Therapeutic Use of Plant Secondary Metabolites

By Bentham Science Publishers

The book is an evidence-based reference about biochemical mechanisms of action of plant secondary metabolites. It conveys an understanding about how plant-based therapies work, and explains their role in the treatment of diabetes, cancer, neurodegenerative disorders, and microbial infections. The 15 chapters in the book are written by eminent scholars, lecturers, and experts in indigenous knowledge systems (IKS), industrial and medicinal plants, phytotherapeutics, and phytoinformatics. Reports on health benefits of specific phytochemicals are also highlighted. In addition to basic concepts in medicinal chemistry and ethnopharmacology, the book covers the role of modern computer techniques in developing new pharmaceuticals from plant sources. Therapeutic Uses of Plant Secondary Metabolites is a timely and valuable reference for both undergraduate and postgraduate students in medicinal chemistry, as well as researchers and professionals in IKS, phytomedicine, ethnopharmacology, phytopharmacology, plant biotechnology, drug discovery and development, and phytotherapeutics.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: Dec 24, 2002
• ISBN: 9789815050622

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The Role of Plant Secondary Metabolites in Health Management

Taofik Olatunde Uthman¹, *

¹ School of Medicine and Department of Biological Sciences, University of Limerick, Limerick, Ireland

Abstract

Plant secondary metabolites (PSM) are bioactive compounds produced by plants for protection against predatory organisms and to attract insects for pollination. Recently, greater attention is being focused on PSM due to their perceived ability to elicit pharmacological activities, including antihypertensive, antiarrhythmic, antimalarial, anticancer, analgesic, antispasmodic, antidiabetic, and antimicrobial effects. Therefore, many plant species are continually screened for PSM, such as alkaloids, flavonoids, terpenes, saponins, cardiac glycosides, fatty acids, steroids, and tannins with a view to exploiting them in the manufacture of drugs and pharmaceuticals. In this review, the pharmacological activities and possible mechanisms of action of selected PSM are discussed.

Keywords: Alkaloids, Biological activity, Flavonoids, Polyphenols, Secondary metabolites, Saponins, Terpenes.

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* Corresponding author Taofik Olatunde Uthman: School of Medicine and Department of Biological Sciences, University of Limerick, Limerick, Ireland; E-mail: [e-mail]

1. Introduction

The term ‘metabolites’ refers to intermediates and products of metabolism. They are usually small molecules with diverse functions, including structural, signaling, stimulatory, inhibitory, catalytic and defensive roles as well as providing fuel. Metabolites in plants can be of two types namely primary and secondary metabolites. Primary metabolites in plants are essential for life processes such as growth and development of cells. They are produced continuously during growth phase of plants where they are involved in important metabolic processes such as photosynthesis and respiration. Primary metabolites are generally heavy molecular weight compounds with diverse structures, including DNA, proteins, carbohydrates, and lipids.

Unlike primary metabolites, secondary metabolites refer to a vast and diverse group of active organic compounds produced by plants for the purpose of increasing the likelihood of their survival by repelling or attracting other organisms. This implies that secondary metabolites play a defensive role against herbivory and other interspecies protection. They are not essential for the growth and development of the producing plants and are often differentially distributed among limited taxonomic groups within the plant kingdom. Their absence does not result in plant death but can impair survivability, fecundity, and aesthetics of plants. Apart from the protective role, some secondary metabolites are involved in the pigmentation of flower and seed, which attract pollinators, thereby enhancing seed dispersal and plant reproduction. More importantly, plant secondary metabolites have been reported to possess a myriad of pharmaceutical properties which can be exploited for human health [1]. Secondary metabolites are biosynthesized from primary metabolites by specialized cell types at distinct developmental stages. They are generally low molecular weight compounds, varying in quality and quantity for a specific plant species depending on location.

