Journal of Ethnopharmacology 119 (2008) 630–652 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm South African Helichrysum species: A review of the traditional uses, biological activity and phytochemistry A.C.U. Lourens a , A.M. Viljoen b , F.R. van Heerden a,∗ a b School of Chemistry, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South Africa a r t i c l e i n f o Article history: Received 13 May 2008 Received in revised form 3 June 2008 Accepted 10 June 2008 Available online 19 June 2008 Keywords: Asteraceae Biological activity Helichrysum Phytochemistry Traditional uses a b s t r a c t Aims of the study: In South Africa, the genus Helichrysum is widely used in traditional medicine. The uses are well documented although renaming of species and the resulting confusing taxonomic nomenclature may cause uncertainty as to which specific species was referred to in some reports. The aim of this paper is to present a collated and coherent overview of the documented traditional uses of Helichrysum species and to update the botanical identity of previously studied species. Materials and methods: Databases (Scifinder, ISI Web of Knowledge) and several books were used to collect in information on South African Helichrysum species. Results: The traditional uses, chemistry and biological activity of Helichrysum species have been summarized. It was attempted to give clarity as to exactly which species is refer to in the ethnobotanical literature. Conclusions: Although a large number of ethnopharmacological uses have been documented and the chemistry of the genus has been studied extensively, only a few South African species have been investigated for their biological activity. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction 2. Traditional uses The genus Helichrysum Mill. derives its name from the Greek words helios (sun) and chrysos (gold) which is appropriate considering the attractive yellow flowers displayed by several species (Pooley, 2003). The genus belongs to the Asteraceae family, tribe Inuleae and subtribe Gnaphaliinae (Hilliard, 1983). This large genus consists of approximately 500–600 species and although Helichrysum species are also found in southern Europe, south-west Asia, southern India, Sri Lanka (previously Ceylon) and Australia, most species occur in Africa, including Madagascar (Hilliard, 1983). In South Africa (including Namibia), the ca. 244–250 species are widely distributed and the tremendous morphological diversity displayed by these species resulted in their subdivision into 30 morphological groups, using the shape and size of the flower heads as differentiating characteristics (Hilliard, 1983). The flower heads are either solitary or occur in compact or spreading inflorescences. The aerial parts are usually hairy or woolly and plants occur as herbs or shrublets that are sometimes dwarfed and cushion forming. They are often aromatic (Pooley, 1998, 2003; Van Wyk et al., 2000). Several Helichrysums are widely used in Southern African traditional medicine as summarised in Table 1. The first written record of the medicinal use of Helichrysum dates back to 1727 when Boerhaave noted that a Helichrysum species was used to treat nervousness and hysteria. The report of a Helichrysum species in the early literature could have been based on knowledge acquired from the local Khoi and San people, but is most probably due to the fact that European botanists used their knowledge of medicinal properties of European genera (Scott and Hewett, 2008). ∗ Corresponding author. Tel.: +27 33 2605886; fax: +27 33 2605009. E-mail address: vanheerdenf@ukzn.ac.za (F.R. van Heerden). 0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.06.011 2.1. Ambiguities in nomenclature As is the case for all ethnobotanical data, the fact that plant names are changed (Germishuizen and Meyer, 2003) and frequently incorrectly cited (Arnold et al., 2002) is quite problematic. To complicate matters further, variation in spelling of names also occurs. Special care needs to be taken when consulting the original texts to unambiguously confirm that a plant selected for a particular study is in fact the same species cited by, for example, Watt and Breyer-Brandwijk (1962). In Table 1, current names are given and previously accepted names are shown in parenthesis. For the sake of clarity, the name as it appears in the reference is sometimes indicated in brackets after the reference. Table 1 Traditional uses and biological activities reported for Helichrysum species Speciesa Plant part used Dosage form Helichrysum acutatum DC. 21c Helichrysum adenocarpum DC. 28 Root Decoction Helichrysum appendiculatum (L.f.) Less. 24 Leaf Eaten raw Plant Plant Root Wound dressing Roots Leaf Helichrysum argyrophyllum DC. 29 Root Infusion Helichrysum aureonitens Sch. Bip. 8 NS Chest problems or infection of the respiratory tract Resp, Infec, Anth, W, P Intestinal troubles Resp Leaves and stems Burnt as incense Used to invoke the goodwill of the ancestors and to induce trances Psy, Psyc, Infect, Insect Arnold et al. (2002), Githens (1949), Mathekga (2001) e , Smith (1895), Smith (1966), Swanepoel (1997), Walker (1996), Watt and Breyer-Brandwijk (1962) Arnold et al. (2002), Batten and Bokelmann (1966), Smith (1966), Walker (1996), Watt and Breyer-Brandwijk (1962) Bd , Fd Poi Chest complaints. Decoction Bd , Fd GIT Poi References Arnold et al. (2002), Cunningham (1988), Hutchings et al. (1996) Arnold et al. (2002), Jacot Guillarmod (1971), Neuwinger (1996), Phillips (1917), Pooley (2003), Walker (1996), Watt and Breyer-Brandwijk (1962) Smallpox Anthelmintic Coughs and colds and applied externally on wounds Applied externally to wounds. Ground leaves are rubbed into areas which cramps or on wounds Ground and burnt and smeared on body to relax body and to reduce swelling Used medicinally as tea Smoked Decoction Extracts Biological activityb GIT Leaf Leaves and stems Helichrysum aureum Houtt. Merr. var. aureum/monocephalum (=Helichrysum fulgidum (L.f.) Willd.) 30h Widely used as traditional medicine, sold commercially in large quantities Used to treat diarrhoea and vomiting in children. Not grazed by stock, preventing soil erosion in overgrazed areas Browsed by animals but poisonous if large quantities is ingested The plants are casually browsed by sheep and said to be a cause of “Geilsiekte” Helichrysum argyrosphaerum DC. 15 Helichrysum asperum (Thunb.) Hilliard and Burtt. (=Helichrysum ericifolium Less.) (Hilliard, 1983) 12f Helichrysum athrixiifolium (Kuntze) Moeser 9f Classification of useb Hutchings et al. (1996), Mathekga (2001) e , Pooley (1998), Van Wyk et al. (2002) Smith (1966) (Helichrysum ericaefolium DC.)g Arnold et al. (2002), Jacot Guillarmod (1971) (Helichrysum athrixifolium O. Hoffm.)g , Phillips (1917) (Helichrysum athrixiifolium O. Hoffm.)g , Watt and Breyer-Brandwijk (1962) (Helichrysum athrixifolium O. Hoffm.)g Bd , Fd , V Afolayan and Meyer (1997) e , Cunningham (1988), Hutchings et al. (1996), Jacot Guillarmod (1971), Mathekga (2001) e , Meyer and Afolayan (1995) e , Meyer et al. (1996) e , Meyer et al. (1997) e , Phillips (1917), Pooley (1998), Pooley (2003), Swanepoel (1997), Walker (1996), Watt and Breyer-Brandwijk (1962) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Leaf Traditional use Commercially sold A remedy for inuresis in children Used topically for skin infections especially against Herpes zoster and infections associated with Herpes simplex Used to keep red mites away Used as tinder to start fire, used to make hats. Used for washing sore eyes Eye 631 Arnold et al. (2002) (Helichrysum fulgidum L.f.) Willd.)g , Batten and Bokelmann (1966) (Helichrysum fulgidum Willd.)g , Jacot Guillarmod (1971) (Helichrysum fulgidum (L.) Willd.)g , Phillips (1917) (Helichrysum fulgidum Willd.)g 632 Table 1 (Continued ) Speciesa Plant part used Dosage form Traditional use Classification of useb References Bd , Fd Mathekga (2001) e Resp, Infect, GIT, Vi, W Bd , Fd , I, My Arnold et al. (2002), Dekker et al. (1983) e , Gelfand et al. (1985) (Helichrysum caespitium Sond.)g , Hutchings and Van Staden (1994), Jacot Guillarmod (1971) (Helichrysum caespitium Sond.)g , Mathekga et al. (2000) e , Mathekga (2001) e , Meyer et al. (2002) e , Neuwinger (1996), Phillips (1917) (Helichrysum caespitium Sond)g , Pooley (1998), Pooley (2003), Swanepoel (1997) e , Watt and Breyer-Brandwijk (1962) M, GIT Bd , Fd Arnold et al. (2002), Jacot Guillarmod (1971), Mathekga and Meyer (1998) e , Mathekga (2001) e , Phillips (1917), Pooley (2003), Watt and Breyer-Brandwijk (1962) Helichrysum bellum Hilliard 28 Helichrysum caespititium (DC.) Harv 12f Plant Crushed and burnt and smoke inhaled Used to treat head and chest colds (headaches) Plant Decoction Root Roots Plant Decoction Drunk by the Kwena and the Kgatla to treat gonorrhoea Nausea Virility Ointment is applied to the roof of the mouth for a depressed fontanelle Used as dressing for open wounds during circumcision rites Protective charm. Mixed with Aster bakerianus (hispidis) and Helichrysum rugulosum Used for fuel in winter Used as an ingredient in an enema for colic Ointment Helichrysum callicomum Harv 2 Enema Helichrysum calocephalum Klatt 23 Helichrysum calophalum Klatt 23 Root Used for hyperfunction of the lower gastro-intestinal tract Bd , Fd Bd , Fd Helichrysum candolleanum Buek 15 Helichrysum chionosphaerum DC. 25 Helichrysum cephaloideum DC. (=Helichrysum adscendens Less. var. cephaloideum Moes.) 24 Tea, infusion Helichrysum cochleariforme DC. (=Helichrysum imbricatum Less.) 15 Helichrysum cooperi Harv. 30 GIT Whole plant Decoction Leaf Ointment, applied after bathing Leaves Irritant poisoning in sheep demonstrated. Known to be poisonous to sheep (symptoms similar to that of poisoning caused by Geigera) Demulcent in coughs and other pulmonary affections. In the Western Cape area the plant is used to treat whooping cough, other coughs, bronchial catarrh and bronchitis Drunk for infections of the respiratory tract Used as love charm. The ointment is applied after bathing and as a result the desired lady finds the man irresistible Used to make Zulu headdress