Phytochemistry and Pharmacognosy Chemical Constituents

Choose two medicinal plants from the list below to research their known chemical constituents. Explain, as far as possible, how their phytochemistry leads to their medicinal actions.

Introduction

Phytochemistry and pharmacognosy are the disciplines that research the presence and activity of chemicals produced by plants. Usually the chemicals under scrutiny result from the secondary metabolism of plants. While primary plant metabolism is directly involved in nutrient cycling and is therefore essential to basic survival, secondary metabolites are usually involved in the plant’s defence mechanisms against threats found in its environment. Both types of pathway are anabolic (Pengelly 1996). The interconnected nature of earth’s biosphere has led plants to innovate a vast array of chemical constituents throughout evolutionary history. Plants and animals are both eukaryotic organisms, and many metabolic pathways share similarities (Pengelly 1996). Many chemicals synthesised by plants act pharmacologically on metabolic pathways in animals. Practitioners of herbal medicine study the ways in which these chemicals promote health in humans.

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Phytochemistry and pharmacognosy bridge the gap between the traditional, vitalist approaches to herbal medicine and the modern evidence-based methods encouraged by the biomedical tradition (Pengelly 1996). Researchers harvest raw plant material and conduct extractions – usually aqueous or ethanolic – and characterise the chemicals they extract based on their chemical structures. Bonding, polarity and three-dimensional conformation, among other qualities, determine the functions conferred on chemicals by their structures.

While plants may contain hundreds of chemicals belonging to classes such as alkaloids, flavonoids, tannins and mucilages, only certain constituents have been subjected to research that investigates the chemical basis for their traditional medicinal uses. These constituents are referred to as the known active constituents. The structures and resulting properties of pharmacologically active constituents can help explain how certain constituents act on particular human tissues, organs and systems. This essay explores the constituents and resulting actions and indications of Tussilago farfara and Agrimonia eupatoria, two medicinal plants found throughout Eurasia and North America.

Tussilago farfara: Important Constituents, Actions and Indications

T. farfarabelongs to the Asteraceae family and is one of the 3% of all angiosperms that contains pyrrolizidine alkaloids (PAs) (Yang & Lin 2002). It is prominent in the Chinese materia medica. Its English common names include coltsfoot, coughwort, horsehoof and foal’s foot. The flower buds and leaves are the main parts used for medicinal purposes. Traditionally and in contemporary herbal medicine, the it is used mainly to treat respiratory conditions including bronchitis, asthma, whooping cough, silicosis and chronic emphysema (Zhao et al. 2014, Hoffman 2003, Priest & Priest 1982).

Li and colleagues (2013) write that the phenolic constiutents in T. farfara are experimentally linked with its antitussive and expectorant actions. Rutin, a glycoside of quercetin and a yellow pigment, is a flavonol (Ganora 2009) found in T. farfaraas well as many other medicinal plants. Flavonols have at least one hydroxyl and ketone group on the central, unsaturated pyran ring of the flavonoid backbone. Flavonoids are produced by the plant’s secondary metabolism to protect their tissues from scavenging free radicals and exhibit similar antioxidant activity in humans. Rutin has anti-inflammatory, anti-viral and anti-bacterial activities (Li et al. (2013) probably linked to its unsaturated phenolic structure. Rutin itself has not been linked to expectoration but may have synergistic effects (ibid.) that promote overall health and convalescence from a respiratory condition.

Chlorogenic acid, or 3-caffeoylquinic acid, is a phenylpropanoid with probable antidiabetic action (Ganora 2009, Gao et al. 2008, Li et al. 2013). Phenylpropanoids are also known as cinnamic acid derivatives and belong to the superclass, phenolic acids. They have carboxyl groups and derive from the parent molecule cinnamic acid, which has a benzene ring bonded to two hydroxyl groups (Ganora 2009). Chlorogenic acid and other cinnamic acid derivatives may accomplish their antidiabetic action by inhibiting mammalian a-glucosidases (Gao et al. 2008), thereby correcting impaired glucose tolerance associated with type 2 diabetes (Van de Laar 2008).

Hoffman (2003) uses T. farfaraas a demulcent, anti-inflammatory expectorant herb due to the presence of mucilages. He also notes the presence of significant concentrations of zinc, which may have therapeutic benefit in respiratory conditions. Priest & Priest (1982) and Cook (1869) also note the demulcent, relaxant and diffusive properties of T. farfarafrom a pragmatic practitioner perspective.

T. farfara, like most other medicinally used plants, contains far more constituents than those explained in depth here. The essential oil content of the aerial parts, for example, is useful for topical use and internally for antispasmodic action (Judzentiene & Budiene 2011). Essential oils are usually monoterpenes and often have antiseptic actions (Ganora 2009), making them beneficial synergistic constituents for respiratory conditions. Like many plants, T. farfara also contains tannins (Hoffman 2009), phytosterols (Kikuchi & Suzuki 1992), triterpenes and pyrrolizidine alkaloids (Zhao et al. 2014), discussed below.

