Lignans

Phenylpropanoid pathway

1. Lignans BY:- SABAL REGMI PURWANCHAL UNIVERSITY

2. LIGNANS In 1936, Haworth defined lignans as “Phenylpropanoid dimers consisting of two phenyl propane units (C6C3) linked by their central C8 carbon .” biosynthetically derived from the P henylpropanoid pathway

3. LIGNAN STRUCTURE: Phenylpropane unit Lignan

4. OCCURRENCE OF LIGNANS Widely distributed in plants. Usually occur in root, stem, bark, fruits and seed parts of plant.

5. LIGNANS OF PODOPHYLLUM Podophyllum is obtained from the dried root and rhizomes of two species of Podophyllum ( Berberidaceae ), the American species P. peltatum and the Indian species P. hexandrum (P. emodi ).

6. Chemistry Podophyllum lignans have 5 rings designated A, B, C, D, and E. Ring A consists of a 1,3- dioxolane cycle, Rings B and C together form the 1,2,3,4- tetrahydronaphthalene substructure Ring D is composed of a y- lactone, R ing E, connected at Ring C, is an aryl side chain. Carbon 4 carries the hydroxyl group involved in the glycosidic linkage, whereas C2 and C3 are involved in the lactone ring D Bonds projecting below and above the plane of the tetracyclic backbone are referred to as α and b , respectively.

7. Pharmacological activity Anticancer activity testicular, lymphoid and myeloid leukemia, stomach, ovarian, brain, breast, pancreatic, and small and non-small cell lung cancers Antiviral activity in the treatment of venereal warts, caused by the human papilloma virus R heumatoid arthritis immunosupressive , antimalarial and antifungal agents

8. Piper Cubeba The berries of P. cubeba are commonly known as cubeb (in Indonesia known as kemukus ) and used in Indonesian traditional medicine to treat gonorrhea, dysentery, syphilis, abdominal pain,diarrhea , enteritis and asthma P. cubeba is important as a source of pepper (the dried berries) for the worldwide spice market

9. (1), cubebinone (2), yatein (3), thujaplicatin trimethylether (4), cubebinin

10. Pharmacological activity Analgesic and anti inflammatory activity Aphrodisiac Antiseptic and diuretic action As a remedy for vomiting, abdominal disorders, indigestion, and amoebic dysentery To treat veneral diseases like gonorrhea Also prescribed for the relief of fever, asthma, sunstroke, rheutasim , malaria etc.

11. Flaxseed ( Linum usitatissimum ) Flaxseed ( Linum usitatissimum L.) is an oilseed used in industrial and natural health products. Flaxseed accumulates many biologically active compounds and elements including linolenic acid, linoleic acid, lignans , cyclic peptides, polysaccharides, alkaloids, cyanogenic glycosides, and cadmium. The prevailing lignan in the flaxseed is secoisolariciresinol diglucoside (SDG) In addition to SDG , smaller quantities of other type lignans such as matairesinol , isolariciresinol , lariciresinol and pinoresinol have also been identifed in the flaxseed.

12. Secoisolariciresinol (SECO) is the aglycone of SDG. SDG-β-D-glucosidase hydrolyses the glucopyranoside bond of SDG and release SECO. It has molecular formula, C 32 H 46 O 16 and molecular weight 686.71. SDG results from the coupling of the 8 and 8′ C-atoms of the side chains of two coniferyl alcohol moieties exists in two isomeric forms in the flaxseed. In faxseed , SDG is stored in an ester-linked with 3-hydroxy-3-methylglutaric acid (HMGA) and other phenolic compounds such as p- coumaric acid and ferulic acid glycosides to form SDG oligomers of unknown . The content of SDG varies between 6-29 g/kg in the defatted flaxseed powder Secoisolariciresinol , R=H Secoisolariciresinol Diglucoside , R= glucose matairesinol

13. Pharmacological activity   Antioxidant inhibition of lipid peroxidation and scavenging of hydroxy radical   A nti-platelet-activation factor (PAF) activity . PAF can induce the release of reactive oxygen species from neutrophils. Antiestrogenic , A nticarcinogenic , A ntiatherogenic A ntidiabetic  activities.

14. Flavonoids The flavonoids are polyphenolic compounds possessing 15 carbon atoms; two benzene rings joined by a linear three carbon chain having the carbon skeleton C6 - C3 - C6 and they are the plant pigments and they are having polar nature and is solouble in methanol and water. Flavonoids constitute one of the most characteristic classes of compounds in higher plants. Many flavonoids are easily recognised as flower pigments in most angiosperm families (flowering plants). They are secondary metabolite and effective in CNS disorders .

15. Easily recognized as flower pigments in most angiosperm plants but are not always flower pigments In plants they repair damage and shield from environmental toxins

16. Tests for flavonoids The extracts were dissolved in ethanol, filtered and subjected to following tests. Shinoda test: The dried extracts were dissolved in 95% ethanol (5ml) and few drops of concentrated hydrochloric acid (HCL) were added. Then the magnesium turnings were put into the solution and observed for appearance of pink color. Lead acetate solution test: To small quantity of above residue, lead acetate solution was added and observed for appearance of formation of yellow colored precipitates.

17. Core structures and nomenclature The nomenclature of flavonoids proper is straight-forward with the aromatic ring A condensed to the heterocyclic ring C and the aromatic ring B most often attached at the C2 position. The various substituents are listed first for the A and C ring and - as primed numbers - for the B ring (note that the numbering for the aromatic rings of the open-chained precursor chalcones is reversed). ( Harborne JB, ed. (1988) The Flavonoids. Advances in Research . Chapman & Hall.)

