The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology.

Author’s Accepted Manuscript The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology Keshika Mahadeo, Isabelle Grondin, Hippolyte Kodja, Joyce Soulange Govinden, Sabina Jhaumeer Laulloo, Michel Frederich, Anne Gauvin-Bialecki www.elsevier.com/locate/jep

PII: DOI: Reference:

S0378-8741(17)30757-2 http://dx.doi.org/10.1016/j.jep.2017.08.023 JEP10993

To appear in: Journal of Ethnopharmacology Received date: 23 February 2017 Revised date: 17 August 2017 Accepted date: 18 August 2017 Cite this article as: Keshika Mahadeo, Isabelle Grondin, Hippolyte Kodja, Joyce Soulange Govinden, Sabina Jhaumeer Laulloo, Michel Frederich and Anne Gauvin-Bialecki, The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology, Journal of Ethnopharmacology, http://dx.doi.org/10.1016/j.jep.2017.08.023 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The genus Psiadia: Review of traditional uses, phytochemistry and pharmacology Keshika Mahadeoa, Isabelle Grondina, Hippolyte Kodjab, Joyce Soulange Govindenc, Sabina Jhaumeer Laullood, Michel Frederiche, Anne Gauvin-Bialeckia,* a

Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, Faculté des Sciences et Technologies, Université de la Réunion, 15 Avenue René Cassin, BP 7151, St Denis Messag Cedex 9, La Réunion 97 715, France b UMR Qualisud, Université de La Réunion, BP 7151, 15 avenue René Cassin, 97744 Saint-Denis Cedex 09, La Réunion, France c Department of Agriculture and Food Science, Faculty of Agriculture, The University of Mauritius, Mauritius d Department of Chemistry, Faculty of Science, The University of Mauritius, Mauritius e Université de Liège, Département de Pharmacie, Centre Interfacultaire de Recherche sur le Médicament (CIRM), Laboratoire de Pharmacognosie, Campus du Sart-Tilman, Quartier hôpital, Avenue Hippocrate, 15 B36 4000 Liège, Belgium

[email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] *Corresponding author

ABSTRACT: Ethnopharmacological relevance: The genus Psiadia Jacq. ex. Willd. belongs to the Asteraceae family and includes more than 60 species. This genus grows in tropical and subtropical regions, being especially well represented in Madagascar and the Mascarene Islands (La Réunion, Mauritius and Rodrigues). Several Psiadia species have been used traditionally for their medicinal properties in Africa and the Mascarene Islands. Based on traditional knowledge, various phytochemical and pharmacological studies have been conducted. However there are no recent papers that provide an overview of the medicinal potential of Psiadia species. Therefore, the aim of this review is to provide a comprehensive summary of the botany, phytochemistry and pharmacology of Psiadia and to highlight the gaps in our knowledge for future research opportunities. Materials and methods: The available information on traditional uses, phytochemistry and biological activities of the genus Psiadia was collected from scientific databases through a search using the keyword ‘Psiadia’ in ‘Google Scholar’, ‘Pubmed’, ‘Sciencedirect’, ‘SpringerLink’, ‘Web of Science’, ‘Wiley’ and ‘Scifinder’. Additionally, published books and unpublished PhD and MSc dissertations were consulted for botanical information and chemical composition. Results: Historically, species of the genus Psiadia have been used to treat a wide range of ailments including abdominal pains, colds, fevers, bronchitis, asthma, rheumatoid arthritis, skin infections and liver disorders among others. Phytochemical works led to the isolation of flavonoids, phenylpropanoids, coumarins and terpenoids. Furthermore, phytochemical compositions of the essential oils of some species have been evaluated. Crude extracts, essential oils and isolated molecules showed in vitro pharmacological activities, such as antimicrobial, anti-viral, antiinflammatory, antiplasmodial and antileishmanial activities. Crude extracts of Psiadia dentata and Psiadia arguta have specifically been found to be potentially useful for inhibition of growth of Plasmodium falciparum.

However, pharmacological data on this particular genus is quite limited. Further research is necessary to determine the active compounds and the underlying mechanisms.

Keywords: Psiadia, terpenoids, flavonoids, antiplasmodial, antimicrobial

TABLE OF CONTENTS 1. Introduction 2. Botany 2.1. Taxonomy 2.2. Conservation 3. Traditional uses 4. Chemical constituents 4.1. Flavonoids 4.2. Phenylpropanoids 4.3. Coumarins 4.4. Terpenoids 4.5. Essential oils 5. Pharmacological activities 5.1. Antimicrobial 5.2. Anti-viral 5.3. Anti-inflammatory 5.4. Antiplasmodial 5.5. Antileishmanial 5.6. Antitrypanosomal 5.7. Anticancer 5.8. Cytotoxicity 6. Conclusions and perspectives 1. Introduction The genus Psiadia, belonging to the Asteraceae family, consists of approximately 60 species growing in tropical and subtropical regions. They are predominantly found in Madagascar and the Mascarene islands (La Réunion, Mauritius, and Rodrigues). Indeed, 28 species were identified in Madagascar (Humbert, 1960) and 26 species are endemic to the Mascarene islands (Bosser et al., 1993; Jacob de Cordemoy, 1895). Some species are native to Arabia and East and South Africa including Psiadia punctulata (DC.) Vatke. Plants of this genus have been used in traditional medicine for a long time. Indeed, seven species are used in ethnomedicine for various ailments, including treatment of abdominal pains, colds, fevers, bronchitis and asthma (Aumeeruddy-Elalfi et al., 2016; Sussman, 1980; Wang et al., 1989). The leaf has the greatest healing properties, being used for example for preparation of decoctions or as plaster for immobilising fractures. Taxonomic studies have been conducted on several species. Based on morphological attributes, five groups of species have been classified. Furthermore, molecular phylogenetic studies have led to the identification of two main species clades (Strijk et al., 2012). Several studies on the phytochemistry and pharmacology of the genus Psiadia have led to the isolation and identification of 73 compounds including flavonoids, phenylpropanoids, coumarins and terpenoids. However, only a few have shown pharmacological properties. Of all identified compounds, the only bioactive compounds are considered to be the isolated flavonoids (Robin et al., 2001; Wang et al., 1989). Crude extracts, as well as essential oils of Psiadia species, have demonstrated various pharmacological properties including antimicrobial (Aumeeruddy-Elalfi et al., 2015; Govinden-Soulange et al., 2004), anti-viral (Fortin et al., 2002; Robin et al., 1998),

antiplasmodial (Jonville et al., 2008, 2011) and anti-inflammatory (Jonville et al., 2011; Recio et al., 1995) activities. This review strives for a complete overview of the existing knowledge on the botany, traditional uses, phytochemistry and pharmacological research of species belonging to the genus Psiadia. Available information on these species enables us to explore their therapeutic potential, to highlight the gaps in our knowledge and to provide the scientific basis for future research. 2. Botany 2.1. Taxonomy Taxonomic studies have been conducted on Madagascar and Mascarene Islands Psiadia species, as the majority of them are to be found in this region. In 1895, Jacob de Cordemoy was the first to recognised four groups of species in La Réunion based on certain morphological features (Table 1). Table 1: Jacob de Cordemoy's grouping of Psiadia species. Groups Species Psiadiastrum P. amygdalina P. anchusifolia P. argentea P. aspera P. callocephala P. frappieri P. lithospermifolia P. salaziana P. scabra P. sericea Tubifera P. insignis P. laurifolia

Plant type

Leaves

Inflorescence

Achenes

Shrubs or sub-shrubs densely hairy.

-

Conical receptacle, female florets with truncated corolla, male florets with tubular corolla.

Compressed.

Small trees.

Leaves are slightly hairy.

Female florets with truncated or short corolla, male florets with tubular corolla.

Compressed.

P. littoralis P. montana P. thermalis

shrubs.

Leaves are hairy, subsessile, slightly lanceolated with penninerve venation.

Much-branched inflorescences.

Very compressed.

P. ambigua P. dentata P. glutinosa P. linearifolia P. retusa

Shrubs or subshrubs.

Hairy or glabrous leaves, hardly glutinous.

Female florets with a distinct ray.

-

Frappieria

Glutinaria

With some name changes and rearrangement of the groups, in 1993, A. J. Scott distinguished five main groupings of species within the Mascarene Islands, Madagascar and Sri Lanka, based on morphological characteristics (Bosser et al., 1993) (Table 2).

