Lignans

Simplidin butyl ether
(-)-Epipinoresinol
10061-38-8
101312-79-2
Formosanol
101312-79-2
1016974-78-9
Olivil monoacetate
1016974-78-9
B0005-053471
Negsehisandrin G
1023744-69-5
B0005-465628
Schisanhenol B
102681-52-7
103001-05-4
103001-05-4
10351-88-9
Phyllanthin
10351-88-9
105256-12-0
105256-12-0
B0005-267074
Trachelosiaside
106647-12-5
B0005-053502
106647-14-7
B0005-458219
106894-43-3
107534-93-0
Anwuligan
107534-93-0

Background


Lignans are known to exhibit a rich structural diversity and a varied biological activity. Both have always attracted considerable attention among phytochemists, botanists, pharmacologists, environmentalists, and recently even experts in food production. This growing interest in bioactive lignans is motivated mainly by their potential use as either phytopharmaceuticals or nutraceuticals. In fact, among the several families of secondary metabolites synthesized by plants, lignans are recognized as a class of natural products with a wide range of remarkable biological activities. Such as antiviral, anticancer, cancer prevention, anti-inflammatory, antimicrobial, antioxidant, immunosuppressive, hepatoprotective and osteoporosis prevention.

Biosynthesis of Lignans

The biosynthesis of lignans is closely related to the biosynthesis of many other phenylpropanoid compounds such as lignin, neolignans, and norlignans. In fact, lignins as well as lignans are biosynthesized through the same pathway in the earlier steps, starting from hydroxycinnamyl alcohols. The synthesis of the hydroxycinnamyl alcohol monomers, precursors of lignans, according to Dewick, takes place from the reaction of l-phenylalanine (l-Phe) and l-tyrosine (l-Tyr), mediated by a series of cinnamic acid derivatives. More specically, the chemical reduction of these acids forms three different alcohols, namely p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol, which are the main precursors of lignins and lignans.

Metabolism of Lignans

Components of orally administered herbal medicines are often converted into pharmacologically active compounds by intestinal flora. Some lignans in plants and natural medicines are called phytoestrogens, because they are transformed by intestinal microflora into molecules as enterodiol (END) and enterolactone (ENL) which show estrogen-like biological activity.

Mazur et al. confirmed that enterolignans are produced and absorbed in the colon mainly from lignan intake in the diet. Later, the metabolism of plant lignans by human faecal microflora was investigated by Heinonen et al.. END has been found, as glucuronides, in the urine of humans, baboons, vervet monkeys, and rats.

Mammalian lignans are formed in the human body in the gastrointestinal tract, where gastrointestinal bacteria hydrolyze the sugar moiety of secoisolariciresinol diglucoside (SDG) to release SECO. This is followed by dehydroxylation and demethylation by the colonic microflora to give the mammalian lignan END. END is presumed to be oxidized by the gastrointestinal microbiota to produce ENL.

Biological Activity of Different Lignan Structures

Despite the impressive progress made in organic chemistry synthetic procedures, about 25% of all prescription medicines to date are still of plant origin. Also, approximately 60% of all drugs under clinical trial for multiple cancer treatments are either natural products, derived from natural products, or contain pharmacophores derived from natural products. These facts make lignan biological activity a key issue in developing final applications, but unfortunately, some of the most interesting products are only in very small amounts in plants. Metabolic engineering offers new perspectives for improving the production of compounds of interest. The production of plant secondary metabolites by means of large-scale culture of plant cells in bioreactors is technically feasible.

Among these pharmacological activities of lignans, their antitumor, anti-inflammatory, immuno-suppressive, cardiovascular, antioxidant, and antiviral actions deserve special mention. In the case of cancer treatments, the search for natural products as potential anticancer agents dates back to the Ebers papyrus in 1550 BC, but the scientific period of this search is much more recent, beginning in the 1950s with the discovery and development of the vinca alkaloids, vinblastine, and vincristine, and the isolation of the cytotoxic PPT. In other areas of medicine, extracts from roots and rhizomes of Podophyllum present cathartic and poisonous properties, as well as purgative, anthelmintic, and vesicant. Olea europaea bark has been employed as antipyretic, antirheumatic, tonic, and also anti-scrofulosis. All these properties are thought to be related to isolated lignans of O. europaea. Only lignans obtained from Podophyllum and NDGA seem to be involved in human and animal intoxications, with some exceptions such as plicatic acid from red cedar (Thuja plicata), which produces asthma and hay fever in some people.

Reference:

Calvo-Flores, F. G., Dobado, J. A., Isac-GarcÃa, J., & MartÃn-MartÃnez, F. J. (2015). Lignin and lignans as renewable raw materials: chemistry, technology and applications. John Wiley & Sons.