Chemical Constituents of Dioscorea Villosa and Eschscholzia Californica

“Choose two medicinal plants and research their known chemical constituents. Explain, as far as possible, how their phytochemistry leads to their medicinal actions.”

 

Introduction

This essay will explore some of the herbal constituents of the medicinal plants Dioscorea villosa and Eschscholzia californica. It will consider the chemical structure and major functional groups of the more researched chemical constituents within the plants and also discuss any known actions for the constituents and relay any indications for the actions or toxicity from the structure of the chemical compounds.

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Dioscorea villosa or wild yam, commonly known as colic root or rheumatism root (Ganora, 2009) is used in herbal medicine with the understanding that it is a plant that possesses actions on the body such as antispasmodic, anti-inflammatory, anti-rheumatic, hepatic, cholagogue and diaphoretic (Hoffman, 2003). Bone (2003) also attributes this plant to be oestrogen-modulating. We will focus on the actions of hepatic, cholagogue and oestrogen-modulating. Dioscorea is of particular interest due to the fact that Dioscorea Mexicana (from the same family) was in fact the original source of compounds used for the semi-synthesis of steroid drugs such as cortisone, prednisone and the androgens and estrogens (Ganora, 2009). Heinrich (2016) mentions the great need in the pharmaceutical industry for steroids and states how this is in fact met from using the plant sterol diosgenin from wild yam.

In regards to oestrogen-modulating, Ganora (2009) highlights how in fact the steroidal saponins within the yams do not act as act as ‘hormone precursors’ inside the body, despite what can be read in some marketing literature. This is due to the fact that the body in fact does not have the enzyme needed to convert these compounds into sex hormones. This does not mean that the compounds do not influence hormonal balance, but it will be in other ways. Bone (2003) discusses in more detail how the steroidal saponins or their metabolites may exert oestrogenic effects as they may be able to bind with oestrogen receptors in the hypothalamus. This would mean that, in pre menopause, the potential interaction of these compounds with receptors in the hypothalamus or pituitary displaces oestrogen from the receptors and blocks oestrogen feedback thus meaning that the body will think that oestrogen levels are lower than what they are and will respond by increasing FSH and oestrogen. This could therefore indicate that steroidal saponins such as dioscin and diosgenin may help to alleviate symptoms of oestrogen withdrawal in the peri and post menopausal low oestrogen environment. It is believed that some menopausal symptoms, like hot flushes, are initiated via the hypothalamus.

Hepatic is quite unspecific as an action, other than indicating a herb’s affinity for the liver. Pengelly (2004) discusses how diosgenin, as the aglycone of dioscin, has been shown to reduce cholesterol absorbed from the diet, which leads to increased hepatic synthesis and subsequent excretion of cholesterol in the faeces. Mills & Bone (2003) similarly discuss how steroidal saponins, such as diosgnenin, resemble cholesterol in their chemical structure which may have a profound effect on cholesterol metabolism in the liver. They go on to state that “Diosgenin interferes with the absorption of cholesterol of both dietary and endogenous origin; such interference is accompanied by increased rates of hepatic and intestinal cholesterol synthesis. Diosgenin also enhances cholesterol secretion into bile which, in conjunction with the unabsorbed cholesterol, results in increased faecal excretion of cholesterol (neutral sterols) without affecting excretion of bile acids.” (Mills & Bone, 2003, p.45) This also indicates Dioscorea’s cholagogue action. In some pharmacological research, Bone (2003) cites that with oral administration of diosgenin, an experimental model had reduced intestinal inflammation and normalized bile secretion. In addition, Accatino (1998) demonstrated how diosgenin reduced the acute cholestatic effect induced by estradiol in rats.

Within the research, although saponins are gastrointestinal irritants (Mills & Bone, 2003), there was no indication for toxicity of these constituents.