The main biotic factor that affects plants is a pathogenic infection caused by bacteria, viruses, fungi, and nematodes. Other biotic antagonists include attacks by mites, insects, mammals, and other herbivorous animals and competition from other plants arising from parasitism and allelopathy. The most significant abiotic environmental stresses faced by plants are excessive temperature and water as well as exposure to radiation and chemicals. To combat these stress factors, plants have evolved a defensive system involving the production of secondary metabolites, which serve to protect against predators and microbial pathogens [2]. These natural products are able to perform a defensive role due to their toxic nature, which allows them to repel herbivores and microbes as well as dominate other plants within the same locality [3]. One of the mechanisms employed by secondary metabolites is acting as antimicrobial agents, which may be pre-formed or induced by infection. Other modes of defense include formation of polymeric barriers to prevent penetration of pathogens, and synthesis of enzymes capable of degrading pathogenic cell wall. It is also possible for plants to employ secondary metabolites as specific recognition and signaling systems, which allows rapid detection of pathogenic invasion and triggering of defensive responses.

Plants can also efficiently respond to environmental stresses through sensors regulated by feedback mechanisms. To achieve this, plants use secondary metabolites as messengers under sub-optimal conditions to trigger their defense mechanism, which involves the production of phytochemicals, hormones and a variety of proteins necessary to protect the ultra-structure of plants from such hazards [4]. Elevated synthesis of secondary metabolites has also been observed under abiotic stresses like salinity and drought. These are utilized efficiently in defense mechanisms and biochemical pathways facilitating water and nutrient acquisition, chloroplast function, ion uptake and balance, synthesis of osmotically active metabolites and specific proteins, production of metabolites acting as osmo-protectants and detoxifying radicals [5].

2. Classification of plant secondary metabolites

It has been estimated that well over 300,000 secondary metabolites exist in nature [6]. There is no rigid scheme for classifying these secondary metabolites due to their immense diversity with respect to structure, function, and biosynthesis. Hence, it is difficult for them to fit perfectly into a few simple categories. For ease of reference, PSM may be grouped based on the presence of a recurring structural feature. For example, flavonoid compounds are oxygenated derivatives of aromatic ring structure, while alkaloids having an indole ring are called indole alkaloids. Terpenes consist of five carbon isoprene units, which are assembled in different ways.

PSM may also be classified according to the genus to which the plant source belongs. For example, morphine and codeine are examples of opium alkaloids. Grouping is also possible according to biological activities and physiological effects they elicit, such as antimicrobials, antibiotics, analgesics, etc. PSM can also be classified based on similarities in biosynthetic pathways. Generally, classifications based on structure and biosynthesis are more realistic and make the most sense.

3. Polyphenols – A major class of plant secondary metabolites

Polyphenols are secondary metabolites essential for the protection and survival of plants. They represent one of the most widespread groups of secondary metabolites in plants, with more than 8,000 identified phenolic structures [7]. These compounds can be found in almost all organs of plants, where they perform a myriad of functions, including skeletal constituents of different tissues and pigmentation of several plant organs [8], defense against various pathogens [9] and signaling molecules in plant cells [10]. The main sources of phenolic compounds are woody vascular plants, especially bark.

3.1. Classes of Polyphenols

Fig. (1) depicts the sub-divisions of polyphenols into different classes based on their chemical structures, namely phenolic acids, flavonoids, stilbenes and lignans [11, 12].

Fig. (1))

Sub-divisions of polyphenols [13].

Fig. (2))

Chemical structure of phenolic acids [7].

3.1.1. Phenolic Acids

Phenolic acids constitute one of the main classes of polyphenolic compounds found in plants where they rarely occur in free form but as esters, glycosides, or amides [14]. The structural variation of phenolic acids depends on the number and position of hydroxyl groups on the aromatic ring. Phenolic acids have two distinctive structures, namely benzoic acid and cinnamic acid derivatives (Fig. 2). The most common benzoic acid derivatives found in the bark of woody plants are vanillic, gallic, syringic and protocatechuic acid [15-17], while p-coumaric, caffeic, ferulic and synaptic acids represent the most common cinnamic acid derivatives [18]. Phenolic acids often occur in bound form and can only be hydrolyzed by acid, alkaline or enzymatic hydrolysis [19, 20].

3.1.2. Flavonoids

Flavonoids are composed of two aromatic rings joined by a unit of three carbon atoms. The unique arrangement of carbon skeleton explains the chemical diversity of this family of compounds [21]. (Fig. 3) presents the six different sub-groups into which flavonoids can be further divided based on the type of heterocycle involved namely flavonols, flavones, isoflavones, flavanones, anthocyanidins, and flavanols [22]. Over 4,000 flavonoids have been identified in plants, with the possibility of many more to be identified [23].

Fig. (3))

Subclasses of flavonoids [22].

