FITOTHERAPY APPLICATIONS

DANILO CARLONI Pharmacist, herbalist, S.I.Fit. (Italian Society of Phytotherapy), SMB Italia (Italian Biotherapy Medical Society) Farmacia Manocchi, P.zza Roma 13, 60019 Senigallia, Italy

Cardiospermum halicacabum for the treatment of dermatitis Cardiospermum halicacabum family: a with a cortison-like action as a valid alternative to traditional dermatological applications

Cardiospermum halicacabum is a tropical plant with interesting potential, making it a strong candidate to Abstractbecome a useful remedy in treating local dermatitis. Nowadays, inflammatory diseases of the skin are having increasingly serious implications: global incidence is more and more widespread and is, unfortunately, increasing. The problem of atopic syndromes is a clear example. The main pharmacological treatments prescribed in medicine foresee the use of cortisone and antihistamine preparations. These therapies, if applied to large areas of the skin and for prolonged periods, can cause adverse reactions, including on a systemic level, which may also occur when these drugs are administered orally. That is why it is important to evaluate the efficacy of natural remedies, such as Cardiospermum halicacabum, which, thanks to its components, is able to control the problem of dermatitis without causing the relative collateral effects, even at paediatric level.

THE SKIN based on cortisone or antihistamine drugs, either via topical or general use; in most cases this approach is effi cacious, he skin, this large involucrum that encloses the entire but has some adverse reactions. Moreover, the problem body, is the most important intermediary between us of dermatitis, due to its relapsing nature, needs prolonged Tand the external world. medical care, therefore, the long term prescription of The skin acts as a barrier against pathogenic cortisone drugs should be carefully considered. Even if microorganisms, as well as against environmental pollution; application is limited to local use, these drugs can cause it protects the internal organs from sudden changes in the same adverse reactions as detected after systemic temperature and it has perfectly organized defence therapy: in certain types of atopic dermatitis the areas of mechanisms. cutaneous application are so extensive that the absorption In an adult, the skin, on average, has a surface area of of the active principles can be signifi cant enough to induce 2 m2 and can weigh from 3-5 kg. It is certainly the organ important systemic effects, especially and dangerously in that is most often exposed to the risk of trauma, infection the paediatric domain. (3) and disease and is constantly stressed and conditioned by For these reasons, evaluating the possibility of using a exposure to solar radiation. (1) remedy of natural origin, allowing the problem of dermatitis It is evident that if cutaneous homeostasis should be to be faced in an effi cacious and safe way and for somehow compromised, the protective functions of the prolonged periods, is an ethical choice. skin could be modifi ed and decreased; thus triggering an infl ammatory effect, classifi ed as dermatitis, which with all the correlated symptoms can lead to staphylococcal and THE PLANT AND ITS CONSTITUENTS streptococcal infections, but also fungi and viruses. (2) Traditional pharmacological therapy, normally with the The phytotherapic approach to dermatitis can benefi t from aim of opposing the dermatitis clinical picture, is generally the properties of an exotic plant native to India and widely

32 Household and Personal Care Today - Vol. 7 nr. 4 October/December 2012 used in Ayurveda: Cardiospermum halicacabum, which compounds are divided into 4 groups, all different, but belongs to the Sapindaceae family. all made of a base structure of long chain fatty acids The name “cardiospermum” derives from the peculiar esterified with a hydroxy isoprenoid or dihydroxy-nitrile appearance of the , which are black, with a light group. heart-shaped spot. The term “halicacabum” comes from The most commonly used pharmaceutical preparations in the Greek for salt-cellar, alluding to the shape of the modern phytotherapy only refer to the green and flowery capsule that contains the seeds. components of the aerial parts and not to the seeds. In the Tamil language, Cardiospermum halicacabum The components of Cardiospermum seem to express is called “Modakathon”, which means “remedy for their anti-inflammatory action with a cortisone-like debilitating pain”, underlining the use that traditional Indian mechanism, in particular by modulating the activation medicine has been making of this plant for centuries: the of phospholipase A2 while maintaining the stability of treatment of acute and chronic infammatory rheumatism. cell membranes. This effect is due to the presence of phytosterols, which are known to be structurally similar to cholesterol and, for this reason, present a certain affinity for lipids in the epidermis and cell membranes. Phytosterols also perform a homeostatic cutaneous and anti-aging action.

