahexaenoic acid), Polyphenols like Quercetin, Anthocyanins and Resveratrol are the Phyto-constituents effective in alleviating eye disorders and play a major role in maintaining healthy eyes thereby helpful in the prevention & treatment of ophthalmic diseases ^2-3.

Vitamin-C (Ascorbic Acid): It is a water-soluble vitamin & an antioxidant present in aqueous humor fluid on the outermost parts of the eyes. Large doses of it are used to treat & prevent glaucoma and cataract (clouding of eye lens) and fight against Age-related Macular Degeneration (AMD), a major cause of vision loss among older ⁴. Oxidative stress is the major contributing factor to the Pathogenesis of AMD. Recommended daily intake of Vit-C is 500mg. It reduces the cellular oxidative stress of the retina or macular region of the eye. Unlike animals, humans cannot synthesize Vit-C because of the liver's absence of the L-gluconolactone oxidase enzyme. Open-angle glaucoma can be reversed by supplementing with high doses of Vit-C. People with high levels of Vit-C have 70% lower risk of developing AMD. Vit-C supports the health of ocular blood vessels. Scientific evidence suggests Vit-C lowers the risk of developing cataracts. When taken in combination with other essential nutrients, it can slow down the progression of AMD and visual acuity loss ⁵.

Vitamin-E: It is a fat-soluble vitamin & an essential micronutrient available in four different forms α-tocopherol (found in retina), β-tocopherol, δ-tocopherol and γ-tocopherol ²⁰. It is an antioxidant that prevents cataract (clouding of eye lens) & fights against Age-related Macular Degeneration (AMD) ⁶. 21 Its deficiency in the body leads to retinal degeneration or damage, loss of photo-receptors & blindness. Recommended daily intake is 400 IU ²². It reduces the cellular oxidative stress of the retina or macular region of the eye. Cataracts occur due to the accumulation of proteins damaged by free radicals ⁷. Long-term supplementation of vitamin E is associated with the slower progression of age-related lens opacification. The vitamin E group (i.e., chroman-6-ols), collectively termed tocochromanols (divided into tocopherols and tocotrienols) ^12-14. There are eight naturally occurring forms of vitamin E: alpha, beta, gamma, and delta classes of tocopherol and tocotrienol, synthesized in plants from homogentisic acid ^16-18. Alpha- and gamma-tocopherols are the two major forms of this vitamin. Vit-E is found in various nuts, seeds, vegetable oils, green leafy vegetables, and fortified cereals. Vit-E absorption depends on vitamin C, vitamin B3, selenium, and glutathione. A diet high in vitamin E cannot have an optimal effect unless it is also rich in these other nutrients. 24 Vitamin E promotes the health of cell membranes and DNA repair & plays a significant role in the immune system functions. Thus, it slows the progression of AMD and visual acuity loss when combined with other essential nutrients ⁹.

Zinc: Zinc is a co-factor of many metabolically active enzymes within the eye. It prevents cataract (clouding of eye lens) & fights against AMD. Retina, in the eyes & vascular or ocular tissue surrounding the retina, contains high levels of zinc in the form of many essential antioxidant enzymes like superoxide dismutase. Zinc forms visual pigments in the retina, so zinc deficiency leads to night blindness. Zinc is abundant in oysters, meat, pumpkin seeds, peanuts, green leafy vegetables, beef, chicken, pork, eggs & coconut water. Recommended daily intake is 80mg ^25-27.

Omega-3-fatty Acids like ALA (Alpha- Linolenic Acid), EPA (Eicosapentaenoic Acid) & DHA (Docosahexaenoic Acid): These are Poly-Unsaturated Fatty Acids (PUFA’s) that are essential for humans but cannot be synthesized in the body even though obtained from the diet. DHA levels are highly found in the cell membranes of the retina of human eyes; hence, they are called Essential Fatty Acids (EFA’s). These are important components of the cell membranes in the body ⁷⁹. They prevent cataracts (clouding of the eye lens), eye dryness called Dry Eye Syndrome (DES), & fight against AMD. They are anti-inflammatory in action (prevents inflammation of lacrimal gland and secretory epithelial cells), reduce the risk of diabetic retinopathy (DR), and prevent its occurrence. These are present in the gut and body tissues of oily fish like tuna, salmon, sardines, herring, anchovies, mackerel & trout. Consumption of DHA, EPA & ALA sources during pregnancy aids in the fetus's proper development of the retina. ALA is found in plant oils such as flaxseed, soybean, and canola. DHA and EPA are found in fish and other seafood ²⁴. The human body can convert some ALA into EPA and then to DHA, but only in tiny amounts. Therefore, getting EPA and DHA from foods & dietary supplements is the only way to increase the levels of omega-3 fatty acids in the body. Thus, Omega-3 fatty acids reduce inflammation, enhance tear production and support the eye’s oily outer layer by increasing oil that flows from the meibomian glands& can play a vital role in preventing or easing the discomfort of dry eyes. Table 1 average daily recommended amounts for ALA are listed below in grams (g). The amount needed depends on age and sex Table 1