Flavonols constitute the most common sub-group of flavonoids and they include such compounds as quercetin, kaempferol and myricetin [24-26], followed by flavones (such as apigenin, luteolin) and flavanols (such as catechin, epicatechin) [27]. Flavanols exist in both monomeric and polymeric forms. The monomeric forms of flavanols include catechin and epicatechin as well as their derivatives such as gallocatechins, which represent the major flavanols found in tea leaves and cacao beans [28]. Catechin and epicatechin form polymeric flavanols, which are often referred to as proanthocyanidins whose polymeric chains can be cleaved by acid catalysis to produce anthocyanidins [7]. Proanthocyanidins are traditionally considered to be condensed tannins dimers, oligomers, and polymers of catechins [29]. Depending on inter-flavanic linkages, oligomeric proanthocyanidins can be A-type structure in which monomers are linked through C2–O–C7 or C2–O–C5 bonding, or B-type in which C4–C6 or C4–C8 are common.

3.1.3. Lignans and Stilbenes

Lignans and stilbenes constitute the last two groups in the polyphenol family. They are closely related and widely distributed in different parts of plants, including roots, rhizomes, stems, bark, leaves, and fruits. Lignans are synthesized by oxidative dimerization of two phenylpropane units forming diverse structures of different linkage patterns. Several lignans, such as secoisolariciresinol, are considered to be phytoestrogens [30]. They are majorly found in linseed, which contains secoisolariciresinol and relatively low quantities of matairesinol. Stilbenes are also biosynthesized from phenylpropanoids which can be further oxidized to form oligomers via two-carbon methylene bridge. Most stilbenes in plants have been reported to act as antifungal phytoalexins, which are synthesized only in response to infection or injury.

Resveratrol is one of the most studied stilbenes, and it is found predominantly in grapes [31].

It exhibits neuroprotective activity against Parkinson’s and Alzheimer’s diseases by virtue of its ability to influence and modulate cellular processes such as signaling, proliferation, apoptosis, redox balance and differentiation [32, 33]. It also plays neuroprotective role through inhibition of nuclear factor κB signaling in the progression of Alzheimer’s disease [34]. Resveratrol also inhibits development of cancers of the lung, skin, breast, prostate, gastric and colon through suppression of angiogenesis and metastasis. The anti-carcinogenic activity of resveratrol is closely linked with its antioxidant activity which involves inhibition of cell cycle enzymes and regulators [35]. Resveratrol functions as an anti-diabetic agent by modulating Sirtuin 1 (SIRT1). A protein which improves glucose homeostasis and insulin sensitivity in humans [36, 37]. The compound also inhibits diabetes-induced nephropathy and ameliorates renal dysfunction through inhibition of K+ ATP and K+ V channel in beta cells [38]. Resveratrol also acts as an anti-aging agent and plays a prominent role in prolonging life span [36].

4. Medicinal plants

Medicinal plants refer to plants whose parts including leaves, root, stem bark, fruits and seeds can be used for treatment and/or management of diseases affecting humans and animals. According to World Health Organization, plants that are rich in substances which can be used for therapeutic purposes or serve as precursors for producing synthetic drugs are referred to as medicinal plants [1]. In most parts of the world, particularly in developing countries, plants are used to treat many ailments affecting humans including diabetes, diarrhea, constipation, ulcer, fever, cold and dental infection. This explains why majority of medications used in traditional healthcare system are derived from plants. Despite advance- ments in the production of synthetic drugs and antibiotics, plants still remain a major source of therapy in many parts of the world.

The widespread use of herbal remedies and preparations have been traced to the presence of specific natural products with medicinal properties [39]. The biological activities exhibited by plants are mainly attributed to the presence of secondary metabolites which are usually expressed in certain parts of the plants [40, 41]. Therefore, medicinal plants are rich sources of secondary metabolites that have been extensively used in the manufacture of drugs and pharmaceuticals [42]. Many of the plant secondary metabolites are produced constitutively in healthy plants in their biologically active forms while others occur as inactive precursors but become activated when there is tissue damage or pathogenic attack.