Table 2: Scott's grouping of Psiadia species based on morphological characteristics. Groups

Species

Plant type

Leaves

Inflorescence

Achenes

P. cataractae (Mauritius) P. dentata (La Réunion) P. mauritiana (Mauritius) P. penninervia (Mauritius)

Shrubs.

Glabrous and glutinous leaves, sometimes puberulent on the young twigs.

Female florets usually have a distinct ray.

Columnar and 6-ribbed.

Group 1

P. punctulata (East Africa, Saoudite Arabia) P. terebinthina (Mauritius) P. viscosa (Mauritius) Group 2 P. arguta (Mauritius) P. canescens (Mauritius) P. ceylanica (Sri Lanka, India) P. lithospermifolia (Mauritius) P. pollicina (Mauritius) P. retusa (La Réunion) P. rodriguesiana (Rodrigues)

Shrubs.

Leaves are densely hairy when young. Glabrous and hardly glutinous on adult shrubs.

Female florets usually have a distinct ray.

Columnar and 6-ribbed.

P. insignis (La Réunion) P. laurifolia (La Réunion)

Small trees.

Leaves are hairy, not glutinous with distinctive kladodromous venation on the leaves.

Much-branched inflorescences with many small heads. Female florets sparsely hispid without a distinct ray.

Achenes compressed.

P. amygdalina (La Réunion) P. anchusifolia (La Réunion) P. boivinii (La Réunion) P. melastomatoides (La Réunion)

Shrubs or small trees.

Leaves are densely hairy, hairs often brownish.

Much-branched inflorescences bearing larger heads containing numerous florets. Female florets are sparsely hispid with a very short ray.

Achenes compressed.

P. argentea (La Réunion) P. aspera (La Réunion) P. callocephala (La Réunion) P. rivalsii (La Réunion) P. salaziana (La Réunion) P. sericea (La Réunion)

Subshrubs.

Leaves are small, sessile and often densely hairy.

The heads are large, subspherical, solitary or in groups of three.

Achenes compressed.

Group 3

Group 4

Group 5

Besides taxonomic studies, molecular phylogenetics have been carried out on Psiadia species and related genera (Strijk et al., 2012). Their focus was on the reconstruction of the evolutionary and biogeographical history of the genus based on DNA sequencing of four molecular markers. Using this different approach, Strijk et al. did not define the same groupings as above (Table 2). They recognised only two clades containing Psiadia species. The first contained species from the Mascarene Islands, Madagascar, continental Asia and South Africa (clade A). The second clade (clade B) contained all species from La Réunion except P. retusa and P. dentata, which were inherent to clade A. Both clades were separated from each other by other genera included in the study. Those findings support the hypothesis of an African origin of Psiadia species. Furthermore, both clades appeared to have a different evolutionary origin and history. The Mascarenes were colonised by two evolutionary very distinct lineages from Madagascar. On one hand, the ancestor of clade A from Madagascar colonised Rodrigues and Mauritius, with some species even reaching La Réunion via

these two islands. This explains the presence of P. retusa and P. dentata in clade A. Secondly, the colonisation of La Réunion from Madagascar by the ancestor of clade B produced the actual species. Furthermore, the study supported the theory that the genus Psiadia has many similarities to the genus Conyza. The taxonomy of the Mascarene and Madagascan species has previously been confused. Some Psiadia species have initially been identified as Conyza species (Table 3). In like manner, Psiadia rotundifolia (Roxb.) Hook. fil, a species endemic to St Helene has been transferred to the genus Commidendrum, endemic to this island. Psiadia rotundifolia is nowadays considered a synonym of Commidendrum rotundifolium (Robx.) DC. according to the website "Catalogue of life". False classification of species has been perceived within the genus Psiadia itself. Psiadia punctulata Vatke and Psiadia arabica Jaub and Spach have been considered as distinct taxa by some researchers based on chemical composition (Juma et al. 2001; Midiwo et al. 2002; Ogweno Midiwo et al. 1997). But these differences could be attributed to ecological adaptations or geographical location since P. punctulata occurs in a wide area from Africa to Arabia. According to the ‘Plant List’ (http://www.theplantlist.org), Psiadia arabica is described as a synonym of Psiadia punctulata. Table 3 summarises all synonyms of Psiadia species based on the website ‘Catalogue of Life’ (http://www.catalogueoflife.org). Table 3: Synonyms of Psiadia species Species Psiadia agathaeoides (Cass.) Humbert

Synonyms Henricia agathaeoides Cass. Nidorella ligulata Scott-Elliot

Psiadia alticola Humbert

-

Psiadia altissima (DC.) Benth. & Hook. fil.

Baccharis madagascariensis (Lam.) Conyza madagascariensis Lam. Microglossa altissima DC. Nirodella altissima (DC.) Benth. & Hook. fil. Psiadia altissima var. andringitrensis Humb. Psiadia altissima var. occidentalis Humb. Psiadia altissima var. stenophylla (Bak.) Humb. Psiadia decurrens Klatt Psiadia stenophylla Baker

Psiadia amygdalina Cordem.

Conyza amygdalina Lam. Conyza pulchra Lam. ex Steud.

Psiadia anchusifolia (Poir.) Cordem.

Conyza anchusifolia Poir. Conyza verbascifolia Bory Inula verbascifolia Hausskn.

Psiadia angustifolia (Humbert) Humbert

Psiadia angustifolia subsp. angustifolia Psiadia angustifolia subsp. linearis (Humbert) Humbert

Psiadia argentea Cordem.

Conyza argentea Lam.

Psiadia arguta (Pers.) Voigt

Baccharis arguta Pers. Conyza balsamica Wall. ex DC. Elphegea lanceolata Cass. Elphegea latifolia Cass. Nidorella compressa Cass. ex Steud. Psiadia balsamica Wall. ex DC. Psiadia trinervia var. balsamica (DC.) Baker

Psiadia aspera (Bory) Cordem.

Conyza aspera Bory

Psiadia boivinii (Klatt) B.L. Rob

Pluchea boivinii Klatt Psiadia frappieri Cordem.

Psiadia cacuminum (Humbert) Humbert

Psiadia leucophylla subsp. cacuminum Humbert

Psiadia callocephala (Bory) Cordem.

Conyza bidentata Steud. Conyza callocephala Bory

Dimorphantes bidentata Cass. Erigeron rutilis Poir. Psiadia canescens A.J. Scott

-

Psiadia cataractae A.J. Scott

-

Psiadia ceylanica (Arn.) Grierson

Amphirhapis zeylanica (Arn.) DC. Microglossa zeylanica (Arn.) Benth. & Hook. fil. Solidago ceylanica Arn.

Psiadia coarctata (Humbert) Humbert

Psiadia altissima subsp. coarctata Humbert

Psiadia coursii Humbert

-

Psiadia decaryi Humbert

-

Psiadia dentata (Cass.) DC.

Elphegea crenata Cass. Elphegea dentata Cass. Psiadia ambigua Cordem. Psiadia trinervia var. dentata (Cass.) Baker

Psiadia depauperata Humbert

-

Psiadia dimorpha Humbert

-

Psiadia dracaenifolia Humbert

-

Psiadia flavocinerea Humbert

-

Psiadia glutinosa Jacq.

Psiadia altissima var. latifolia Humbert

Psiadia godotiana Humbert

-

Psiadia grandidentata Steetz

-

Psiadia hendersoniae S. Moore

-

Psiadia hispida Benth. & Hook.f.

Psiadia inaequidentata Humbert

Microglossa hispida DC. Nirodella hispida Benth. & Hook. fil. Psiadia auriculata Baker -

Psiadia incana Oliv. & Hiern

Vernonia gomphophylla Baker

Psiadia insignis Cordem.

-

Psiadia laurifolia (Lam.) Cordem.

Conyza dilatata Steud. Conyza laurifolia Lam. Fimbrillaria tubifera Cass.

Psiadia leucophylla Humbert

Cacalia leucophylla Humbert Conyza leucophylla (Baker) Kuntze Conyza miniata Klatt Vernonia leucophylla Baker

Psiadia linearifolia DC.

Elphegea lanceolata Cass.

Psiadia lithospermifolia Cordem.

Conyza lithospermifolia Lam. Elphegea hirta H. Cass.

