Secondary Metabolites: The Natural Remedies

*Hudu Garba Mikail, Mamman Mohammed, Habib Danmalam Umar and Mohammed Musa Suleiman*

### **Abstract**

The chapter discusses the meaning and origin of some important classes of secondary metabolites such as alkaloids, terpenoids, tannins, flavonoids, saponins, glycosides, and phenolic compounds, etc., produced by some bacteria, fungi, or plants. Very important drugs that are used clinically are derived from these secondary metabolites. Several reports obtained in scientific journals and books written by different scientists working or who have worked in the fields of natural products medicine were reviewed. These different classes of secondary metabolites have shown activity against varied diseases, and compounds that are of novel structure and activity have been isolated and characterized from them. The chapter highlights the economic impacts of these chemical compounds including their role in improving human and animal health and well-being by serving as sources of some antibiotics, anticancer, anti-inflammatory, antifertility, antidiabetics, analgesics, growth promoters, etc. Secondary metabolites are also used to enhance agricultural productivity, they find uses as pesticides, insecticides, and preservatives. Some folkloric uses of secondary metabolites chemical compounds based on reliable sources of information and genuine scientific investigations are highlighted.

**Keywords:** secondary metabolites, natural remedies, phytochemical constituents, bioactive compounds

#### **1. Introduction**

Metabolomics is the study of metabolites within biofluids, cells, tissues, or organisms [1]. Whereas collectively, metabolites and their interactions are known as metabolome [2].

Metabolites are small molecules produced by metabolic reactions; these molecules are intermediate or end products of metabolic reactions. The metabolic reactions are catalyzed by naturally occurring enzymes within the organisms' cells [3]. Compounds derived from primary and secondary metabolism are known as primary and secondary metabolites, respectively.

Primary metabolites are indispensable compounds used by organisms for their growth, development, and reproduction; these compounds are synthesized by the cells as a result of metabolism during the growth phase. Primary metabolites are referred to as central metabolites due to their key role in maintaining normal physiological

processes. Primary metabolites include vitamins (B2 and B12), lactic acid, amino acids, polyols, alcohols such as ethanol, nucleotides, organic acids, etc. [3, 4].

The current chapter discusses the meaning and origin or sources of some important classes of secondary metabolites such as alkaloids, terpenoids, tannins, flavonoids, saponins, cardiac glycosides, phenolic compounds, etc., the economic impacts of secondary metabolite compounds including their role in improving human and animal health and well-being (as antibiotics, anticancer, anti-inflammatory, antifertility, antidiabetics, pain relievers, growth promoters, etc.). The chapter addresses the role of secondary metabolites in enhancing agricultural productivity (as pesticides, insecticides, preservatives, etc.); it also discusses the important present-day drugs derived from secondary metabolites, as well as some important biological/pharmacological effects or activities of different classes of the secondary metabolites and their folkloric usage based on reliable sources of information and genuine scientific investigations.

#### **1.1 The meaning and origin of important classes of secondary metabolites**

Secondary metabolites also known as phytochemical constituents, bioactive compounds, specialized metabolites, secondary products, or toxins are organic compounds produced by organisms such as plants, fungi, or bacteria as a result of secondary metabolic processes that lead to production and accumulation of diverse chemical compounds known as secondary metabolites. These compounds are not required for primary metabolic processes by the organisms [3–5]. Secondary metabolites are formed toward the end of the growth phase; thus, they are not directly involved in the normal physiologic processes of the organism such growth and development as well as reproductive processes. Instead, they increase the organism's survivability through mediation of ecological interaction, to the organism, this serves as a selective advantage [4, 5]. Interspecies defenses such as defense against herbivory by plants are part of the important roles of secondary metabolites. However, humans use secondary metabolites as medicines, recreational drugs, flavorings, pigments, etc. [6].

Secondary metabolites are classified commonly based on their vast structural diversity, biosynthesis, and function. According to the literature, over 2140, 000 secondary metabolites are known; however, the main classes of secondary metabolites are five, which include alkaloids, terpenoids and steroids, nonribosomal polypeptides, polyketides and fatty-acid-derived substances, and enzyme cofactors [7].

#### **1.2 The origin and sources of some important classes of secondary metabolites**

Secondary metabolite is a term coined in 1910 by a Medicine and Physiology Nobel Prize laureate, Albert Kossel [8]. Friedrich Czapek, a Polish botanist, 30 years later described them as metabolic nitrogenous end products [9].

Secondary metabolites are produced by plants, fungi, or bacteria as well as many marine organisms such as snails, corals, tunicates, and sponges [10]. There are 150, 000–200, 000 bioactive compounds derived from the plant kingdom, 50, 000–100, 000 from animal kingdom, and 22,000–23, 000 from microbes [11].