TABLE 1: DAILY INTAKE OF ALPHA LINOLEIC ACID DEPENDS ON AGE AND SEX

Omega-3s are found naturally in some foods and are added to some fortified foods. One can get adequate amounts of omega-3s by eating a variety of foods, including the following:

1. Fish and other seafood (especially cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines).
2. Nuts and seeds (walnuts, brazil nuts, cashew nuts, peanuts, lentils, chia seeds, flax seeds, hemp seeds, beans).
3. Plant oils (such as flaxseed oil, soybean oil, olive oil and canola oil).
4. Fortified foods (such as certain brands of eggs, yogurt, juices, milk, soy beverages, and infant formulas).

Omega-3 dietary supplements include fish oil, krill oil, cod liver oil, and algal oil (a vegetarian source that comes from algae) ^20-24. They provide a wide range of doses and forms of omega-3s. A deficiency of omega-3s can cause AMD & Dry eye disease. AMD is a major cause of vision loss among older adults. People who get higher amounts of omega-3s from the foods they eat may have a lower risk of developing AMD. If someone has AMD, taking omega-3 supplements does not prevent the disease from worsening or slowing down vision loss. Dry eye disease occurs when tears don’t provide enough moisture, causing eye discomfort and vision problems. Getting more omega-3s from foods or supplements, mainly EPA and DHA helps relieve symptoms of dry eye disease ^30-35.

Vitamin- A is a group of antioxidants that play an important role in vision. There are two types of vitamin -A depending on the kind of food source it comes from.

1. Retinol- Derived from animals. Present in beef, chicken liver, milk & cheese. It is utilized directly by the body.
2. Provitamin A- ex: Beta carotene, Present in colorful fruits& vegetables.

Carotenoids are present in all the sources of Vit-A are converted either into retinol or provitamin A, in the body after food consumption. Carrots, sweet potatoes, spinach, kale, cantaloupes have carotenoids which get converted into retinol. Vit-A prevents night blindness & dry eyes ^50-55. Its deficiency may cause blindness. It is essential for maintaining the eyes' light-sensing cells (photoreceptors). It is a component of a protein called rhodopsin, which helps the retina to absorb light. It is found in animal-derived food sources like liver, egg yolks, and dairy products. It is obtained from antioxidant plant compounds like provitamin-A carotenoids (beta-carotene) in carrots, and sweet potatoes. Consumption of fruits and vegetables rich in vitamin-A have a decreased risk for any stage of AMD ^31-38. Vit-A protects the eye's surface (cornea) and is essential for good vision. It treats superior limbic keratoconjunctivitis, an eye inflammation. The eye’s light-sensitive retina (thin layer of tissue at the back of the eye) requires adequate vitamin A for proper function ³⁹.

Omega-6-fatty Acid Like Gamma Linoleic Acid (GLA) and Arachidonic Acid (AA): These are abundantly found in prime rose oil and starflower oil, Sunflower oil, rape seed, corn, peanut, chicken, eggs, cereals, grains & bread and helps in reducing eye dryness. ALA and GLA relieve ocular discomfort and corneal epithelial defects due to DES ^{1, 2, 3}.

Combination of Vitamin B6, B9 & B12: Combining these three vitamins can lower levels of homocysteine, a protein in your body that may be associated with inflammation and an increased risk of AMD.

Vitamin-B2 (Riboflavin): It is a potential antioxidant& helps in reducing oxidative stress in the eyes. Recommended daily intake is 1.1- 1.3 mg. It is present in oats, milk, yogurt, beef & fortified cereals. Its deficiency causes cataracts & corneal vascularization (dryness, burning, itching & lacrimation).

Vitamin-B3 (Niacin): It is an antioxidant that prevents glaucoma, a condition in which the optic nerve in the eye gets damaged. It is present in fish, beef, mushrooms, chicken, peanuts& legumes.

Vitamin B1 (Thiamine): It reduces the risk of cataracts. Administration of thiamine 100 mg three times a day reduces albumin excretion in urine, which indicates Diabetic Retinopathy (DR) in type 2 Diabetes; thus, it treats DR in its early stages. It is mostly present in bread, cereals & pasta.