Psiadia lucida (Cass.) Drake

Conyza flexilis DC. Glycideras lucida Cass. ex DC. Glycyderas lucida (Cass.) Cass. Microglossa mikanioides Baker Microglossa sessilifolia DC. Psiadia madagascariensis DC. Psiadia tortuosa Klatt

Psiadia marojejyensis (Humbert) Humbert

Psiadia leucophylla subsp. marojejyensis Humbert

Psiadia mauritiana A.J Scott

-

Psiadia melastomatoides (Lam.) A.J. Scott

Conyza melastomatoides Lam. Erigeron jussievi Spreng. Erigeron scaber Pers. Fragmosa aspera Rafin. Pluchea spicata Klatt Psiadia scabra Cordem.

Psiadia minor Steetz

-

Psiadia mollissima O.Hoffm.

-

Psiadia montana (Cordem.) Cordem.

Frappieria littoralis Cordem. Frappieria montana Cordem. Frappieria thermalis Cordem. Psiadia francavillea Klatt Psiadia littoralis (Cordem.) Cordem. Psiadia thermalis (Cordem.) Cordem.

Psiadia nigrescens Humbert Psiadia pascalii Labat & Beentje

Psiadia nigrescens var. ciliata Humbert Psiadia nigrescens var. latifolia Humbert -

Psiadia penninervia DC.

Psiadia trinervia var. lanceolata Baker

Psiadia pollicina A.J Scott

-

Psiadia pseudonigrescens Buscalioni. & Muschl.

-

Psiadia punctulata (DC.) Oliv. & Hiern ex Vatke

Baccharis resiniflua Steud. & Hochst. ex DC. Nidorella punctulata DC. Psiadia aparine Muschl. Psiadia arabica Jaub. & Spach Psiadia dodonaefolia Steetz Psiadia resiniflora Sch. Bip. ex Schweinf. Psiadia resiniflua (Hochst. & Steud. ex DC.) Schwein. & Aschers. Psiadia vernicosa Schinz

Psiadia retusa DC.

Alix salsifolia Comm. ex. DC.

Psiadia rivalsii A.J. Scott

-

Psiadia rodriguesiana Balf. fil.

-

Psiadia salaziana Cordem.

-

Psiadia salviifolia Baker

Psiadia salviifolia subsp. mandrarensis Humbert Psiadia salviifolia subsp. salviifolia

Psiadia schweinfurthii Balf. fil.

-

Psiadia sericea (Bory) Cordem.

Conyza sericea Bory

Psiadia serrata (Humbert) Humbert

Psiadia altissima subsp. serrata Humbert

Psiadia tanala Humbert

-

Psiadia tardieuana Humbert

-

Psiadia terebinthina A.J. Scott

-

Psiadia tsaratananensis Humbert

-

Psiadia vestita Humbert

-

Psiadia viscosa (Lam.) A.J. Scott

Baccharis viscosa Lam. Elphegea minor Cass. Elphegea quinquenervia Cass.

Psiadia glauca Ayres ex Baker Psiadia integerrima var. minor (Cass.) DC. Psiadia integerrima var. quinquenervia (Cass.) DC. Psiadia integerrima var. trinervia (Willd.) DC. Psiadia trinervia Willd.

2.2. Conservation In 1997, several Psiadia species were listed in the IUCN Red List of Threatened Species due to critical decrease in population: P. arguta, P. canescens, P. lithospermifolia, P. mauritiana, P. melastomatoides, P. penninervia, P. pollicina, P. retusa, P. rivalsii, P. rodriguesiana, P. salaziana and P. terebinthina (Walter and Gillett, 1998). Several factors are responsible for the decrease in the population numbers of these species: galloping urbanisation, difficulties of seed germination and propagation of invasive plants. Conservation efforts through cuttings and seeds have led to the recovery of some species and their exclusion from the IUCN Red List. Today, two species remain registered in the IUCN Red List of Threatened Species (2016): Psiadia cataractae, a critically endangered specimen endemic to Mauritius and Psiadia schweinfurthii an extinct species previously found in Yemen. According to the IUCN, ex situ conservation of P. cataractae through cuttings and seeds is ongoing. Psiadia coronopus (Lam.) is a threatened endemic species from Rodrigues. Here, 94% of the endemic flora are either endangered or extinct (Krogstrup and Nørgaard, 1991). Because of the vulnerability of P. coronopus, Krogstrup and Nørgaard developed a vegetative propagation method of this species. This was the first attempt of conservation of a Psiadia species. Following this study, plants were re-established in botanical gardens. Psiadia arguta commonly known as ‘Baume de l’île Plate’ is endemic to Mauritius. This species was endangered (registered in the IUCN Red List 1997). Nowadays, Psiadia arguta is completely extinct on Mauritius due to galloping urbanisation and the fact that seeds cannot easily be propagated. Nevertheless, some wild specimens can still be found on Ilot Gabriel, a small islet off the north coast of Mauritius. For conservation of Psiadia arguta, Kodja et al. (1998) provides a micropropagation method through cotyledonary axillary bud culture. Thus, these cultures led to the re-establishment of new specimens in botanical gardens. Recent research has revealed the potential of P. arguta in the inhibition of the growth of Plasmodium falcifarum (Jonville et al., 2008, 2011). However, the active molecules behind the antiplasmodial activity have not been described. Multiplication and acclimatisation of this species via micropropagation is a good way to identify active compounds without destroying wild specimens. Three other Psiadia species from Mauritius that were registered in the IUCN Red List 1997 were studied for botanical conservation. Preliminary works were carried out on P. lithospermifolia, P. penninervia and P. terebinthina for regeneration and micropropagation purposes (Kodja and Govinden-Soulange, unpublished results). 3. Traditional uses Of 60 species of Psiadia, seven have been reported to show benefits in treating various ailments in traditional medicine. Those include: P. altissima, P. ceylanica, P. dentata, P. punctulata, P. salviifolia, P. terebinthina and P. arguta. Regardless of the treatment method, Psiadia leaves are the most beneficial part of plant. Among others, they are used as expectorant for treatment of bronchitis and asthma (Aumeeruddy-Elalfi et al. 2016; Sussman 1980; Wang et al. 1989). Of all African species, P. punctulata is the only one reported in African folk medicine. Decoctions of leaves are a popular remedy for abdominal pains and colds. They are also used as expectorant for bronchitis and asthma and have analgesic effects (Keriko et al., 1997). In Kenya, roots of P. punctulata are used by the Maasai for treatment of malaria (Koch et al., 2005). The Bedouin, an Arab seminomadic group, are known to apply leaves of P. punctulata as a plaster cast for broken bones (Keriko et al., 1997). In Ayurvedic medicine, leaves of P. ceylanica are employed for fractures and the treatment of boils, eczema, food poisoning and asthma.

A summary of traditional uses of Psiadia species and methods of preparation are presented in Table 4. Psiadia species have diverse medicinal applications in different regions of the world and in different cultures. Independently of species and their geographical localisation, the main traditional uses that are common between species are the treatment of cough and asthma, of broken bones and burns. These four traditional uses clearly deserve to be investigated.

Table 4: Summary of traditional uses of Psiadia species Species

Origin

Plan t part used -

Psiadia altissima (DC.) Drake

Madaga scar

Psiadia arguta (pers.) Voigt

Mauritiu s

Leav es

Psiadia ceylanic a (Arn.) Grierson

Sri Lanka

Leav es

Psiadia dentata DC.

Reunion

-

Psiadia punctula ta (DC.) Vatke

East Africa

Leav es

Root s

Tradition al uses

Treatmen t of skin disorders, syphilis, stomach, dental pain, cough suppressa nt. Expectora nt. Healing of minor wounds and burns, pulmonar y infections , respirator y disorders, asthma, cough, indigestio n. Fractures, boils, eczema, food poisoning , asthma. Treatmen t of abscesses . Treatmen t of colds, fevers, abdomina l pains, analgesic, expectora nt for bronchitis and asthma, removal of ectoparas ite from cattle. Plaster

Preparatio n and administra tion -

References

Crushed leaves, poultice, leaves infusion.

(Sussman, 1980; Wang et al., 1992)

-

http://www.instituteofayurveda.org/plants/plants_detail.php? i=217&s=English_name

-

(Robin et al., 1998)

Decoction. Leaves mix with goat fat apply to heal burns. Dried leaves. Pounded, mixed with water. -

(Keriko et al., 1997)

(Danthu et al., 2007)

(Koch et al., 2005)

Psiadia salviifoli a Bak.