Toxicity in Tussilago farfara

Relative to other medicinal plants, a fair amount of phytochemical research has been conducted on T. farfara, especially in Asia and Eastern Europe, perhaps due to its infamous, and potentially toxic, PA content. PAs are recognisable for their necine system, composed of two fused five-carbon rings that each bind an atom of nitrogen (Ganora 2009). The more toxic PAs have a double bond in the ring system, rendering them more reactive than alkaloids that have only single bonds (ibid.). PAs must be metabolically activated by the liver before they become toxic. Yang and Lin (2002) identify two major pathways by which PAs generate toxic pyrrolic metabolites in the liver: hydrolysis and N-methylation (Yang & Lin 2002). In severe toxicity, tumours and genotoxic effects can result from lipid peroxidation, DNA cross-linking and DNA protein cross-linking by PAs. Senecionine and senkirkine have been extracted from T. farfara, two chemicals which Yang and Lin class as tumourigenic alkaloids. Their structures are illustrated below.   

Fig 1. Pyrrolizidine alkaloids found in T. farfara(sourced from Yang & Lin 2002). Both chemicals contain ketone and methyl functional groups. senkirkine would be less polar that senecionine due to the former’s additional methyl group attached to the nitrogen in the necine system.

T. farfaraalso contains the PA tussilagine (Natural Medicines 2018b). As a result of its PA content, T. farfarashould be prescribed for a maximum of 4-6 weeks per year (Hoffman 2003). However, Li and colleagues (2013) reported that the PA content observed in their hot water extract was so low that a nuclear magnetic resonance (NMR) peak barely observed. It is impossible to generalise, however, given the heterogeneity of raw plant samples due to variation in environment. In vivo studies of PA toxicity have indicated that glycyrrhizin and glycyrrhetinic acid from Glycyyrrhiza glabrareduced the hepatotoxic activity of PAs. This may be a moluecular basis for the custom in Traditional Chinese Medicine (TCM) of adding G. glabra to formulations to harmonise the medicine’s action in the body (Yang & Lin 2002).  

Agrimonia eupatoria: Important Constituents, Actions and Indications

A. eupatoria of the rosaceae family has an affinity for the mucous membranes (Lyle 1932) which can be directed towards action on specific organs or tissues when synergistically combined with other herbs (Pengelly 1996). Infections, inflammation and irritation afflict the mucous membranes, and A. eupatoria’s tannin, essential oil, flavonoid glycoside, polysaccharide and glycosidal bitter content lend the herb its astringent, tonic and vulnerary actions, antiseptic (Hoffman 2003). It is therefore indicated in conditions including haematuria, diarrhea (Ghaima 2013), bloody stool, uterine haemorrhage, productive coughs (Cook 1869), rheumatism, arthritis, urinary incontinence, cystitis, laryngitis and topically for wounds and bruises (Hoffman 2003, Priest & Priest 1982).

The aerial plant parts are most frequently used. It is well known for its anti-inflammatory and antioxidant actions, probably linked to its polyphenolic content. A. eupatoria extracts have experimentally increased total antioxidant capacity (TAC) in the plasma of test subjects and after 30 days levels of inflammatory markers had significantly decreased (Ivanova et al. 2013). Flavonols rutin, quercetin and kaempferols and a range of flavanols are responsible for these actions due to their unsaturated phenol ring structure, the ketone groups of the flavonols and protein binding reactive groups of the catechin based proanthocyanidins (Ganora 2009, Al-Snafi 2015, Correia et al. 2006). Condensed tannin (proanthocyanidin) content of A. eupatoria has been measured at between 3-21% in a range of extracts (Al-Snafi 2015).

Ethanolic and aqueous extracts of A. eupatoria have different chemical profiles and therefore have different actions on tissues. Ethanolic extracts have a stronger antibacterial effect than the aqueous extracts (ibid., Ghaima 2013). Pure water is more polar than water mixed with ethanol (Ganora 2009) and is therefore more effective at drawing the monoterpene volatile oil components out of the plant tissues. The volatile oils in A. eupatoria have experimentally been antibacterial activity against Staphylococcus aureus, Streptococcus spp., Bacillus subtilis and even Mycobacterium tuberculosis, as well as antiviral action against Hepatitis B and Columbia SK virus (Al-Snafi 2015). Tannins also act against infections by inhibiting microbial enzymes, adhesion and transport proteins (Ghaima 2013). Tannins are generally large polyphenolic molecules with many hydroxyl groups bonded to the phenol rings. Hydroxyl groups make molecules more reactive because of their redox potential, making them likely to structurally alter proteins and therefore alter or inhibit their function. A. eupatoria is therefore indicated in infections of the mucosa, and practitioners say that it is safe for use in children and older people and has not been found to exhibit any toxicity (Natural Medicines 2018a, Hoffman 2003).

Conclusion

Given the evolutionarily linked nature of plant and animal metabolisms, it comes as little surprise that phytochemicals exert a wide range of actions on human physiology and can promote health and healing in diseased tissue states. The very chemicals that herbs like A. eupatoria and T. farfara synthesise to maintain their own immunity and health also serve medical herbalists in their practice.

References

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         Hwangbo, C. et al. (2009) The anti-inflammatory effect of tussilagone, from Tussilago farfara, is mediated by the induction of heme oxygenase-1 in murine macrophages. International Immunopharmacology. 9(13-14); 1578-8

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