Introduction

Today’s lifestyle is a leading cause to many human diseases. Allopathic medicines often work effectively against the disease but may show extreme side effects in certain cases. Commonly manifested side effects of allopathic medicines are face swelling, rashes on the body, itching, headache, inflammation, and drug resistance. A safer alternative to treat diseases is herbal or plant derived medicines that have been used since the ancient period (Kaberaet.al 2014). India and China provide the best example of the early use of medicinal plants. Both countries enlist countless plant-derived medicines (Tang et.al 1992).The diversity of medicinal plants depends on many factors such as climate, altitude, seasonal fluctuations etc. While many plants are perennial and live for many years contributing as a consistent source of medicinal compounds, other plants have shorter life span ranging from seasonal to annual or biennial. There is a huge variety of seasonal plants that show medicinal properties, some plants grow in summer, some in winters, and some plants occur only in the spring season. Some examples of medicinal plants that grow in different seasonsare Achilleafilipendulina, Santolinachamecyparissus,and Menthalongifolia grows in summer, Cistusmonspeliensi, Ocimumgratissimum grows in the spring season (Soniet.al 2015).

The versatile and vast pharmacological effects of medicinal plants are completely dependent on their phytochemical constituents. Various phytochemicals of plants have been isolated for drug discovery and development.Modern analytical techniques such as electrophoresis, chromatography, enzymology, and isotope techniques have been used to characterize phytochemicals, elucidate their structural formulas and decipher their biosynthetic pathways (Hussein et.al 2018, Okada et.al 2010). To explore the therapeutic use of plants, it is pertinent to have deep understanding of phytochemistry and have detailed knowledge of phytochemical composition of plant extracts which further can be used to develop different medicines.

Generally, the phytochemicals are divided into two categoriesi.e. primary and secondary metabolites based on their role in different metabolic processes.Primary metabolites are involved in primary processes such as respiration, growth, cell division, photosynthesis and food storage. The biomolecules such as carbohydrates, amino acids and lipids are categorized as primary metabolites as they are fundamental reactants and intermediates in carbon metabolism, nitrogen metabolism and associated pathways (Seigleret.al 1995). On the other hand, secondary metabolites are derived from primary metabolites in a very small amount, usually at a certain growth stage or to serve a specific function. Secondary metabolites provide the ability to defend against biotic and abiotic stress in plants. The mechanism of defence in plants varies according to the specific requirements of plants and is affected by physiological conditions, climate variations and environmental factors (Ballhornet.al 2009, Blank et.al 2012).

Plant secondary metabolites are broadly divided into three categories: Terpenoids, Alkaloids, and Phenolics (Savithramma et.al 2011). Each of these classes of secondary metabolites includes a huge array of compounds that have been found effective to treat different diseases, some of these compounds are- atropine, codeine, morphine, and nicotine, coming under alkaloids; linalool comes under terpenoids, while flavonoids, lignans and proanthocyanidins are categorized asphenolics. In the present review, secondary metabolites are studied thoroughly that include properties of secondary metabolites, biosynthetic pathways of secondary metabolites, structures and classification of secondary metabolites, and their pharmacological activities.Pharmacological activities of some secondary metabolites that have been used to treat various diseases are enlisted in the given table (Table 1).

Table 1: Pharmacological Activities of Secondary Metabolites.

Zhang et.al 1987

Vreeet.al 2000

Mwitaet.al 2012

Rhoades et.al 1976

Zhang et.al 2010

Description of classes of secondary metabolites

Secondary metabolites can be classified based on their chemical composition. These phytochemicals are divided into three broad categories-Alkaloids,Phenolics and Terpenoids, as already mentioned above. A brief description of each of these categories is given further.

