A Review Article on Linum Usitatissimum a Life Saving Drug Now a Days

About Author: Amarjeet Singh¹, Dharmendra Kumar², Jatin Sharma², Dr. H. S. Lamba³
1. Subharamania Bharti College Of Science& Technology, Board of Technical Education, Delhi
Holambi Khurd, Delhi-82
2. School of Pharmaceutical Sciences, Shobhit University
NH-58 modipuram, Meerut, U.P India
3.H.R.Institute of Pharmacy, U.P. Technical University
Morta,Ghaziabad,U.P.India

Abstract
Flax (also known as common flax or linseed, binomial name: Linum usitatissimum) is a member of the genus Linum of the family Linaceae. Its origin is uncertain,but it is regarded as indigenous to India.It is cultivated extensively as a source of fibres in Egypt,Algeria,Spain,Italy and Greece while as a source of oil in Turkey, Afghanistan and India.In Russia, it is cultivated for both oil and fibre.Flax seeds come in two basic varieties: (1) brown; and (2) yellow or golden. Most types have similar nutritional characteristics and equal amounts of short-chain omega-3 fatty acids. Linseed  contains numerous beneficial components includingalpha-linolenic acid (ALA), cyanogenic glycosides (linamarin, linustatin, neolinustin), unsaturated fatty acids (linolenic acid, linoleic acid, oleic acid), soluble flaxseed fiber mucilage (D-xylose, L-galactose, L-rhamnose, d-galacturonic acid), lignans (secoisolariciresinol diglycoside (SDG)), monoglycerides, triglycerides, free sterols, sterol esters, hydrocarbons (protein), phenylpropane derivatives.

All these components have number of medicinal properties like antilipemic effects, Lowering the cholesterol, protecting against heart disease and controling high blood pressure,controling constipation, haemorrhoids, diverticular disorders and gallstones, treating acne, eczema, psoriasis, sunburn and rosacea. More over it minimises nerve damage that causes numbness and tingling as well as other disorders, treats menopausal symptoms, menstrual cramps, female infertility and endometriosis,fights prostate problems, male infertility and impotence, slows antiarrhythmic effects, anticoagulant and antiplatelet effects, antidiabetic effects, antineoplastic effects, antioxidant effects, arterial compliance,cognitive effects, inflammation andweight loss effects. Because of its link to good health, it improves immune system and vision.Linseeds contain 6.5 percent moisture, 20.3 percent protein, 37.1 percent fat, 2.4 percent minerals, 4.8 percent fiber and 28.9 percent carbohydrate sof edible portion. Its mineral and vitamin contents are calcium, phosphorus, iron, carotene, thiamine, riboflavin and niacin. Its calorific value is 530. Because of these properties it is being considered as a life saving drug.

Reference ID: PHARMATUTOR-ART-1129

Introduction
Flax (Linum usitatissimum L.) is one of the important species cultivated as an oil seed crop in some area of the world. Flax seed is used for oil production and also in food industries because of its nutritional merits, essential poly unsaturated fatty acids such as alpha-linolenic acid and rich supply of soluble dietary fiber. Flaxseed oil is used as an industrial drying  oil due to its high linolenic acid content.

Flax (also known as common flax or linseed) (binomial name: Linum usitatissimum) is a member of the genus Linum in the family Linaceae. It is native to the region extending from the eastern mediterranean to India and was probably first domesticated in the fertile crescent. It is known as Agasi/Akshi in Kannada, (Jawas/Javas) or (Alashi) in Marathi and (Tisi) in Hindi, in Telugu it is called (ousahalu). Flax was extensively cultivated in ancient Ethiopia and ancient Egypt. In a prehistoric cave in the Republic of Georgia, dyed flax fibers have been found that date to 30,000 BC.

One hundred grams of ground flax seed supplies about 450 kilocalories, 41 grams of fat, 28 grams of fiber, and 20 grams of protein.

Because of its link to good health, flaxseed is fast becoming a new food in many diets. Bakers and commercial food companies use flaxseed as a unique ingredient in everything from yeast breads, to bagels and cookie mixes. Not only do muffins and breads baked with flax taste great, but studies also find that these foods provide health benefits. Flaxseed adds a pleasant flavor to many basic foods, but its unique blend of goodness also packs a strong nutritious punch.