According to several authors, phytosterols could stimulate fibroblast activity, thus promoting granulation of damaged areas and tissue to repair the typical damage caused by scratching which is so frequent in the case of dermatitis. Moreover, the cortisone-like action of the phytosterols allows for good control of pruritus symptoms, an activity which is potentiated by the presence of tannins in the Cardiospermum phytocomplex, known to have an astringent and haemostatic effect when applied locally. Picture 1. Cardiospermum halicacabum. Additionally tannins are able to inhibit hyaluronidases; an enzyme which takes part in the inflammatory process, since it degrades hyaluronic acid and at the same time The plant belongs to a tropical climber species, promotes histamine release. (17) widespread in India, but also very well-known and The plant contains a good quantity of triterpene cultivated in South America and . saponines, the local effects of which have not yet In North America Cardiospermum halicacabum is known been clearly defined. Nevertheless, this category of by the name “balloon ”, or balloon plant, alluding to substances has already shown important activity against the fact that the plant is a climber and produces globular inflammation; one significant example is that of liquorice capsules similar to small balloons. flavonoids (12). It can reach, and sometimes exceed, a height of 3m. Its intense green leaves are 5-6cm long, petiolate, compound, imparipinnate and lanceolate in shape with TESTING AND ACTIVITY a notched edge. Its flowers are small and white with 3-5 petals, held on a long peduncle. It produces a globular Thanks to the peculiar formulation of its phytocomplex, shaped capsule that is divided internally into three cells. Cardiospermum halicacabum has been always Each cell contains one , as large as a pepper grain, appreciated by popular medicine for its analgesic black in colour with a characteristic white heart-shaped and anti-inflammatory properties. These therapeutical spot. indications raised strong interest in the academic world Cardiospermum grow at altitudes of up to 1500m. and nowadays have been evaluated and confirmed by several in vitro and in vivo studies. The characteristics of the Cardiospermum halicacabum In the first studies done, results showed that the phytocomplex highlight a series of components that alcoholic extract of the aerial parts produces sedative are strong candidates in expressing a significant anti- and painkilling effects. When administrated via the inflammatory action, even at cutaneous level. intraperitoneal route in mice, it expressed a marked The main active components of the plant are extracted depressive effect on the Central Nervous System; once from the flowering aerial parts. They include a substantial again, similar administration in mice demonstrated group of saponins such as glycosidic triterpenes (4), analgesic action in the heat radiation test. The analgesic hydrolysable tannins (5), traces of alkaloids, quebrachitol, and anti-inflammatory properties of Cardiospermum a particular alcohol with a base structure that can be halicacabum have also been confirmed in the traced to that of inositol, several flavonoids, amongst “granuloma pouch test” conducted on rats. It showed which apigenin and luteolin, pentacyclic triterpenes an action comparable to that of phenylbutazone (13) such as glutinone, beta-amirenone, beta-amyrin (6), and the same result has been seen in the carrageenan- and especially plant sterols, such as beta-sitosterol, induced swelling test (14). campesterol, stigmasterol (7,8,9,10,11,12). An interesting study conducted by Sadique and Oil is extracted from the seeds (33%) and contains a collaborators, compared the effects of Cardiospermum significant quantity of cyanolipids (13-55%). These rare halicacabum to those of hydrocortisone for the control

Household and Personal Care Today - Vol. 7 nr. 4 October/December 2012 33 of artificially induced inflammation in laboratory animals. Cardiospermum halicacabum, these levels were not Also in this case the plant highlighted marked anti- subjected to any decrease and were maintained at the inflammatory activity, although this was lower than the same level as the control group (15). drug, the mechanism was similar to that of the steroid. These results are confirmed by an additional study A multicentric observational study, in which 833 individuals, conducted by P. Pratheeshkumar and Girija Kuttan, affected by various forms of dermatitis, including published in the Asian Pacific Journal of Cancer allergic dermatitis, were enrolled for four weeks, showed Prevention vol. II, 2010, where the methanolic extract therapeutical effi cacy in 80% of cases, with improvement of Cardiospermum halicacabum, opposed the and remission of typical symptoms. immunosuppressive effects and oxidative stress induced The effi cacy of Cardiospermum also appeared in by cyclophosphamide (CTX). This chemotherapeutic lichenifi cation, which characterize a chronic state of drug is known to produce myelosuppression, as disease, in 72% of cases. Tolerability was good/very highlighted by a decreased WBC count. Co-treatment good in 87% of patients and was confi rmed by unbiased with Cardiospermum countered these onsets, increased examination by medical doctors. the relative organ weights of spleen, as well as thymus, when compared to the group treated with just CTX. Cardiospermum also significantly increased the glutathione (GSH) levels in animals treated with CTX, while highlighting antioxidant properties and further reducing the enhanced levels of pro-inflammatory cytokines like TNF-α, IFN-γ and IL-2. (16)

Picture 2.

Table 1. Multicentric observational study, conducted in 140 centers in Germany, Spain and the Netherlands. A formulation based on Cardiospermum halicacabum 10% was used. In green the data relative to remission, in pink those relative to symptom relief (R.Niedner, J.Toonstra).