#### **1.3 Plant secondary metabolites**

Plants are the major sources of secondary metabolites; they produced 80% of the known secondary metabolites occurring in nature [10]. Secondary metabolites are

used by carnivorous plants to attract, capture, digest, and assimilate the prey [12]. One of the early known plant secondary metabolites is morphine, isolated in 1804 [11].

#### **1.4 Fungal secondary metabolites**

In 1928, Alexander Fleming while working at St Mary's Hospital in London discovered the most known secondary metabolite, the penicillin. Penicillin was discovered experimentally from a mold, the *Penicillium notatum* [13, 14].

#### **1.5 Bacterial secondary metabolites**

Oligosaccharide, b-lactam, polyketide, non-ribosomal pathways, and shikimate are the main secondary metabolite production pathways in bacteria [15]. Although bacterial secondary metabolites have some beneficial effects, many are toxic to mammals through secretion of exotoxin, botulinum toxin secreted by *Clostridium botulinum* bacteria is a very good example [15].

#### **1.6 The alkaloids**

The name alkaloid was introduced by Carl Friedrich Wilhelm Meißner, in the year 1819. The name was derived from Latin root alkali, rooted from Arabic word al-qalwi meaning plants ashes. The wide usage of the word alkaloid came after J. Oscar's publication in the year 1880 in Albert Ladenburg, the chemical dictionary [16].

A large variety of organisms produced alkaloids; these chemical compounds are derived from plants, bacteria, fungi, and animals [17]. Morphine was the first individual alkaloid isolated in 1804 from the opium poppy plant (*Papaver somniferum*) [18].

#### **1.7 The cardiac glycosides**

The ancient Romans, Syrians, and Egyptians used cardiac glycosides contained in plant extracts for medicinal purposes, the plant extracts from *Urginea maritima* (Scilla), squill, or sea onion were used as emetics and heart tonics. African warriors in the medieval age used Strophanthus species as arrows head poison against their targets. Cardiac glycosides were established in the twentieth century as agent for the treatment of heart failure [19].

Early writings of 1250 BC mentioned *Digitalis purpurea*; digitalis was included in herbal collections used in prescription by the Welsh family physicians. The origin of digitalis was from the foxglove plant. A botanist and physician of English origin, William withering in the eighteenth century described the foxglove plant's clinical effects in a published monograph. He was the first investigator of the systemic bioactivity of digitalis. "An account of the Foxglove and some of its medical uses with practical remarks on dropsy, and other diseases" is a book authored by William Withering in 1785 reporting the toxicity and indications of digitalis [19].

Plant is main source of cardiac glycosides; however, bufadienolide was isolated from frogs and mammalian tissues that are rich sources of endogenous digitalis; this show that animal species are also good sources of cardiac glycosides [20].

#### **1.8 The flavonoids**

Flavonoids or bioflavonoids are yellow compounds derived from the Latin word Flavus, meaning yellow, their natural coloration [21]. Albert Szent-Györgyi and some group of scientists in the 1930s discovered that crude yellow extracts from lemons, oranges, etc., were more effective at preventing scurvy than vitamin C. They referred to these compounds as citrin or vitamin P, which were later discovered to be hesperidin, neohesperidin, etc., belonging to flavonoids rather than the vitamins [22].

Flavonoids are compounds belonging to polyphenolic structural class of secondary metabolites. They are widely found in vegetables, fruits, flowers, wine, tea, grains, roots, bark, and stem [23, 24]. Flavonoid compounds are found in several parts of plants, they are products extracted from plants using various extraction techniques such as chromatography [25].

#### **1.9 The phenolic compounds**

Phenolic compounds are secondary metabolites produced by the secondary metabolic pathways of plants [26]. They are derived from pentose phosphate and shikimic acid of plants through metabolization of phenylpropanoid [27, 28]. The composition of phenolic substances or polyphenols includes tannins, flavonoids, lignans, coumarins, and phenolic acids [26], colored anthocyanins [29]; these compounds are naturally found in vegetables, fruits, leaves, and roots among other products of plant origin [26, 27].

#### **1.10 The tannins**

Tannins are group of astringent and complex polyphenolic compounds found in plants, which can bind and precipitate proteins; the word tannin was derived from the usage of this compound in tanning animal hides and skins to make leather [30]; the term was first introduced in 1796 [31]. Commonly, tannins are found in wood, buds, fruits, leaves, stems, roots, seeds, and in the bark of trees [32]. Condensed tannins are the most abundant polyphenols, which are virtually found in plant families [33].

#### **1.11 The terpenoids**

Terpenoids or isoprenoids are modified terpenes [34, 35]; terpenoids usually contain additional functional group and oxygen [35]. These chemical compounds are the largest class of secondary metabolites representing 60% of the natural products known [36].