Flaxseed is rich in dietary fiber and alpha-linolenic acid, an essential omega-3 fat which may protect against heart disease and cancer. Flaxseed also provides a plentiful supply of lignans - cancer blocking components, which animal studies show reduce the formation of tumors. Recent scientific reports point out that flaxseed can have a positive influence on everything from blood cholesterol levels to laxation, from cancer to diseases of the heart, and immune systems such as arthritis and lupus.  Although about 42% of flaxseed is oil, very little of that fat is saturated. More than 70% of the fat in flaxseed is of the healthy polyunsaturated type. In fact, a unique feature of the polyunsaturated fats in flaxseed is the high ratio of alpha-linolenic acid (an omega-3 fat) to linoleic (an omega-6 fat). Nutritionists consider alpha-linolenic and linoleic fatty acids as essential because the body cannot manufacture them from any other substances. That means you must eat them as part of your diet.  Another positive aspect of flaxseed is that it contains both soluble and insoluble dietary fiber rather than large amounts of one type of fiber. Studies show that the soluble fiber in flaxseed can lower your blood cholesterol levels while the insoluble fiber, like that in wheat bran, is helpful for regulating bowel movements and preventing constipation.

Add flaxseed to your baked goods for a pleasant nutty taste. Flaxseed not only adds flavor, but also extra texture and good nutrition to your breads and other home-baked goodies. You can also use flaxseed as a substitute for some or all of the oil or shortening called for in a recipe. Cooks recommend a 3 to 1 substitution ratio. For example, 3 tablespoons of ground flaxseed added to a recipe can replace 1 tablespoon of the butter, margarine or cooking oil. When flaxseed is used instead of oil, baked goods tend to brown more rapidly. Flaxseed mixed with water can also replace an egg in selected recipes like pancakes, muffins and cookies. Each egg in the recipe would be equivalent to 1 tablespoons of ground flaxseed mixed with 3 tablespoons of water. Test a recipe first to determine if it meets your expectations.

MORPHOLOGICAL CHARACTER:
Flax is an erect annual plant growing to 1.2 m (3 ft 11 in) tall, with slender stems. The leaves are glaucous green, slender lanceolate, 20–40 mm long and 3 mm broad. The flowers are pure pale blue, 15–25 mm diameter, with five petals; they can also be bright red. The fruit is a round, dry capsule 5–9 mm diameter, containing several glossy brown seeds shaped like an apple pip, 4–7 mm long.

Flax seeds come in two basic varieties: (1) brown; and (2) yellow or golden. Most types have similar nutritional characteristics and equal amounts of short-chainomega-3 fatty acids. The exception is a type of yellow flax called solin (trade name Linola), which has a completely different oil profile and is very low in omeg.a-3 FAs. Although brown flax can be consumed asreadily as yellow, and has been for thousands of years.

Brown flax seed Golden flax seed
Flax fibers are amongst the oldest fiber crops in the world. The use of flax for the production of linen goes back at least to ancient Egyptian times. Dyed flax fibers found in a cave in Dzudzuana (prehistoric Georgia) have been dated to 30,000 years ago. Flax fiber is extracted from the bast or skin of the stem of the flax plant. Flax fiber is soft, lustrous and flexible; bundles of fiber have the appearance of blonde hair, hence the description "flaxen". It is stronger than cotton fiber but less elastic. The best grades are used for linen fabrics such as damasks, lace and sheeting. Coarser grades are used for the manufacturing of twine and rope.

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Distribution: Its origin is uncertain,but it is regarded as indigenous to India.It is cultivated at present extensively as a source of fibres in Egypt,Algeria, Spain,Italy and Greece while as a source of oil in Turkey, Afghanistan and India . In Russia, it is cultivated for both oil and fibre.(Kokate et al.,2007)

Scientific classification:

Components of flaxseed: Alpha-linolenic acid (ALA), cyanogenic glycosides (linamarin, linustatin, neolinustin), unsaturated fatty acids (linolenic acid, linoleic acid, oleic acid), soluble flaxseed fiber mucilage (d-Xylose, L-Galactose, L-Rhamnose, d-galacturonic acid), lignans (secoisolariciresinol diglycoside (SDG)), monoglycerides, triglycerides, free sterols, sterol esters, hydrocarbons (protein), balast, phenylpropane derivatives. Components of flaxseed oil: Alpha-linolenic acid (ALA), unsaturated fatty acids (linolenic acid, linoleic acid, and oleic acid). Components of flax root: The roots of L. usitatissimum contain measurable concentrations of lignans and isoflavones.