distinctive to married women Used as a fumigant and as part of a traditional remedy for snakebite. Poi Arnold et al. (2002) refers to others using Helichrysum calocephalum Schltr, which is classified as Helichrysum ecklonis Sond (Germishuizen and Meyer, 2003) Swanepoel (1997), information obtained from TRAMED database. It is not clear to these authors whether this use pertains to Helichrysum calocephalum Klatt or Helichrysum ecklonis Sond Mathekga (2001) e Mathekga (2001) e Van Wyk et al. (2002), Watt and Breyer-Brandwijk (1962) Resp Arnold et al. (2002), Neuwinger (1996), Smith (1966), Swanepoel (1997), Watt and Breyer-Brandwijk (1962) M, Fum, Snakebite Arnold et al. (2002), Hutchings et al. (1996), Pooley (1998), Pooley (2003), Walker (1996), Watt and Breyer-Brandwijk (1962) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Biological activityb Helichrysum crispum (L.) D. Don. 17 Used medicinally as a calming tea Coughs, bronchitis, urinary tract infections and tuberculosis. Resp, Renal B Arnold et al. (2002) (with reference to Smith, 1966), Kling as quoted by Salie et al., 1996e , Roberts (1990) (Helichrysum crispum)g These authors are not certain whether Kling is referring to Helichrysum crispum (L.) D. Don. or Helichrysum crispum Less. Helichrysum cymosum (L.) D. Don. 8 Used to invoke the goodwill of the ancestors and to induce trances Used to treat colds and coughs Used as emetic and purgative Filtrate drunk to treat colds and fever Vapour bath used to treat headaches M, Psy, Resp, GIT, P Bd , Fd , Pl Arnold et al. (2002), Bhat and Jacobs (1995), Kokwaro as quoted by Neuwinger (1996), Neuwinger (1996), Pooley (2003), Van Vuuren et al. (2006) e , Van Wyk et al. (2000) Used as medicinal tea. Woolly coat used for tinder boxes Used to induce trances NS Used to treat head colds Used to treat hiccups Browsed by stock Resp, GIT Arnold et al. (2002), Hutchings and Van Staden (1994), Jacot Guillarmod (1971), Neuwinger (1996), Phillips (1917), Smith (1966), Watt and Breyer-Brandwijk (1962) Used by the Xhosas to ward of evil magic spells, which follow on seeing iChanti, the water snake Used to treat diarrhoea in children. M, GIT Batten and Bokelmann (1966), Jacot Guillarmod (1971), Phillips (1917), Pooley (2003), Watt and Breyer-Brandwijk (1962) Used to invoke the goodwill of the ancestors Commercially sold M Arnold et al. (2002), Cunningham (1988), Hutchings et al. (1996) Leaf Root Leaf Leaf Decoction/tea Extract Boiled, and vapours from boiling leaves inhaled Plant Burned and smoked inhaled Helichrysum dregeanum Sond. and Harv. 9 Leaf Smoked Infusion Helichrysum ecklonis Sond (=Helichrysum calocephalum Schltr.) 28 Helichrysum epapposum Bolus 3 Root Decoction Leaves and stems Burned as incense Leaves and stems Helichrysum excisum (Thunb.) Less. 12 Helichrysum felinum Less. 17 Helichrysum flanaganii Bolus 13 Helichrysum foetidum (L.) Moench 30 f Psy Leaves Burned Incense M Plant Extract is drunk/smoke inhaled Used to induce trances Psy, Infect, Resp, W, Eye, P Leaf Leaf Extract Wound dressing Leaf Root Leaf Preparation Extract Used to treat flu (influenza) Used to treat circumcision and infected wounds (festering sores) Applied to treat Herpes Eye problems, used to bath eyes Used in making headdress distinctive of married women Aromatic and astringent (used to draw out infection). Used to treat menstrual pain Plant Helichrysum glomeratum Klatt 6 Helichrysum griseum Sond (=Helichrysum agrostophilum Klatt) 23h Helichrysum gymnocomum DC. 4 Stems and leaves Burned as incense Ointment Helichrysum herbaceum (Andrews) Sweet 29 Stems and leaves d B ,F Arnold et al. (2002), Lucas and Pike (1971), Smith (1966) Arnold et al. (2002), Hutchings et al. (1996), Mathekga (2001) e , Neuwinger (1996) Bd , I Bd , I Lourens et al. (2004) e Lourens et al. (2004) e Walker (1996) B Arnold et al. (2002), Batten and Bokelmann (1966) (Helichrysum foetidum Cass.)g , Gerstner (1938) (Helichrysum foetidum Cass)g , Hulme (1954), Hutchings et al. (1996), Kokwaro quoted by Neuwinger (1996), Neuwinger (1996) Roberts (1990), Rwangabo, quoted by Neuwinger (1996), Steenkamp et al. (2004) e , Swanepoel (1997), Van Wyk and Gericke (2000), Watt and Breyer-Brandwijk (1962) (Helichrysum foetidum Cass.)g B, Fd Mathekga and Meyer (1998) e , Mathekga (2001) e Arnold et al. (2002), Phillips (1917) Preventative charm against illness. Burnt as fuel in winter Used to invoke the goodwill of the ancestors Mixed with fat, only the wives of chiefs were previously allowed to use it Used to fumigate sick rooms Commercially sold M Skin, M, Fum Bd , Fd Cunningham (1988), Drewes and Van Vuuren (2008) e , Hutchings et al. (1996), Phillips (1917) Used to invoke the goodwill of the ancestors M Bd , Fd Arnold et al. (2002), Cunningham (1988), Hutchings et al. (1996), Mathekga (2001) e , Neuwinger (1996), Pooley (1998), Pooley (2003) Commercially sold 633 Stems and leaves Burned as incense d A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Helichrysum dasymallum Hilliard (=Helichrysum lanatum Harv.) 21 Helichrysum decorum DC. 30 Speciesa 634 Table 1 (Continued ) Plant part used Dosage form Traditional use Classification of useb Helichrysum hypoleucum Harv 16 Helichrysum indicum (L.) Grierson (=Helichrysum expansum (Thunb.) Less.) 15 Helichrysum kraussii Sch. Bip 8 Burned and crushed Leaf Decoction Root and leaves Infusion Dried flower and seed Smoked in a pipe Plant Burnt, salt is added to ash and ingested by mouth Root Root Helichrysum lepidissimum S. Moore 19 Helichrysum litorale Bolus (=Leontonyx angustifolius DC. =Leontonyx spathulatus Less.) 14 Plant Helichrysum longifolium DC. 24 Leaf Mixed with salt and other ingredients Powder or ointment Tea Leaf Root Mathekga and Meyer (1998) e , Mathekga (2001) e Arnold et al. (2002), Jacot Guillarmod (1971) Bd , Fd Arnold et al. (2002), Arnold and Gulumian as quoted by Neuwinger (1996), Bremner and Meyer (2000) e , Mathekga (2001) e , Gelfand et al. (1985), Mabogo (1990), Neuwinger (1996), Swanepoel (1997), Walker (1996), Watt and Breyer-Brandwijk (1962) M Skin, M, Resp, Infect Venereal disease Applied to child’s side with small amount given orally Used as a body perfume Used medicinally as tea The Xhosa grind and boil the leaves and use it as a wash for pain after circumcision The powdered root is used for intestinal parasites and for ticks on poultry Skin Dlamini (1981), Watt and Breyer-Brandwijk (1962) W, Skin Smith (1966), Swanepoel (1997), Watt and Breyer-Brandwijk (1962) W Bd , Fd Dilika et al. (1997) e , Mathekga (2001) e Resp, P Bd , Fd , My, V Smith (1966) Arnold et al. (2002), Lall and Meyer (1999) e , Lall et al. (2006) e , Mathekga (2001) e , Smith (1966) P, Anthel Bd , Fd Smith (1966) (Helichrysum miconiaefolium DC.)g , Arnold et al. (2002), Mathekga (2001) e , Swanepoel (1997) B, Fd B, Fd Mathekga (2001) e Mathekga (2001) e Arnold et al. (2002), Jacot Guillarmod (1971), Pooley (1998), Pooley (2003), Phillips (1917) (Helichrysum mundii, Harv.)g , Watt and Breyer-Brandwijk (1962) Helichrysum montanum DC. 22 Helichrysum monticola Hilliard 28 Helichrysum mundtii Harv. 23 Plant Decoction Chest complaints Resp Helichrysum natalitium DC. 3 Leaves and stems Burnt as incense Used to invoke the goodwill of the ancestors Commercially sold M Leaves and stems Bd , Fd Used to drive bad spirits away, used to wash body The Karanga smoke this as a remedy for coughs and pulmonary tuberculosis Cough Dried and pounded or mixed with lard or fat, was used for applying to ulcers. In the Western Cape province an ointment for boils, carbuncles and abscesses is made from this plant, Cyanella lutea and “tiendaegeneesbossie” Used by the Pondos to treat circumcision wounds. The leaves are heated over very hot ash before being used as a bandage for the treatment of wounds after circumcision Excellent stock feed Used as bedding. Used medicinally as tea. Used for cough, fever, headache, colds and chest pain Helichrysum lucilioides Less. 12 Helichrysum melanacme DC. 8 Helichrysum miconiifolium DC. 23 Mixed with Conyza pinnata. Crushed and burnt to drive sickness from a room Use to wash keloid scars References Arnold et al. (2002), Cunningham (1988), Hutchings et al. (1996), Pooley (2003) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Plant Biological activityb Helichrysum nudifolium (L.) Less. var. nudifolium =H coriaceum Harv.f =also Helichrysum gerberifolium A. Rich, =also Helichrysum leiopodium DC. =also Helichrysum nudifolium var. quinquenerve =also Helichrysum nudifolium var. leiopodium) 23 Leaf Leaf Plant Leaf/plant Root Leaf Root/Leaf Plant/leaf Leaf Burnt as incense To invoke the goodwill of the ancestors Infusion Colds (Zulu and Khoi—administration route not indicated) Used to treat colds by the Xhosa Regarded as demulcent, used to treat catarrh, phthisis and other pulmonary affections Respiratory infections Coughs and colds Wounds Applied to sores on the genitalia by the Xhosa Headache Rectal prolapse Protection of children from illness Eaten raw Infusion Wound dressing Leaf Leaf Plant Decoction Infusion Infusion on hot stones Plant Poultice Decoction Root Decoction Helichrysum nudifolium var. oxyphyllum (=Helichrysum oxyphyllum DC. =also Helichrysum undatum Less.) 23 Helichrysum nudifolium var. pilosellum (=Helichrysum latifolium (Thunb.) Less. =Helichrysum pilosellum (L.f.) Less.) 23 Leaf Roots Helichrysum nudifolium var. pilosellum (=Helichrysum pilosellum (L.f.) Less. =Helichrysum pedunculare (L.) DC. var. pilosellum) 23h Infusion Ground and burnt Bd , Fd , I Chest problems, used as emetic by the Zulu To encourage weaning in babies Diseases in goats Used as steam bath to treat fever and nightmares Swellings Colic in children (administered as enema) Rubbed into scarifications over bruises. Used as tea Internal sores (intestinal ulceration) Protective charm against thunder M Used for “doctoring’ people who wish some deed concealed and who are afraid of being found out M, GIT Ingredient in colic remedy Stomach ache in children Ground and burnt near cattle suffering from black leg As an antiseptic and to induce fast healing: used after circumcision to prevent inflammation externally Also