Polyphenols: There are various types of polyphenols & among them, flavonoids are especially helpful in alleviating eye-related problems. Flavonoids are found mostly in apples, onions, dark chocolate, and red cabbage. There are various types of flavonoids & among them, quercetin, belonging to the flavonols group and other group called anthocyanins, play a major role in maintaining healthy eyesight.

Quercetin: It is aunique flavonol, belonging to flavonoid group, abundantly found in Yellow onion, Curlykale, Leek, Cherrytomato, Broccoli, Apple, Green and black tea, Black grapes, and Blueberry. It protects against cataracts & diabetes-induced retinal lesions. It acts as an antioxidant; thus, it protects the body against ROS produced during normal oxygen metabolism.

Free radicals (ROS) interfere with cellular functions & cause lipid peroxidation, causing cell death. To protect this cellular death from ROS, living organisms have developed antioxidant line of defense systems like enzymatic and nonenzymatic antioxidants, that check ROS levels and repair oxidative cellular damage regularly. The major enzymes, constituting the first line of defense, directly involved in the neutralization of ROS are: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). The second line of defense is by radical scavenging antioxidants such as vitamin C, vitamin A and plant phytochemicals like quercetin. They inhibit the oxidation chain initiation & prevent chain propagation, termination of a chain by the reaction of two radicals. The repair and de novo enzymes act as the third line of defense by repairing damage and reconstituting membranes. These include lipases, proteases, DNA repair enzymes and transferases ^{49, 40, 41}.

Anthocyanins: These are naturally occurring coloring pigments, antioxidants, phytochemical flavonoid compounds, group red purple pigments of phenolic groups found in plants with red, blue, and purple colored flowers, fruits, and vegetables ^{5, 7}. Ex: Cyanidin, Delphinidin.

Berries such as blueberry, bilberry (Vaccinium myrtillus), blackcurrant, Grape skin, Maqui berry, dried cornelian cherry, strawberry, and wolfberry (goji berry), are rich in anthocyanins ⁸. These are found in wines, tea, nuts, fruits, cocoa, cereals, honey, olive oil, vegetables, blackcurrant, red cabbage, red radish, and black carrot. Cyanidin and Delphinidin are anthocyanin aglycones present in bilberry ⁹. These promote the synthesis and regeneration of rhodopsin to protect the retina from exposure to UV, visible light, and irradiation ^{10, 11}. As well as to improve vision and increase blood supply to the retina ^{12, 13}.

They play a major role in the inhibition of enzymes, protection against DNA cleavage, anti-inflammatory activity, estrogen activity (modulation of the development of symptoms of hormone-dependent disease), and stimulation of cytokine production thereby regulating immune responses, peroxidation, a decrease of capillary permeability and fragility and membrane hardening ^{60, 61, 62} and ⁶³.

They inhibit lens opacity, cataractogenesis, and ROS. They protect retinal cells from diabetes-induced oxidative stress & inflammation, and protect retinal neurons from functional damages ^{47, 58, 56, 77, 76}.

Other Polyphenols Like Resveratrol: It is a polyphenolic phytoalexin with various bioactivities associated with health promotion. It is readily absorbed by other human dietary sources like peanuts, peanut butter, grapes and red wine. It has antioxidant activity and thus inhibits apoptosis and low-density lipoprotein (LDL) oxidation. Resveratrol is a stilbenoid, a fat-soluble compound & a derivative of stilbene, which is produced in plants with the help of stilbene synthatase enzyme. It reduces cell damage from free radicals, which are generated when cells burn nutrients in the mitochondria. It suppresses oxidative stress, inhibits cataract formation, and prevents diabetic retinopathy ^{67, 71, 72} and ⁷³.

Carotenoids: Lutein, meso-zeaxanthin, and zeaxanthin are dietary carotenoid xanthophylls found throughout the visual system except for the cornea, vitreous, and sclera. It is mostly found in the retina, the most metabolically active body tissue. The macula is a specialized part in the posterior pole of the retina since it mediates central vision, provides the sharpest visual acuity, and facilitates the best color discrimination. As the major functional component in the macular region, macular pigment (MP) was uniquely concentrated in the inner and central layers and mainly composed of xanthophyll carotenoids, including lutein, zeaxanthin and meso-zeaxanthin, which play pivotal role in maintaining the normal morphology and function of the macula.

