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Introduction
In recent years, the cosmetic industry has become increasingly interested in using plantderived natural products in cosmetic formulations. This is not merely a marketing tool, but
* To whom correspondence should be addressed: (T) J.Wilkinson@mdx.ac.uk 44 181 362 6425; (F) 44 181 805 0702. E-mail:
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a result of the plant material itself having biological activity that is benecial to skin [1]. The use of horse chestnut preparations as herbal medicines has been adequately described elsewhere, so this paper therefore focuses on the biological potential of extracts from this species as cosmoceuticals and for skin-care products.
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R2 Ac Ac H Ac Ac H
R R R R
R1 R1 R1 R1
Rutinoside: Kaempferol 3-O-rutinoside Rhamnoside: Kaempferol 3-O-rhamnoside Glucose: Astragalin Arabinoside: Kaempferol 3-arabinoside
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Other constituents Seeds of A. hippocastanum have also been described as containing starch (4050% weight) [6], sugars, proteins (specically the globulin, hippocastanine, containing L-( )lysine and L-( )-tryptophan), a fatty oil (containing oleic, linoleic, linolenic, stearic and palmitic acids) and purines (adenosine, adenine and guanine). [5]
Bark
The bark of Aesculus hippocastanum, in common with the seeds, has been described as containing the saponin mixture escin [3]. Coumarin glycosides, including esculin, scopolin and fraxin, and their respective aglycones, esculetin, scopoletin and fraxetin, are also present in the bark of A. hippocastanum (Figure 4), in contrast to seed tissues, in which these compounds have not been detected. The avonoid glycoside quercitrin (Figure 2), and its corresponding aglycone have also been detected in bark tissues. Additional compounds, including allantoin, sterols, leucocyanidin, leucodelphinidin, catechol tannins and alkanes have also been described as occurring in bark tissues. [3]
R1 R2 R3
Figure 4. Coumarins and coumarin glycosides present in the leaves and bark of Aesculus hippocastanum.
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Leaves
In common with the bark of A. hippocastanum, leaf tissues contain the coumarin glycosides scopolin, fraxin and esculin (Figure 4) [3]. A range of avonoid glycosides of quercetin (e.g. quercitrin, rutin, isoquercitrin and quercetin 3-arabinoside) and the corresponding glycosides of kaemperfol have also been detected in leaf tissues (Figure 2). In addition to these glycosides, escin has been detected (but only in trace amounts), as well as leucanthocyans, cis,trans-polyprenols, amino acids, fatty acids and sterols (sitosterol, stigmasterol and campesterol).
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1 Ground tissue consists of proteoglycans and glucosaminoglycans, including hyaluronic acid. Cellular components (broblasts, macrophages, plasma cells, adipocytes and mast cells) and tissues (collagen, elastic and reticular bres) omitted for clarity. 2 Fluid leakage due to capillary permeability and density of surrounding ground substance. Increased capillary permeability can result in oedema typical of diseases resulting from venous insufciency.
Figure 5. Simplied representations of capillary vessel permeability in connective tissues. Left: Permeability in tissue containing normal amounts of hyaluronic acid in ground substance. Right: Increased permeability, as a result of reduced hyaluronic acid content (due to hyaluronidase activity).
Flavonoids As a class of phytochemicals, avonoids are widely accepted as possessing a range of biological activities [12] which may be of relevance in the context of topical application of avonoid-containing preparations. Some of these activities are listed in Table I. In the specic case of horse chestnut avonoids, rutin has been described as possessing radical scavenging, anti-bacterial and anti-viral activities, and is also used medicinally in the treatment of varicosis and capillary fragility [13]. Quercitrin and isoquercitrin are also antibacterial (e.g. against Pseudomonas maltophilia), and the former additionally possesses anti-haemorrhagic activity [13]. Proanthocyanidin A2 has been demonstrated to possess a range of biological activities, similar to those of escin, which would be benecial in cosmetic applications [5, and refs.
Table I. General biological activities of flavonoids Activity Reduction of capillary fragility and permeability Anti-inammatory Anti-allergenic Anti-bacterial Anti-viral Enzyme inhibitory
Activities as described in Bruneton (1995) [6]
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therein]. These activities are primarily venotonic and vasoprotective, such as depermeabilisation of capillaries, but also include wound healing, powerful antioxidant, antiinammatory, and anti-enzymatic properties. In a similar manner to escin, proanthocyanidin A2 has been shown to be able to inhibit lipid peroxidation, which is indicative of cellularprotective effects of this compound. Similarly, proteolytic enzymes in the extravascular matrix are inhibited by proanthocyanidin A2, with -glucuronidase, elastase and collagenase all being more strongly inhibited than hyaluronidase. Compounds such as proanthocyanidin A2 may well be at least partly responsible for the differences between the venotonic effects of escin (which inhibits hyaluronidase [11]), and the more powerful effects of crude A. hippocastanum extracts.