externally applied to wounds and used for infections of the respiratory tract As an antiseptic Stomach ailments W, Resp, GIT Arnold et al. (2002), Gerstner (1938) (Helichrysum undifolium, also Helichrysum leiopodium DC.)g , Githens (1949) (Helichrysum nudifolium, also Helichrysum leiopodium)g , Glover et al. quoted by Neuwinger (1996), Hulme (1954), Hutchings et al. (1996), Hutchings and Johnson (1986), Hutchings and Van Staden (1994), Jacot Guillarmod (1971) (Helichrysum nudifolium var. leiopodium)g , Jäger et al. (1996) e , Mabogo (1990), Phillips (1917) (Helichrysum leiopodium DC.)g , Rood (1994), Smith (1895) (Helichrysum nudiflorum)g , Smith (1966) (Helichrysum coriaceum Sond. and Helichrysum nudifolium var. quinquenerve)g , Swanepoel (1997) e (Helichrysum gerberifolium)g , Van Wyk et al. (2000), Neuwinger (1996) (also Helichrysum gerberifolium Sch. Bip)g , Watt and Breyer-Brandwijk (1962) (Helichrysum gerberaefolium Sch. Bip. Ex A.Rich)g Arnold et al. (2002), Gertsner (1938), Hutchings et al. (1996) B, Fd Arnold et al. (2002) (H. pilosellum)g , Hulme (1954) (Helichrysum latifolium)g , Hutchings et al. (1996) (Helichrysum pilosellum (L.f.) Less.)g , Jacot Guillarmod (1971) (Helichrysum latifolium (Thunb.) Less.)g , Mathekga and Meyer (1998) e , Mathekga (2001) e , Neuwinger (1996) (Helichrysum pilosellum (L.f.) Less.)g , Phillips (1917) (Helichrysum latifolium Less.)g , Phillips (1917) (Helichrysum latifolium Less.)g , Pooley (2003) (Helichrysum pilosellum)g , Swanepoel (1997), Walker (1996) (Helichrysum pilosellum (L.f.) Less.)g , Watt and Breyer-Brandwijk (1962) (Helichrysum latifolium Less.)g A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Root Smoke inhaled Infusion Powder mixed with butter and eaten Decoction M, Resp, W, Infect, P, Skin, GIT Arnold et al. (2002), the sources below are indicated in Arnold et al., under Helichrysum pedunculare DC.: Batten and Bokelmann (1966) (isicwe, isiGqutsi)i , Githens (1949) (Helichrysum pedunculare)g , Smith (1895) (isi-Cwe.)i , Smith (1966) 635 Table 1 (Continued ) Dosage form Traditional use Classification of useb Biological activityb References Helichrysum odoratissimum (L.) Sweet 4 Leaf/ground plants Used as wound dressing/leaf pulp Wounds and burns W, Fum, Psy, Psyc, M, Resp, Eye, GIT, P Bd , Fd , My Adjanohoun quoted by Neuwinger (1996), Arnold et al. (2002), Baerts and Lehmann quoted by Neuwinger (1996), Cunningham (1988), Dlamini (1981), Hutchings and Johnson (1986), Hutchings et al. (1996), Hutchings and Van Staden (1994), Jacot Guillarmod (1971), Kokwaro quoted by Neuwinger (1996), Lall and Meyer (1999) e , Lourens et al. (2004) e , Mathekga and Meyer (1998) e , Mathekga (2001) e , Neuwinger (1996), Pooley (1998), Pooley (2003), Rwangabo quoted by Neuwinger (1996), Smith (1966), Swanepoel (1997), Van Puyvelde et al., 1989, Van Wyk et al. (2000), Van Wyk and Gericke (2000), Watt and Breyer-Brandwijk (1962) B, Fd Mathekga and Meyer (1998) e , Mathekga (2001) e Plant Ointment Leaf Ash is rubbed into scarifications Burnt as incense Tea Plant, leaf, stems Root Leafy twigs Leaf and twigs Smoke inhaled Leaf Ash is eaten Extract or sap used as eye drop Decoction Extract Sap Extract Ash is eaten Tea Decoction Leaf Leaf Leaf and twigs Smoke inhaled Infusion Decoction Leafy twigs Leaf Decoction Decoction Aerial parts Leaf Root Leaf The Southern Sotho use this plant to fumigate huts It is mixed with fat to form pleasantly smelling ointment, formerly only used by wives of chiefs Insanity, possession Used to invoke the goodwill of the ancestors, protective charm Aids sleep, relieves muscle tension and cramps Used as a sedative and to treat insomnia and as protective cleanser. Colds, coughs Coughs Conjunctivitis Abdominal pain Used to treat dehydration Heartburn, flatulence Purgative (extract is drunk) Vomiting Colic and stitch Febrile convulsions (part of preparation) Headache Fever (also used as wash) Used to treat female sterility, menstrual pain and eczema in Rwanda Tonic for pregnant women Galactagoque Used a bedding material since it is an effective insect repellent. Sold commercially. The Xhosa also use the plant for spiritual purposes, as a fumigant when a baby is born Helichrysum oreophilum Klatt 21 Helichrysum pallidum DC. (=Helichrysum agrostophilum Klatt (in part) =Helichrysum undatum (Thunb.) Less. var. agrostophilum (Klatt) Moeser =Helichrysum undatum var. pallidum 23h Helichrysum panduratum O. Hoffm. 18 Helichrysum pandurifolium Schrank. (=Helichrysum auriculatum Less.) 18 Preventative charm for illness Roots Bathing in decoction Leaf Decoction Plant Sap Infusion, demulcent Burnt as fuel in winter The act of forgetting, The bath is suppose to make a person invisible/or forgotten by his enemies, witchcraft Febrile convulsions in children (part of a preparation) M P, Infect Arnold et al. (2002), Jacot Guillarmod (1971) (Helichrysum undatum var. agrostophilum)g , Phillips (1917) (Helichrysum undatum Less., var. pallidum and Helichrysum agrostophilum Klatt)g A, I Adjanohoun quoted by Neuwinger (1996), Haerdi quoted by Neuwinger (1996), Neuwinger (1996), Neuwinger (1996), Pooley (1998), Swanepoel (1997) e Used to treat malaria in children Used to make herbal tea Respiratory conditions Backpain, heart trouble, kidney disease, kidney stones Historically been used as a tea Resp, P, Ca, Renal Arnold et al. (2002), Roberts (1990) (Helichrysum auriculatum Less.)g , Rood (1994), Smith (1966) (Helichrysum auriculatum Less.)g , Swanepoel (1997), Watt and Breyer-Brandwijk (1962) (Helichrysum auriculatum Less.)g A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Plant part used 636 Speciesa Helichrysum patulum (L.). Don. (=Helichrysum crispum Less.) 18 Infusion Helichrysum pedunculatum Hilliard and Burtt Leaf and root (=Helichrysum pedunculare DC.) 23 Heart trouble, backache, kidney disease, also ‘heart weakness’ (also heart treatment in animals). Stress and fatigue Hyperpiesa, (hyperpepsia is probably a spelling error in Neuwinger), coronary thrombosis, bladder conditions/infections Asthma, Influenza Gynaecological disorders Used as bedding P, Ca, Renal, Resp As an antiseptic and to induce fast healing: used after circumcision to prevent inflammation externally W, Resp, Infect, GIT Neuwinger (1996) (Helichrysum crispum Less.)g , Roberts (1990) (Helichrysum crispum)g , Scott et al. (2004), Smith (1966) (Helichrysum crispum Less.)g , Watt and Breyer-Brandwijk (1962) (Helichrysum crispum Less.)g Arnold et al. (2002), Batten and Bokelmann (1966) (Helichrysum pedunculare DC.g , isiCwei , isiGqutsii , Xhosa), Bhat and Jacobs (1995) (Helichrysum pedunculatum Hilliard and Burttg , isiCwei , siGgutsii , Xhosa), Dilika et al. (1997) e , Gerstner (1938) (Helichrysum pedunculare DC.g , isiCwei , Zulu), Githens (1949) (Helichrysum pedunculareg , isicwei , Zulu), Hutchings et al. (1996) (Helichrysum pedunculatum Hilliard et Burtt)g , Meyer and Dilika (1996) e , Rood (1994) (Helichrysum pedunculatumg , ery’kuei , Fingo), Smith (1895) (Helichrysum pedunculare DC.g , isiCwee ), Smith (1966) (Helichrysum pedunculare DC.)g , Neuwinger (1996) (Helichrysum pedunculatum Hilliard and Burtt)g , Swanepoel (1997), Watt and Breyer-Brandwijk (1962) (Helichrysum pedunculare DC.)g Bd Arnold et al. (2002), Lourens et al. (2004) e , Kirstenbosch Botanical Garden, Neuwinger (1996), Roberts (1990) (Helichrysum peteolatum)g , Scott et al. (2004), Smith (1966) (Helichrysum petiolatum DC.)g , Van Wyk et al. (2000) Also externally applied to wounds and used for infections of the respiratory tract As an antiseptic Stomach ailments Helichrysum petiolare Hilliard and Burtt 18 Leaf Tea Helichrysum platypterum DC. 20 Helichrysum psilolepis Harv. 22 Root Decoction Root Crushed and sucked Root Decoction Coughs, colds, catarrh, headache, fever, menstrual disorders, urinary tract infections Antiseptic wound dressing Tea taken for heart conditions, stress, hypertension, anxiety and over-excitement Used as bedding Renew virility in men Vi Dysmenorrhoea P Arnold et al. (2002), Jacot Guillarmod (1971), Phillips (1917), Watt and Breyer-Brandwijk (1962), Jakupovic et al., 1987 Bd , Fd Used to weave hats Helichrysum rotundatum (=H coriaceum (DC.) Harv.)f Helichrysum rugulosum Less. 9 Enema Helichrysum setosum Harv. 30 Leaf Decoction Root Powdered and rubbed into the wound Used as tea NS Protective charm (with Helichrysum callicomum and Aster bakerianus Colic (an ingredient) Used to fumigate huts when children are ill (cold) M, GIT, Fum Love potion Epilepsy Fumigate rooms Snakebite, roots are also mixed with the flesh of the snake and put in the patient’s porridge M, Epilepsy, Fum, Snakebite A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 B Arnold et al. (2002), Jacot Guillarmod (1971), Mathekga (2001) e , Phillips (1917), Neuwinger (1996), Watt and Breyer-Brandwijk (1962) Smith (1966) (Helichrysum coriaceum Sond.)g Bd , Fd Arnold et al. (2002), Dlamini (1981), Jacot Guillarmod (1971), Mathekga and Meyer (1998) e , Mathekga (2001) e , Phillips (1917), Pooley (1998), Pooley (2003), Watt and Breyer-Brandwijk (1962) Chabra quoted by Neuwinger (1996), Jacot Guillarmod (1971), Lucas and Pike (1971), Neuwinger (1996), Phillips (1917), Watt and Breyer-Brandwijk (1962) 637 Speciesa Plant part used Dosage form Traditional use Classification of useb Helichrysum simillimum DC. 8 Helichrysum splendidum (Thunb.) Less. 22 Roots Smoke inhaled Burnt, powdered plant material Used to treat rheumatism Fuel plant in the mountains The leaves are boiled and the steam inhaled to induce sweating It is used together with Senecio species to treat pimples Headaches Powder applied to cuts in the skin of a sick person Decoction Leaf Helichrysum subglomeratum Less. 6 Helichrysum sutherlandii Harv. 17 Aerial parts Plant Helichrysum tomentosulum (Klatt) Merxm 1 Twigs Extract Plant Smoke inhaled Root Decoction Bd , Fd Mathekga (2001) e Arnold et al. (2002), Dlamini (1981), Jacot Guillarmod (1971), Pooley (2003), Swanepoel (1997) P, Skin P M I Bd , Fd Used for washing sore eyes Eye Bd , Fd Used as a perfume (subsp.) aromaticum Twigs are pounded in water and used as mouth wash for tooth ache The entire