1. Lutein: It is a carotenoid xanthophyll. It prevents cataract development (clouding of the eye lens) & fights against the progression of Age-related Macular Degeneration (AMD). Thus, it protects the eyes from photooxidative damage. It is a yellow carotenoid antioxidant, known as a macular pigment because it is present in macula (the central part of the retina made of light-sensitive cells on the back wall of the eyeball). The human body cannot synthesize lutein, so it must be obtained from the diet. It is mostly present in eggs and green leafy vegetables like spinach, kale, broccoli, collards. Recommended daily intake is 10mg.
2. Meso-zeaxanthin: It is a carotenoid xanthophyll with antioxidant & anti-inflammatory properties. It filters blue light & macular pigments and thus helps in reducing the incidence of eye diseases. The human body can synthesize meso-zeaxanthin, which is also obtained from diet such as eggs, green leafy vegetables like spinach, kale, broccoli & collards.
3. Zeaxanthin: It is a carotenoid xanthophyll. It prevents cataracts (clouding of eye lens), Inhibits diabetic retinopathy, and fights against the progression of Age-related Macular Degeneration (AMD). It is a yellow carotenoid antioxidant, known as a macular pigment because it is present in macula (the central part of retina made of light-sensitive cells on the back wall of eyeball). The human body cannot synthesize zeaxanthin, so it must be obtained from the diet. It is in eggs, green leafy vegetables like spinach, kale, broccoli, and collards. Recommended daily intake is 2mg ¹⁴.

High intake of xanthophyll-containing foods elevates levels of plasma lutein and zeaxanthin ^{15, 16}. Lifestyle and dietary factors (physically inactive, poor diet, and smoking) affect the degeneration of macular pigment & increase the risk of AMD. Inflammation of macular pigment among heavy smokers was higher than among light or non-smokers ^{17, 70, 71, 72, 73}. Lutein and zeaxanthin reduce the risk of chronic eye diseases, including cataracts and age-related macular degeneration (AMD). These plant-based pigments also appear to lower the risk of developing type 2 diabetes, a leading cause of blindness. They are also protective antioxidants like internal sunglasses, absorbing damaging blue light that Indians are exposed to daily. In the initiation and progression of AMD, cataract, diabetic nephropathy & glaucoma, aspects that play a major role are inflammation & oxidative stress. Phytochemicals like carotenoids and polyphenols have antioxidant activity and thus helps in alleviating these ophthalmic diseases ^{30, 71, 72, 73}.

The actual mechanism involved in the alleviating eye diseases by carotenoids and polyphenols is,

1. Mitigating the production of reactive oxygen species (ROS).
2. Inhibiting Tumor Necrosis factor (TNF-α) and Vascular endothelial growth factor pathway.
3. Suppressing p53-dependent apoptosis.
4. Suppressing the production of inflammatory markers like interleukins (IL’s) Ex: IL- 8, IL-6, IL-1a, and endothelial leucocyte adhesion molecule ^{70, 71, 72, 73}.

Polyphenols possess antioxidant, anti-inflammatory, antiallergic, antimicrobial, and antiviral effects. They help in scavenging free radicals, ameliorating inflammation, improving ocular blood flow, signal transduction, reduction of apoptosis in the RPE, opacification of the suppressive lens, and inhibition of the blood-retinal barrier. The retina is highly susceptible to oxidative stress due to its rich content of poly-unsaturated fatty acids & oxygen and its heavy exposure to light.

In addition, oxidative stress can be involved in producing severe inflammation by increasing the proinflammatory cytokines in the retinal tissue. These cytokines degrade the RBB and produce vascular cell death & apoptosis through tumor necrosis factor-α, chemotactic proteins, intercellular adhesion molecule 1 and IL-1β.

Selenium:  It is an essential trace element, a strong antioxidant, found in several enzymes of the human body. Selenium is a micronutrient that is essential for the proper functioning of all organisms. It protects the eyes by reducing AMD risk and prevents the development of cataracts, AMD & retinitis pigmentosa. It reduces cellular oxidative stress of the retina or macular region of the eye ^{28, 29}. Selenium is existed as selenocysteine residues in two Selenoproteins like Cytosolic or classical Glutathione Peroxidase enzyme cGPx-1) & Plasma GPx-3.

This element is a co-factor of many enzymes, for example, glutathione peroxidase or thioredoxin reductase. Insufficient supplementation of this element increases the risk of developing many chronic degenerative diseases. Selenium is important for protecting against oxidative stress, demonstrating the highest activity as a free radical scavenger and anti-cancer agent.