Recent work done by M. S. Sheeba and V. V Asha and published in the Journal of Ethnopharmacology 124, CONCLUSIONS 7-2009, confirms the anti-inflammatory and analgesic activity of Cardiospermum halicacabum and suggest The collection of these data leads to Cardiospermum additional mechanisms of action. In particular the study halicacabum being considered as a plant with interesting shows that the ethanolic extracts of the plant are able potentiality of action in many forms of skin inflammation. to significantly inhibit the expression of COX-2, TNF-a and In particular, the safety of use suggests indication in iNOS, induced by stimulation with LPS rat cells, through many forms of dermatitis in paediatrics, in adults and in modulation of NF-kB synthesis. the elderly. The plant has indications in atopic dermatitis, The study was conducted on RAW264.7 cells of the in contact dermatitis, in keratosis and in lichenification, macrophage cell line of the mouse and also verified the where, thanks to the anti-inflammatory and skin-loving possible toxicity of the extracts regarding the vitality of activity of its components is succeeds in re-establishing the cell culture: after 48 hrs of co-incubation, no toxicity cutaneous homeostasis while calming important symptoms effects were observed, even with increasing dosage of the such as pruritus. extract. It can also be useful in the treatment of seborrhoeic The Sheeba and Asha test partially clarified the mechanism dermatitis, cradle cap in babies and the increasingly with which this phytocomplex explicates its already known frequent sun-rashes, where it mimics cortisone activity but analgesic and anti-inflammatory effects, but during the without producing phenomena of photosensitization. study other very interesting data came up, which confirm The data on safety of use, at the current stage of the great safety in the usage of this plant. As a matter of research, candidate the Cardiospermum halicacabum fact, contextually to the evaluation of concentrations of extracts as one of the first choice topical anti- TNFα, COX-2, iNOS and NF-kβ, the levels of COX-1 were inflammatory treatments, even for the most serious and also evaluated. These levels are normally inhibited by the relapsing forms. The selective action of the plant towards activity of the well-known anti-inflammatory drugs, with anti-inflammatory mediators prevents the final user serious consequences for the stability of the digestive from experiencing consequences linked to the systemic system’s mucosa, nephritic functionality and the activity effects that are potentially consequent to extensive and of platelets. After introduction into the cell culture of prolonged use of preparations for local treatment.

34 Household and Personal Care Today - Vol. 7 nr. 4 October/December 2012 7. Wiesenauer M.: Phytopraxis. Springer (2006). 8. Bachmann C. Cardiospermum bei dermatologischen Problemen ARS Medici Thema Phytotherapie (2010) 9. Mikolajczak K.L.. Smith C.R. Tjarks L.W. Cyanolipidsof Cardiospermum halicacabum L . and Other Sapindaceous Seed Oils-Lipids 5,Vol. 10 pp.812-817 (1970) 10. Kastener L. Kopp B. Phytopharmaka in der Dermatologie University of Vienna 11. Merklinger S. Ekzembehandlung mit Cardiospermum halicacabum Phytotherapie (1995) 12. Pedretti M. Chimica e farmacologia delle Piante Medicinali; ed. Studio Edizioni Picture 3. Constitutional neurodermititis treated with a 13. Gopalakrishnan C. Dhananjayan R. and Lalitha Kameswaran Cardiospermum halicacabum ointment, applied 3 times a Studies on the Pharmacological actions of Cardiospermum day. Left photograph before therapy, right photograph halicacabum Medical Chemistry Research Centre , after 10 days of treatment. Department of Pharmacology, Madras Medical College, Ind. J. Physiol and Pharmacol. 10-11-1976 14. Sadique J. Chandra T. Thenmozhi V. Elango V. Biochemical Modes of Action of Cassia Occidentalis and BIBLIOGRAPHY Cardiospermum Halicacabum in Inflammation; Journal of Ethnopharmacology Vol. 19 pp. 201-212 (1987) 1. Scesa C. Fototipo e Fotoprotezione : differenze fi siologiche e 15. Sheeba M.S. Asha V.V. Cardiospermum halicacabum diversità di risposta all’esposizione solare Kosmetica (2001) ethanol extract inhibits LPS induced COX_”, TNF-α and 2. Pescari M. Dermatite atopica e da pannolino, cause, prevenzione iNOS expression, which is mediated by Nf-kB regulation, in e trattamento con le piante medicinali, Aboca Edizioni pp.3-17 Raw264.7 cells Journal of Ethnopharmacology Vol.124 pp. (2010) 39-44 (2009) 3. Josep del Hoyo, Calduch, Grossi C. Medicina e Salute Grandi 16. Pratheeshkumar P. Kuttan G. Cardiospermum halicacabum Opere vol.1 edi-ermes, ISBN 88-7051-128-6 (1993) inhibits Cyclophosphamide Induced Immunosuppression and 4. Watt J.M, Breyer-Brandwijk M.G. The Medicinal and Poisonous Oxidative Stress in Mice and also Regulates iNOS and COX-2 Plants of Southern and Eastern Africa E.&S. Livingstone Ltd, Gene Expression in LPS Stimulated Macrophages Asian Pacifi c Edinburgh london: p.930 (1962) Journal of Cancer Prevention Vol. 11 pp. 1245-1252 (2010) 5. Loacker Rimedia: Dermatiti e prurito di diversa origine, Halicar 17. Capasso F. Grandolini G. Izzo A.A. Fitoterapia “Impiego DHU B457-02/2012 Dep. AIFA 02/08/2011 razionale delle droghe vegetali”, ed. Springer p. 117 (2006) 6. Schwabe W. Erste Erfahrungen mit einigen exotischen Heilpfl anzen in homöopathischer Verarbeitung. Allg Hom. Ztg 217, A particular thank to Dr. Floriana Raso Regulatory Affairs Vol. 4 pp.146-153 (1972) Department Loacker Remedia.

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