Helichrysum italicum: from traditional use to scientific data.
BACKGROUND
Helichrysum italicum (Roth) G. Don fil. (family Asteraceae) has been used for its medicinal properties for a long time and, even nowadays, continues to play an important role in the traditional medicine of Mediterranean countries. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. This review aims to provide an overview of the current state of knowledge of the pharmacological activities of Helichrysum italicum, as well as its traditional uses, toxicity, drug interactions and safety.


METHODS
The selection of relevant data was made through a search using the keywords "Helichrysum italicum" and "H. italicum" in "Directory of Open Access Journals", "Google Scholar", "ISI Web of Knowledge", "PubMed", "ScienceDirect" and "Wiley Online Library". Information obtained in local and foreign books and other sources was also included.


RESULTS
There are reports on the traditional use of Helichrysum italicum in European countries, particularly Italy, Spain, Portugal and Bosnia and Herzegovina. In these countries, its flowers and leaves are the most used parts in the treatment of health disorders such as allergies, colds, cough, skin, liver and gallbladder disorders, inflammation, infections and sleeplessness. In order to validate some of the traditional uses of Helichrysum italicum and highlight other potential applications for its extracts and isolated compounds, several scientific studies have been conducted in the last decades. In vitro studies characterized Helichrysum italicum as an antimicrobial and anti-inflammatory agent. Its flavonoids and terpenes were effective against bacteria (e.g. Staphylococcus aureus), its acetophenones, phloroglucinols and terpenoids displayed antifungal action against Candida albicans and its flavonoids and phloroglucinols inhibited HSV and HIV, respectively. Helichrysum italicum acetophenones, flavonoids and phloroglucinols demonstrated inhibitory action in different pathways of arachidonic acid metabolism and other pro-inflammatory mediators. Regarding Helichrysum italicum in vivo activity, the highlight goes to the anti-erythematous and photoprotective activities of its flavonoids, demonstrated both in animals and humans, and to the anti-inflammatory properties exhibited by its flavonoids, acetophenones and phloroglucinols, as seen in animal models. Concerning its safety and adverse effects, while Helichrysum italicum does not display significant levels of cytotoxicity or genotoxicity, it should be noticed that one of its flavonoids inhibited some CYP isoforms and a case has been reported of an allergic reaction to its extracts.


CONCLUSIONS
Helichrysum italicum is a medicinal plant with promising pharmacological activities. However, most of its traditionally claimed applications are not yet scientifically proven. Clinical trials are needed to further confirm these data and promote Helichrysum italicum as an important tool in the treatment of several diseases.
CICS-UBI - Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Electronic address: danielantunesviegas@gmail.com.
Daniel
D
Antunes Viegas
CICS-UBI - Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Electronic address: apo@fcsaude.ubi.pt.
Ana
A
Palmeira-de-Oliveira
Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. Electronic address: ligia@ff.uc.pt.
Lígia
L
Salgueiro
CICS-UBI - Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; Child and Women Health Department, Centro Hospitalar Cova da Beira EPE, Covilhã, Portugal. Electronic address: jmo@fcsaude.ubi.pt.
José
J
Martinez-de-Oliveira
CICS-UBI - Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; Pharmacy Department, Centro Hospitalar Cova da Beira EPE, Covilhã, Portugal. Electronic address: rpo@fcsaude.ubi.pt.
Rita
R
Palmeira-de-Oliveira
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D005060:Europe; D036562:Helichrysum / Q000737:chemistry* / Q000145:classification; D006801:Humans; D008519:Medicine, Traditional; D028321:Plant Preparations / Q000737:chemistry* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D028321:Plant Preparations
12-O-tetradecanoylphorbol-13-acetate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 5-LO; 5-Lipoxygenase; Anti-inflammatory; Antimicrobial; COX; CYP; Everlasting; HIV; HSV; Helichrysum italicum; Herpes Simplex Virus; IC; ID; IL; LC; LPS; LTB(4); LTR; MIC; MTT; PGE(2); PLA(2); TNFα; TPA; Traditional medicine; UVB; cyclooxygenase; cytochrome P450; human immunodeficiency virus; inhibitory concentration; inhibitory dose; interleukin; lethal concentration; leukotriene B4; lipopolysaccharides; long terminal repeat; minimum inhibitory concentration; phospolipase A(2); prostaglandin E2; tumor necrosis factor α; ultraviolet radiation B