The vast and versatile pharmacological effects of medicinal plants are basically dependent on their phytochemical constituents. Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.
- secondary plant metabolites
Plant chemistry is the basis of the therapeutic uses of herbs. A good knowledge of the chemical composition of plants leads to a better understanding of its possible medicinal value. Modern chemistry has described the role of primary plant metabolites in basic life functions such as cell division and growth, respiration, storage and reproduction. They include the components of processes such as glycolysis, the Krebs or citric acid cycle, photosynthesis and associated pathways. Primary metabolites include small molecules such as sugars, amino acids, tricarboxylic acids, or Krebs cycle intermediates, proteins, nucleic acids and polysaccharides. Eventually, the primary metabolites are similar in all living cells .
Secondary plant metabolites are numerous chemical compounds produced by the plant cell through metabolic pathways derived from the primary metabolic pathways. The concept of secondary metabolite was first defined by Albrecht Kossel, Nobel Prize winner for physiology or medicine in 1910 . Thirty years later, Czapek described them as end-products . According to him, these products are derived from nitrogen metabolism by what he called ‘secondary modifications’ such as deamination. In the middle of the twentieth century, advances of analytical techniques such as chromatography allowed the recovery of more and more of these molecules, and this was the basis for the establishment of the discipline of phytochemistry.
Secondary metabolites have shown to possess various biological effects, which provide the scientific base for the use of herbs in the traditional medicine in many ancient communities. They have been described as antibiotic, antifungal and antiviral and therefore are able to protect plants from pathogens. Besides, they constitute important UV absorbing compounds, thus preventing serious leaf damage from the light. It was noticed that some herbs as forage grasses such as clover or alfalfa can express estrogenic properties and interact with fertility of animals .
Secondary plant metabolites are classified according to their chemical structures into several classes. In this chapter, the nature of secondary plant metabolites will be discussed as a foundation for a review of the main categories of constituents considered to be of therapeutic importance. Each section includes an overview of a class of the secondary plant metabolites regarding structure, botanical distribution and generalizations about pharmacology, followed by examples of representative molecules. The classes of secondary plant metabolites include:
Phenolics probably constitute the largest group of plant secondary metabolites. They share the presence of one or more phenol groups (Figure 1) as a common characteristic and range from simple structures with one aromatic ring to highly complex polymeric substances. They are widespread in plants where they contribute significantly to the color, taste and flavor of many herbs, foods and drinks. Some phenolics are valued pharmacologically for their anti-inflammatory activities such as quercetin or antihepatotoxic properties such as silybin. Others exert phytoestrogenic activity as genistein and daidzein, while others are insecticidal as naringenin . Many of the phenolic molecules are also effective antioxidants and free radical scavengers, especially flavonoids. Phenolics can be classified according to their structure or biosynthetic origin. According to their structures, phenolics can be classified into:
Chromones and xanthones
2.1. Simple phenolics
Phenolic acids are ubiquitous among plants; although free phenols are rare, gallic acid is relatively widespread and is the parent compound of the gallotannins (Figure 2). Gallic acid is well known for its astringent properties but has demonstrated many other activities in vitro, including antibacterial, antiviral, antifungal, anti-inflammatory, antitumor, antianaphylactic, antimutagenic, choleretic and bronchodilatory actions. It also inhibits insulin degradation and promotes smooth muscle relaxation . The phenolic compounds in this group vary according to their functional group, which may be hydroxyl, aldehydic, or carboxylic group; these include eugenol (a phenolic phenylpropane), vanillin (a phenolic aldehyde) and salicylic, ferulic and caffeic acids (phenolic acids). Hydroquinone is also among the most widely distributed of the simple phenols, occurring in a number of plants as the glycoside arbutin. Glycoside formation is common, and the widely distributed glycoside coniferin and other derivatives of phenolic cinnamic alcohols are precursors of lignin [7, 8].