• acetic acid, chlorides of calcium, magnesium and potassium                            
• Fixed oil, Linamarin, glucoside,mucilage,phosphate,resins
• Sugar, sulphates,wax

Linseed linum usitatissimum contains numerous beneficial components including Palmitic, Stearic, Arachidic and Oleic fatty acids.

CHEMICAL STRUCTURE OF CONSTITUENTS:

TRADITIONAL AND CLINICAL USES:

• Flaxseed is most commonly used as a laxative.
• Flaxseed is also used for hot flashes and breast pain.
• Flaxseed oil is used for different conditions than flaxseed, including arthritis.
• Both flaxseed and flaxseed oil have been used for high cholesterol levels and in an effort to prevent cancer.
• The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.:
• Abdominal pain, acute respiratory distress syndrome (ARDS), allergic reactions, antioxidant, benign prostatic hypertrophy (BPH), bipolar disorder, bladder inflammation, blood thinner, boils, bowel irritation, bronchial irritation, burns (poultice), catarrh (inflammation of mucous membrane), colon cancer, cough (suppression or loosening of mucus), cystitis, depression, diarrhea, diabetic nephropathy, diverticulitis, dry skin, dysentery, eczema, emollient, enlarged prostate, enteritis, eye cleansing (debris in the eye), gastritis, gonorrhea, headache, infections, inflammation, irritable bowel syndrome, liver protection, malaria, melanoma, menstrual disorders, ovarian disorders, pimples, psoriasis, rheumatoid arthritis, skin infections, skin inflammation, sore throat, stomach upset, stroke, ulcerative colitis, upper respiratory tract infection, urinary tract infection, vaginitis, vision improvement.

Antilipemic effects: Proposed lipid-lowering effects of flaxseed (not flaxseed oil) have been attributed to the fiber component consisting of d-xylose, l-galactose, l-rhamnose, d-galacturonic acid, and galactose. It has been reported that defatted flaxseed (equivalent tothe fiber component of flaxseed) can significantly reduce levels of total cholesterol and low-density lipoproteins (LDL, and triglycerides.

Lower cholesterol: protect against heart disease and control high blood pressure: Several studies indicate that flaxseed oil, as well as ground flaxseeds, can lower cholesterol, thereby significantly reducing the risk of heart disease. Taking flaxseed oil may also protect against angina (chest pain) and high blood pressure.

Control constipation, haemorrhoids, diverticular disorders and gallstones: Because they are high in dietary fibre, ground flaxseeds can help ease the passage of stools and thus relieve constipation, haemorrhoids and diverticular disease.

Treat acne, eczema, psoriasis, sunburn and rosacea: The essential fatty acids in flaxseed oil are largely responsible for its skin-healing powers. Red, itchy patches of eczema, psoriasis and rosacea often respond to the EFA's anti-inflammatory actions and overall skin-soothing properties.

Minimise nerve damage that causes numbness and tingling as well as other disorders: The EFAs in flaxseed oil assist in the transmission of nerve impulse, making the oil s potentially valuable in treating conditions of numbness and tingling. The oil's nerve-nourishing actions may also help in the treatment of Parkinson's disease, a degenerative disorder of the nervous system, and protect against the nerve damage associated with diabetes and multiple sclerosis.

Treat menopausal symptoms, menstrual cramps, female infertility and endometriosis: Because the hormone-balancing lignans and plant estrogens (phytoestrogens) in flaxseed oil help stabilise a woman's estrogen-progesterone ratio, they can have beneficial effects on the menstrual cycle, and relieve the hot flashes of perimenopause and menopause. . Flaxseed oil may also improve uterine function and thus  treat fertility problems.

Fight prostate problems, male infertility and impotence: The EFAs in flaxseed oilmay help to prevent swelling and inflammation of the prostate, the small gland located below the bladder in males that tends to enlarge with age. The EFAs also play a role in keeping sperm healthy, which may be of value in treating male infertility, and they can improve blood flow to the penis, a boon for those suffering from impotence.

Antiarrhythmic effects: Limited human study and scientific reviews suggest a possible antiarrhythmic effect of ALA and omega-3 fatty acidsHowever, another study found that antiarrhythmic effects were concentration-dependently enhanced by DHA and EPA, but not by ALA. Higher intake of dietary linolenic acid might be associated with a reduced risk of abnormally prolonged repolarization in men and women.

Anticoagulant and antiplatelet effects: Available data specific to flaxseed (which is unique from fish oil in that it contains up to 20% omega-6 fatty acids and its omega-3 fatty acids must be converted into eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA)) are conflicting regarding its effects on platelet function.