plant is placed on red hot coals and smoke inhaled for body pain. The same treatment is used by pregnant women suffering from antepartum haemorrhage Bladder problems (dribbling) Used as thatching. P, Renal Heavily grazed The Swazi use the plant as a purgative or an emetic. They add one teaspoon of the plant to soft porridge which is then eaten by the patient Bd , Fd GIT Jäger et al. (1996) e Arnold et al. (2002), Jacot Guillarmod (1971), Mathekga (2001) e , Phillips (1917), Pooley (1998), Pooley (2003), Watt and Breyer-Brandwijk (1962) Arnold et al. (2002) (Helichrysum fulgidum (L.f) Willd.)g , Batten and Bokelmann (1966) (Helichrysum fulgidum Willd.)g , Drewes et al. (2006) e , Jacot Guillarmod (1971) (Helichrysum fulgidum (L.) Willd.)g , Phillips (1917) (Helichrysum fulgidum Willd.)g Neuwinger (1996), Van Wyk and Gericke (2000), Von Koenen (2001) Bd , Fd Helichrysum trilineatum DC. 22 Helichrysum umbraculigerum Less. 5 Helichrysum uninervium Burtt Davy 12 References Bremner and Meyer (1998) e , Mathekga (2001) e Mathekga (2001) e , Pooley (1998) Swanepoel (1997) a Where the species name has been changed, the previously accepted name is given in brackets. The following species are no longer classified as Helichrysum: Helichrysum capillaceum (Thunb.) Less. (Phillips, 1917; Jacot Guillarmod, 1971; Watt and Breyer-Brandwijk, 1962) accepted name now Troglophyton capillaceum subsp. capillaceum (Thunb.) Hilliard and B.L. Burtt (Gibbs Russell et al., 1987); Helichrysum orbiculare (Thunb.) Druce (Smith, 1966) accepted name now Plecostachys serpyllifolia (P.J, Bergius) Hilliard and B.L.Burtt (Gibbs Russell et al., 1987); Helichrysum sesamoides Willd. (Smith, 1966) accepted name now Edmondia sesamoides (L.) Hilliard (Gibbs Russell et al., 1987); Helichrysum vestitum (L.) Willd. (Smith, 1966) accepted name now Syncarpha vestita (L.) B. Nord. (Gibbs Russell et al., 1987); Helichrysum hochstetteri (A. Rich) Hook. F. (Githens, 1949) and Helichrysum stenopterum DC. (Dlamini, 1981) accepted name now Achyrocline stenoptera (DC.) Hilliard (Gibbs Russell et al., 1987). b Abbreviations used: A = analgesic activity determined; Anth = anthelmintic; B = antibacterial activity determined; Ca = cardiac conditions; Eye = used in eye conditions; F = antifungal activity determined; Fum = used as fumigant, often plants are burnt in room of a sick person; GIT = gastrointestinal conditions, which include mainly colic, nausea and vomiting, diarrhoea and stomach pain; I = anti-inflammatory activity determined; Infect = conditions associated with infections, such as gonorrhoea and smallpox; Inflam = conditions associated with inflammation such as swelling, menstrual pain; Insect = plants are used to deter insects such as red mites; M = used in a magical sense, to invoke the goodwill of the ancestors and as charms (protective, love); My = antimycobacterial activity determined; NS = not specified; P = conditions associated with pain, inflammation and fever, which include headache, convulsions and dysmenorrhoea; Pl = antiplasmodial (antimalarial) activity determined; Psy = psychotropic use—plants that are used to induce trances; Psyc = psychological conditions such as inuresis in children and insomnia; Poi = possible poison, mainly when stock ingest excessive amounts; Renal = conditions associated with kidney and bladder problems; Resp = respiratory conditions, which include colds, coughs, flu, tuberculosis; Skin = used for skin conditions such as keloid scars, abscesses, as ointments; W = used to dress wounds; V = antiviral activity determined; Vi = used for virility in men. c The number refers to the morphological group according to Hilliard (1983). d Antimicrobial activity of 1 mg/ml or less observed for one or more micro-organisms. e Reference associated with biological activity. f In some cases the author name, as indicated in the source, is not present in either Hilliard (1983) or Germishuizen and Meyer (2003). The current author is then chosen. g In cases where the name in the source and the current name differ, the name used in the source is indicated in brackets for clarification. h In cases where the old name is used to describe two different species in the current system, the uses are indicated under both the current names. i Vernacular name. A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Helichrysum tenax M.D. Hend var. tenax (=Helichrysum fulgidum (L.f) Willd. 30h Biological activityb 638 Table 1 (Continued ) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 In some cases, one species name was changed to another, for example Helichrysum adscendens Less. var. cephaloideum Moeser. in Watt and Breyer-Brandwijk (1962) is now known as Helichrysum cephaloideum DC. In other instances, a Helichrysum species now belongs to a different genus for example, Helichrysum capillaceum (Thunb.) Less. (Watt and Breyer-Brandwijk, 1962) is now classified as Troglophyton capillaceum subsp. capillaceum (Hilliard, 1983). Sometimes the same species name with only a different author name refers to a different species, for example Helichrysum calocephalum Schltr, which is now classified as Helichrysum ecklonis and not Helichrysum calocephalum Klatt (Gibbs Russell et al., 1987; Germishuizen and Meyer, 2003). Batten and Bokelmann (1966), Jacot Guillarmod (1971), Phillips (1917) and Watt and BreyerBrandwijk (1962) all used Helichrysum calocephalum Schltr., which is now recognised as Helichrysum ecklonis, but in Arnold et al. (2002) there is no reference to Helichrysum ecklonis yet the abovementioned sources are used as references under Helichrysum calocephalum Klatt. The specific Helichrysum species referred to when Helichrysum crispum is used in ethnobotanical literature is also ambiguous. Germishuizen and Meyer (2003) stated that Helichrysum crispum of authors other than (L.) D. Don. is Helichrysum patulum (L.) D. Don. and not Helichrysum crispum (L.) D. Don. In Watt and Breyer-Brandwijk (1962) and Smith (1966), the name appears as Helichrysum crispum Less. therefore indicating Helichrysum patulum, although Arnold et al. (2002) cited the name Helichrysum crispum (L.) D. Don. (with reference to Smith, 1966) as well as Helichrysum patulum with reference to Watt and Breyer-Brandwijk (1962). Roberts (1990) used Helichrysum crispum without an author name, causing uncertainty as to which particular species is referred to; the cited medicinal uses are however similar to those indicated by Watt and Breyer-Brandwijk (1962) for Helichrysum crispum Less. Salie and co-workers (1996) determined that Helichrysum crispum (L.) D. Don. had weak (10 mg/ml) antimicrobial activity against Pseudomonas aeruginosa. Both Salie et al. (1996) and Swanepoel (1997) use the name Helichrysum crispum (L.) D. Don., but when indicating its traditional uses refer to Watt and Breyer-Brandwijk (1962). Scott et al. (2004) showed that Helichrysum patulum had antimicrobial activity against Staphylococcus aureus in the disc diffusion assay that was comparable to that of the ciprofloxacin control, while the traditional uses indicated correspond very well to those reported in Watt and Breyer-Brandwijk (1962) for Helichrysum crispum Less. Both species occur in the same region making exclusion of one species on the basis of distribution impossible. Helichrysum pedunculare DC. is another name with an unfortunate and confusing history. In this case, it seems that Helichrysum pedunculare DC. in ethnobotanical literature could refer to either Helichrysum pedunculatum Hilliard and Burtt or Helichrysum nudifolium var. pilosellum (previously known as Helichrysum pedunculare (L.) DC. var. pilosellum) (Hilliard, 1983; Arnold et al., 2002; Germishuizen and Meyer, 2003). The vernacular name and uses indicated by for example Watt and Breyer-Brandwijk (1962) for Helichrysum pedunculare DC. and Bhat and Jacobs (1995) for Helichrysum pedunculatum Hilliard and Burtt. is similar. According to Hilliard (1983), Helichrysum pedunculare (L.) DC. is also a synonym for Helichrysum odoratissimum (L.) Sweet. In some instances it is impossible to decide to which species an author refers, for example Helichrysum agrostophilum Klatt (Watt and Breyer-Brandwijk, 1962) that was in part changed to Helichrysum pallidum DC. and in part to Helichrysum griseum Sond (Germishuizen and Meyer, 2003). 639 2.2. Administration routes Plant parts used include the leaves, stems, flowers, roots and sometimes the whole plant. The plant remedies are administered in different ways, including the preparation of teas, inhalation of smoke and vapours and placement of leaves in the form of a poultice on wounds to prevent infection (Table 1). Several of these species are known by the same vernacular names, for example Helichrysum cymosum, Helichrysum nudifolium, Helichrysum odoratissimum and Helichrysum petiolare are all known as imphepho which indicates that they can be used interchangeably, as Van Wyk et al. (2000), noted that “use often depends on local availability rather than preference for a particular species”. 2.3. Traditional uses of South African Helichrysum species The traditional uses of Helichrysum in South Africa are summarised in Table 1. There are several recurring South African traditional uses for plants from this genus. Smoke is often inhaled to induce trances or to invoke the goodwill of the ancestors. They are often used to treat respiratory conditions and leaves are often applied as wound dressings. They are used in the treatment of gastro-intestinal disorders such as abdominal pain and colic and also eye conditions. They also seem to have an effect on the relief of pain and inflammation as they are used to treat menstrual pain, rheumatism and headaches. The plants are used to fumigate huts and also used as bedding to repel insects. 