Lignans- the active principles of Bhumi Amla, flax seed etc.

(Photos: Secoisolariciresinol, Phyllanthus and Sesame)

Many students get confused between lignan and lignin. Lignin(the main hydrophobic cell wall component of all vascular plants) is a polymer of hundreds of C9 phenyl propanes having very high molecular weight while Lignans are dimers formed by linking two cinnamic acids/cinnamyl alcohols, through the -carbons of their aliphatic side chains. The total number of lignans identified is 500 and more. The aromatic rings are often oxygenated and additional rings are also formed in the molecule. Optical activity is exhibited by many lignans. Once considered as typical heartwood constituents associated with lignin (so the name lignans), these compounds are located in leaves, fruits and in exudates of many plants. The richest source of lignans are the knots of Norway spruce (Picea abies) containing up to 30% (w/w) lignans and the predominant member here is 7-hydroxymatairesinol. Lignans are found to occur esterified with organic acids (3-hydroxy, 3-methyl glutaric acid) or as glycosides. The glycosides identified are about 85. Secoisolariciresinol occurs as a diglucoside in flax seeds. More than 15 lignans are found in foodstuffs. Some of them are lariciresinol, pinoresinol, syringaresinol. medicaresinol, secoisolariciresinol and matairesinol.

Lignans are classified into five types based on the skeletons and cyclisations (For a detailed discussion see my book Analytical methods….)

There are mixed lignans in which a lignan skeleton is incorporated in another compound of different bio-synthetic origin. They are:

(1) Flavono-lignans like silybin from Silybium marianum and hydnocarpin from Hydnocarppus wightiana

(2) Coumaro-lignans such as hyosgerin from Hyoscyamus niger seeds

Lignans are extensively used as antioxidants in food. Their actions include inhibition of superoxide ion formation, increase in cellular glutathione, inhibition of i-NOS etc. The stability of sesame oil is attributed to the lignan, sesamin, present in it. The same lignan forms the synergistic ingredient in pyrethrum insecticides. Podophyllotoxin, the principal component of Podophyllum resin along with - and -peltatins exhibits powerful cathartic action. Podophyllotoxin, being cytotoxic, is found useful in treating human malignancies (neoplasms). A large number of lignans exhibit anticancer as well as antimicrobial properties. Lignans of flax are found to interact with estrogen receptors and thus are estrogenic in nature e.g. secoisolariciresinol and matairesinol and thus can suppress developing of cardiovascular diseases (Westcott and Muir, 2003). The role of these compounds in controlling breast and prostrate cancer (though doubted), is yet to be proved.

Other biological properties of lignans are anti-invasive (antimicrobial, antifungal, antiviral and antineoplastic), insecticide and antifeedant activities (Harmatha and Dinan, 2003), immunomodulatory, effects on apoptosis, cardiovascular system and diabetes and hepatoprotective activities also are attributed to lignans.

The plants containing lignans are as follows

1. Phyllanthus amarus – Bhoomi Amla

The whole plant, which forms the drug, contains lignans, phyllanthin (a diaryl butane, major constituent, 0.5%) and, hypophyllanthin (aryltetrahydronaphthalene, upto 0.2%) as major constituents. P. amarus is known for the hepatoprotective action it exerts, an action due to the lignans. The drug exhibits antiviral actions on hepatitis B. It is also used as hypoglycemic, diueretic and hypotensive.

2. Flax seed is the dried ripe seed of Linum usitatissimum L. (also known as Linseed, a fibre plant of paramount importance. Linseed contains 30-40% fixed oil, 25-30% protein, 5-6% mucilage. But the major compounds having a profound effect on health is the “lignans” found in the flax shell. Flax seed is the richest source of lignans in the plant kingdom, containing up to 800 times more than any other plant source. The vast majority of lignans are located in the hull that encases the seed. There are 27 different lignans in the flax seed, the major being secoisolariciresinol diglucoside (SDG) and its aglycone, secoisolariciresinol. When the plant lignan SDG (from flaxseed) is ingested, it is converted in the colon by bacteria to the mammalian lignans enterodial (ED) and enterolactone (EL). Thus, the plant lignan SDG act as source of mammalian lignans ED and EL.

The flax seed lignan is found to reduce of cancer cell growth, suppress (upto 34.4 percent) the development of atherosclerosis, lower LDL cholesterol and levels of HDL cholesterol, lower sugar levels in people with diabetes, reduce prostate size (in case of enlarged prostate), improve immune system (especially for HIV and AIDS patients) and preventi hair loss and thinning hair are other benefits of flax seed lignans. Flax seed oil is the the richest source of ALA in the North American diet. ALA is anti-inflammatory, reduce high cholesterol levels in blood, in treating Sjogren’s syndrome (the dryness of the eyes), reduce menopause symptoms and good for skin and hair.

