Hans & Elzbieta Brand continue their discussion on the opportunities for the use of anthraquinones, and also naphthoquinones in the design of functional C&T products, a clear demonstration of the reduction in boundaries between C&T and pharmacy
St John's wort (INCI: Hypericum perforatum) - during the dark ages the flowers were collected on the day before St John's day (23 June) and hung in the house to ward off evil spirits, or to drive out the devil from those who were thought to be possessed. It was believed that if a person stepped on the plant after dark they would be transported by a magical horse around the heavens and returned to earth only as the sun rose; a good excuse for staying late in the local tavern!
It is also claimed that on 29 August, the day on which John the Baptist was beheaded, blood-red stains appear on the leaves of St John's wort. The red oil produced on grinding the plant probably gave rise to associations with Christian virtues in that it symbolises the spilled blood of Christ and thus became a weapon against the devil.
The red colour of St John's wort comes from a dianthron with the name hypericin and is present in the oil at ~0,12-0,15%. Also present are related substances such as pseudohypericin (one of the methyl groups has been converted into a hydroxymethyl group) and emodinanthranol (which is also found in Aloe barbadensis).
St John's wort oil has been demonstrated to have a similar efficacy as selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), sertraline (Zoloft) and paroxetine (Paxil). Needless to say these ingredients are strictly forbidden in personal care and cosmetic products, but Hypericum perforatum is not. Taking St John's wort extract improves mood, decreases anxiety and somatic symptoms and decreases insomnia related to mild to severe major depression. It was originally thought that hypericin was responsible for the anti-depression activity, but it is now believed that another ingredient present in St John's wort is the active principle - hyperforin. From a molecular point of view, hyperforin is an extremely interesting species. It has a bicyclic structure with an enol structure, stabilised by a carbonyl group, with four isoprene side chains, betraying its biosynthetic pathway (via mevalonic acid). St Johns's wort can be considered an option for short-term treatment of mild depression.
We prefer to discourage our ever expanding reading audience from going into the treatment of mental disorders by means of personal care and cosmetic products, but isn't it true that the use of our products contributes to the wellness of users? A decent amount of St John's wort oil in your cosmetic cream or gel and you can improve the feeling of well-being of your customer. Call it an endorphin-like activity, which is a contraction of the word endogenous morphine. In other words, morphine-like products that are produced in the body, that interact with the opiate receptors when the time is right.
Endorphins improve your mood, relieve pain, make you sleep well etc. These are peptides produced by the pituitary gland and the hypothalamus and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. In other words, they might work as natural pain killers. Three groups of endorphins are known: the a-, b- and g-endorphin; b-endorphin is the most active in pain relief, made of a backbone of 31 amino acids. The production of b-endorphin is stimulated by capsaicin, one of the active species of Piper nigrum. Capsaicin is well-known in the personal care and cosmetic industry for its pain relief abilities, but you have to be careful not to use it on damaged skin. There is now also sufficient evidence that during acupuncture a significant amount of b-endorphin is released, giving the patient the feeling that the treatment is beneficial and a general feeling of well-being becomes apparent, frequently associated with healing.
St John's wort also contains other active species, in particular flavonoids derived from quercetin.
Hyperoside also occurs in coltsfoot (INCI: Tussilago farfara) and has major anti-ageing/anti-wrinkle activity, next to its profound activity to reduce capillary fragility and elastase inhibitory qualities. Isoquercitrin is a use-ful anti(retro)viral agent; for quercitrin no activity has (yet) been reported. Coltsfoot is under scrutiny, and already forbidden in a number of countries in food supplements, because of the presence of pyrrolizidine alkaloids such as senkirkine and senecionine.
Another botanical source for anthraquinoids is Senna extract (INCI: Cassia italica). The applicable parts of senna are the leaves and the fruits. Both are stimulant laxatives. Senna contains dianthrons comparable to hypericin (condensed anthraquinones) named sennosides A & B, next to minor amounts of sennosides C & D (whereby one of the carboxyl groups is present as a hydroxymethyl group). The dianthrone glycosides are not present in the fresh leaf, but appear to be formed during the drying process. Hydrolysis of sennoside A results in the formation of rheinanthrone (3-carboxy-1,8-dihydroanthraquinone). Sennocide, frequently offered as the calcium salt, is a well-established laxative.
Sennosides, next to aloe-emodin, emodin and rhein are also found in rhubarb (INCI: Rheum undulatum). Botanically the more common names are Rheum palmatum (Chinese rhubarb; Turkey rhubarb) and Rheum rhabarbarum (wild rhubarb). Both plants belong to the family Polygonaceae. Rhubarb has very broad leaves and elongated, often reddish petioles (leaf stalks). The petioles of rhubarb are edible, though the leaves are very toxic. The roots and rhizomes of Rheum palmatum and the roots of Rheum rhabarbarum are used in medicinal treatments. Chinese rhubarb, also named Dahuang, is medicinally considered stronger than American rhubarb. It is interesting to note that several rhubarb species are excellent providers for stilbene derivatives, products going back to the early times of oral contraceptives.
The toxicity of the leaves of rhubarb originates from the presence of large amounts of oxalic acid. Interestingly, oxalic acid in personal care and cosmetics is allowed to a maximum of 5%, but only in hair care products, accompanied with the wording “for professional use only”. Strange really when you can buy as much of the stuff as you like from your local greengrocer or supermarket.
Dyed in the grain
The French name for The Netherlands is Les Pays-Bas. Literally translated that means the ‘low lands’, and the reasoning behind the name is pretty obvious. The name Brazil comes from the Portuguese word ‘braza’ meaning red. In early Portuguese times quite a bit of Brazilwood (Caesalpinia brasiliensis) was imported from South America to obtain a red dye to paint textiles. Brazilwood, also named redwood, was quite abundant on the Brazilian coasts, hence the name Brazil. There are even dyestuffs with the names brazilin and brazilein.