2.4. Correlation between medicinal uses and morphological groups Plants from almost all morphological groups are used medicinally and the broad spectrum of uses are not restricted to a specific morphological group. In some cases there does seem to be a relationship between the morphological group (according to Hilliard, 1983) or adjacent morphological classes and the traditional uses of these plants. Helichrysum epapposum (group 3), Helichrysum natalitium (group 3), Helichrysum gymnocomum (group 4) and Helichrysum odoratissimum (group 4) all share the Zulu/Xhosa name imphepho and all are burnt as incense to invoke the goodwill of the ancestors. However, this particular use applies to many species such as, Helichrysum cymosum (group 8), Helichrysum petiolare (group 18), Helichrysum dregeanum (30) and in some sources Helichrysum nudifolium (23) share the same vernacular name and use. Helichrysum cymosum (group 8), Helichrysum kraussii (group 8), Helichrysum melanacme (group 8), Helichrysum athrixiifolium (group 9) and Helichrysum dregeanum (group 9) are all used to treat respiratory complaints such as coughs and colds. The administration route of these remedies do however vary; for Helichrysum arthrixiifolium the leaf is smoked, for Helichrysum kraussii the dried flowers and seeds are smoked in a pipe, for Helichrysum cymosum a decoction of leaves is drunk, for Helichrysum dregeanum the leaf is smoked and the administration route is not indicated in the source for Helichrysum melanacme. South African species are not often used to treat heart and kidney ailments. Both Helichrysum pandurifolium and Helichrysum patulum belongs to group 18, and are indicated in the treatment of kidney disease and heart disorders. Both are also used to treat backpain and respiratory conditions by the same administration route. Plants from groups 23 and 24 are often used to treat wounds. The leaves of Helichrysum miconiifolium (group 23), Helichrysum nudifolium (group 23), Helichrysum pedunculatum (group 23), Helichrysum appendiculatum (group 24) and Helichrysum longifolium (group 24) are all used as wound dressings. However, Helichrysum foetidum (group 30) is mentioned as a replacement for Helichrysum pedun- 640 A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 culatum in the treatment of circumcision wounds (Gerstner, 1938). The species constituting group 23 are also used for respiratory conditions including, Helichrysum mundtii, Helichrysum nudifolium and Helichrysum pedunculatum. Root decoctions of both Helichrysum adenocarpum and Helichrysum ecklonis belonging to group 28 are used to treat diarrhoea in children, while a root infusion from Helichrysum argyrophyllum (group 29) is used to treat intestinal troubles. It is interesting to note that the only two species indicated for the treatment of snakebite both belong to group 30, namely Helichrysum cooperi and Helichrysum setosum. 3. Phytochemistry The chemistry of this genus is complex with a wide variety of chemical classes occurring as is evident from the three major publications by Bohlmann and Jakupovic (Bohlmann and Zdero, 1980a; Jakupovic et al., 1986; Jakupovic et al., 1989) in which a total of 63 South African Helichrysum species were investigated chemically. The classes of compounds isolated from the South African Helichrysum species are summarised in Table 2 and Fig. 1. Acylphloroglucinols (1–3) are common, often with prenyl or geranyl side chains. The replacement of the cinnamic moiety by other acyl CoA derivatives in the biosynthesis of the main constituents seem to be characteristic (Jakupovic et al., 1989). The presence of humulone derivatives, such as helihumulone (4) is also widespread (Jakupovic et al., 1989). Flavonoids (5–11) derived from phloroglucinol are very common and often have unsubstituted B rings (Bohlmann and Abraham, 1979a,d; Jakupovic et al., 1986) which is a characteristic feature of plants from the Inuleae tribe (Harborne, 1977). The presence of 6and 8-hydroxyflavonols and their methyl ethers (7) are also frequent as in other members of the tribe (Harborne, 1977). A wide variety of chalcones (8–10) are also found, including dihydrochalcones (11), pyranochalcones (10) and those substituted with prenyl (9) or geranyl groups. As in other Inuleae species, these chalcones are often accompanied by their structurally and biogenetically related flavanones (Harborne, 1977) as can be seen for Helichrysum acutatum (5 and 8) (Bohlmann and Abraham, 1979c), Helichrysum cymosum (Jakupovic et al., 1989) and Helichrysum oreophilum (Jakupovic et al., 1986). The presence of ␣-pyrones (12) is rather common (they occur in plants from morphologic groups 1, 2, 4, 12, 15, 18, 19 and 24) and they are often isolated from the roots of these plants (Hänsel et al., 1980; Jakupovic et al., 1986, 1989). Different types of diterpenes occur; these include the kaurenoic acid type (15, Jakupovic et al., 1989) as well as those derived from helifulvanic acid (13, Bohlmann et al., 1980b). Sesquiterpenes representing a variety of skeletal types occur, as is characteristic for the rest of the family (Hegnauer, 1977). Some skeletal types, such as the humulenes, are widely distributed across the genus, whereas others such as the guaianolides (16) are restricted to a few species (morphological groups 10 and 22). Helichrysum species are known for their aromaticity and a variety of monoterpenes are reported in the essential oils of some species (Lourens et al., 2004; Frum and Viljoen, 2006; Van Vuuren et al., 2006; Asekun et al., 2007). Squalene is the most common triterpene found and is often in high concentration. Another unusual type of compound that occurs is thiophene derivatives (17, 18) which have been isolated from the roots of species such as Helichrysum acutatum and Helichrysum tenuifolium. These thiophenes are the result of addition reactions of a common chloro-acetylene precursor with H2 S (Bohlmann and Abraham, 1979b,c). Simple polyacetylenes (20) are widespread. Acetylenics with pyran (19) and furan moieties, some with epoxy and/or chlorine substitution, occur in these plants and is characteristic of the Gnaphaliineae (Harborne, 1977). As for the traditional uses, one particular class of compound is not restricted to a particular morphologic group. However, there are some compounds that occur mainly in a specific morphological class. For example, phloroglucinols (excluding those belonging to the flavonoid class) feature as major compounds in morphological classes 2, 3, 4, 12, 14, 15, 20, 24 and 28. Flavonoids are present in almost all of the morphological groups, but a large number are found in plants from groups 8, 9 and 27. Diterpenes were isolated in large quantities from species in groups 23, 25 and 30 (all 10 plants investigated in this group had this type of compound as the major chemical species). Helichrysum umbraculigerum from group 5 seems to be the only species investigated that contains compounds of the cannabigerol type (21) as the major constituent and Helichrysum dasyanthum (group 10) and Helichrysum splendidum (group 22) contain mainly sesquiterpenes of the guaianolide type (which is absent in the other species). Plants from groups 6, 18 and 19 are also rich in sesquiterpenes (Table 2). Although there seem to be similarities in the chemistry of the European and South African species, the Australian species are chemically different from their South African counterparts (Jakupovic et al., 1989, 1989a). 4. Biological activity 4.1. Anti-infective activity Considering the traditional uses of this genus (specifically the treatment of wounds and respiratory tract infections and the application as a fumigant for example), there seems to be a strong indication that these plants and their compounds should exhibit antimicrobial activity. Several studies on the antimicrobial activity of Helichrysum species was done by the group of Meyer from the University of Pretoria, South Africa. Extracts of several species (Table 1) were submitted to antibacterial testing using a group of randomly selected bacteria which normally included the Gram-positive bacteria: Bacillus cereus, Bacillus pumilis, Bacillus subtilis, Micrococcus kristinae, Staphylococcus aureus and the Gram-negatives: Enterobacter cloaceae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens. Acetone extracts were mostly tested, but in a few cases methanol, water and dichloromethane extracts were used. Assays involving agar dilution and direct autobiography were employed (Meyer and Afolayan, 1995; Meyer and Dilika, 1996; Afolayan and Meyer, 1997; Dilika et al., 1997; Mathekga and Meyer, 1998; Bremner and Meyer, 2000; Mathekga et al., 2000; Mathekga, 2001). Antifungal activity was also determined for fungi such as Aspergillus flavus, Aspergillus niger, Cladosporium cladosporioides, Cladosporium cucumerinum, Cladosporium sphaerospermum and Phytophthora capsici (Mathekga, 2001). Reports on antimicrobial activities from other laboratories include the relatively weak antimicrobial activity (Gibbons, 2004) documented for extracts of Helichrysum foetidum (MIC’s of more than 4 mg/ml against all selected bacteria in the 96-well plate assay, Steenkamp et al. (2004) and Helichrysum crispum (L.) D. Don. where MIC’s of 10 mg/ml were reported against Pseudomonas aeruginosa and Candida albicans (Salie et al., 1996). Activities ranging from 0.078 to 0.3 mg/ml against Gram-positive bacteria, Gram-negative bacteria and yeasts were also reported for a Helichrysum cymosum extract (Van Vuuren et al., 2006). Acetone and methanol extracts of Helichrysum odoratissimum (incorrectly identified as Helichrysum dasyanthum in Lourens et al., 2004), Helichrysum excisum, Helichrysum felinum and Helichrysum petiolare displayed activity against Staphylococcus aureus and Bacillus cereus. The species with the best Table 2 Classes of compounds isolated from South African Helichrysum species Species Morphologic group Flavonoid derivativesa , b A B X X C D E Phloroglucinolsb Pyronesb Diterpenesb Terpenesb Otherb Reference X X X Bohlmann and Abraham (1979c) X Bohlmann et al. (1980a) F Helichrysum acutatum DC.c Roots and aerial parts 21 Helichrysum adenocarpum DC.c Roots and aerial parts 28 Helichrysum albirosulatum Killick Roots and aerial parts 6 Helichrysum allioides Less. Roots 23 Helichrysum anomalum Less. Aerial parts 9 Helichrysum appendiculatum (L.f.)c Less. Aerial parts 24 Helichrysum argentissimum J.M. Wood. Roots 28 Helichrysum argyrolepis MacOwan Aerial parts 