Alkaloids

Alkaloids are nitrogen-containing compounds which are widely distributed among large number of plant families. These compounds can be found in the whole plant or sometimes in a specific part of the plant. It is a highly diverse and large group consisting of more than 1800 alkaloids, all of which are different from each other and have different chemical structures. Alkaloids contain one or more nitrogen groups in their chemical structures. A number of researches have shown potential pharmacological effects and curative properties of alkaloids against many human diseases and disorders. There isa huge list of alkaloids that are used in pharmacological activities. Some of the alkaloids are enlisted in the Table 2 given below (Egamberdie va et.al 2017).

Table 2: List of plants that contain pharmacologically important alkaloids.

Phenolic compounds

Phenolic compounds encompass a large number of phytochemicals consisting of one or more phenol groups. Phenols are responsible for the color, flavor, and taste of many herbs that are used in drinks and food. These secondary metabolites are highly valued for their pharmacological activities. Phenols are also used in many drugs due to their important pharmacological properties such as antioxidant, anti-microbial, anti-inflammatory, anti-cancer etc.  Phenols are classified on the basis of their different chemical structures, enlisted in Table3 given below, along with their respective pharmacological activities(Puneetet.al 2013, Montanheret.al 2007, Serafiniet.al 2010).

Table 3: Classification of phenolic compounds with their pharmacological activities.

Terpenes

Terpenes also form a diverse group of plant secondary metabolites that mainly consist of a five-carbon isoprene unit. Terpenes are classified according to the number of isoprene units in the molecule,the classes are summarized in Table4 (Hoffmann et.al 2003).

Table 4: Classification of terpenes.

Isovalenic acid

Essential oils

(C20)

(C30)

(C40)

Some secondary metabolites recognized for their pharmacological activities along with their general chemical structures and examples are enlisted in Table 5.

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Properties of phytochemicals and Pharmacological activities of plants

Plants survived on the planet for more than 400 million years. Plants cannot move from one place to another so they have to face lots of biotic and abiotic stress that are represented in Figure1. Plants neither have any active weapon to attack plant-eating animals or herbivores and microbes,nor do they have any shield to protect themselves from environmental stress. Secondary metabolites serve as the defense system of plants as they protect them from all the biotic and abiotic stresses (Asif 2015). Owing to their bio activity, secondary metabolites have been historically used not only in Indian medicines (Ayurveda) but also used traditionally in Kampo medicines, European medicines, American, Australian, and traditional medicine system of Africa.There is extensive research that has been carried out in search of novel and safe plant derived medicine. For example, Alorkpaet.al 2016 extracted out bio active compounds from Carica papaya leaves and investigated their antimicrobial activity. They identified the presence of many secondary metabolites such as alkaloids, flavonoids, saponins and glycosides and found that the extracts showed antimicrobial activity against human pathogenic bacteria and fungi. Plant derived extracts and compounds have many beneficial uses due to their biochemical, pharmaceutical and therapeutic properties. Some of the uses and beneficial properties of phytochemicals are enlisted in Table 6 given below.

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Table 6: Example of plant molecules that used for human health.