5. Plants secondary metabolites in health management

It is noteworthy that the traditional use of plant extracts for the formulation of herbal remedies provides the foundation for the establishment of modern system of medicine. The therapeutic effect of plant materials can be attributed to the combinations of secondary metabolites present in the plant such as alkaloids, flavonoids, terpenes, saponins, cardiac glycosides, fatty acids, steroids, and tannins. To date, several plant species are continually screened for these secondary metabolites with a view to isolating them for drug manufacture. This section explores secondary metabolites from plants that have been exploited in health management due to their biological activities.

5.1. Alkaloids

Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. They are extremely toxic and bitter but show marked therapeutic effects in small quantities [43]. Therefore, plant alkaloids and their synthetic derivatives are used as medicinal agents in many parts of the world [44]. According to reports, about 12,000 known alkaloids have been exploited as pharmaceuticals due to their potent biological activities [1]. The pharmacological activities of alkaloids include antihypertensive, antiarrhythmic, antimalarial, anticancer, analgesic, antispasmodic, antidiabetic, and antimicrobial effects [45].

For instance, benzylisoquinoline and indoquinoline alkaloids have been shown to have antiviral and antibacterial activities respectively while quinine alkaloid is widely known for its antimalarial activity against the plasmodium parasite [46]. Alkaloids extracted from different plants also exhibited antidiabetic property through inhibition of alpha amylase activity [47-49]. Morphine and its methyl ether derivative codeine are well known alkaloids with potent analgesic activity used for pain relief [45]. Some alkaloids such as vincristine and vinblastine have anticancer property; cocaine is used as an anesthetic while ephedrine relieves asthma and common cold [50]. Notably, alkaloids are also known for their neuro-protective activity against diseases such as epilepsy, dementia, depression, Parkinson’s and Alzheimer’s disease [51]. Alkaloids exert their neuroprotective action via inhibition of acetyl cholinesterase and increasing the level of gamma-aminobutyric acid among others [52, 53].

5.2. Flavonoids

Flavonoids have been reported to have potent antioxidant, anti-cancer, antidiabetic, anti-inflammatory, and antimicrobial activities [54]. For instance, kaempferol, quercetin and lutein isolated from different plants exhibit potent antioxidant activity through lipid peroxidation [55]. Other mechanisms of antioxidant action employed by flavonoids include scavenging of reactive oxygen species or suppression of its formation, and upregulation or protection of antioxidant defenses [56].

Flavonoids are known to be synthesized by plants in response to microbial attacks. It is therefore not surprising that they possess antimicrobial activity against a wide array of microorganisms including bacteria, viruses, and fungi. For instance, flavonoids extracted from different parts of Sida acuta showed antifungal activity against Candida albicans [57]. Their mode of antimicrobial action may be related to their ability to inactivate microbial adhesins, enzymes and cell envelope transport proteins. Most of the antiviral activity of flavonoids revolve around their ability to inhibit various enzymes associated with the life cycle of viruses.

Inflammation is a normal biological process that results from tissue injury, pathogenic infection, and chemical irritation. It is initiated by migration of immune cells from blood vessels and release of mediators at the site of damage. Certain members of flavonoids including hesperidin, apigenin, luteolin, and quercetin exhibit significant anti-inflammatory activity. Much of the anti-inflammatory activity of flavonoids is achieved through the biosynthesis of cytokines that mediate adhesion of circulating leukocytes to sites of injury. Some flavonoids also act by inhibiting the production of prostaglandins, which are powerful proinflammatory signaling molecules. Anthocyanins represent an important subset of flavonoids and they have been reported to slow down the aging process through their potent antioxidant/anti-inflammatory activities [58-60]. Catechins also possess strong anti-aging activity, hence consuming green tea rich in catechins, may delay the onset of aging [61]. Several other flavonoids such as apigenin, quercetin, naringenin, catechin, rutin, and venorutin have hepatoprotective activity through their ability to improve cell viability and inhibit cellular leakage of liver aspartate aminotransferase (AST) and alanine amino- transferase (ALT) caused by xenobiotics.

Several studies have implicated flavonoids like catechin, anthocyanin, epicatechin, epigallocatechin, epicatechin gallate, and isoflavones as potent antidiabetic agents [62, 63]. The mechanisms by which the antidiabetic activity is achieved include inhibition of glucose absorption in the gut, inhibition of glucose uptake by peripheral tissues [64], and inhibition of intestinal glycosidases and glucose transporter [65]. Flavonoids also demonstrate significant α-amylase inhibitory activity further indicative of their anti-diabetic potential [47-49, 66]. Quercetin, protocatechuic acid and anthocyanins showed strong antidiabetic activity by inhibiting lipid peroxidation [67] and attenuating diabetic nephropathy [68].