Diosgenin – Diosgenin is the aglycone basis for the steroidal saponins found in Yam species, including dioscin (Ganora, 2009)

PubChem (2019) describes the chemical structure as “Diosgenin is a sapogenin that is spirostan which is substituted by a hydroxy group at the 3beta position, contains a double bond at the 5-6 position, and has R- configuration at position 25. It has a role as an apoptosis inducer, an antiviral agent, an antineoplastic agent and a metabolite. It is a 3beta-sterol, a spiroketal, a hexacyclic triterpenoid and a sapogenin. It derives from a hydride of a spirostan.”

Dioscin – Steroidal saponin (Mills& Bone, 2000)

PubChem (2019) describes the chemical structure of Dioscin as “a spirostanyl glycoside that consists of the trisaccharide alpha-L-Rha-(1->4)-[alpha-L-Rha-(1->2)]-beta-D-Glc attached to position 3 of diosgenin via a glycosidic linkage. It has a role as a metabolite, an antifungal agent, an antiviral agent, an antineoplastic agent, an anti-inflammatory agent, a hepatoprotective agent, an apoptosis inducer and an EC 1.14.18.1 (tyrosinase) inhibitor. It is a spirostanyl glycoside, a spiroketal, a hexacyclic triterpenoid and a trisaccharide derivative. It derives from a diosgenin. It derives from a hydride of a spirostan.”

 

Eschscholzia californica, commonly known as California Poppy, is from the Papaveraceae family. It is used in herbal medicine for its actions of nervine, hypnotic, antispasmodic and anodyne (Hoffman, 2003) It is also known as a mild sedative (Bone, 2003). These actions are more complex to integrate to a constituent as they have more general actions on the nervous system which encompasses many systems working together. Ganora (2009) describes it as a “herb that is used as an antispasmodic nervine sedative for anxiety and insomnia.” (Ganora, 2009, p. 160)

California poppy is known to contain a complex mix of isoquinoline alkaloids including various aporphines as well as many isoquinoline derivative: pavines (eschscholzidine and californidine), sanguinarine and chelerythrine (Ganora, 2009). This essay will focus of eschscholtzidine, sanguinarine and chelerythrine. The class of isoquinoline alkaloids are large and diverse. Bone (2003) states that Isoquinoline alkaloids are known to possess in vivo sedative activity. Structurally they have molecules based on tetrahydroisoquinolone nucleus which is two joined six-membered rings. One of the rings contains a nitrogen atom in position 2. Many of these alkaloids are tetracyclic or pentacyclic however varying numbers and kinds of rings can be incorporated. Biosynthetically they are derived from the amino acids phenylalanine and or tyrosine. There are many subclasses of isqoquinoline alkaloids such as aporphine and protoberberines. Protoberberines are based on a benzyltetrahydroisoquinoline ring system with an extra carbon atom, the majority are tetracyclic and bear one or two methylenedioxy groups. These alkaloids are found within California poppy (Ganora, 2009)

Considering the anodyne action of California poppy, Yashpal, (1995) demonstrates how chelerythrine, a well known protein kinase C inhibitor, caused significant reductions of nociceptive responses when the activation of protein kinase C in the spinal cord dorsal horn neurons contributed to persistent pain following noxious thermal and chemical stimulation.

Looking at the nervine aspect of the herb and its attributed anxiolytic actions also, a study found that some alkaloids administered through a hydroethanolic extract of eschscholzia (especially N-methyllaurotetanine) were able to affect serotonin receptors in vivo (Ganora, 2009). On a similar theme alkaloids from California poppy enhanced gamma-aminobutyric acid (GABA) binding to rat brain synaptic membrane receptors which could indicate a benzodiazepine-like activity. Although not specifically attributed to clear constituents, California poppy exhibited dose-dependent binding to benzodiazepine receptors and displaced the benzodiazepine flurazepam from the receptor. (Bone, 2003)

With regards to the sedative nature of California poppy, Bone (2003) describes how California poppy extract inhibits the enzymatic degradation of catecholamines and the synthesis of epinephrine in vitro. He attributes the preservation of high levels of catecholamines to explaining the sedative and antidepressant activity of California poppy.