Secondary metabolites work alone or in combination with other compounds/ metabolites to cure diseases. Such combinations can enhance the efficacy of treatment of a disease which have been proven in many studies (Wink et.al 2015). Many phytochemicals have shown great success to defeat the dreadful disease like cancers (Secaet.al 2018, Rainaet.al 2014).The medicinal plant Hypericumper for atum is used for it anti-depressant, anti-inflammatory, antiviral, anticancer, and antibacterial properties. This plant contains fluoxetine and sertraline that cures depression, and other metabolites like hypericin, hyperforin, flavonoids and xanthones,which further enhance its medicinal value (Shakyaet.al 2017).Badgujaret.al in 2014 studied the use of Ficuscarica to treat many disorders that are related to the digestive, endocrine, reproductive, and respiratory system. Ficuscaricabelongs to angiosperm genera and consists of more than 800 different species. Phaleriamacrocarpa belongs to Thymelaeaceae family and has been traditionally used in Malaysia and Indonesia.Many diseases such as rheumatism, high blood pressure, diabetes mellitus, cancer, skin diseases, allergies, stroke, migraine, and hemorrhoids have been treated using this plant(Or et.al 2016). Echinacea purpurea, a medicinal herb with many secondary metabolites, has been used to cure anxiety, depression, cytotoxicity, and mutagenic disorders. However the use of this plant has been controversial as apart from its beneficial effects,it has potential side effects that are revealed by many studies, such as abdominal pain, nausea, angioedema, rash, and pruritus were reported in many patients after treatment (Manayiet.al 2015).Ziziphora species comprises a large number of flowering plants that belong to Lamiaceae family and further have been classified into 236 genera and 6900-7200 species. These plants are rich in essential oils or many secondary metabolites used in the field of pharmaceutical, medicinal, traditional, and folk medicines. This species is used to treat cold, fever, inflammation, intestinal disorders, insomnia, and cardiovascular malfunction for centuries (Mohammad hosseini et.al 2017). Secondary metabolites investigation on Thymus alternates showed that this species contains terpenoids, pentacyclic, and betulinic acid. Thephytochemicals of this plant have been used as flavoring agents while for medicinal purpose it has been found effective against cancer cell lines (Acquaet.al 2017).  PhyllanthusUrinarica L. genus belonging to Phyllantaceae family has been investigated asa rich source of lignans, tannins, flavonoids, phenolics, terpenoids, and other secondary metabolites. These secondary metabolites cure jaundice, diabetes, malaria, and liver disease. This plant also shows activity against cancer, microbial infections, and cardiovascular effects (Geethangili et.al 2018).

Some more investigations are there that represent the pharmacological activity of medicinal plants. Ipomoea batata L., commonly known as sweet potato, is widely consumed all over the world. It has many beneficial effects on human health as it contains many vitamins and phytochemicals. These phytochemicals also reveal activity against cancer, diabetes, inflammation, and antioxidants. Sweet potato also contains beta-carotene and a precursor of vitamin A that helps to cure night blindness and overcome the deficiency of vitamin A (Ghasemzadeh et.al 2016). South Indian grass that belongs to Cyperaceae species possesses large number of secondary metabolites that belong to classes alkaloids, flavonoids, steroids, phenols, and quinones. Out of all the phytochemicals, this grass contains alkaloids in a large amount and also shows many pharmaceutical activities that cure microbial infections and inflammation (Babuet.al2014). Capparisspinosa has lots of secondary metabolites that help to improve biomarkers of cardiovascular diseases and diabetes (Zhang et.al  2018). Glycyrrhizaglabra root revealed the presence of many phytochemicals. These phytochemicals are very beneficial for human health in the enhancement of memory, cures depression, helps to maintain the glucose level in the body, and shows many other pharmacological effects (Ali Esmail AL-Snafi 2018).Ocimum sanctum L. commonly known as Holy basil or Tulsi, is used in India as medicine sinceancient times as it helps to improve stress, inflammation, and cancer (Sing et.al 2018, Siva et.al 2016).