Flavonoids have been reported to improve blood circulation and lower blood pressure. For instance, quercetin prevents incidence of coronary heart disease by inhibiting the expression of metalloproteinase 1 and disruption of atherosclerotic plaques [69]. Catechins obtained from tea also prevent invasion and proliferation of smooth muscle cells in the arterial wall thereby slowing down the formation of atheromatous lesion [70].

Many flavonoids such as catechins, isoflavones, and flavanones showed protective effects in cancer cell lines by reducing the number and growth of tumor cells [71] although their mechanisms of action differ [72]. Theaflavins and thearubigins are prominent flavonoids in black tea with potent anticancer activity particularly against prostate carcinoma cells [73]. Quercetin is a potent flavonol that reduces the incidence of cancers of the prostate, lung, stomach, and breast. Quercetin has also been reported to possess anticancer property against benzo(a)pyrene induced lung carcinogenesis, an effect attributed to its free radical scavenging activity [74]. The major anticancer mechanisms of flavonoids include downregulation of mutant p53 protein, cell cycle arrest, inhibition of tyrosine kinase, inhibition of heat shock proteins, excretion of tumor cells by increasing the expression of phase II conjugating enzymes, and inhibition of expression of Ras proteins.

5.3. Terpenes

Terpenes are diverse naturally occurring organic compounds found widely in plants where they form the major constituent of essential oils. Their oxygen-containing derivatives are called terpenoids and they are formed when terpenes are modified chemically by such processes as oxidation or re-arrangement of carbon skeleton. Common sources of terpenes include tea, thyme, cannabis, lemon, and orange. They can be classified as mono, di, tri, tetra, and sesquiterpenes according to the number of isoprene units found in their structures. Terpenes have been reported to have a wide range of medicinal and health benefits among which are antiplasmodial, antiviral, anticancer, antidiabetic and antidepressant activities [75].

The potent antiplasmodial activity of terpenes can be exploited in the development of antimalarial drugs. The mechanism of action involves binding of terpenes to the hemin portion of infected erythrocytes which eventually kill the parasites without any serious side effects [76, 77]. Specifically, beta-myrcene, limonene and caryophyllene are powerful terpenoid compounds with proven antiplasmodial activity [78-81]. Thus, terpenes can be used as a safer and cost-effective alternative for the treatment of malaria.

Monoterpenes form a major constituent of essential oils in plants that have shown good results against viral diseases. These monoterpenoid oils namely carvone, carveol limonene, alpha- and beta-pinene, caryophylene, camphor, beta-ocimene, proved to be virucidal against three major human viruses namely herpes simplex virus-1 (HSV1), dengue virus type 2, and Junin virus [82]. The emergence of novel viral diseases has further necessitated the search for more effective antiviral agents from terpenes. This has led to the discovery of alpha- and beta-pinene, beta-ocimene, and 1,8-cineole used in the treatment of severe acute respiratory syndrome corona virus (SARS CoV) [83]. Different mechanisms of action have been proposed for the antiviral activity of these terpenes including direct inactivation of free viral particles and induced cell cycle arrest at G0 or G1 phase. This points to the fact that a combination of different terpenes may act as better antiviral agents rather than a single one [84].

The medicinal benefits of terpenes extend beyond antiplasmodial and antiviral activities as they are also known for their anticancer property. A combination of terpenes comprising monoterpenes, diterpenes and sesquiterpenes have been used for the treatment of colon, brain, and prostate cancers. For example, limonene has been reported to exhibit potent anticancer activity via different mechanisms of action. One of these is induction of transforming growth factor B-1 and mannose-6-phosphate/insulin-like growth factor II receptors [85]. Further studies also reported that limonene works by eliminating cancer cells through induction of apoptosis [86]. The lipophilic nature of limonene is also an indication that it can serve as a potent anticancer agent since it has the tendency to be stored in fatty tissues of the body [87]. Other terpenes with anticancer activity include thymoquinone, thermoquinone, alloocimene, camphor, beta-myrcene, pinene, alpha- and gamma-thujaplicin, terpinene, thymohydroquinone, carvone, camphene, and cymene [88-90].