Madaga scar

Aeri al part s

Psiadia terebint hina A.J. Scott

Mauritiu s

Leav es

cast for broken bones. Skin infection, scabies. Treatmen t of malaria. Dysentery , liver disorders, hypertens ion. Calming effect in cases of asthma. Applied on abscesses and boils.

-

(Dennis, 1973)

Decoction. Leaf poultice.

(Aumeeruddy-Elalfi et al., 2016)

4. Chemical constituents Several species have been the subject of a preliminary phytochemical screening: P. arguta, P. viscosa, P. lithospermifolia, P. amygdalina, P. anchusifolia, P. argentea, P. boivinii, P. callocephala, P. dentata, P. laurifolia and P. retusa. Different classes of compounds have been detected: phenolic compounds, consisting of coumarins, tannins, phenols and flavonoids; terpenes, including sesquiterpene lactones and saponosides; and anthraquinones (Kauroo et al., 2016; Lavergne, 2016). Five particular species have been studied for their phytochemical composition: P. arguta, P. dentata, P. punctulata, P. terebinthina and P. viscosa. Phytochemical investigations have led to the isolation and identification of 73 compounds. The different classes of molecules that have been identified are described as follows: flavonoids (56.0%), terpenoids (30.0%), phenylpropanoids (12.6%) and coumarins (1.4%). Their structures are comprehensively summarised in Table 5. Table 5: Chemical constituents isolated in Psiadia species Compounds

Substituents

Molecular weight

References

Flavonoids 1. R1 = R3 = R4 = H, R2 = CH3, Ermanin 2. R1 = R2 = R3 = H, R4 = OCH3, 5,7,4’-Trihydroxy-3,5’-dimethoxyflavone 3. R1 = CH3, R2 = R3 = H, R4 = OCH3, Pachypodol 4. R1 = R2 = CH3, R3 = OCH3, R4 = H, 5-Hydroxy-3,6,7,4’-tetramethoxyflavone

314 330

5. R1 = OCH3, R2 = H, R3 = CH3, 5,3’-Dihydroxy-6,7,2’,4’,5’-pentamethoxyflavone, (psiadiaradin) 6. R1 = R2 = H, R3 = CH3, 5,3’-Dihydroxy-7,2’,4’,5’-tetramethoxyflavone 7. R1 = H, R2 = R3 = CH3, 5-Hydroxy-7,2’,3’,4’,5’-pentamethoxyflavone (2-methoxycorymbosin) 8. R1 = R2 = R3 = CH3, 5-Hydroxy-6-methyl-7,2’,3’,4’,5’pentamethoxyflavone

404

9. R1 = R3 = OH, R2 = H, Kaempferol 3,7-dimethyl-ether 10. R1 = R2 = R3 = OH, 5,3’,4’-Trihydroxy-3,7-dimethoxyflavone 11. R1 = R2 = OH, R 3= OCH3, Ayanin

314

344 358

374 388

(Abou-Zaid et al., 1991; Jakobsen et al., 2001; Robin et al., 1998)

(El-Feraly et al., 1990; Juma et al., 2001; Mossa et al., 1992)

402

330 344

(Marie et al., 2006; Wang et al., 1989)

Coumarin

12. R1 = R2 = OH, R3 = OCH3, Casticin 13. R1 = OH, R2 = R3 = OCH3, Artemetin, 14. R1 = R3 = OH, R2 = H, Penduletin 15. R1 = R2 = R3 = OH, Chrysosplenol-D

374 388 344 360

16. R1 = R2 = R4 = OH, R3 = OCH3, 5,7,4’-Trihydroxy-3,3’-dimethoxyfIavone 17. R1 = R2 = R4 = OH, R3 = H, Isokaempferide 18. R1 = R2 = R3 = R4 = OH, 5,7,3',4'-Tetrahydroxy-3-methoxyflavone, Quercetin 3-methyl ether

330

19. R1 = R2 = R4 = OH, R3 = OCH3, 5,7,4’-Trihydroxy-3,8,3’-trimethoxyflavone 20. R1 = R2 = OH, R3 = R4 = OCH3, 5,7-Dihydroxy-3,8,3’,4’-tetramethoxyflavone 21. R1 = R2 = R3 = OH, R4 = H, 5,7,4’-Trihydroxy-3,8-dimethoxyflavone

360

22. R1 = H, R2 = R3 = CH3, 5,7-Dihydroxy-2’,3’,4’,5’-tetramethoxyflavone 23. R1 = R2 = CH3, R3 = H, 5,4’-Dihydroxy-7,2’,3’,5’-tetramethoxyflavone 24. R1 = R3 = H, R2 = CH3, 5,7,4’-Trihydroxy-2’,3’,5’-trimethoxyflavone 25. R1 = R2 = H, R3 = CH3, 5,7,3’-Trihydroxy-2’,4’,5’-trimethoxyflavone

374

27. R1 = OH, Apigenin 28. R1 = OCH3, Acacetin

270 284

(Abou-Zaid et al., 1991)

29. R1 = H, R2 = CH3, Chrysoeriol 30. R1 = H, R2 = H, Luteolin 31. R1 = Glc, R2 = H, Luteolin-7-O-glucoside

300 286 448


32. R1 = H, R2 = Glc, Orientin 33. R1 = Glc, R2 = Glc, Orientin-7-O-glucoside

448 610


34. R1 = Glc, R2 = H, Isoorientin 35. R1 = Glc, R2 = Glc, Isoorientin-7-O-glucoside

448


36. Cirsilineol

344


37. Gardenin B

358


38. Gardenin C

404


39. R1 = OH, 5,3’-Dihydroxy-6,7,4’,5’-tetramethoxyflavone 40. R1 = OCH3, 5-Hydroxy-6,7,3’,4’,5’-pentamethoxyflavone

374


300 316

(Wang et al., 1989)

(Marie et al., 2006; Robin et al., 1998; Wang et al., 1989)

(Wang et al., 1989) 374 330

374 360

(Juma et al., 2001; Midiwo et al., 2002; Mossa et al., 1992)

360

388

41. Isoobtusitin

276

(Fortin et al., 2001; Jakobsen et al., 2001)

42. Z-Eicosanyl p-coumarate

444


43. E-Eicosanyl p-coumarate

444


44. E-Docosyl-p-coumarate

472

(Juma et al., 2001)

45. Z-Docosyl-p-coumarate

472

(Juma et al., 2001)

46. 3-Caffeoylquinic acid

354

(Marie et al., 2006)

47. Caffeic acid

180

(Wang et al., 1992)

48. 3,4-Di-O-caffeoyl-(1S,3R,4R,5R)-1,3,4,5tetrahydroxycyclohexanecarboxylic acid

516

Wang et al., 1992)

49. 3,4-Di-O-caffeoylquinic acid

516

Wang et al., 1992)

50. 3,5-Di-O-caffeoylquinic acid

516

Wang et al., 1992)

51. Psiadin

318

(Jakobsen et al., 2001; Midiwo et al., 2002; Mossa et al., 1992)

52. (2S, 5R, 8R, 9R, 10R) (ent)-Kaur-16-en-2α, 18, 19-triol

320

(El-Domiaty et al., 1993; Midiwo et al., 2002)

Hydroxycinnamic acids

Diterpenes

53. (2R, 5R, 8R, 9R, 10R) (ent)-Kaur-16-en-2α, 18, 19-triol

320

(El-Domiaty et al., 1993; Midiwo et al., 2002)

54. (ent)-Kaur-16-en-2α, 18, 19-triol

320

(Ogweno Midiwo et al., 1997)

55. (ent)- 16β, 17-Dihydroxykauran-20-oic acid

336

(Midiwo et al., 2002; Ogweno Midiwo et al., 1997)

56. Kaur-16-ene-18,19-diol

304

(Midiwo et al., 2002)

57. Kaur-16-en-2-one, 6,18,19-trihydroxy-, (5α,6α,8β,9α,10β,13β)

334

(El-Domiaty et al., 1993)

58. Trachyloban-2β,6β, 19-triol

320


59. 2-Oxotrachyloban-18,19-diol

318


60. Trachyloban-2β,19-diol

304


61. Information not available

304



288



334



318


65. Ciliaric acid

318

(Ogweno Midiwo et al., 1997)

66. 6α,18,19-ent-Trachylobantriol

320

(Juma et al., 2006)

67. 2α,17,18-ent-Trachylobantriol

320

(Juma et al., 2006)

68. 2β,6α,18,19-ent-Trachylobantetraol

336

(Juma et al., 2006)