29 Helichrysum argyrophyllum DC.c Aerial parts and roots 29 Helichrysum asperum (Thunb.) Hilliard et Burtt. var. albidulum (DC.) Hilliard Aerial parts 12 Helichrysum athrixiifolium (Kuntze)c Moeser Aerial parts and roots 9 Helichrysum aureonitens Sch. Bip.c Roots and aerial parts 8 Helichrysum aureum (Houtt.) Merr.c Aerial parts and roots 30 XX X Jakupovic et al. (1989) Helichrysum aureum (Houtt.) Merr. var. monocephalum (DC.) Hilliard Aerial parts and roots 30 XX X Bohlmann et al. (1978a) Helichrysum auriceps Hilliard Roots 24 X Helichrysum bellum Hilliard Aerial parts and roots 28 X Helichrysum caespititium DC. Harv.c Whole plant Aerial parts 12 X X Bohlmann et al. (1980a), Bohlmann et al. (1978a) X X X X X Jakupovic et al. (1989) X Bohlmann et al. (1980a) X X X Bohlmann et al. (1984) X X X XX Jakupovic et al. (1989), Bohlmann and Zdero (1973) Jakupovic et al. (1989) XXXX X Bohlmann et al. (1980a) X Bohlmann and Ates (1984) X XX X X X X Bohlmann and Ziesche (1979), Afolayan and Meyer (1997), Meyer et al. (1997) X Bohlmann and Zdero (1980) X Bohlmann and Zdero (1979a) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 X Bohlmann and Zdero (1973) Dekker et al. (1983), Mathekga et al. (2000) 641 642 Table 2 (Continued ) Species Morphologic group Flavonoid derivativesa , b A B C D E Phloroglucinolsb Pyronesb Diterpenesb Terpenesb Otherb Reference XX X X XX X Bohlmann and Abraham (1979a) (Helichrysum calliconumd ) Bohlmann et al. (1984) F 2 Helichrysum candolleanum H. Buek Aerial parts 15 Helichrysum cephaloideum DC. Roots and aerial parts 24 Helichrysum cerastioides DC. Aerial parts 15 Helichrysum chionosphaerum DC. Aerial parts and roots 25 X Helichrysum chrysargyrum Moeser Aerial parts and roots 22 X Helichrysum confertum N.E.Br Roots 17 Helichrysum cooperi Harv.c Roots and aerial parts 30 Helichrysum cooperi ps. aff. Helichrysum cooperi Harv. Helichrysum cymosum (L.) D. Don.c Aerial parts ? Helichrysum cymosum (L.) Don. ssp.c calvum Roots and aerial parts 8 Helichrysum cymosum (L.) D. Don.c ssp. cymosum Helichrysum dasyanthum (Willd.) Sweet Aerial parts 8 Helichrysum dasymallum Hilliard (=Helichrysum lanatum Harv.) Roots 21 Helichrysum decorum DC.c Aerial parts 30 Helichrysum drakensbergense Killick Roots and aerial parts 19 Helichrysum dregeanum Sond. and Harv.c Aerial parts 9 X X X Helichrysum felinum Less. Aerial parts 17 X X X 8 X X X Jakupovic et al. (1989) X XXX XX X X Hänsel et al. (1980), Bohlmann and Zdero (1980), Jakupovic et al. (1986) X XXX XX XX X Bohlmann et al. (1984), Jakupovic et al. (1989) (Helichrysum cerastroides DC. supsp. aurosicum Merxm. et A. Schreiberd ) X Bohlmann et al. (1980b), Jakupovic et al. (1989) X X Bohlmann et al. (1979a) XX Bohlmann et al. (1978a) X Bohlmann et al. (1978a) X XX Wright (1976) X X XX X X X Bohlmann et al. (1979b) X Van Vuuren et al. (2006) X 10 Jakupovic et al. (1989) X X XX X Jakupovic et al. (1989) X Bohlmann and Zdero (1973) (Helichrysum lanatum DC.d ) X Bohlmann et al. (1980a) X X XX X X Bohlmann and Suwita (1979) Jakupovic et al. (1989) Jakupovic et al. (1989) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Helichrysum callicomum Harv.c Aerial parts and roots Helichrysum flanaganii Bolusc Aerial parts and roots 13 Helichrysum foetidum (L.) Moench.c Roots 30 Helichrysum fulvum N. E. Br. Aerial parts and roots 30 Helichrysum glaciale Hilliard Aerial parts 27 Helichrysum glomeratum Klatt Aerial parts 6 Helichrysum grandiflorum (L.) D. Don. Roots 17 Helichrysum gymnocomum DC.c Roots and aerial parts 4 Helichrysum gymnocomum DC.c Flowers 4 X Helichrysum herbaceum (Andrews) Sweetc Aerial parts 29 X Helichrysum heterolasium Hilliard Aerial parts 30 Helichrysum hyphocephalum Hilliard Aerial parts and roots 27 Helichrysum indicum (L.) Griersonc Aerial parts 15 X Helichrysum infaustum J.M. Wood. and M.S. Evans Aerial parts 4 X Helichrysum kraussii Sch. Bip.c Aerial parts, flowers and roots 8 Helichrysum krebsianum Less. Aerial parts 23 Helichrysum krookii Moeser Roots and aerial parts 5 Helichrysum lepidissimum S. Moore Aerial parts 19 Helichrysum litorale Bolusc (=Leontonyx angustifolius DC., =Leontonyx spathulatus Less.) 14 X Bohlmann et al. (1980a) XX X Bohlmann and Zdero (1973) X Bohlmann et al. (1979c) Bohlmann et al. (1980a) X X X Bohlmann and Suwita (1979) XX X X X X Drewes and Van Vuuren (2008) XX X X X XX XX X X Bohlmann and Mahanta (1979) (Helichrysum gymnoconum DC.d ) X X Bohlmann et al. (1979a) XX X Bohlmann and Abraham (1979a) X X Bohlmann and Abraham (1979d) (Helichrysum hypocephalum Hilliardd ) Jakupovic et al. (1989) X X X Bohlmann and Suwita (1979) XX Jakupovic et al. (1989), Bremner and Meyer (2000), Candy et al. (1975), Candy and Wright (1975) X XX X X Bohlmann et al. (1980a) X X XX A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 XX Bohlmann and Zdero (1973) X X Bohlmann et al. (1980a) X Jakupovic et al. (1989) Bohlmann and Suwita (1978) (Leontonyx spathulatus Less.d ) 643 Species 644 Table 2 (Continued ) Morphologic group Flavonoid derivativesa , b A B C X D E Phloroglucinolsb Pyronesb Helichrysum miconiifolium DC.c Roots 23 Helichrysum mimetes S. Moore Aerial parts 19 Helichrysum mixtum (Kuntze.) Moeser Roots 24 XX Helichrysum moeseranium Thell. Aerial parts 22 X Helichrysum monticola Hilliard Aerial parts and roots 28 X Helichrysum mundtii Harv.c (=Helichrysum mundii Harv.)d Roots and aerial parts 23 X Helichrysum nanum Klatt Aerial parts 6 X Helichrysum natalitium DC.c Aerial parts and roots 3 XX Helichrysum nudifolium L. Less. var. nudifoliumc Aerial parts and roots 23 XX Helichrysum nudifolium var. oxyphyllum (=Helichrysum oxyphyllum DC.)c Aerial parts 23 Helichrysum nudifolium var. pilosellum (=Helichrysum latifolium Less.)c Helichrysum nudifolium var. pilosellum (=Helichrysum pilosellum (L.f.) Less.) Roots 23 X X X X X 21 Helichrysum pagophilum M.D. Hend. Aerial parts 27 X Bohlmann et al. (1980a) Jakupovic et al. (1986) XX XX Jakupovic et al. (1986) Jakupovic et al. (1989) X XX X X X Jakupovic et al. (1989), Bohlmann and Zdero (1980a) X X Bohlmann et al. (1978b), Bohlmann et al. (1980a) X X Bohlmann and Suwita (1979) X X Bohlmann and Zdero (1979a) X XXX X X X Jakupovic et al. (1986), Bohlmann et al. (1978a) (Helichrysum nudifolium L. Less.d ) Bohlmann and Zdero (1973) (Helichrysum nudifolium L. Less.d ) Bohlmann et al. (1980a) (Helichrysum oxyphyllum Klattd ) X Bohlmann and Zdero (1973) (Helichrysum latifolium Less.d ) Jakupovic et al. (1986) (Helichrysum pilosellum (L.f.) Less.d ) XX X X X X XX X X Reference Lall et al. (2006) 23 Helichrysum oreophilum Klatt. Aerial parts Otherb X X X X X Van Puyvelde et al. (1989), Hänsel et al. (1980), Bohlmann and Zdero (1973) Jakupovic et al. (1986), Bohlmann et al. (1980a) Bohlmann et al. (1980a) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 8 4 Terpenesb F Helichrysum melanacme (DC.) Harv.c Shoots Helichrysum odoratissimum (L.) Sweetc Aerial parts and roots Diterpenesb 23 Helichrysum panduratum O.Hoffm.c Aerial parts 18 Helichrysum patulum (L.) D. Don.c (=Helichrysum crispum Less.) Aerial parts 18 Helichrysum pedunculatum Hilliard and Burttc Leaves 23 Helichrysum petiolare Hilliard and B.L. Burtt.c Aerial parts 18 Helichrysum platypterum DC.c Aerial parts and roots 20 Helichrysum polycladum Klatt Aerial parts and roots 8 Helichrysum populifolium DC. Roots 16 Helichrysum reflexum N. E. Br. Aerial parts 29 Helichrysum revolutum (Thunb.) Less. Aerial parts 9 Helichrysum retortoides N.E. Br. Aerial parts 26 Helichrysum rosum (Berg.) Less. Aerial parts 9 Helichrysum nudifolium L. Less. var. nudifolium (=Helichrysum coriaceum Harv.) Roots 23 XX Helichrysum ruderale Hilliard and B.L. Burtt. Aerial parts 30 X Helichrysum rugulosum Less.c Aerial parts and roots 9 Helichrysum scabrum (Thunb.) Less. Aerial parts 9 Helichrysum setosum Harv.c Aerial parts 30 Helichrysum spiralepis Hilliard and Burtt. (=Leontonyx squarrosus) 14 XX XX X X X X X X X X X XXX X Bohlmann et al. (1980a) X Bohlmann and Abraham (1979b) X Bohlmann and Suwita (1979) (Helichrysum crispum Less.d ) XX X X XX X X X Dilika et al. (2000) X Jakupovic et al. (1989), Bohlmann and Zdero (1973) (Helichrysum petiolatum DC.d ) X Jakupovic et al. (1986), Bohlmann et al. (1980a), Bohlmann and Zdero (1979a), Jakupovic et al., 1987 X Bohlmann et al. (1980a) X Bohlmann et al. (1980a) Bohlmann et al. (1985) (Helichrysum refluxum N. E. Br.d ) XX X Jakupovic et al. (1989) X XX X X X Bohlmann et al. (1980a) X Jakupovic et al. (1989) X Bohlmann et al. (1984a) (Helichrysum coriaceum Harv.d ) Bohlmann et al. (1980a) XX X A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Helichrysum pallidum DC.c Aerial parts and roots Bohlmann and Misra (1984) Jakupovic et al. (1989) X XX XX Jakupovic et al. (1986) X Bohlmann and Suwita (1978) (Leontonyx squarrosusd ) 645 646 Table 2 (Continued ) Flavonoid derivativesa , b Morphologic group Helichrysum splendidum (Thunb.) Less.c Aerial parts and roots 22 Helichrysum subfalcatum Hilliard Aerial parts 6 Helichrysum subglomeratum Less.c Aerial parts 6 X X Helichrysum sutherlandii Harv. (=Helichrysum suterlandii Harv.)c Aerial parts and roots 17 X X Helichrysum swynnertonii S. Moore Aerial parts and roots 25 Helichrysum tenax var. tenax M.D. Hend. Leaves 30 Helichrysum tenuiculum DC. Aerial parts and roots 8 X Helichrysum tenuifolium Killick. Aerial parts and roots 22 X Helichrysum thapsus (O. Kuntze) Moeser Aerial parts 23 X Helichrysum tomentosulum Klatt. Merxm subsp. aromaticum (Dinter) Merxm.c Aerial parts 1 Helichrysum tricostatum (Thunb.) Less. Aerial parts 11 Helichrysum trilineatum DC. Shoots and roots 22 Helichrysum umbraculigerum Less. Aerial parts 5 Helichrysum vernum Hilliard Roots 28 Helichrysum zeyheri Less. Aerial parts 1 A a b c d B C D X X E Phloroglucinolsb Pyronesb Diterpenesb Terpenesb Otherb Reference XXX X Bohlmann and Suwita (1979a), Jakupovic et al. (1989) F X X Bohlmann et al. (1980a) X Jakupovic et al. (1989) X X Bohlmann et al. (1978b), Bohlmann et al. (1980a) X Bohlmann et al. (1980a) Drewes et al. (2006) XX X X X X X X X X Bohlmann et al. (1979b) XX X X Bohlmann and Abraham (1979b) Bohlmann and Zdero (1983) X Jakupovic et al. (1989) X Jakupovic et al. (1989) X X X X A = flavanone, B = chalcone, C = dihydrochalcone, D = flavonol, E = flavone, F = other flavonoids. X = 3 or less compounds isolated; XX = 4–9 compounds isolated; XXX = 10 or more compounds isolated, XXXX = more than 20 compounds isolated. Used in traditional medicine. Name as used in reference. X X Bremner and Meyer (1998), Bohlmann et al. (1980a) X XXX Bohlmann and Hoffmann (1979) X Bohlmann et al. (1980a) X Jakupovic et al. (1986) A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Species A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 Fig. 1. Compounds isolated from South African Helichrysum species. 