The widespread use of terpenes in cancer treatment is hinged on the fact that it is unlikely to pose any serious side effect since it is a natural compound.

According to reports, terpenes also form the bulk of natural compounds used in the treatment of diabetes [91, 92]. Notable among the terpene compounds used as antidiabetics is a diterpenoid lactone called andrographolide which is obtained from A. paniculata leaves [93]. The compound enhances glucose utilization in the muscle by activating alpha-adrenoreceptors which causes the release of beta-endomorphin, thereby reducing plasma glucose concentration [93]. Another commonly used terpene in the treatment of diabetes and its complications is curcumin, popularly known as turmeric [94]. Curcumin acts as an antidiabetic by activating the enzymes that are essential for glycolysis in the liver [95].

Terpenes have also found relevance in the management of depression which is a major health challenge in both developed and developing countries [96, 97]. Some of the terpenes implicated as antidepressants include linalool and beta-pinene, beta-caryophyllene, hyperforin [98, 99]. These terpenes act by interacting with the 5HT1A receptors of the serotonergic pathway, adrenergic receptors, and dopaminergic receptors [99, 100].

5.4. Saponins

Saponins are naturally occurring plant glycosides with structures consisting of a sugar moiety linked to a hydrophobic aglycone called sapogenin. There are more than 100 plant families containing saponins belonging to different classes [101]. Saponins are known for their foaming properties in aqueous solutions and they generally impart bitter and astringent taste. Intravenous administration of saponins has been reported to be toxic due to their hemolytic activity on human erythrocytes [102]. Despite this untoward effect, saponins still offer several pharmacological properties, including anticancer, antidiabetic, antimicrobial, anti-obesity and hypoglycemic activities [103, 104].

Saponins from ginseng and soy have been reported to be effective against different cancer cell lines, including hepatocellular carcinoma cell line, fibrosarcoma cell line, HeLa, and promyelocytic leukemia cells [105, 106]. With respect to antidiabetic activity, saponin compounds such as saxifragifolin B and saxifragifolin D [107], α-hederin [108], glochierioside A [109] and filiasparoside C [110] demonstrate potent hypoglycemic effect. The mechanisms of action include restoration of insulin response, an increase in plasma insulin concentration, induction of insulin release from the pancreas as well as inhibition of α-amylase and α-glucosidase activities [111]. Saponins also act by delaying the transfer of glucose from stomach to small intestine [112] or by repairing pancreatic beta cells, thereby stimulating the release of insulin [113, 114].

Saponins also demonstrate a wide spectrum of antimicrobial activity against many harmful organisms. For instance, they showed potent antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumoniae [115]. In other studies, saponins also demonstrate biological activity against Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis, Candida albicans, Candida parapsilosis, Candida pseudotropicalis and Candida stellatoidea [116, 117].

Investigation of anti-obesity activity of saponins indicates that they are potent modulators of body weight. A possible mechanism of action by which this is achieved is via inhibition of pancreatic lipase and modulation of adipogenesis [118]. Saponins also promote normal blood cholesterol levels by binding to bile causing cholesterol to be excreted rather than being reabsorbed back into the bloodstream [119]. The operation of many cholesterol drugs follows this pattern.

Conclusion

Although PSM are primarily produced by plants to enhance their survival by providing protection against predators and microbial pathogens. These seemingly toxic compounds are being used in health management. It is a common practice in many parts of the world, particularly in developing countries, to use plants for the treatment of different ailments affecting humans. The therapeutic activity produced by these medicinal plants have been attributed to secondary metabolites, including alkaloids, flavonoids, terpenes, saponins, cardiac glycosides, fatty acids, steroids, and tannins. Of the different PSM, polyphenols particularly flavonoids seem to produce the widest range of pharmacological potential, including antioxidant, anti-cancer, antidiabetic, anti-inflammatory, and antimicrobial activities. In spite of the impressive use of PSM in health management, particularly at the traditional healthcare level, a multitude of plant species are yet to be screened for already known and novel secondary metabolites. Additionally, out of those that have been identified, many have not reached the stage of clinical trials for the development of new lead therapeutics for common ailments. This indicates that a lot still needs to be done in exploiting the full advantage of PSM in the management of health. Therefore, the continuous search for PSM is imperative with a view to isolating them for drug manufacture.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

References