The pharmacological properties of these widely found constituents are probably best demonstrated by the urinary tract antimicrobial arbutin  and the anti-inflammatory salicylates . A property shared by all phenols is antimicrobial activity. In fact, phenol itself was the first antiseptic used in surgery .
The pharmacological activities of many plants are attributed to simple phenolics among which the antimicrobial and diuretic activities of
Tannins are polyphenols which have the ability to precipitate protein. These compounds have been used for decades to convert raw animal hides into leather. In this process, tannin molecules crosslink the protein and make it more resistant to bacterial and fungal attack. Today, however, many substances considered to be tannins by virtue of their structure and biosynthetic origin have limited, if any, ability to make leather . There are two major types of tannins: hydrolyzable tannins and condensed tannins. Hydrolyzable tannins are formed from several molecules of phenolic acids such as gallic and hexahydroxydiphenic acids, which are united by ester linkages to a central glucose molecule. Two principal types of hydrolysable tannins are gallotannins and ellagitannins, which are, respectively, composed of gallic acid and ellagic acid units. Ellagitannins found in plants of medicinal interest and for which structures have been elucidated include geraniin (isolated from
Condensed tannins, or proanthocyanidins, are compounds whose structures are based on oligomeric flavonoid precursors and vary in the type of linkages between flavonoid units; hydroxylation patterns; stereochemistry of carbons 2, 3 and 4 of the pyran ring and the presence of additional substituents. Some drugs (e.g.,
Tannin-containing drugs act as antidiarrhoeals and have been employed as antidotes in poisoning by heavy metals and alkaloids. Epigallocatechin-3-gallate, the active principal in tea, has been shown to be antiangiogenic in mice.
Coumarins are derivatives of benzo-α-pyrone, the lactone of
Flavonoids are the largest group of naturally occurring phenols. More than 2000 of these compounds are now known, with nearly 500 occurring in the free state . The structural skeleton of flavonoids includes a chroman ring bearing an aromatic ring in position 2, 3 or 4. Flavonoids may be divided into various classes according to the oxidation level of the central ring (ring C). The most common of these are anthocyanins, flavones and flavonols. The flavones and their close relations are often yellow (Latin
2.5. Chromones and xanthones
These compounds are structural derivatives of benzo-γ-pyrone, and although not of great pharmaceutical importance, a few compounds are worthy of mention; eugenin is found in the clove plant and khellin from mustard seeds . More complex are the furanochromones, the active constituents of the fruits of
Stilbenes are a relatively small, but widely distributed, group of plant secondary metabolites found mostly as heartwood constituents in a heterogeneous assembly of plant species. They are especially important in the heartwood of trees of the genera
Lignans are dimeric compounds formed essentially by the union of two molecules of a phenylpropene derivative reported from the members of Asteraceae (e.g.,
Alkaloids are organic compounds with at least one nitrogen atom in a heterocyclic ring. Their definition is problematic, as they do not represent a homogeneous group of compounds from any standpoint, whether chemical, biochemical, or physiological. Except for the fact that they are all nitrogen-containing compounds, no general definition fits all alkaloids. Alkaloids can be divided according to their basic chemical structure into different types. The following are basic types of alkaloids: acridones, aromatics, carbolines, ephedras, ergots, imidazoles, indoles, bisindoles, indolizidines, manzamines, oxindoles, quinolines, quinozolines, phenylisoquinolines, phenylethylamines, piperidines, purines, pyrrolidines, pyrrolizidines, pyrroloindoles, pyridines and simple tetrahydroisoquinolines .
Although plants containing alkaloids have been used by man for at least 3000 years as medicines, teas and potions, the compounds responsible for activity were not isolated and characterized until the nineteenth century . Alkaloids are not common in lower plants. Lysergic acid derivatives and sulfur-containing alkaloids, e.g., the gliotoxins, are detected in fungi. Concerning the pteridophytes and gymnosperms alkaloids reported for their medicinal uses include the lycopodium, ephedra and
Alkaloids demonstrate a diverse array of pharmacological actions including analgesia, local anesthesia, cardiac stimulation, respiratory stimulation and relaxation, vasoconstriction, muscle relaxation and toxicity, as well as antineoplastic, hypertensive and hypotensive properties. The activity of alkaloids against herbivores, toxicity in vertebrates, cytotoxic activity, the molecular targets of alkaloids, mutagenic or carcinogenic activity, antibacterial, antifungal, antiviral and allelopathic properties have been reported in literature. Many alkaloids are sufficiently toxic to animals to cause death if eaten. Several (e.g., nicotine and anabasine) are used as insecticides [1, 8].