Although California poppy is a member of papaveraceae, it is considered a safe herb and through research there was no indication of toxicity from the structure of the chemical compounds. In fact a Canadian study suggests that chelerythrine can attenuate the development of morphine dependence. (Mills & Bone, 2003) However on PubChem isolated sanguinarine is considered toxic. This is when it is important to remember that there are hundreds, if not thousands, of constituents at work within a whole plant so sanguinarine may be toxic in isolation but within the plant as a whole, there is no indication of toxicity. In fact Ganora (2009) states that ‘Sanguinarine is antibacterial, antiviral, antifungal and anti-inflammatory. ‘ (Ganora, 2009, p.161)

Eschscholtzidine

PubChem (2019) describes the chemical structure of Eschscholtzidine as “a heteropentacyclic isoquinoline alkaloid having a tertiary amino bridging group. It is an isoquinoline alkaloid, a tertiary amine and an organic heteropentacyclic compound.”

Sanguinarine

PubChem (2019) explains that “Sanguinarine is a benzophenanthridine alkaloid, an alkaloid antibiotic and a botanical anti-fungal agent.

Sanguinarine is banned by FDA. Sanguinarine is a quaternary ammonium salt from the group of benzylisoquinoline alkaloids. It is extracted from some plants, including bloodroot (Sanguinaria canadensis), Mexican prickly poppy Argemone mexicana, Chelidonium majus and Macleaya cordata. Sanguinarine is a toxin that kills animal cells through its action on the Na+-K+-ATPase transmembrane protein. Epidemic dropsy is a disease that results from ingesting sanguinarine.”

Chelerythrine

PubChem (2019) describes the chemical structure of Chelerythrine as “a benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae. It has a role as an EC 2.7.11.13 (protein kinase C) inhibitor, an antibacterial agent and an antineoplastic agent. It is a benzophenanthridine alkaloid and an organic cation.”

 

Word count – 1529 words

Reference List

         Accatino, L et al. (1998)Effects of diosgenin, A plant‐derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat,

Hepatology 28(1):129-140

Bone, K. (2003) A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient, USA: Elsevier Ltd.

Ganora, L. (2009) Herbal Constituents: Foundations of Phytochemistry, USA: Herbalchem Press

Hienrich, M et al. (2016) Fundamentals of Pharmacognosy and Phytotherapy, China: Elsevier Ltd.

Hoffman (2003) Medical Herbalism, USA: Healing Arts Press

Mills & Bone (2000) Principles and Practice of Phytotherapy, UK: Churchill Livingstone

molview.org (no date) Diosgenin, Available at: http://molview.org/?cid=99474 (Accessed 12th April 2019)

molview.org (no date) Sanguinarine, Available at: http://molview.org/?cid=5154 (Accessed 12th April 2019)

molview.org (no date) Chelerythrine, Available at: http://molview.org/?cid=2703 (Accessed 12th April 2019)

Pengelly, A. (2004) The Constituents of Medicinal Plants, UK: CABI Publishing

PubChem, (2019) Chelerythrine, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/chelerythrine (Accessed 24th April 2019)

PubChem, (2019) Dioscin, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Dioscin (Accessed 24th April 2019)

PubChem, (2019) Diosgenin, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/diosgenin (Accessed 24th April 2019)

PubChem, (2019) Eschscholtzidine, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Eschscholtzidine(Accessed 24th April 2019)

PubChem, (2019) Sanguinarine, Available at: https://pubchem.ncbi.nlm.nih.gov/compound/sanguinarine (Accessed 24th April 2019)

Yashpal, K et al. (1995) Noxious thermal and chemical stimulation induce increases in 3H-phorbol12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C, Journal of Neuroscience 1995, 15 (5 Pt 1): 3263-3272

Bibliography

Gafner, S. et al (2006) Alkaloids from Eschscholzia californica and Their Capacity to Inhibit Binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A Receptors in Vitro, J Nat Prod 2006; 69(3): 432-435.

Neal, M (1997) Medical Pharmacology at a Glance, UK: Blackwell Science Ltd.