3. Sesame seeds.

Sesamum indicum L. (Pedaliaceae). The seeds contain about 50% fixed oil, 24% proteins, 5% mucilage and 2.3% minerals. There are sixteen types of lignans isolated from sesame. Most of them are fat soluble aglycones and therefore elute into the oil on extraction. The remaining are glycosylated and have been isolated from the oil free meal. The major aglycon lignans are sesamin and sesamolin and minor aglycones are sesamol, sesaminol, sesamolinol, pinoresinol, matairesinol, lariciresinol and episesamin. The lignan glycosides include mono- di- and triglucosides of sesaminol, sesamolinol and pinoresinol. Sesame lignans are found to have multiple physiological functions, such as decreasing blood lipids and arachidonic acid levels, increasing antioxidative ability and γ-tocopherol bioavailability, and providing anti-inflammatory function and estrogenic activity (Wu et al., 2007). These lignans are found to modify not only the mRNA levels of many enzymes involved in hepatic fatty acid oxidation, but also those of proteins involved in the transportation of fatty acids into hepatocytes and their organelles, and regulating hepatic concentrations of carnitine, CoA and malonyl-CoA.

4. Cubeb, Kabab Chini (Piper cubeba Linn.- Piperaceae)

Cubeb is a native of E. India and Malaya; the dried unripe fruits of which are used as a spice (Explained in Spices). Cubeb contains lignans, 7.5% resins, 8% gum, 1% fixed oil and 18% volatile oil. The lignans present are cubebin (0.8%), hinokinin, clusin, dihydrocubebin, cubebinolide, cubebinone and 5’’methoxyhinokinin. Cubeb is a carminative, antiseptic and is used medicinally for urinogenital diseases.

5. Mandrake/May-apple (Podophyllum peltatum L.- Berberidaceae)

The rhizome and roots yield 2-8% of a resin consisting of a group of lignans. The three principal lignans podophyllotoxin, alpha-, and beta-peltatins amount to 20%, 10% and 5% respectively. These compounds occur as glycosides or as aglycones. Also present in the resin are demethylpodophyllotoxin, dehydropodophyllotoxin, quercetin and starch.

Mandrake is a drastic purgative. Podophyllotoxin shows excellent antimitotic action and are used to treat all types of cancers. Indian podophyllum (Podophyllum emodi Wall.) also contain similar lignans and is used thus.

6. Kasmari, Gmelina (Gmelina arborea Roxb. - Verbenaceae)

Heartwood yields ceryl alcohol ,b-sitosterol, gmelinol, cluytyl ferulate and lignans such as arborone, 7-oxodihydrogmelinols, arboreal, gmelanone, 6’’- bromoisoarboreol, epieudesmin and gummidiol. Wood is hypoglycaemic and also used in skeletal fractures. The various parts are used in fever, dropsy, anasarca, spleen troubles, rheumatism, delirium, small pox, syphilis, asthma and diarrhoea.

7.Magnolia wine, Wu-wei-zi (Schisandra chinensis Linn.- Schisandraceae)

Schisandra is a native of China. The fruits contain lignans such as schisandrin, deoxyschisandrin, gomisin and pregomisin, essential oil and numerous acids.

In Chinese medicine, the berries are used as a tonic, astringent and expectorant and for hepatitis and diarrhoea. The other uses include as a kidney tonic, for physical exhaustion and insomnia and as a chemotherapy support. The lignans in Schisandra are found to regenerate liver tissue damaged by hepatitis, alcohol and other disorders.

8. Flavanolignans from Silybium.

The seeds of Silybium marianum Gaertn (Milk thistle- Asteraceae) is the only drug showing genuine antihepatotoxic properties. Main constituents of the seed are flavonolignans such as silychristin , silydianin , silybinin A , silybinin B, isosilybinin A and isosilybinin B and taxifolin collectively known as silymarin. Silymarin has been used to cure liver and gallbladder disorders including hepatitis, cirrhosis and jaundice, protect brain and prevent X-ray. Moreover, recent studies indicated that it also reduces biliary cholesterol levels, prevents and treats cancer.

Source:

Analytical Methods for Medicinal Plants and Economic Botany, M. Daniel & Denni Mammen (2016) Scientific Publishers, Jodhpur, Pages 290.

Mammen Daniel