Examples of some alkaloids:
Nicotine is found in the tobacco plant (
Caffeine occurs in a number of botanically unrelated species, including coffee (
Vinblastine is isolated from
Saponins are compounds that possess a polycyclic aglycone moiety with either a steroid (steroidal saponins) or triterpenoid (triterpenoidal saponins) attached to a carbohydrate unit (a monosaccharide or oligosaccharide chain) (examples illustrated in Figures 8 and 9). These sugar units are composed variously of pentoses, hexoses, or uronic acids. This hydrophobic-hydrophilic asymmetry means that these compounds have the ability to lower surface tension and are soap-like. They form foam in aqueous solutions and cause hemolysis of blood erythrocytes in vitro. The aglycone portion of the saponin molecule is called the
Saponins have demonstrated numerous pharmacological properties. Some saponins have antitumor, piscicidal, molluscicidal, spermicidal, sedative, expectorant and analgesic properties. Glycyrrhizin from
Terpenes are the largest and most diverse group of plant secondary compounds. The name “terpene” is derived from the word “turpentine,” which in turn comes from the old French
They consist of
They consist of
They consist of
They are composed of
Terpenes having 25 carbons and
They consist of
One group of compounds showing a range of interesting biological activity is the quassinoids isolated from
Terpenes also include sesquarterpenes (
Lipids comprise a group of naturally occurring molecules that include fixed oils, waxes, essential oils, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), phospholipids and others. Lipids serve various biological actions as major structural components of all biological membranes and as energy reservoirs and fuel for cellular activities in addition to being vitamins and hormones [39, 40]. Although lipids are considered primary plant metabolites, recent studies revealed pharmacological activities to members of this class of phytochemicals.
6.1. Fixed oils
Fixed oils constitute of high molecular aliphatic long-chain fatty acids, such as palmitic, stearic and oleic acids, esterified with glycerol. Fixed oils contain a relatively higher percentage of liquid glycerides (polyunsaturated) such as glycerin oleate, while fats are rich in solid glycerides such as glycerin stearate. . Flax and linseed and its oil are obtained from
Waxes are lipoidal matter constituting mainly from long aliphatic chains that may contain one or more functional groups. They may contain hydroxyl groups as in the case of primary and secondary long-chain alcohols that are frequently present in the form of esters. Others contain unsaturated bonds, aromatic systems, amide, ketonic, aldehydic or carboxylic functional groups. On the other hand, synthetic waxes constitute of long-chain hydrocarbons (alkanes or paraffins) that lack functional groups. They are similar to the fixed oils and fats since they are esters of fatty acids, but with the difference that the alcohol is not glycerin. The seeds of
6.3. Essential oils
Essential oils are volatile aromatic complex mixtures of relatively low molecular weight compounds. Although they may contain up to 60 components, yet they are characterized by the presence of two or three major components at fairly high concentrations (20–70%) compared to other components present in trace amounts. For example,
Carbohydrates are universally present in living beings on our planet. As the first product of photosynthesis, carbohydrates are the starting point for all phytochemicals and also, by extension, for all animal biochemicals. More carbohydrates occur in nature than any other type of natural compound. The most abundant single organic substance on Earth is cellulose, a polymer of glucose, which is the main structural material of plants. Although carbohydrates are primary metabolites, they are incorporated in plenty of secondary metabolites through glycosidation linkages. Polymers of simple sugars and uronic acids produce mucilages and gums .