It is present in organic forms in food, as exemplified by seleno methionine and seleno cysteine. Extreme selenium deficiencies are widespread among people all over the world. Therefore, it is essential to supplement the deficiency of this micronutrient with selenium-enriched food or yeast cell biomass in the diet. WHO recommends a daily dose of selenium at 55 µg for adults. The combined interaction of selenium and tocopherol gives the best results in protecting organs against the destructive effects of free radicals. The combination of these compounds effectively protects mitochondria, cytochrome, and microsomal membranes from the oxidation of fatty acids.

Protein-rich foods contained higher levels of selenium, whereas low levels were found in plants containing low protein. The main sources of selenium in the diet are foods like brazil nuts, cereals, chocolate, broccoli, beef kidney, bread, meat and dairy products, marine fishes, pork, seafood, and milk. A rich source of selenium is found in sea salt, eggs (only in case of Se-yeast supplementation of feed), giblets, yeast (yeasts containing selenium), bread, mushrooms, garlic, asparagus, kohlrabi (enriched with this element). A relatively low selenium content characterizes fruits and vegetables. The bioavailability of selenium is increased in the presence of Vit-A, C & E.

The severity and irreversibility of cataracts and AMD have generated interest in preventing or delaying their progression. Nutrition plays an important role in reducing the risk of developing age-related eye disease. Adding certain nutrients to one’s diet daily through foods or supplements can help preserve vision.

Table 2: Several researches have shown eating more fruits and vegetables can help protect against eye disease and can also help overall health. One should eat foods rich in certain vitamins and minerals to keep the eyes healthy. These vitamins and minerals are called antioxidants. Antioxidants help keep our cells and tissues healthy. The following foods may help stop the occurrence or slow the progression of certain eye diseases Table 2.

TABLE 2: FOODS MAY HELP STOP THE OCCURRENCE OR SLOW THE PROGRESSION OF CERTAIN EYE DISEASES

TABLE 3: NUTRITIONAL CONTENT OF COMMONLY AVAILABLE FRUITS IN INDIA THAT AID IN MAINTAINING HEALTHY EYE SIGHT IS AS FOLLOWS

TABLE 4:  NUTRITIONAL CONTENT OF THE COMMONLY AVAILABLE VEGETABLES IN INDIA THAT AID IN MAINTAINING HEALTHY EYE SIGHT IS AS FOLLOWS

These fruits and vegetables contribute to preserving vision and even reversing visual impairment. Due to the side effects of allopathic drugs, now a day’s huge numbers of herbal drugs are used to treat eye diseases. This review mentions Phyto-constituents, which are effective in alleviating eye disorders, and potential medicinal plants used in the prevention & treatment of eye dysfunctions. Thus, this review provides a platform for the researcher to develop more efficient new herbal formulations. Table 5 More than 100 Potential medicinal plants and their Phyto-constituents that can be used as products that aid in the prevention & treatment of eye dysfunctions are listed in the following table.

TABLE 5: MORE THAN 100 POTENTIAL MEDICINAL PLANTS AND THEIR PHYTO-CONSTITUENTS THAT CAN BE USED AS PRODUCTS THAT AID IN PREVENTION& TREATMENT OF EYE DYSFUNCTIONS ARE LISTED IN THE FOLLOWING TABLE

CONCLUSION: The eye is one of the most sensitive organs of the human body and is continuously exposed to different environmental agents, so it is very important to take care of the eyes. Poor vision makes it harder to read, drive, and cook. Many eye problems and diseases can be treated if caught early. Ophthalmologists will examine eyes for signs of vision problems or eye diseases. It's the best way to find out if glasses or contacts are needed in the early stages of a serious but treatable eye disease. Taking care of the eyes also may benefit overall health. People with vision problems are more likely than those with good vision to have diabetes, poor hearing, heart problems, high blood pressure, lower back pain, and stroke, and have an increased risk for falls, injury, and depression. Older adults tend to have more vision problems. Eating plenty of right dark leafy greens such as spinach, kale, or collard greens and fish that is high in omega-3 fatty acids, maintaining a healthy weight, Wearing protective eyewear when playing sports or doing activities around the home, smoking cessation, wearing UV radiation blocking sun glasses, Cleaning hands and contact lenses properly to avoid the risk of infection etc., are the steps to protect vision.

ACKNOWLEDGEMENT: The author thanks the management of the Mansarovar Global University Educational Society for providing the facilities to carry out this review study.

CONFLICTS OF INTEREST: The author declares no conflict of interest.

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    Rangu T, Suddagoni S, Akula G and Phanindra SS: Biological significance of phyto-constituents of medicinal plants in maintaining vision & healthy eye sight. Int J Pharm Sci & Res 2023; 14(1): 198-13. doi: 10.13040/IJPSR.0975-8232.14(1).198-13.

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