69. R1 = OH, Psiadiol

318

(Canonica et al., 1967, 1969a, 1969b)

70. R1 = H, 6-Deoxypsiadiol

302

(Canonica et al., 1967, 1969a, 1969b)

71. Isopsiadiol

318

(Canonica et al., 1969b)

72. 7,7-Dimethyl-2-methylenebicyclo [3.1.1] heptan-6-ol acetate

194

(Gauvin et al., 2004)

73. 6,6,8,9-Tetramethyltricyclo[3.3.3.0]undec-7-en2-ol

220

(Gauvin et al., 2004)

Acetylated Monoterpene

Sesquiterpene alcohol

4.1. Flavonoids Phytochemical investigation of Psiadia species has led to the isolation of 40 flavonoids, represented mostly by flavonols and flavones. The chemical composition of P. viscosa (synonym P. trinervia) leaves was first investigated for antimicrobial agents (Wang et al., 1989). Activity-guided isolation of the dichloromethane extract yielded the following compounds: kaempferol 3,7-dimethyl-ether (9), 5,3',4'-trihydroxy-3,7-dimethoxyflavone (10), ayanin (11), casticin (12), artemetin (13), penduletin (14), chrysosplenol-D (15), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (16) and 5,7,4'trihydroxy-3,8,3'-trimethoxyflavone (19). These molecules were purified by silica gel column chromatography. Acidic hydrolysis of the methanol extract and purification on silica gel or diol column chromatography led to the isolation of active

compounds chrysosplenol-D (15), isokaempferide (17), 5,7,3',4'-tetrahydroxy-3-methoxyflavone (18) and 5,7,4’-trihydroxy3,8-dimethoxyflavone (21). The investigation of the chloroform extract of P. punctulata aerial parts resulted in the isolation of the new flavone psiadiarabin (5) with a tetraoxygenated ring B (Al-Yahya et al., 1987). Three related flavones were also isolated: 5,3'dihydroxy-7,2',4',5'-tetramethoxyflavone (6), 5-hydroxy-7,2',3',4',5'-pentamethoxyflavone (7), 5,7,3'-trihydroxy-2',4',5'trimethoxyflavone (25) (El-Feraly et al., 1990; Mossa et al., 1992). Chromatographic separation of an aqueous ethanolic extract of the leaves of P. punctulata afforded 16 flavonoids: apigenin (27), acacetin (28), chrysoeriol (29), luteolin (30), luteolin-7-O-glycoside (31), orientin (32), orientin-7-O-glucoside (33), isoorientin (34), isoorientin-7-O-glucoside (35), cirsilineol (36), gardenin B (37), 5-hydroxy-3,6,7,4'-tetramethoxyflavone (4), 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (39), 5-hydroxy-6,7,3',4',5'-pentamethoxyflavone (40) and gardenin C (38) (Abou-Zaid et al., 1991). From the leaf exudate, three new flavonoids were purified in addition to compounds (7) and (25) that had been previously described (Juma et al., 2001). These three molecules were isolated by silica gel chromatography: 5,7-dihydroxy-2’,3’,4’,5’-tetramethoxyflavone (22), 5,4’-dihydroxy-7,2’,3’,5’-tetramethoxyflavone (23) and 5,7,4’-trihydroxy-2’,3’,5’-trimethoxyflavone (24). From P. dentata leaves methanolic crude extract, the diethyl ether fraction was further investigated to obtain the two following flavonoids: ermanin (1) and isokaempferide (17) (Robin et al., 1998). Further studies on the dichloromethane extract of leaves yielded the isolation of 3-methoxyflavones: 5,7,4’-trihydroxy-3,5’-dimethoxyflavone (2), pachypodol (3) and 5-hydroxy-3,6,7,4’-tetramethoxyflavone (4) (Jakobsen et al., 2001). A phytochemical investigation of P. terebinthina leaves resulted in the isolation of isokaempferide (17), quercetin-3methyl ether (18) and kaempferol-3,7-dimethyl ether (9) (Marie et al., 2006). 4.2. Hydroxycinnamic acids and coumarins Thus far, one coumarin and nine hydroxycinnamic acids have been identified in Psiadia species. Indeed, E- and Zeicosanyl-p-coumarates (42, 43) have been purified from a methanol extract of fresh P. punctulata leaves (Keriko et al., 1997). These two compounds were isolated on normal and reverse-phase columns and preparative TLC. Later on, E- and Zdocosyl-p-coumarates (44, 45) were obtained from the same species from the ethyl acetate extract by silica gel chromatography (Juma et al., 2001). From P. dentata chloroform and dichloromethane extracts, a novel coumarin was isolated with an unusual 7-Oprenylation: this compound is isoobtusitin (41) (Fortin et al., 2001; Jakobsen et al., 2001). Four phenolic compounds were isolated by gel filtration and reverse-phase chromatography in P. viscosa methanol extract: caffeic acid (47), 3,4-di-Ocaffeoyl-(1S,3R,4R,5R)-1,3,4,5-tetrahydroxycyclohexane carboxylic acid (48), 3,4-di-O-caffeoylquinic acid (49) and 3,5-di-Ocaffeoylquinic acid (50) (Wang et al., 1992). 4.3. Terpenoids Terpenoids are the second class of molecules that have been well studied, especially in P. punctulata. Indeed, 20 diterpenes, mostly of ent-kaurene and trachyloban types, have been identified in this species. The first diterpene to be isolated from the chloroform extract of P. punctulata aerial parts was the new kaurene diterpene psiadin (51) (Mossa et al., 1992). Three other kaurene diterpenes were purified later from the same extract: (ent)-kaur-16-en-2α,18,19-triol (52) and its epimer, and kaur-16-en-2-one,6,18,19-trihydroxy-,(5α,6α,8β,9α,10β,13β) (57) (El-Domiaty et al., 1993). Investigation of the leaf exudate resulted in the identification of (ent)-16β,17-dihydroxykauran-20-oic acid (55) and two trachyloban diterpenes: 2-oxotrachyloban-18,19-diol (59) and trachyloban-2β,6β,19-triol (58) (Ogweno Midiwo et al., 1997). Midiwo et al. reported the presence of the kaurene diterpene kaur-16-ene-18,19-diol (56) and six trachyloban diterpenes (60), (61), (62), (63), (64) and (65) (Midiwo et al., 2002). Besides, three new trachyloban diterpenes have been characterised from the leaf exudate of P. punctulata: 6α,18,19-ent-trachylobantriol (66), 2α,17,18-ent-trachylobantriol (67) and 2β,6α,18,19-ent-trachylobantetraol (68) (Juma et al., 2006). P. altissima leaves have been investigated and three new oxygenated diterpenoids were purified from the leaves and characterised: psiadiol (69), 6-deoxypsiadiol (70) and isopsiadiol (71) (Canonica et al., 1967, 1969a, 1969b). 4.4. Essential oils The leaf essential oil composition of Psiadia species has been well documented. Many papers have reported the gas chromatographic (GC) analysis of volatile oils from different species, including P. altissima (Ramanoelina et al., 1994), P.

anchusifolia (Gauvin et al., 2004; Gauvin and Smadja, 2005), P. argentea (Gauvin and Smadja, 2005), P. arguta (GovindenSoulange et al., 2004; Gurib-Fakim et al., 2000), P. boivinii (Gauvin and Smadja, 2005), P. lithospermifolia (Ameenah GuribFakim, 1995; Govinden-Soulange et al., 2004), P. lucida (Andriamanantoanina et al., 2004), P. penninervia (GovindenSoulange et al., 2004), P. punctulata (Mekkawi et al., 1984), P. salaziana (Gauvin and Smadja, 2005), P. salviifolia (Dennis, 1973), P. terebinthina (Govinden-Soulange et al., 2004) and P. viscosa (Ameenah Gurib-Fakim 1995; Govinden-Soulange et al. 2004). The essential oil composition of these species is described in Table 6. Gauvin and Smadja (2005) conducted a comparative study of the volatile constituents of four species from Reunion Island, according to their development stage, with gas chromatography coupled to mass spectrometry (GC/MS). The results showed that these species are dominated by the presence of the acetylated monoterpene 7,7-dimethyl-2methylenebicyclo[3.1.1]heptan-6-ol acetate (72) and the sesquiterpene alcohol 6,6,8,9-tetramethyltricyclo[3.3.3.0]undec-7en-2-ol (73). These two new compounds were isolated by column chromatography and identified for the first time in the essential oil of leaves of P. anchusifolia (Gauvin et al., 2004). However, species from Mauritius appeared to be predominated by shikimic acid derivatives such as isoasarone and isoeugenol. Information gathered from essential oil studies of Psiadia species could help to re-evaluate the relationships between the species in order to identify whether there is congruence between taxonomic and molecular phylogenetic studies.