647 648 A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 activity was the acetone extract of Helichrysum odoratissimum with an MIC of 0.016 mg/ml against Staphylococcus aureus (which correlates well with the values obtained by Mathekga and Meyer, 1998). Helichrysum species are often used to treat respiratory conditions and tuberculosis (Table 1). Extracts of Helichrysum odoratissimum and Helichrysum melanacme showed activity against Mycobacterium tuberculosis at concentrations of 0.5 mg/ml (Lall and Meyer, 1999; Lall et al., 2006). The acetone extract of Helichrysum caespititium inhibited a drug sensitive-strain of Mycobacterium tuberculosis at a concentration of 0.5 mg/ml in the agar plate method and a MIC of 0.1 mg/ml was observed using the rapid radiometric method (Meyer et al., 2002). The water extract caused partial inhibition at the highest concentration of 5 mg/ml. In some cases the antimicrobial activity of isolated compounds was determined. Flavonoids are generally one of the largest classes of antibacterial compounds (Gibbons, 2004). Galangin (3,5,7trihydroxyflavone) isolated from Helichrysum aureonitens (Meyer and Afolayan, 1995), inhibited the growth of four Gram-positive bacteria (three Bacillus species and Micrococcus kristinae) as well as the Gram-negative Enterobacter cloaceae (Afolayan and Meyer, 1997). The highest activity observed was against Bacillus cereus, Micrococcus kristinae and Enterobacter cloaceae at 0.1 mg/ml. In other studies by Cushnie et al. (2003) and Cushnie and Lamb (2006), the activity of galangin was shown against six strains of ␤-lactam sensitive and resistant strains of Staphylococcus aureus and 16 strains of 4-quinolone resistant strains of the bacterium at MIC’s of approximately 50 ␮g/ml. Galangin also displays some antifungal activity against fungi such as Aspergillus tamari (35% growth inhibition at 0.5 mg/ml) (Afolayan and Meyer, 1997). These results support the use of Helichrysum aureonitens in the treatment of skin infections, often caused by Staphylococcus aureus. Another flavonoid, 3-O-methylquercetin was isolated from Helichrysum odoratissimum and antimicrobial activity determined for a broad range of micro-organisms including Gram-negative bacteria such as Salmonella typhimurium (MIC = 50 ␮g/ml), Grampositive bacteria, such as Staphylococcus aureus (MIC = 6.25 ␮g/ml) and fungi, for example Candida albicans (MIC = 12.5 ␮g/ml), in the microdilution method (Van Puyvelde et al., 1989). Bremner and Meyer (1998) also reported on the anti-staphylococcal activity for pinocembrin chalcone (8, isolated from Helichrysum trilineatum), as well as pinocembrin (5) that was obtained as an artifact during the isolation procedure. Flavonoids isolated from the flowers of Helichrysum gymnocomum exhibited promising antimicrobial activity against a wide variety of Gram-positive and Gram-negative organisms as well as yeasts. An MIC of 8 ␮g/ml was for example observed against Cryptococcus neoformans for 5,7-dibenzyloxyflavanone (Drewes and Van Vuuren, 2008). Two chalcones isolated from Helichrysum melanacme (9, 10) exhibited MIC’s of 0.05 mg/ml against the drug sensitive H37Rv strain of Mycobacterium tuberculosis. The activity of the chalcones was higher than that of the crude extract but a combination of the two chalcones did not result in an improved MIC (Lall et al., 2006). There are also reports on the antimicrobial activity of compounds other than flavonoids. Activity against Gram-positive bacteria was observed for both linoleic and oleic acids, isolated from antibacterial extracts of Helichrysum pedunculatum (a plant used to treat circumcision wounds, Dilika et al., 2000). The MIC of both fatty acids was 1.0 mg/ml for Staphylococcus aureus and Micrococcus kristinae in the agar diffusion assay. The MIC’s was 0.05 mg/ml of each fatty acid when they were administered at the same time (Dilika et al., 2000). Kaurenoic acid (15, a diterpene), isolated from Helichrysum kraussii, exhibited a MIC as low as 1 ␮g/ml against Escherichia coli and MIC’s of 10 ␮g/ml against Bacillus cereus, Bacillus sub- tilis, Staphylococcus aureus and Serratia marcescens (Bremner and Meyer, 2000). Significant antimicrobial activity was also observed for monomeric (14) and dimeric diterpenes from Helichrysum tenax var. tenax. MIC values as low as 3.1 and 3.6 ␮g/ml were determined against Bacillus cereus whereas MIC’s as low as 41.5 ␮g/ml were determined for a Gram-negative organism such as Pseudomonas aeruginosa (Drewes et al., 2006). MIC’s of 100 ␮g/ml were observed for prenylated butyrylphloroglucinol (3) isolated from Helichrysum kraussii against Bacillus cereus, Bacillus pumilis, Bacillus subtilis, Micrococcus kristinae, Staphylococcus aureus, Serratia marcescens and Escherichia coli in an agar diffusion assay (Bremner and Meyer, 2000). The same phloroglucinol was isolated from Helichrysum gymnocomum and MIC’s of below 100 ␮g/ml (6–45 ␮g/ml) were reported for Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Cryptococcus neoformans and Candida albicans (Drewes and Van Vuuren, 2008). A difference in assays employed, inoculum size and possibly different strains of the same micro-organism used may account for the observed difference in activity. A structurally related phloroglucinol also exhibited promising antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa and Cryptococcus neoformans (Drewes and Van Vuuren, 2008). Caespitin (1) and caespitate (2) (both phloroglucinols) exhibited antimicrobial activity against several bacteria as well as fungi (Dekker et al., 1983; Mathekga et al., 2000). Caespitin (1) was active against Staphylococcus aureus, Streptococcus pyogenes, Cryptococcus neoformans, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis although neither the method used nor the level of activity, are indicated in the relevant article (Dekker et al., 1983). Caespitate (2), exhibited antibacterial activity against the Gram-positive Bacillus cereus, Bacillus pumilis, Bacillus subtilis, Micrococcus kristinae and Staphylococcus aureus at concentrations of 0.5 ␮g/ml in the agar dilution method (Mathekga et al., 2000). This compound also exhibited antifungal activity which ranged from 0.5 to 1.0 ␮g/ml against Aspergillus flavus, Aspergillus niger, Cladosporium cladosporioides, Cladosporium cucumerinum, Cladosporium sphaerospermum and Phytophtora capsici (Mathekga et al., 2000). Caespitate (2) was also active against several Mycobacterium tuberculosis strains at a concentration of 0.1 mg/ml which was similar to the MIC observed for the crude extract of Helichrysum caespititium (Meyer et al., 2002). Several caespitin derivatives were synthesised with MIC values as low as 2 ␮g/ml against Staphylococcus aureus and Streptococcus pyogenes. These compounds also exhibit antifungal activity. The possible development of antimicrobial resistance was examined as well as the development of cross resistance with known antimicrobials (Van der Schyf et al., 1986). For helihumulone (4), a phloroglucinol of the humulone type, activity was exhibited for a broad range of micro-organisms with some promising results, for example 16 ␮g/ml against Pseudomonas aeruginosa. The antimalarial activity of this compound was determined to be 15 ␮g/ml (Van Vuuren et al., 2006). As previously mentioned, the South African Helichrysums contain a large amount of phloroglucinol derivatives and considering the promising antimicrobial activity observed for this type of compound, it seems a class well worth investigating. Aqueous extracts of Helichrysum aureonitens exhibited antiviral activity against the Herpes simplex virus type I in vitro at a concentration of 1.35 mg/ml (Meyer et al., 1996). The flavone, galangin, isolated from this plant also exhibited antiviral activity against Herpes simplex virus type I and the Coxsackie virus at concentrations of 6 ␮g/ml (Meyer et al., 1997). The antiviral activity was also determined for a crude ethanolic extract of Helichrysum melanacme and its isolated constituents. The activity of the isolated prenylated chalcone (9) and a pyranochalcone (10) was lower A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 (IC50 = 0.1 mg/ml) against the Influenza A virus than that of the crude extract (0.01 mg/ml) although a combination of the two chalcones resulted in an improved IC50 (0.01 mg/ml, Lall et al., 2006). In summary, the crude extracts generally show some degree of antimicrobial activity, which is usually higher against Grampositive organisms than against Gram-negative organisms. Although the antibacterial and antifungal activities of these plants are well documented, antimalarial, antimycobacterial and antiviral data are scarce. Isolated compounds sometimes exhibit more superior activity when compared to the crude extract, but often the crude extract has similar activity. Correct identification of plant material is crucial as misidentification of plant material can lead to incorrect reporting (Lourens et al., 2004). The selected range of concentrations is often on the high side (Gibbons, 2004, considered values of below 1 mg/ml for extracts and 64 ␮g/ml for single chemical entities as significant); for example a range of 10–100 mg/ml was used for Helichrysum pedunculatum extracts (Meyer and Dilika, 1996). Positive controls (antibiotics) are absent in some of the assays (Mathekga et al., 2000), making it difficult to comparatively assess the activity of a particular extract or compound. The fact that different assays are employed impairs comparison of data between different laboratories (assays relying on diffusion are especially suspect since a low rate of diffusion would present a low activity, which is not always a true representation). Microbial strains are often not referenced and the number of colony forming units not mentioned (Meyer and Afolayan, 1995). Extracts also often do not dissolve completely in the solvents used and as Cushnie illustrated with galangin (2003) this can have a profound effect on the MIC’s observed (Cushnie et al., 2003). Chemical classes such as the flavonoids, acylphloroglucinols and diterpenes from South African Helichrysum species exhibit promising antimicrobial activity and plants that contain these compounds seems potential candidates for further study. 