Carbohydrates consist of carbon, hydrogen and oxygen with the last two elements usually present in the same proportions as in water. They are classified into four chemical groups: monosaccharides, disaccharides, oligosaccharides and polysaccharides. Monosaccharides contain from three to nine carbon atoms, although those with five and six carbon atoms (pentoses, C5H10O5, and hexoses, C6H12O6) are accumulated in plants in greatest quantity. Condensation of monosaccharides results in the other types according to the number of saccharide units involved. In addition to the important biological and structural function of carbohydrates in plants, some members show medicinal effects such as mucilage. Mucilage, viscous sticky material produced by almost all plants and some microorganisms, plays a protective role in thickening membranes in plants. It also serves in storage of water and food and in seed germination. Chemically it constitutes of a polar glycoprotein and an exopolysaccharide. Mucilage is used medicinally as demulcent. Cactus (and other succulents) and
According to the abovementioned data, there are several classes of secondary plant metabolites that are responsible for the biological activities of herbal medicines. Eventually, secondary plant metabolites exert their action on molecular targets that differ from one case to the other. These targets may be enzymes, mediators, transcription factors or even nucleic acids. The use of herbal medicines should be based on comprehensive phytochemical studies for the determination of the chemical constituents of the herbs involved. Hence the knowledge of the resultant pharmacological and toxicological effects can be deduced, as well as the possible synergistic or antagonistic effects due to the use of multiple component herbal formulae. For this reason, the isolation and structural elucidation of secondary plant metabolites, though ancient, is still a huge and fast growing approach, and the techniques used for separation and analysis are advancing continuously.
Seigler DS. Plant Secondary Metabolism. New York: Springer Science: Business Media; 1995. ISBN: 978-1-4613-7228-8; ISBN: 978-1-4615-4913-0 (eBook). DOI: 10.1007/978-1-4615-4913-0
Jones ME, Kossel A. A biographical sketch. Yale Journal of Biology and Medicine. 1953; 26(1):80-97
Bourgaud F, Gravot A, Milesi S, Gontier E. Production of plant secondary metabolites: A historical perspective. Plant Science. 2001; 161:839-851
Bennets HW, Underwood EJ, Shier FL. A specific breeding problem of sheep in subterranean clover pastures in Western Australia. Australian Veterinary Journal. 1946; 22(1):2-12
Goławska S, Sprawka I, Łukasik I, Goławski A. Are naringenin and quercetin useful chemicals in pest-management strategies? Journal of Pest Science. 2014; 87(1):173-180
Harborne JB, Baxter H. Phytochemical Dictionary: A Handbook of Bioactive Compounds from Plants. London; Washington, DC: Taylor & Francis; 1993
Evans WC. Pharmacognosy. 16th ed. Edinburgh London New York Philadelphia St Louis Sydney Toronto; 2009
Hoffmann D. Medical Herbalism : The Science and Practice of Herbal Medicine. Healing Arts Press One Park Street, Rochester, Vermont; 2003. ISBN: 978-089281749-8
Zbigniew S, Beata Ż, Kamil J, Roman F, Barbara K, Andrzej D. Antimicrobial and antiradical activity of extracts obtained from leaves of three species of the genus Pyrus. Microbial Drug Resistance. 2014; 20(4):337-343. DOI: 10.1089/mdr.2013.0155