Table 6: Leaf essential oil composition and major compounds of some Psiadia species Species

Oxygenated monoterpenes % -

Sesquiterpenes hydrocarbons % -

Oxygenated sesquiterpenes % -

Major compounds (%)

References

P. altissima

Monoterpenes hydrocarbons % -

β-Pinene (39.7)

(Ramanoelina et al., 1994)

P. anchusifolia

0.2-2.5

12.8-14.9

13.5-11.3

38.6-41.8

7,7-Dimethyl-2-methylenebicyclo [3.1.1] heptan-6-ol acetate (66) (12.0-14.1) 6,6,8,9Tetramethyltricyclo[3.3.3.0]undec7-en-2-ol (67) (19.2-20.5)

(Gauvin et al., 2004; Gauvin and Smadja, 2005)

P. argentea

0-1.2

20.8-45.8

1.5-2.0

30.5-43.2

7,7-Dimethyl-2-methylenebicyclo [3.1.1] heptan-6-ol acetate (66) (18.2-41.4) 6,6,8,9Tetramethyltricyclo[3.3.3.0]undec7-en-2-ol (67) (28.3-39.3)

(Gauvin et al., 2004; Gauvin and Smadja, 2005)

P. arguta

t-5.6

0.6-2.2

0.3-1.5

0.3-13.1

Isoeugenol (56.5) Caryophyllene oxide (13.1) Vanillin (10.5)

(Aumeeruddy-Elalfi et al., 2015; GovindenSoulange et al., 2004)

P. lithospermifolia

-

-

32.7

-

(E)-Isoasarone (51.5)

(Govinden-Soulange et al., 2004)

P. lucida

57.1

3.3

28.9

4.2

Limonene (10.2) Terpinolene (38.0) α-Humulene (21.2)

(Andriamanantoanina et al., 2004)

P. penninervia

1.9

3.8

7.6

6.4

-


P. salaziana

5.0-7.3

19.9-22.7

15.3-15.5

40.2-39.7

7,7-Dimethyl-2-methylenebicyclo (Gauvin et al., 2004; [3.1.1] heptan-6-ol acetate (66) Gauvin and Smadja, (18.6-21.2) 2005) 6,6,8,9-Tetramethyltricyclo[3.3.3.0]undec7-en-2-ol (67) (28.5-26.6)

P. salviifolia

9.7

13.0

32.1

42.7

-

(Dennis, 1973)

P. terebinthina

0.3-12.9

0.0-2.1

7.7-56.9

0.0-5.0

Acetyl eugenol (10.9) α-Curcumene (39.7)

(Aumeeruddy-Elalfi et al., 2015; GovindenSoulange et al., 2004)

P. viscosa

0.4

1.5

32.7

4.9

Pentyl 4-(1-methylethyl benzoate) (25.9) (Z)-Isoasarone (13.4)


Table 7: Pharmacological activities of Psiadia species Psiadia species Antimicrobial P. arguta

Part used

Extracts/compounds

Active concentration

Leaves

Essential oil

Model used

Effect

References

0.03%

In vitro Agar-well diffusion

Weak to moderate inhibitory effect against B. cereus, S. aureus, Ps. aureofaciens, A. ochraceus, C. pseudotropicalis, K. lactis, F. moniliforme.


Essential oil

-

In vitro Micro-dilution broth susceptibility assay

Moderate bactericidal effect on P. aeruginosa (MIC = 0.25 mg/mL), S. aureus (MIC = 0.5 mg/mL) and S. epidermidis. (MIC = 0.25 mg/mL), Bacteriostatic effect against E. coli (MIC = 1 mg/mL), and S. aureus (MIC = 2 mg/mL). Fungicidal effect against A. niger (MIC = 4 mg/mL), C. albicans (MIC = 2 mg/mL). Synergic effect of P. arguta and Pimenta dioica essential oil against E. coli (MIC = 0.25 mg/mL).


Hexane extract

-

In vitro Micro-dilution

Inhibitory effect against K. pneumoniae (MIC = 19.53 μg/mL), P. aeruginosa (MIC = 78.12 μg/mL), E. coli (MIC = 19.53 μg/mL), S. aureus (MIC = 19.53 μg/mL), E. faecalis (MIC = 19.53 μg/mL), B. cereus (MIC = 19.53 μg/mL).

(Kauroo et al., 2016)

Ethyl acetate extract

-



Methanol extract

-


Inhibitory effect against K. pneumoniae (MIC = 156.25 μg/mL), P.

aeruginosa (MIC = 39.06 μg/mL), E. coli (MIC = 156.25 μg/mL), S. aureus (MIC = 78.12 μg/mL), E. faecalis (MIC = 1250.00 μg/mL), B. cereus (MIC = 39.06 μg/mL). P. altissima

Leaves

Essential oil

-


Inhibition effect against S. aureus (MIC = 0.33 mg/mL), S. lutea (MIC = 0.125 mg/mL), B. subtilis (MIC = 0.166 mg/mL), B. catarrhalis (MIC = 0.05 mg/mL), K. pneumoniae (MIC > 1 mg/mL), E. coli (MIC > 1 mg/mL), B. bronchiseptica (MIC > 1 mg/mL), Moraxella glucidolytica (MIC > 1 mg/mL), S. dysenteriae (MIC > 1 mg/mL).

(Ramanoelina et al., 1987)

P. lithospermifolia

Leaves

Hexane extract

-





-



Methanol extract

-


Inhibitory effect against K. pneumoniae (MIC = 625 μg/mL), P. aeruginosa (MIC = 625.00 μg/mL), E. coli (MIC = 312.50 μg/mL), S. aureus (MIC = 78.12 μg/mL), E. faecalis (MIC = 1250.00 μg/mL), B. cereus (MIC = 78.12 μg/mL).

Essential oil

0.03%


Inhibitory effect against B. cereus, S. aureus, Ps. aureofaciens, two Aspergillus spp., C. pseudotropicalis, K. lactis and F. moniliforme


P. lucida

Leaves

Essential oil

-


Inhibition of growth of E. coli, S. boydii, Salmonella sp., S. aureus, E. faecalis and B. subtilis.

(Andriamanantoanina et al., 2004)

P. punctulata

Leaves and flowers

Aqueous extract

-

In vitro Agar diffusion

(Mothana et al., 2011)

CMI > 1000 μg/mL

In vitro micro-dilution assays

Inhibitory effect against S. aureus, M. flavus and two multi-resistant strains S. epidermidis, and S. aureus. Activity against S. aureus, B. subtilis and M. flavus.

-

In vitro Agar diffusion

CMI > 1000 μg/mL CMI = 500 μg/mL

In vitro Micro-dilution In vitro Micro-dilution

0.03%


Weak inhibition of B. cereus, S. aureus, Ps. aureofaciens, A. ochraceus, C. pseudotropicalis, K. lactis and F. moniliforme.


-

In vitro Micro-dilution broth susceptibility assay

Bactericidal effect on 12 bacteria including moderate bactericidal effect against E. coli ATCC strain (MIC = 0.5 mg/mL), and clinical isolate (MIC = 4 mg/mL), K. pneumonia (MIC = 4mg/mL), S. aureus (MIC = 0.5 mg/mL), P. aeruginosa ATTC strain (MIC = 0.25 mg/mL) and clinical isolate (MIC = 4 mg/mL) and S. epidermidis (MIC = 0.25 mg/mL). Fungicidal effect against A. niger (MIC = 2 mg/mL), C. albicans ATTC strain (MIC = 1 mg/mL), C. albicans clinical isolate (MIC = 16 mg/mL) and C. tropicalis (MIC = 1 mg/mL).


-

In vitro Bioautographic assays

Antimicrobial activity against C. cucumerinum and B. cereus.

(Wang et al., 1989)

Methanol extract

P. terebinthina

P. viscosa

Leaves

Leaves

Essential oil

Dichloromethane extract

Inhibitory effect against S. aureus, B. subtilis M. flavus and three multiresistant strains S. epidermidis, S. haemolyticus and S. aureus. Activity against B. subtilis. Activity against S. aureus and M. flavus.