Genus Macaranga Thou.Belongs to Euphorbiaceae that comprises 300 species of plants. These species are mainly found in the tropics of Africa, Australia, Pacific regions, and Asia. This genus is traditionally used to treat cuts, sore, bruises, boils, and swelling (Magadulaet.al 2014). Pleurotussajorcajuis commonly known as mushrooms, are great source of primary and secondary metabolites and contain about 40-49% of protein. Apart from this mushrooms have anticancer, antidiabetic, antibacterial, and anti-inflammation activities. Mushrooms also play an important role in healing (Devi et.al 2015). Cymbopogancitratusstapf, Eugenia unifloraleaves and Citrullus vulgaris schard also contain many primary and secondary metabolites that are reported by Geethaet.al 2014, Daniel et.al 2014 and Hannah et.al 2015. Calophyllum Inophyllum belongs to clusiaceae family and it occurs above the high tide mark along the sea coast of Northern Australia and expanding throughout South India and S south-East Asia. This plant species contains lots of secondary metabolites in their root, stem, and leaves that help to fight against microbial infections, inflammation, and used in cosmetics (Sunduret.al 2014).Morusalba belongs to Moraceae family and contains many medicinal plants, and has numerous applications in various fields such as agriculture, food, cosmetic and pharmaceutical industries. Pharmacological activities of these plants help in the treatment of an inflammatory condition, gastrointestinal disorder, cancer, and microbial infections with the help of many secondary metabolites (Hussainet.al 2017). Another study was performed by B. J. Divya and other scientists in 2017 that worked on Allium sativum. Allium sativum belongs to the family Amaryllidaceae and commonly known as garlic. In this study, to extract secondary metabolites from garlic cloves different chemicals and techniques were used. Hexane, ethyl acetate, methanol and water revealed steroids, alkaloids, flavonoids and other bioactive compounds. These phytochemicals of garlic cloves have been used to treat several infections from ancient period.

Momordicadiocca commonly known as Kakrol or spiny gourd is mainly found in India and Bangladesh, and is not only used as medicinal plant but also consumed as vegetable on a large scale. This plant consist of many minerals compositions, preventive, protective and curative agents in their root, stem and fruit. This plant includes many pharmacological activities such as anti-oxidant, analgesic, nephron protective, neuro protective, antiallergic, antimalarial, hepato protective and antihe patotoxic activity  (Talukdar and Hossain 2014). Genitinais an important genus of Gentianaceae family that comprises 400 species and distributed all over the world. Based on investigation, this plant is used traditionally in Iran. This plant species consist lots of phytochemicals such as gentipicroside, xanthones, monoterpenes, alkaloids and flavonoids. This plant species has lots of promising bioactive agents are present that cure menstrual over bleeding, animal venom poisoning, infected wounds, injuries, vitiligo and swelling of liver, spleen, stomach and sprain of muscles (Mirzaeeet.al 2017). Some more medicinal plants with their pharmacological activities are summarized in Table 7 given below.

Table 7: Pharmalogical activities of medicinal plants with their common names.

By using advance research technologies, scientists are working hard to produce rich variety of phytochemicals under laboratory conditionsusing plant cell cultures (Yueet.al 2014). Guerrieroet.al 2018,culturedArtemisia, Coffeaarabica L. and Urticadioica L. to produce large amount of secondary metabolites terpenoids, alkaloids and phenolic compounds respectively. Many trans genes such as rol ABC genes are also used by Kianiet. al. 2015, to increase the production of phytochemicals. Secondary metabolites are extracted from many plant species and used to make many drugs that cures different disorders. There are number of drugs that are composed of heterogenous phytochemicals and are available in market. Some of the drugs are enlisted in Table 8 (Garnatjee.al 2017). These drugs not only cure the diseases but also solve the problem of drug resistance and provide a new path for scientist to discover more drugs to fight against dreadful diseases (Anandet.al 2019).

Table 8: Commercially available plant derived medicines.

Conclusion

Plants are a valuable resource that yields numerous phytochemicals which can be used as potential drugs to treat and prevent many human ailments and diseases. These drugs also provide a safer alternative to allopathic medicines overcoming the problems of drug resistance, toxicity and side effects. The bioactivity of plant extracts and their component phytochemicals have been studied extensively and put to use since ancient times. Novel approaches are now being explored for enhanced production and efficient yielding of secondary metabolites through cell and tissue cultures. Advances in cell line culture allowing in-vitro bioactivity testing also opens avenues for faster drug development.

Acknowledgment

We sincerely acknowledge the contribution of Dr. Shilpa S. Chapadgaonkar, Associate Professor, Department of Biotechnology, MRIIRS, Faridabad, India, in form of her valuable inputs to the co-authors in preparing the manuscript.

Conflicts of Interest

The authors declare that there is no conflicts of interest.

Funding Source

There is no funding source

References