Figuring out figs…
- Fresh figs in a conical flask with a Pasteur pipette. The molecule shown is ferulic acid, which is present in figs and thought to have anticancer properties.
Figs are a versatile fruit with a unique and earthy flavour. They can be cooked in pastries, reduced into chutney or simply eaten fresh. Fig latex can be used to soften meat, coagulate milk and treat skin infections and here we examine the chemistry of fig latex and its medicinal properties.
1. Figs grow on a species of plant called Ficus carica. Ficus carica originate from West Asia and fossil records suggest that figs are one of the oldest fruits to be cultivated by humans. They have an oval shape and an inverted flower structure, consisting of a central cavity, which is anthropoid and fleshy, enclosed in a thick and leathery skin. When figs are cut at the stem, a thick and milky substance seeps out of the figs, which is called fig latex. The picture above shows fresh figs, cut into sections and placed in a large conical flask. Conical flasks are typically used in the laboratory for mixing and boiling liquids. The narrow neck makes them ideal for these tasks as it helps to avoid spillages and prevents solvents from evaporating easily. The smaller conical flask contains a model of ferulic acid, one of the main constituents of fig latex.
Interestingly, figs rely on wasps to facilitate reproduction. Fig wasps mate inside the fig and then females deposit their eggs inside the flowers. The females deliver pollen to neighbouring figs but the wingless males die inside the figs after mating. Fortunately, chemicals decompose the wasps that die inside the fruit – perhaps this is the origin of their ‘unique and earthy’ flavour…! The mutually dependent relationship between fig trees and fig wasps is described as symbiotic. There are some interesting images of this process here.
Figs in bloom.
The medicinal properties of figs have been reported in many historical texts. In the Bible, figs are recommended as treatment for boils (2 Kings 20:7) and Mohammed is quoted in the Qur’an praising the medicinal properties of figs: “…eat from these fruits for they prevent haemorrhoids, prevent piles and help gout”. Over one thousand years later, a plethora of scientific papers has been published confirming that figs are effective at treating a variety of skin disorders.
2. A study in 2011 found that Ficus carica latex contains a variety of organic acids, including ferulic acid and caffeic acid (figure 2). Organic acids have a hydrocarbon component bonded to an acid group. The acid group can lose a hydrogen ion (H+) when dissolved in solution – this is why acids are sometimes referred to as ‘proton donors’. An example of an organic acid is acetic acid, which is the main component of vinegar (Scheme 1). In this example, the acidic group is a carboxylic acid. Other common organic acids include citric acid, caffeic acid and oxalic acid. To find out more about these compounds, check out our blog posts on apples and rhubarb.
Scheme 1. Acetic acid in solution, showing the loss of its proton. The ease with which an acid loses its proton is a measure of the strength of the acid.
The reaction arrow in Scheme 1 is drawn going both forwards and backwards because the reaction is reversible. The system is said to be in equilibrium. The strength of an acid is determined by the position of equilibrium. When the position of equilibrium lies towards the products (the loss of H+), the acid is a strong acid. For weak acids, the position of equilibrium lies towards the reactants. Chemists use these ideas about equilibrium position to quantify the strength of acids by using pKa values. The smaller the pKa value a compound has, the stronger the acid is. Fortunately, organic acids such as acetic acid and ferulic acid have pKa values of around 5, making them weak acids. So, you don’t need to worry next time you have figs for breakfast!
Table 1. Structures of three organic acids and their pKa values: acetic acid (for reference), ferulic acid and caffeic acid (which are both found in fig latex).
3. The aforementioned study reported that a group of organic acids extracted from fig latex by hexane exhibited antiviral activity against the herpes virus (HSV-1) in vitro. Unfortunately, the acids were not tested individually so it’s not possible to know which of the chemicals exhibits antiviral activity or if a few of the molecules work in combination with one another. Details of the experiment can be read here: H. L. Aref, B. Gaaliche, A. Fekih, M. Mars, M. Aouni, J. P. Chaumon, K. Said, Natural Product Research, 2011, 25, 310.
The authors of the report concluded that ferulic acid is the most likely molecule to have antiviral properties. Ferulic acid is present in many botanical species and its medicinal properties were first employed by herbal chemists in China. It can be synthesized in the lab by condensation of vanillin with malonic acid (Scheme 2 shows the net reaction). Condensation reactions are popular in organic chemistry. They comprise of two large molecules joining together in the presence of a catalyst and releasing a small molecule. In this reaction, the catalyst used is benzylamine (J. Sci. Food. Agric. 2004, 84, 1261–1269). Benzylamine acts as a base to convert malonic acid into an enolate. Benzylamine is ideal for this reaction because it is bulky and therefore will not act as a nucleophile. This reaction produces a mixture of cis-ferulic acid and trans-ferulic acid.
Scheme 2. The net condensation reaction between malonic acid and vanillin in production of ferulic acid. The first step shows the deprotonation of of malonic acid and the formation of an enolate which then reacts with vanillin. A mixture of isomers is formed.
A slice of fig in a conical flask
In 2001, another group of chemists extracted a mixture of 6-O-acyl-beta-D-glucosyl-beta-sitosterol compounds from fig latex and found that the mixture had inhibitory effects on the proliferation of cancer cells. The group developed this study further by preparing these compounds synthetically. They found that 6-0-palmitoyl-β-D-glucosyl-β-sitosterol inhibited the growth of Raji cells by approximately 50%. Raji cells are commonly used in biomedical science to improve understanding of cell malignancies. The anti-cancer activity of this compound was also tested on leukaemia and lymphoma cells. It was found to have similar effects. (S. Rubnov, Y. Kashman, R. Rabinowitz, M. Schlesinger and R. Mechoulam, J. Nat. Prod., 2001, 64, 993–996). Not only does Ficus carica latex appear to possess anti-cancer properties, but more recent work has revealed that it may also have anti-hypertensive properties too. A significant reduction in blood pressure was observed when glucose induced hypertensive rats were treated with aqueous F. carica extract. More details can be found here.
Sadly, fig latex is present in the fruit in only very small quantities and one would have to consume hundreds of figs in hope of experiencing any health benefits. However, figs are rich in fibre and minerals and besides… they are delicious.
Contributors: Olivia Hogan (research, writing, photos, images), Angus Voice (photos, editing, additional information), Natalie Fey (images, final edit).
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