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Antidiabetic effects: Flax has been studied for its effects on blood sugar, but reports are inconclusive. In a case series, postprandial glucose was reduced by 27% following meals with flaxseed. In a case series including 15 obese patients, Nestel et al. reported that a four-week diet high in alpha-linolenic acid (ALA) (20g from margarine products based on flax oil) diminished insulin sensitivity. In men with type 2 diabetes, ingestion of omega-3 fatty acids (not specific to flax) showed increases in fasting glucose levels and a 22% increase in mixed meal glucose levels.

Antineoplastic effects: In 2005, flaxseed was one of the most commonly used products for treating breast cancer. Flaxseed contains the highest amount of plant lignans and flaxseed and its defatted meal are the highest producers of mammalian lignans enterolactone and enterodiol (mean 60,110 ± 7,431) compared to other oilseeds, legume hulls, seaweeds and cereal brans.

Antioxidant effects: Lignans can act as platelet-activating factor-receptor antagonists, and inhibit the production of oxygen free radicals by neutrophils.Secoisolariciresinol diglycoside (SDG), a plant lignan found in flaxseed, has been found to possess antioxidant properties. Theoretically, flaxseed (not flaxseed oil) may increase lipid peroxidation and thus may increase oxidative injury. Diets supplemented with defatted flaxseed have been associated with a decrease in protein thiol groups, suggesting an increase in oxidative stress.

Arterial compliance: In a case series including 15 obese patients, it was found that a four-week diet high in alpha linolenic acid (ALA) (20g from margarine products based on flax oil) improves arterial compliance.

Cognitive effects: Preliminary evidence supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to attention deficit hyperactivity disorder (ADHD). Supplementation with flax in these populations resulted in an increase in alpha-LNA and a slight decrease in the ratio of arachidonic acid to eicosapentaenoic acid (EPA).

Inflammation/immune function: Flaxseed and flaxseed oil may possess anti-inflammatory properties due to the presence of ALA which when converted to EPA and DHA, inhibit neutrophil inflammatory responses in humans. These abilities may also result from the inactivation of LTA (leukotriene) epoxide hydrolase which decreases leukotriene B4 formation, and from the inhibition of leukotriene B4 and platelet-activating factor-stimulated chemotaxis via attenuation of the formation of [3H] inositol tris-phosphate by the phosphatidylinositol-selective phospholipase C. It has also been found that ALA decreases the production of arachidonic acid, thereby causing a reduction in inflammation.

Weight loss effects: There is limited research on the effects of flaxseed flour in obese patients. Early study has not shown evidence of benefit in weight loss or reduction of BMI, although there may be a role of flax in treating inflammation associated with obesity. In one study, ingestion of alpha-linolenic acid (derived from flax) in combination with arginine and yeast RNA was associated with weight gain in HIV patients.

Nutrative for health: Linseed contain moisture 6.5 percent, protein 20.3 percent, fat 37.1 percent, minerals 2.4 percent, fiber 4.8 percent and carbohydrates 28.9 percent per 100 grams of edible portion. Its mineral and vitamin contents are calcium, phosphorus, iron, carotene, thiamine, riboflavin and niacin. Its calorific value is 530.

Flax seed   :  Nutritional value per 100 g (3.5 oz)

MECHANISM OF ACTION: SDG, as well as its mammalian lignan metabolites, enterolactone (EL) and enterodiol (ED), have weak estrogenic activity as measured in in vivo and in vitro assays. SDG, EL and ED have a number of antioxidant activities, including inhibition of lipid peroxidation and scavenging of hydroxy radicals. SDG also has anti-platelet-activation factor (PAF) activity. PAF can induce the release of reactive oxygen species from neutrophils. SDG, via its metabolite EL, has been found to inhibit estrogen synthase (aromatase) and to stimulate the synthesis of sex hormone binding globulin (SHBG). Both of these actions could account for the possible anti-estrogen activity of SDG.(kaithwas et al.,2010)

There is evidence in in vitro and animal research that SDG may have some ability to reduce cholesterol levels and protect against atherosclerosis; it may also have some anticancer and antidiabetic effects. The possible anticarcinogenic, antiatherogenic and antidiabetic activities of SDG are thought to be due, in large part, to the antioxidant activities of its metabolites EL and ED.

