**2. Phenolics**

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 Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants http://dx.doi.org/10.5772/intechopen.76139 13

**Figure 1.** Phenol.

and associated pathways. Primary metabolites include small molecules such as sugars, amino acids, tricarboxylic acids, or Krebs cycle intermediates, proteins, nucleic acids and polysac-

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 [2]. Thirty years later, Czapek described them as end-products [3]. 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

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

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

charides. Eventually, the primary metabolites are similar in all living cells [1].

phytochemistry.

12 Herbal Medicine

of animals [4].

• Phenolics • Alkaloids • Saponins • Terpenes

• Lipids

• Carbohydrates

**2. Phenolics**

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 [5]. 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:


#### **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 [6]. 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 [9] and the anti-inflammatory salicylates [10]. A property shared by all phenols is antimicrobial activity. In fact, phenol itself was the first antiseptic used in surgery [11].

**Figure 2.** Gallic acid.

The pharmacological activities of many plants are attributed to simple phenolics among which the antimicrobial and diuretic activities of *Arctostaphylos uva-ursi* were attributed to its phenolic content [12]. *Capsicum* spp. showed circulatory stimulant, rubefacient and analgesic activities due to the presence of capsaicinoids, which are simple phenolic compounds [13]. Moreover, the cholagogue activity of *Cynara scolymus*, the anthelmintic activity of *Dryopteris filix-mas*, the anti-inflammatory analgesic activity of *Filipendula ulmaria* as well as the anticatarrhal and diuretic activities of *Solidago virgaurea* are all attributed to the action of simple phenolics [8]. **Figure 3** illustrates some examples of simple phenolics.

presence of additional substituents. Some drugs (e.g., *Camellia sinensis* (tea), *Hamamelis virgin-*

Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants

http://dx.doi.org/10.5772/intechopen.76139

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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. *Vaccinium oxycoccos* (cranberry) juice has long been used as urinary antiseptic [18], which was scientifically proven in a randomized, doubleblind, placebo-controlled trial that has been carried out on 153 elderly women [19]. **Figure 4**

Coumarins are derivatives of benzo-α-pyrone, the lactone of *O*-hydroxycinnamic acid, coumarin. Some 1000 natural coumarins have been isolated. Coumarin itself has been found in about 150 species belonging to over 30 different families. The richest sources of coumarin are sweet clover or melilot (*Melilotus* spp.), *Dipteryx odorata* (tonka bean) and *Galium odoratum* (sweet woodruff) [8]. Aesculetin, umbelliferone and scopoletin are common coumarins present in plants both in the free state and as glycosides. Plants rich in coumarins include *Atropa belladonna*, *Datura stramonium* (Solanaceae), *Daphne mezereum* (Thymeliaceae), *Ruta graveolens* (Umbelliferae) and certain *Aesculus hippocastanum* (Horse-chestnut) (Hippocastanaceae) and certain Rosaceae [7]. Anti-inflammatory, anticoagulant, anticancer and anti-Alzheimer's activities are the most important biological activities reported for coumarins [20]. Examples

*iana* leaves and bark) contain both hydrolyzable and condensed tannins [17].

illustrates some examples of hydrolysable tannins.

of coumarins are shown in **Figure 5**.

**2.3. Coumarins**

**Figure 3.** Examples of simple phenolics.

#### **2.2. Tannins**

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 [14]. 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 *Geranium robertianum* (Herb Robert) and *Geranium maculatum* (American cranesbill) [15]) and tellimagrandins 1 and 2 [16] (isolated from *Quercus alba* (Oak bark), *Punica granatum* (pomegranate) and *Filipendula ulmaria* (Meadowsweet)) [7].

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 Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants http://dx.doi.org/10.5772/intechopen.76139 15

**Figure 3.** Examples of simple phenolics.

presence of additional substituents. Some drugs (e.g., *Camellia sinensis* (tea), *Hamamelis virginiana* leaves and bark) contain both hydrolyzable and condensed tannins [17].

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. *Vaccinium oxycoccos* (cranberry) juice has long been used as urinary antiseptic [18], which was scientifically proven in a randomized, doubleblind, placebo-controlled trial that has been carried out on 153 elderly women [19]. **Figure 4** illustrates some examples of hydrolysable tannins.