Amann R, Peskar BA. Anti-inflammatory effects of aspirin and sodium salicylate. European Journal of Pharmacology. 2002; 447(1):1-9
Pelczar MJ, Chan ECS, Krieg NR. Control of microorganisms, the control of microorganisms by physical agents. In: Microbiology. New York: McGraw-Hill International; 1988. pp. 469-509
Eric Y. Botanical medicines for the urinary tract. World Journal of Urology. 2002; 20(5):285-293
Spiller F, Alves MK, Vieira SM, Carvalho TA, Leite CE, Lunardelli A, Poloni JA, Cunha FQ, de Oliveira JR. Anti-inflammatory effects of red pepper ( Capsicum baccatum) on carrageenan- and antigen-induced inflammation. The Journal of Pharmacy and Pharmacology. 2008; 60(4):473-478. DOI: 10.1211/jpp.60.4.0010
Hagerman AE, Butler LG. The specificity of proanthocyanidin-protein interactions. The Journal of Biological Chemistry. 1981; 10(256):4494-4497
Catarino MD, Silva AMS, Cruz MT, Cardoso SM. Antioxidant and anti-inflammatory activities of Geranium robertianumL. decoctions. Food & Function. 2017; 8(9):3355-3365. DOI: 10.1039/c7fo00881c
Yi Z, Wang Z, Li H, Liu M. Inhibitory effect of tellimagrandin I on chemically induced differentiation of human leukemia K562 cells. Toxicology Letters. 2004; 147(2):109-119
Puneet G, Aditi S, Vinayak K, Anant GN, Samir D, Nikhil M. Camellia sinensis(tea): Implications and role in preventing dental decay. Pharmacognosy Reviews. 2013; 7(14):152-156. DOI: 10.4103/0973-7847.120515
Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews. 2008; 1:CD001321. DOI: 10.1002/14651858.CD001321.pub4
Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. Journal of the American Medical Association. 1994; 271(10):751-754
Xu L, Wu Y, Zhao X, Zhang W. The study on biological and pharmacological activity of coumarins. In: Asia-Pacific Energy Equipment Engineering Research Conference; (AP3ER 2015). pp. 135-138
Montanher AB, Zucolotto SM, Schenkel EP, Fröde TS. Evidence of anti-inflammatory effects of Passiflora edulisin an inflammation model. Journal of Ethnopharmacology. 2007; 109(2):281-288
Serafini M, Peluso I, Raguzzini A. Flavonoids as anti-inflammatory agents. The Pro-ceedings of the Nutrition Society. 2010; 69(3):273-278. DOI: 10.1017/S002966511000162X
Susana J, Beatriz GM, Fabiana CM, Maria AD, Moacir GP. Antifungal activity of five species of Polygala. Brazilian Journal of Microbiology. 2011; 42(3):1065-1075. DOI: 10.1590/S1517-838220110003000027
Gehm BD, McAndrews JM, Chien P, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proceedings of the National Academy of Sciences of the United States of America. 1997; 94(25):14138-14143
Saeidnia S, Gohari AR, Mokhber-Dezfuli N, Kiuchi F. A review on phytochemistry and medicinal properties of the genus Achillea. Daru. 2011; 19(3):173-186
Sharma PR, Shanmugavel M, Saxena AK, Qazi GN. Induction of apoptosis by a synergistic lignan composition from Cedrus deodarain human cancer cells. Phytotherapy Research. 2008; 22(12):1587-1594. DOI: 10.1002/ptr.2511
Mbaze LM, Lado JA, Wansi JD, Shiao TC, Chiozem DD, Mesaik MA, Choudhary MI, Lacaille-Dubois MA, Wandji J, Roy R, Sewald N. Oxidative burst inhibitory and cytotoxic amides and lignans from the stem bark of Fagara heitzii(Rutaceae). Phytochemistry. 2009; 70(11-12):1442-1447. DOI: 10.1016/j.phytochem.2009.08.007
Tadeusz A. Alkaloids: Chemistry, Biology, Ecology, and Applications. 2nd ed. Amsterdam, Netherlands: Elsevier; 2015. ISBN: 13: 978-0444594334