Pharmacodynamics/Kinetics:
There are limited pharmacokinetic data available for flaxseed. Urinary excretion of lignan metabolites has been reported as a dose-dependent biomarker of flaxseed intake. Diets consisting of 5-10g of ground flaxseed per day significantly increased the urinary excretion of enterodiol, enterolactone, and total lignans vs. a diet without flaxseed. There is substantial inter-individual variation in plasma concentrations and urinary excretion of enterolignans.

Bioavailability: In a randomized, crossover study, healthy subjects supplemented their diet with 0.3g whole, crushed, or ground flaxseed per kilogram of body weight per day). The mean relative bioavailability of enterolignans from whole flaxseed compared with ground flaxseed was 28% (p≤0.01), whereas that of crushed flaxseed compared with ground flaxseed was 43% (p≤0.01). Crushing and milling of flaxseed substantially improve the bioavailability of the enterolignans.

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Metabolism: Alpha-linolenic acid (ALA) is a major dietary (n-3) fatty acid. ALA is converted to longer-chain (n-3) PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Precursors from unground whole flaxseed are converted by the bacterial flora in the colon to mammalian lignans.

Side Effects and Cautions

• Flaxseed and flaxseed oil supplements seem to be well tolerated. Few side effects have been reported.
• Flaxseed, like any supplemental fiber source, should be taken with plenty of water; otherwise, it could worsen constipation or, in rare cases, even cause intestinal blockage.
• The fiber in flaxseed (not flaxseed oil)may lower the body's ability to absorb medications that are taken by mouth. Flaxseed should not be taken at the same time as any conventional oral medications or other dietary supplements. Drugs used by mouth should be taken one hour before or two hours after flaxseed to prevent decreased absorption
• Consumption of flaxseed (not flaxseed oil) may reduce the absorption of vitamins or supplements taken by mouth at the same time. Therefore, vitamins and supplements should be taken an hour before or two hours after a dose of flaxseed to prevent decreased absorption. Flaxseed may alter the effects of psyllium and vitamin E in particular.
• Tell your health care providers about any complementary and alternative practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.
• People with diarrhea, irritable bowel syndrome, diverticulitis, or inflammatory bowel disease (Crohn's disease or ulcerative colitis) should avoid flaxseed due to its possible laxative effects
• People with diabetes should use caution if taking flaxseed products by mouth, as the omega-3 fatty acids in flaxseed and flaxseed oil may increase blood sugar levels.
• The use of flaxseed or flaxseed oil during pregnancy and breastfeeding is not recommended. Animal studies show possible harmful effects, and there is little information in humans. Flaxseed may stimulate menstruation or have other hormonal effects and could be harmful to pregnancy.
• unripe flaxseed pods are believed to be poisonous and should not be eaten.
• Raw flaxseed or flaxseed plant may increase blood levels of cyanide, a toxic chemical (this effect has not been reported when flaxseed supplements are taken at recommended doses).
• Do not apply flaxseed or flaxseed oil to open wounds or broken skin.

Toxicity:
Possible. Linamarin, as a result of the action of linase enzyme, produces cyanogenetic glycosides. To avoid them it is advised to eat the seeds whole or to carry out cold infusions or to boil them at least during 10 minutes. Big quantities of this plant should not be ingested. Many investigators consider that the quantity of glycosides that can be liberated is not big enough as to be toxic.

Linseed flour, used externally, can produce reactions to the skin if it is too old and it has become rancid, so we should use it quickly after grinding the seeds. Under the same conditions flax oil can also be irritating to the skin.

Symptoms: Asphyxia, bad breath, vomiting, sickness, acceleration of the heart rate, cardiorespiratory breakdown and death

Conclusion:
Both oil content and lignin content of the seed have number of therapeutic activities like allergic reactions, antioxidant, , bronchial irritation, burns (poultice), catarrh (inflammation of mucous membrane), colon cancer, cough (suppression or loosening of mucus), cystitis, depression, diarrhea, diabetic nephropathy, diverticulitis, dry skin, dysentery, eczema, emollient, enlarged prostate, enteritis, eye cleansing (debris in the eye), gastritis, gonorrhea, headache, infections, inflammation, urinary tract infection, vaginitis ,and vision improvement etc. all these therapeutic value makes the seed propitious seed.

Acknowledgements: Author would like to thank Mr. Dharmendra  Kumar, Jatin Sharma and  from Shobhit Universities and Dr. H. S. Lamba from H.R.Institute of pharmacy for their consistent support and kind cooperation for my work.

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