Actives compounds: Ayanin

MIC = 20 μg/spot MIC = 20 μg/spot MIC = 5 μg/spot MIC = 5 μg/spot MIC = 0.25 μg/spot

Antimicrobial activity against C. cucumerinum. Antimicrobial activity against C. cucumerinum. Antimicrobial activity against C. cucumerinum. Antimicrobial activity against C. cucumerinum. Activity against B. cereus.

5,7,4’-Trihydroxy-3,8dimethoxyflavone

MIC = 4 μg/spot MIC = 0.25 μg/spot MIC = 0.5 μg/spot

Activity against B. cereus. Activity against B. cereus. Activity against B. cereus.

Hexane extract

-




-



Methanol extract

-



Essential oil

0.03%


Weak inhibition of B. cereus, S. aureus, Ps. aureofaciens, A. ochraceus, C. pseudotropicalis and K. lactis.


Methanol extract

666 μg/mL

In vitro

83 μg/mL

In vitro

100% inhibition of poliovirus type 2. 100% inhibition of

(Fortin et al., 2002; Robin et al., 1998, 2001)

Casticin Chrysosplenol-D 5,7,4’-Trihydroxy-3,8dimethoxyflavone 5,7,4’-Trihydroxy3,3’dimethoxyflavone Chrysosplenol-D Isokaempferide

Antiviral P. dentata

Leaves


P. retusa

Leaves

Anti-inflammatory P. arguta Branches

Leaves

P. dentata

Antiplasmodial P. arguta

Aerial parts

Leaves

In vitro

Actives compounds: Ermanin

8 mg/mL

In vitro

Isokaempferide

1 mg/mL

In vitro

Methanol extract

ED50 = 400 μg/mL

In vitro

Low inhibition of poliovirus type 2.

(Fortin et al., 2002)

Aqueous extract

5.5 mg

In vivo (TPA)induced mouse ear oedema

(Recio et al., 1995)

100 mg/Kg (0.5 mL)

In vivo Carrageenaninduced mouse paw oedema

Moderate topical antiinflammatory activity (65% oedema inhibition). Moderate oral antiinflammatory activity.

Methanol extract

IC50 = 20 μg/mL

Significant inhibition of NO production.

(Jonville et al., 2011)


IC50 = 13 μg/mL

In vitro LPS-stimulated Raw 264.7 murine macrophages

Methanol extract

IC50 = 21 μg/mL

Significant inhibition of NO production.


IC50 = 85 μg/mL

In vitro LPS-stimulated Raw 264.7 murine macrophages

Methanol extract

IC50 = 22.4 μg/mL

In vitro P. falciparum 3D7 In vitro P. falciparum W2

Significant inhibition of growth of P. falciparum

IC50 = 26.1 μg/mL


IC50 = 10.1 μg/mL IC50 = 8.4 μg/mL 50 mg/Kg

In vitro P. falciparum 3D7 In vitro P. falciparum W2 In vivo Female mice infested by P. berghei NK173

200 mg/Kg

P. dentata

P. punctulata

Aerial parts

Aerial parts

poliovirus type 2. Inhibition of poliovirus type 2.

ED50 = 80 μg/mL

Methanol extract

IC50 = 15.0 μg/mL


IC50 = 7.0 μg/mL

Methanol extract

IC50 = 39.3 μg/mL

In vitro P. falciparum 3D7

Complete cytopathic inhibition Complete cytopathic inhibition

Strong inhibition of NO production (Jonville et al., 2011)

Low inhibition of NO production. (Jonville et al., 2008)

Significant inhibition of growth of P. falciparum

Strong inhibition of growth of P. falciparum. Strong inhibition of growth of P. falciparum. 75,5% inhibition of growth of P. berghei after 7 days postinfection. 86,7% inhibition of growth of P. berghei after 7 days postinfection. Strong antiplasmodial activity.


Strong antiplasmodial activity. In vitro P. falciparum

Low antiplasmodial activity.

(Abdel-Sattar et al., 2010)

Antileishmanial P. punctulata

Stem bark and leaves

Aqueous and methanol extracts

IC50 = 2.2 mg/mL

In vitro L. major promastigotes Infected mouse peritoneal macrophages

Low antileishmanial effect.

(Githinji et al., 2010)

Aerial parts

Methanol extract

IC50 = 32.4 μg/mL

In vitro L. infantum

Low antileishmanial effect.


Methanol extract

IC50 < 0.25 μg/mL

In vitro T. cruzi

Strong inhibition of growth of T. cruzi.


IC50 = 0.33 μg/mL

In vitro T. b. brucei

Strong inhibition of growth of T. b. brucei.

IC50 = 32 μg/mL IC50 = 37 μg/mL

DLD-1

Significant antiproliferative effect. Significant antiproliferative effect.

IC50 = 23 μg/mL IC50 = 25 μg/mL

DLD-1

IC50 = 188 μg/mL IC50 = 136 μg/mL

DLD-1

IC50 = 56 μg/mL IC50 = 35 μg/mL

DLD-1

IC50 = 300 μg/mL IC50 > 500 μg/mL

5637

Very weak cytotoxicity.

MCF-5

Very weak cytotoxicity.

IC50 = 41.9 μg/mL IC50 = 93 μg/mL

5637

Moderate cytotoxicity.

MCF-5

Low cytotoxicity.

-

In vitro Colorectal and hepatocellular cancer cells.

Antiproliferative effect.

(Orabi et al., 2015)

IC50 = 43 μg/mL IC50 = 24 μg/mL IC50 = 16.3 μg/mL

WS-1



WS-1

Significant cytotoxicity.

WI-38

Significant cytotoxicity.

Antitrypanosomal P. punctulata Aerial parts

Anticancer P. arguta

Leaves

Methanol extract


P. dentata

Aerial parts

Methanol extract


P. punctulata

Leaves and flowers

Aqueous extract

Methanol extract

Actives compounds: Psiadin

Cytotoxicity P. arguta

Leaves

Methanol extract Dichloromethane extract

A-549

A-549

A-549

A-549


Significant antiproliferative effect. Significant antiproliferative effect. Weak antiproliferative effect. Weak antiproliferative effect.


Moderate anticancer effect. Significant inhibitory effect. (Mothana et al., 2011)


P. dentata

Aerial parts

Methanol extract Dichloromethane extract

P. punctulata

Aerial parts

Methanol extract

IC50 = 125 μg/mL IC50 = 55 μg/mL

WS-1

Low cytotoxicity.

WS-1


IC50 = 6.43 μg/mL

MRC-5

High cytotoxicity.


MIC: minimum inhibition concentration ED50: 50% effective dose IC50: 50% inhibition concentration WS-1: human skin fibroblast WI-38: human normal foetal lung fibroblast DLD-1: human colorectal adenocarcinoma cells A-549: human lung carcinoma cells 5637: human urinary bladder carcinoma cells MCF-5: human breast cancer cell

5. Pharmacological activities Several Psiadia species have been studied for their biological properties, including antimicrobial, antiplasmodial and anti-inflammatory. All pharmacological activities, captured in various publications are recapitulated in Table 7. Moreover, a P. altissima aqueous extract has been recorded in the INPI patent database. It is mainly used for the production of drugs with diuretic, choleretic or spasmolytic properties (approved in 1963). 5.1. Antimicrobial The use of Psiadia species for skin infections, pulmonary infections, dental pain and syphilis could be justified by their antimicrobial activities. P. altissima essential oil was first studied for its antimicrobial potential. The essential oil demonstrated an inhibitory effect on several bacteria (Ramanoelina et al., 1987). Further investigations on P. arguta, P. viscosa, P. lithospermifolia, P. lucida, P. penninervia and P. terebinthina essential oils and extracts showed that they inhibited the growth of several bacteria and fungi (Table 6) (Andriamanantoanina et al., 2004; Aumeeruddy-Elalfi et al., 2015; Govinden-Soulange et al., 2004; Kauroo et al., 2016). Tests performed on the antibiotic potentiating activity of the essential oil of P. arguta demonstrated the synergic effect of essential oils of P. arguta and Pimenta dioica combined with gentamicin against E. coli (ATCC 25923). Indeed, gentamicin inhibited growth of E. coli at an MIC dose of 2 mg/mL, while the two essential oils combined with gentamicin at an MIC dose of 0.25 mg/mL (Aumeeruddy-Elalfi et al., 2015). Wang et al. (1989) concentrated their work on the antibacterial and antifungal properties of the dichloromethane extract of P. viscosa (synonym P. trinervia). The extract of P. viscosa showed antimicrobial activity against Cladosporium cucumerinum and Bacillus cereus on autobiographic assays. Results emanating from activityguided isolation indicated that compounds active against C. cucumerinum and B. cereus are ayanin, casticin, chrysosplenol-D, 5,7,4’-trihydroxy-3,8-dimethoxyflavone, 5,7,4’-trihydroxy-3,3’-dimethoxyflavone and isokaempferide. They concluded that a 5,7-dihydroxy substitution is required for good antibacterial activity. In contrast, the antifungal compounds tend to be flavonol 3-methyl ethers with acetylated groups. Psiadia punctulata has been studied for antimicrobial activities against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6059), Micrococcus flavus (SBUG 16), Escherichia coli (ATCC 11229), Candida maltosa (SBUG) and multi-resistant Staphylococcus strains: S. epidermidis 847, S. haemolyticus 535 and S. aureus north German epidemic strain (Mothana et al., 2011). Methanolic and aqueous extracts were evaluated using leaves and flowers as plant materials. The aqueous extract exhibited an inhibition effect against several microorganisms. This can justify the usage of a decoction of P. punctulata leaves for the treatment of skin infections.