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Table II. Superoxide-anion, hydroxyl radical and singlet oxygen scavenging activities of Aesculus hippocastanum and antioxidants IC50 Treatment Aesculus hippocastanum L-Ascorbic acid dl- -Tocopherol DMSO Sodium azide g (dry material) ml 0.01 0.39 38.70
1
Hydroxyl radicals 7.79 3.30 253.70 (2.55 0.26 0.03 38.70 0.1) 105
8.99
Data represent mean standard deviation (n 3). Data using L-Ascorbic acid, dl- -Tocopherol, DMSO and Sodium azide are included as reference values, IC50 values for these compounds are expresed as gml 1 Modied from Masaki et al., 1995 [16].
was found to be signicantly reduced in experiments using A. hippocastanum extracts [16]. Such inhibition was comparable to that obtained by including the anti-oxidant -tocopherol in the assay. Cultured broblasts, which are cells usually found in the connective tissue secreting a matrix associated with the repair and isolation of wounded tissues, were also strongly protected by the extract of A. hippocastanum from damage caused by active oxygen species in vitro. Almost four times the number of these cells survived damage induced by oxygen species, generated using the hypoxanthine/xanthineoxidase system, in the presence of the A. hippocastanum extract than when the extract was absent. Solar protective effects Closely linked to the anti-ageing effects of A. hippocastanum are its potential applications in cosmetics with sun-screen properties. A recent study [17] has investigated the potential use of plant extracts, including A. hippocastanum seed extract, as novel anti-solar agents, based on their ability to absorb light. Such absorption is of particular interest in the ultraviolet region of the spectrum, as UV radiation has been linked with a number of cutaneous conditions, including sunburn, photosensitivity, actinic elastosis, cutaneous degeneration and perhaps most importantly, skin cancer [10, 17]. Although an extract of A. hippocastanum did not display signicant UV-absorbing properties when studied in isolation [in which it had a sun protection factor (SPF) of 0], when combined with a synthetic sunscreen, octylmethoxyciunamate, signicant increases in the effectiveness of the synthetic compound were demonstrated (SPF rose from 4 to 6 on the addition of the A. hippocastanum extract; Table III). Whilst the precise reasons for this improvement of SPF remain unresolved, the authors speculated that such an increase may be as a result of synergistic interactions between components of the A. hippocastanum extract and octylmethoxycinnamate [17]. Venous effects One of the most widely used applications of A. hippocastanum is in the treatment of poor circulation, and its associated conditions. Whilst many of these studies rely on oral delivery of the extracts to improve circulation, conditions such as varicose veins, phlebitis
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10% dry extract 0.091 0.079 0.065 0.053 0.045 0.038 0.034 0
10% dry extract 2% octylmethoxycinnamate 0.528 0.569 0.598 0.625 0.651 0.625 0.553 6b
SPF Sun protection factor 2% octylmethoxycinnamate has an SPF rating of 4 Modied from Ramos et al., 1996 [17].
and post-thrombotic syndrome have all been treated using gels containing escin [5, and refs. therein], suggesting that the topical administration of extracts, as would be the case in the application of cosmetics, is potentially an equally valid delivery system. The positive effects of A. hippocastanum extracts on circulation are due to a range of complex interactions with veins, the lymphatic system, capillaries and connective tissue. Extracts of A. hippocastanum have been demonstrated to possess venotonic effects in vitro and in vivo, in both animal and human systems [5, and refs. therein]. For example, A. hippocastanum extract led to an increase in pressure of ow through both normal and constricted isolated veins, and an increased effect of noradrenaline on increasing the blood pressure (and consequently ow) through such vessels [18]. Similarly, capillaries have been shown to be strengthened by administration of A. hippocastanum extract. In addition to the direct effects of A. hippocastanum extract on blood vessels, benet may also be gained from the protective effects of the extract on connective tissues which surround the capillary vessels. In chronic venous insufciency, the capillaries become highly permeable, resulting in water and proteins leaving the vascular system, which in turn cause swelling; this may be as a result of the degradation of the extracellular matrix surrounding the microvasculature (Figure 5). The main component of this extracellular matrix is hyaluronic acid, a simple glucosaminoglycan consisting of up to several thousand sugar residues; levels of this compound are usually regulated by the enzyme hyaluronidase, which promotes the degradation of hyaluronic acid. Recently, escin and its aglycone, escinol, have been demonstrated to possess non-competitive antihyaluronidase activity (Table IV), even at concentrations well below that expected as a result of topical application of these compounds [11]. This inhibition of hyaluronidase should lead to the recovery of the integrity of hyaluronic acid, and consequently the extracellular matrix surrounding the microvasculature, and may therefore be responsible for some of the benecial effects of A. hippocastanum extracts.
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Triterpene sapogenin Steroidal sapogenin c Obtained from leaf tissues Modied from Facino et al., 1995 [11].
b
d e
One of the conditions associated with venous insufciency is the development of oedematous panniculopathies (inammation of the sub-cutaneous layer of fat, leading to tender nodules, typically on the thighs and breasts), and this condition has recently been treated with phytochemicals from horse chestnut. Application of an emulsion containing escin and biological carriers, such as -sitosterol and phosphatidylcholine, over a 30 day treatment period, led to signicant improvements to both thigh and breast pauniculopathies in human volunteers. These improvements were ascribed to improvements in microcirculation, as recorded by Laser Doppler Flowmetry, resulting in reduced swelling and normalisation of skin temperature [5, and refs. therein].
Conclusions
In addition to the existing uses of extracts of horse chestnut as treatments for venous insufciency, preparations containing phytochemicals from horse chestnut have considerable potential for inclusion in a range of cosmetic formulations. Inclusion of horse chestnut extracts (especially those from the seeds of the plant, rather than the more poorlycharacterised extracts from leaf and bark tissue) could result in a number of benecial actions on the skin after topical administration. Such effects would include potent antioxidative activity, which could help decrease the visible signs of skin ageing, anti-bacterial and anti-viral properties (largely due to avonoids), reduction in skin reddening and cutaneous swelling as a result of effects on capillary vessels and their surrounding connective tissues (due to saponins and the epicatechin dimer proanthocyanidin A2) and also the potential synergistic enhancement of the efcacy (SPF) of sun screens.
References
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