4.2. Other biological data Unpublished work done by Noristan laboratories indicates that fractions of the extract of Helichrysum caespititium exhibits anti-inflammatory activity of up to 82% at 360 mg/kg in the carrageenan test done on rats and prevents platelet aggregation (Swanepoel, 1997). Ethanolic extracts of Helichrysum subglomeratum and Helichrysum nudifolium inhibited prostaglandin synthesis in vitro by 69 and 96% (50 ␮g of plant extract used), respectively (Jäger et al., 1996). The group at Noristan determined that fractions of a Helichrysum nudifolium extract also reduced edema in the carrageenan assay by approximately 30% at 300 mg/kg in rats (Swanepoel, 1997). These results indicate that Helichrysum nudifolium has both in vitro and in vivo anti-inflammatory activity, possibly due to the inhibition of the cyclooxygenase enzymes. The group at Noristan observed that the second of three fractions obtained after gradient column chromatography (using petroleum ether, ethyl acetate and methanol) of a dichloromethane/methanol extract from Helichrysum panduratum showed a 79% reduction in pain experienced in the writhing pain test at 500 mg/kg. Edema was also reduced by 50% in the carrageenan test indicating that this plant has both anti-inflammatory and analgesic properties. It was also antihypertensive (a reduction of 6% in mean blood pressure was observed after administering a dose of 300 mg/kg) and weakly antimicrobial (Swanepoel, 1997). A fraction from a dichloromethane/methanol extract of Helichrysum petiolare investigated by the group from Noristan determined that administration of 300 mg/kg of extract to mice reduced mean blood pressure by 21% and resulted in a 6% reduction in heart rate (Swanepoel, 1997). Acetone extracts of Helichrysum excisum (IC50 = 35 ␮g/ml) and Helichrysum felinum (IC50 = 39 ␮g/ml) 649 inhibited the 5-lipoxygenase enzyme which also plays a role in inflammation. Antioxidant activity (as indicated with the DPPH assay) of acetone and methanol extracts of Helichrysum odoratissimum, Helichrysum excisum, Helichrysum felinum and Helichrysum petiolare was comparable to that of vitamin C, as expected for species rich in phenolic compounds (Lourens et al., 2004). European research further highlights the antioxidant and antiinflammatory effects displayed by plants from this genus. It is quite often the flowers that are investigated, a plant part that are seldom investigated in South African research (Drewes and Van Vuuren, 2008; Table 2). Antioxidant activity was reported for flower extracts from Helichrysum stoechas (Carini et al., 2001), Helichrysum arenarium (Czinner et al., 2000; Czinner et al., 2001) and Helichrysum italicum (Facino et al., 1990). In vivo (topical) antiinflammatory activity comparable to that of the indomethacin standard was observed for an acetophenone derivative, gnaphaliin (a flavonoid) and ursolic acid isolated from Helichrysum stoechas (Recio et al., 1991). In vivo and in vitro anti-inflammatory activity was also observed for acetophenone glucosides, flavonoids and other compounds isolated from Helichrysum italicum (Sala et al., 2001, 2002, 2003a,b) as well as for extracts from Helichrysum compactum (Süzgeç et al., 2005). These promising results indicate that more research should be undertaken on the anti-inflammatory activity of South African species, as many similar compounds appear in the South African and European species. As previously mentioned, Helichrysum species are often burnt as incense to invoke the goodwill of the ancestors, in protective and other charms and to induce trances. It is also used in the treatment of insanity, possession, used as a sedative to treat insomnia and as a protective cleanser (Table 1). Their traditional uses indicate that these plants may exhibit psychotropic effects. Stafford et al. (2005) determined the GABA-receptor binding effect of extracts from Helichrysum argyrolepis, Helichrysum herbaceum, Helichrysum nudifolium, Helichrysum ruderale, Helichrysum rugulosum, Helichrysum simillimum and Helichrysum umbraculigerum by using the 3 H-Ro 15-1788 binding assay. Helichrysum ruderale and Helichrysum umbraculigerum exhibited the most pronounced effects, while Helichrysum herbaceum, Helichrysum rugulosum and Helichrysum simillimum showed moderate to good dose dependant activity. There appears to be a large divide between the rich chemical data available and biological testing on compounds isolated from the South African species. One chemical class, the ␣-pyrones will be discussed as an example. By our rough estimate, 28 different pyrones were isolated from South African Helichrysum species. The same type of compounds was isolated from European species and rather interesting biological activity was observed. Italipyrone, plicatipyrone, a mixture of helipyrones and a mixture of homoarenol and arenol were all active against Bacillus subtilis, Staphylococcus aureus, S. epidermidis and Mycobacterium phlei using the agar diffusion method with the highest MIC being 25 ␮g/ml and the lowest 3 ␮g/ml (Ríos et al., 1991). Antifungal activity was also reported for ␣-pyrones isolated from Helichrysum decumbens (Tomás-Lorente et al., 1989). Pyrones (like arzanol and helipyrone) showed significant antioxidant activity and arzanol was not toxic at all concentrations tested (Rosa et al., 2007). Most interesting though is the findings by Appendino et al. (2007) that arzanol inhibits HIV-I replication in Tcells and inhibited NF-␬B (IC50 = 5 ␮g/ml) indicating that this group of compounds may exhibit both antiviral and anti-inflammatory properties. To our knowledge, none of the unique pyrones isolated from South African species were evaluated for biological activity. Most concerning is the almost complete absence of toxicity data for the South African species of this genus. In very few cases, for example where antiviral and antimalarial activities were determined (Meyer et al., 1996, 1997; Lall et al., 2006; Van Vuuren 650 A.C.U. Lourens et al. / Journal of Ethnopharmacology 119 (2008) 630–652 et al., 2006) toxicity is mentioned. Toxicity of the diterpenes is well known (for example IC50 values of below 4 ␮g/ml was reported for three diterpene lactones from Parinari capensis; Uys et al., 2002), and several Helichrysum species contain high amounts of these compounds, to name but one example. Furthermore, Reid et al. (2006) screened 42 medicinal South African plants for mutagenicity, which included Helichrysum herbaceum, Helichrysum nudifolium, Helichrysum ruderale, Helichrysum rugulosum, Helichrysum simillimum and Helichrysum umbraculigerum. The only three plants that showed mutagenic activity were all Helichrysums, namely Helichrysum herbaceum (at 5 mg/ml), Helichrysum rugulosum (at 5 mg/ml) and Helichrysum simillimum (at 0.05 mg/ml). These results highlight both the need and importance of toxicity and safety data for plants of this genus. In general, there also seems to be a large need for in vivo validation of in vitro results since the effectiveness of these extracts and their compounds have not been validated in living organisms. 5. Conclusion Helichrysum species are used extensively in ethnomedicine in South Africa and many of the uses are associated with the treatment of infections, e.g. it is used widely for treatment of respiratory diseases and wound dressing (Table 1). The large morphological diversity of the genus is complemented by chemical diversity as illustrated by the range of novel compounds isolated from the genus. Despite the extensive past and present traditional uses, the unrivalled botanical diversity, and the chemical complexity, it remains ironic that explorations of the biological activities of indigenous species are comparatively poorly studied. The genus is notoriously challenging from a taxonomic perspective and several examples have been highlighted to emphasise the importance of correct botanical identification when embarking on ethnopharmacological and phytochemical studies. There is an interesting relationship between the morphological classification and the classes of chemical compounds isolated from a specific morphological group and there are certain classes of compounds, e.g. diterpenes, guaianolides, acylated phloroglucinols and ␣-pyrone derivatives, for which one can predict in which species they are most likely to occur. This may be important in the search of new plant-derived drugs, e.g. acylated phloroglucinols show potential as anti-staphylococcal drug leads (Gibbons, 2004) and ␣-pyrone derivatives have anti-HIV properties (McGlacken and Fairlamb, 2005; Appendino et al., 2007). It is clear that Helichrysum is an interesting genus from an ethnobotanical, phytochemical and pharmacological perspective but that biological data to correlate the ethnobotany to the chemistry are often still lacking. To advance our knowledge on this fascinating genus a multidisciplinary approach involving botanists, chemists and ethnopharmacologists is required. Acknowledgements The authors thank Ms Mienkie Welman from the South African National Biodiversity Institute, Pretoria, for her help with enquiries on name changes and taxonomy and the National Research Foundation (South Africa) for the financial support of this project. References Afolayan, A.J., Meyer, J.J.M., 1997. 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