The main insoluble redwoods are sandalwood (Pterocarpus santalinus; indigenous to south India); narrawood (Pterocarpus indicus; Burma, Philippines), barwood (Pterocarpus soyauxii and Pterocarpus erinaceus) and camwood (Baphia nitida; West Africa). These redwoods give us dyes with excellent fastness to chemicals and light that allow dark red and brown colours to be obtained. Major colouring matters are also the santalins (first isolated in 1833) and santarubins (condensed biflavonoids). They occur also in sandalwood for example, which is today better known because of the essential oil used in fragrances. Hamish McNab of the University of Edinburgh published in 2004 an interesting paper on these dyes giving a historical perspective. There are still a number of natural anthraquinone dyes around, although their use has been superseded by the use of synthetic dyes because of the price of the natural products.
Only a limited number of the dyes mentioned in table 1 are also found in the database of the Enterprise, although the extracts of the plants are usually permitted without restriction. Lady's bedstraw (Galium verum) is interesting; the Highlanders in Scotland used this plant to dye their tartans, to curdle milk (probably because of the tannins present) and to colour their cheese. This is still practised today in Cheshire, known for its outstanding cheese quality. Lady's bedstraw is used in OTC cosmetic products for poorly healing wounds and to stop bleeding.
Next to the anthraquinones are the related naphthoquinones used as dyes. Some of those dyes are presented in Table 2.
Shikonine is produced in the roots of Lithospermum erythrorhizon (member of the family Boraginaceae) and has antimicrobial properties. It also has anti-tumour and contraceptive properties. It is used externally to treat nappy rash, burns, cuts, wounds, abscesses, eczema and haemorrhoids. The plant is used in commercial skin care products, although the commercial impact is limited because of the intense colour that the extract will impart to something like a cream.
Anchusa tinctoria (alkannet) [INCI: Alkanna tinctoria] provides alkannin, a derivative of 5,8-dihydroxynaphthoquinone, better known as alizarin black. It has an isoprenoid side chain carrying a hydroxyl group. Thus it has a chiral carbon atom, and the optical isomer is the previously discussed shikonine.
The medical use of Anchusa tinctoria goes back to Hippocrates, the renowned doctor and philosopher living in 4th century BC Greece. Not until 1976 did Papageorgiou describe the results of experiments, which confirmed the wound healing properties and antimicrobial properties of alkannet root extract and this was the first time alkannin and derivatives thereof as the active components were identified. More recently, such compounds were demonstrated to exhibit significant anti-tumour, antibacterial and anti-inflammatory activity.
The wound healing properties of alkannet are not just spectacular, they are magic. In cases where synthetic pharmaceutical products fail, the use of alkannet gives a very good chance of success. In addition to the wound healing properties of Anchusa tinctoria (and Lithospermum erythrorhizon) these extracts have been used effectively in traditional Chinese medicine for hundreds of years as a cancer treatment, with proven efficacy. An elegant review has been published by Papageorgiou, Assimopoulou et al, Angew Chemie, 38,270-300 (1999).
Lawsone, 2-hydroxy-1,4-naphthoquinone, comes from the henna plant [INCI: Lawsonia inermis]. This dye is still very popular for dyeing hair, but its use has been restricted because of the photochemical activity of lawsone. Futhermore, many henna powders in the marketplace are contaminated with p-phenylene diamine, a well-known carcinogen. European Union authorities regularly recall henna powders from the market, mostly those of Indian origin.
Juglone comes from black walnut (Juglans nigra) and is toxic to many plants. Topical application results in a {2+2} photoadduct with the cytosine moiety of the genetic material, comparable to the photoadduct of psoralens with cytosine. Consequently cell reproduction comes to a full stop. Juglone is therefore phototoxic and genotoxic. Lapachol compares chemically to lawsone, to such an extent that on the 3-position an isoprene unit is present and because of that the {2+2} photoaddition is less likely to occur due to steric hindrance. Consequently the phototoxicity of lapachol is markedly lower than lawsone and juglone.
The naphthoquinone backbone, as it occurs in a number of natural dyes, is also present in vitamin K. Vitamin K, more precisely vitamin K2, is produced in the intestinal tract with the help of Echerischia coli. Humans live in symbiosis with this organism that is frequently less pleasant when the balance is lost. Vitamin K is an oil-soluble vitamin and is encountered in two forms. Vitamin K1, also called phylloquinone, is found in plants. Vitamin K2, with the nickname menaquinone, is produced by bacteria such as Escherichia coli. We are forced to live in symbiosis with bacteria to satisfy our needs for vitamin K2.
Vitamin K3, menadione, is a synthetic form of this vitamin which is manmade, with limited activity compared to vitamin K1 and K2. Vitamin K3 is the simplest version identified as 2-methyl-1,4-naphthoquinone. Both phylloquinone and menaquinone are more complex and also have a polymeric side chain on the 3-position identified as a phytyl group (polyisoprene).
Vitamin K is required for the maintenance of normal blood coagulation by facilitating the production and/or release of various plasma proteins required for blood coagulation, including prothrombin for example. Although it has been suggested that vitamin K may play a role in electron transport and oxidative phosphorylation in micro-organisms, these functions have yet to be confirmed in higher animals. Vitamin K is not a regular ingredient in personal care and cosmetic products, and in some countries, eg France, it is forbidden.
Anthraquinones, and also naphthoquinones offer interesting opportunities for the design of functional C&T products, although their use is yet another example of the fact that boundaries between C&T and pharmacy are coming down.