Benowitz NL. Pharmacology of nicotine: Addiction, smoking-induced disease, and therapeutics. Annual Review of Pharmacology and Toxicology. 2009; 49:57-71. DOI: 10.1146/annurev.pharmtox.48.113006.094742
Benowitz NL. Clinical pharmacology of caffeine. Annual Review of Medicine. 1990; 41(1):277-288
Moudi M, Go R, Yong Seok Yien C, Nazre M. Vinca alkaloids. International Journal of Preventive Medicine. 2013; 4(11):1231-1235
Assa Y, Shany S, Gestetner B, Tencer Y, Birk Y, Bondi A. Interaction of alfalfa saponins with components of the erythrocyte membrane in hemolysis. Biochimica et Biophysica Acta. 1973; 307(1):83-91
Güçlü-Üstündağ Ö, Mazza G. Saponins: Properties, applications and processing. Critical Reviews in Food Science and Nutrition. 2007; 47:231-258. ISSN: 1040-8398. DOI: 10.1080/ 10408390600698197
Hikino H. Recent research on oriental medicinal plants. ln: Wanger H, Hiniko H, Farnsworth NR, editors. Economic and Medicinal Plant Research. Vol. 1. London: Academic Press; 1985. pp. 53-85
Bagci E, Yazgın A, Hayta S, Cakılcıoglu U. Composition of the essential oil of Teucrium chamaedrysL. (Lamiaceae) from Turkey. Journal of Medicinal Plants Research. 2010; 4(23):2587-2589
Akihisa T, Koike K, Kimura Y, Sashida N, Matsumoto T, Ukiya M, Nikaido T. Acyclic and incompletely cyclized triterpene alcohols in the seed oils of theaceae and gramineae. Lipids. 1999; 34(11):1151-1175
Ishikura H, Mochizuki T, Izumi Y, Usui T, Sawada H, Uchino H. Differentiation of mouse leukemic M1 cells induced by polyprenoids. Leukemia Research. 1984; 8(5):843-852
Culioli G, Mathe C, Archier P, Vieillescazes C. A lupane triterpene from frankincense ( Boswelliasp., Burseraceae). Phytochemistry. 2003; 62:537-541. DOI: 10.1016/S0031-9422(02)00538-1
Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CR, Shimizu T, Spener F, van Meer G, Wakelam MJ, Dennis EA. Update of the LIPID MAPS comprehensive classification system for lipids. Journal of Lipid Research. 2009; 50(Suppl):S9-S14. DOI: 10.1194/jlr.R 800095-JLR200
Subramaniam S, Fahy E, Gupta S, Sud M, Byrnes RW, Cotter D, Dinasarapu AR, Maurya MR. Bioinformatics and systems biology of the lipidome. Chemical Reviews. 2011; 111(10):6452-6490. DOI: 10.1021/cr200295k
Richard D, Kefi K, Barbe U, Bausero P, Visioli F. Polyunsaturated fatty acids as antioxidants. Pharmacological Research. 2008; 57(6):451-455. DOI: 10.1016/j.phrs.2008.05.002 Epub 2008 May 18
Wilhelm R, Hermann M. Bolt “Esters, Organic” Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH, Verlag GmbH and Co.KGaA; 2012. DOI: 10.1002/14356007.a09_565.pub2
Pazyar N, Yaghoobi R, Ghassemi MR, Kazerouni A, Rafeie E, Jamshydian N. Jojoba in dermatology: A succinct review. Giornale Italiano di Dermatologia e Venereologia. 2013; 148(6):687-691
Pichersky E, Noel JP, Dudareva N. Biosynthesis of plant volatiles: Nature’s diversity and ingenuity. Science. 2006; 311(5762):808-811
Masotti V, Juteau F, Bessiere JM, Viano J. Seasonal and phenological variations of the essential oil from the narrow endemic species Artemisia molinieriand its biological activities. Journal of Agricultural and Food Chemistry. 2003; 51:7115-7121. DOI: 10.1021/jf034621y
Asif HM, Akram M, Saeed TM, Khan I, Akhtar N, Ur Rehman R, Ali Shah SM, Ahmed K, Shaheen G. Review paper carbohydrates. International Research Journal of Biochemistry and Bioinformatics. 2011; 1(1):001-005
Anbalahan N. Pharmacological activity of mucilage isolated from medicinal plants. International Journal of Applied and Pure Science and Agriculture. 2017; 3(1):98-113.e-ISSN: 2394-5532, p-ISSN: 2394-823X