18. Flavonoids & their examples Flavone:- Luteolin , Apigenin , Tangeritin Flavonol :- Quercetin , Kaempferol , Myricetin , Fisetin , Isorhamnetin , Pachypodol , Rhamnazin Flavanone:- Hesperetin , Naringenin , liquiritin , liquiritigenin Eriodictyol , Homoeriodictyol Flavanonol - Taxifolin , Dihydrokaempferol

19. Flavonoids in Ginkgo Biloba Ginkgo biloba , known as  ginkgo  or as the   maidenhair tree ,  is the only living species in the division Ginkgophyta , all others being extinct. It is found in fossils dating back 270 million years . Ginkgo biloba leaves are said to contain as many as 20 types of favonoids , and among these are quercetin, kaempferol and isorhamnetin , 3 types that are present in large quantities.

20. Antiviral can inhibit reverse transcriptase , part of the replication process of retroviruses . The therapeutic relevance of this inhibition has not been established. Asthma is an effective bronchodilator and helps reduce the release of histamine and other allergic or inflammatory chemicals in the body. has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation Eczema Serum IgE levels are highly elevated in eczema patients, and virtually all eczema patients are positive for allergy testing. Excessive histamine release can be minimized by the use of antioxidants. Quercetin has been shown to be effective in reducing IgE levels in rodent models. Pharmacological activity / Uses

21. Inflammation Quercetin has been reported to be of use in alleviating symptoms of pollinosis . An enzymatically modified derivative was found to alleviate ocular but not nasal symptoms of pollinosis . Studies done in test tubes have shown quercetin may prevent immune cells from releasing histamines which might influence symptoms of allergies. A study with rats showed that quercetin effectively reduced immediate-release niacin (vitamin B 3 ) flush, in part by means of reducing prostaglandin D2 production. A pilot clinical study of four humans gave preliminary data supporting this. Quercetin may have properties of a calcineurin inhibitor, similar to cyclosporin A and tacrolimus , according to one laboratory study.

22. Fibromyalgia Quercetin may be effective in the treatment of fibromyalgia because of its potential anti-inflammatory or mast cell inhibitory properties shown in laboratory studies Cancer Laboratory studies have investigated Quercetin's potential for use in anti-cancer applications. The American Cancer Society says quercetin has been promoted as being effective against a wide variety of diseases, including cancer.

23. Metabolic syndrome Quercetin has been shown to increase energy expenditure in rats , but only for short periods (fewer than 8 weeks). Effects of quercetin on exercise tolerance in mice have been associated with increased mitochondrial biogenesis .In mice, an oral quercetin dose of 12.5 to 25 mg/kg increased gene expression of mitochondrial biomarkers and improved exercise endurance. It has also been claimed that quercetin reduces blood pressure in hypertensive and obese subjects in whom LDL cholesterol levels were also reduced. In vitro studies showed quercetin and resveratrol combined inhibited production of fat cells and vascular smooth muscle cell proliferation. Supplements of quercetin with vitamin C and niacin does not cause any significant difference in body mass or composition and has no significant effect on inflammatory markers, diagnostic blood chemistries, blood pressure, and blood lipid profiles.

24. Monoamine-oxidase inhibitor Possibly an active component of heather ( Calluna vulgaris ), quercetin was suspected from a bioassay test on crude extracts to selectively inhibit monoamine oxidase , possibly indicating pharmacological properties. Prostatitis Quercetin has been found to provides significant symptomatic improvement in most men with chronic prostatitis , a condition also known as male chronic pelvic pain syndrome .

25. Liquorice Licorice ( Glycyrrhiza glabra ) is a traditional medicinal, sweet and soothing herb growing in several regions of the world. The biologically-active components of licorice are well known as glycyrrhizic acid, liquiritin , glabridin and liquiritigenin .

26. anti-inflammatory , anti-bacterial , antioxidative , anti-viral expectorant properties and effective in the detoxification and protection of the liver. Pharmacological activity / Uses

27. Quassinoids ( Quassia wood) Scientific Name(s): Quassia is a collective term for 2 plants:  Picrasma excelsa  and  Quassia amara  L. Family: Simaroubaceae . Common Name(s):  Bitter wood , picrasma , Jamaican quassia ( P. excelsa ), Surinam quassia ( Q. amara ), Amara species , Amargo , Surinam wood , ruda   Chemical constituents most species of quassia contain quassin and isomers of neoquassinl , volatile oil, gummy extractive pectin, woody fiber, tartrate and sulphate of lime, chlorides of calcium, sodium, various salts such as oxalate and ammoniacal salt, nitrate of potassa and sulphate of soda.  Quassia amara , specifically, contains both beta- carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids

28. Basic structure of Quassinoid

29. Uses and Pharmacology Quassia has been used as an insecticide . Traditional use includes remedies for infestations of lice or worms, anorexia, and dyspepsia. Certain tribes have used the plants to treat measles and fever, and as a mouthwash. antilarval activity (by inhibition of cuticle development has been used successfully to treat head lice possesses antibacterial and antifungal activity. antileukemic properties when tested in animals. Antitumor activity in mice has been demonstrated, as well as in vitro activity of quassin against human nasopharynx carcinoma . antifertility effects.