Psiadia species extracts and essential oils appeared to have antimicrobial activities against several microorganisms including Bacillus cereus, Staphylococcus aureus, Streptococcus spp., Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus spp.. In fact, these microorganisms are common agents of respiratory infections (Dasaraju and Liu, 1996). P. arguta, P. lithospermifolia and P. viscosa extracts displayed high antimicrobial activities with MIC value less than 100 μg/mL against some of these microorganisms. According to literature, a high antimicrobial activity relates to MIC below 100 μg/mL (Cos et al., 2006). Those results could explain the employment of Psiadia species for treatment of respiratory disorders. These three species clearly deserve to be studied for characterisation of active compounds. 5.2. Anti-viral Several Psiadia spp. have been used to treat ailments of possible viral origin, e.g. cough, fever and colds via leaves decoction. To justify these traditional usages, Robin et al. (1998) screened the antiviral potential of seven Psiadia species endemic to La Réunion: P. amygdalina, P. anchusifolia, P. argentea, P. boivinii, P. dentata, P. laurifolia and P. montana. The methanol crude extract of each plant was tested for their in vitro antiviral effect against herpes simplex virus type 1 (HSV-1), poliomyelitis type 2 (poliovirus) and vesicular stomatitis (VSV). In this experiment, P. dentata was the only species that displayed an antiviral effect (Table 6). Fractionation of the methanol crude extract led to isolation of two active flavonoids: ermanin and isokaempferide. However, the activity of these two compounds against poliovirus type 1 had already been demonstrated (De Meyer et al., 1991; Vanden Berghe et al., 1986). Later on the same authors analysed the antipoliovirus properties of these two compounds and their mechanisms of action (Robin et al., 2001). In the evaluation of inhibition of poliovirus type 2 replication, isokaempferide showed the highest antiviral activity. The flavonoid inhibited replication at concentrations 10-fold, 2-fold and 200-fold lower than ermanin, 3-methylquercetin and guanidine respectively. Cytotoxicity assays of ermanin and isokaempferide were performed on Vero cells and 50% cytotoxic concentrations were determined (CC50). In comparison with the reference compounds, 3-methylquercetin (CC50 = 27 μM) and guanidine (CC50 = 911 μM), ermanin (CC50 = 197 μM) and isokaempferide (CC50 = 107 μM) were less cytotoxic than 3-methylquercetin but more than guanidine. They concluded that isokaempferide was the most active and selective compound against poliovirus among the compounds tested. As ermanin, isokaempferide and 3-methylquercetin are structurally related molecules and showed to have different antipoliovirus activity and cytotoxicity, this difference could be due to their substituents. Indeed, they demonstrated that the presence of a methoxyl group at C-3 and a hydroxyl group at C-4' contribute to antipoliovirus activity and the nature of the group at C-3' and C-4' determine the toxicity. The antipoliovirus activity of these compounds seemed to be related to the methoxyl group in C-3 as has been demonstrated previously in other compounds (Castrillo et al., 1986; De Meyer et al., 1991; Van Hoof et al., 1984; Wang & Hostettmann, 1990). Furthermore, the mechanism of action of isokaempferide has been determined and the results indicated that the flavonoid inhibited the late steps of poliovirus type 1 replication cycle and, more specifically, inhibition of genomic RNA synthesis. Fortin et al. (2002) screened the antiviral activity of 36 medicinal plants from La Réunion against HSV-1 and poliovirus. Among these species, eight Psiadia spp. have been investigated for their antiviral properties: the species are the same as those studied by Robin et al. (1998) with addition of P. retusa. The screening showed that methanol extracts of P. dentata and P. retusa were active against poliovirus only. However, P. dentata methanol extract was the most active (ED50 = 80 μg/mL) (ED50: concentration required to inhibit viruses by 50%). Off all Psiadia species that have been tested for antiviral activity, P. dentata methanol extract was the only one to be active against poliovirus. After fractionation of this extract, the activity was found to be related to several flavonoids. In comparison to the other eight species, we can hypothesise that the antiviral activity of P. dentata might be related to its wealth of bioactive flavonoids. 5.3. Anti-inflammatory As part of their research into the anti-inflammatory potential of plant species from Central America and Africa, Recio et al. (1995) screened an aqueous extract of P. arguta. Evaluations of topical and oral anti-

inflammatory activity were performed on 12-O-tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema and carrageenan-induced mouse paw oedema, respectively. P. arguta aqueous extract was assayed topically at a concentration of 5.5 mg and showed a moderate anti-inflammatory activity (65% of oedema inhibition). This positive response on the TPA-induced oedema model indicates that the extract acts on the inhibition of Protein Kinase C (PKC). Indeed, TPA stimulates the activation of PKC, which produces exocytosis, modulation of ion conductance and other events related to the inflammatory response. On oral application, P. arguta exhibited a moderate activity compared to the positive control indomethacin. One hour, 3 h and 5 h after administration of phlogistic agent, P. arguta aqueous extract showed 25, 33 and 16% of oedema inhibition respectively while indomethacin displayed higher percentages of inhibition: 42, 46 and 31% respectively. Later on, Jonville et al. (2011) screened the anti-inflammatory activity of 19 species from Mauritius and La Réunion island in order to identify potent anti-inflammatory agents. The 19 species included P. arguta and P. dentata dichloromethane and methanol extracts. Anti-inflammatory activity was assessed in vitro using LPSstimulated Raw 264.7 murine macrophages ((ATCC #TIB-71) and NO production was quantified which is an important target for inflammatory diseases. The dichloromethane extract of P. arguta exhibited a high activity with IC50 = 13 μg/mL compared to the positive control L-NAME (IC50 = 129 μg/mL). The anti-inflammatory activity of P. arguta and P. dentata extracts might be related to phenolic compounds detected in the crude extracts. Flavonoids are common anti-inflammatory agents (Sae-Wong et al., 2011; Sudsai et al., 2014; Vigil de Mello et al., 2016). Several flavonoids have been identified in P. dentata (Fortin et al., 2001; Robin et al., 1998) and phenolic compounds such as phenols, tannins, coumarins and flavones have been detected in P. arguta methanol crude extracts (Govinden-Soulange, thesis, unpublished data). 5.4. Antiplasmodial P. punctulata is the only Psiadia species listed in African folk medicine for treatment of malaria. P. punctulata roots were employed by the Maasai as antimalarial agents. Koch et al. (2005) investigated 21 plants used by this ethnic group as a cure for malaria and/or malaria-like symptoms. Among the species tested, P. punctulata root bark extract was tested on D6 clone of Plasmodium falciparum in culture. The extract displayed no activity compared to the other plant species. However, a recent study displayed the antiplasmodial activity of the methanol extract of P. punctulata on chloroquine-sensitive Plasmodium falciparumGHA-strain (Abdel-Sattar et al., 2010). Jonville et al. (2008) decided to screen the antimalarial potential of nine species from Reunion. P. arguta was selected amongst the plants tested. The methanol and dichloromethane extracts of each plant were tested in vitro against Plasmodium falciparum 3D7 and W2 strains and in vivo in female mice infested by Plasmodium berghei NK173. P. arguta dichloromethane extract displayed a strong activity against both strains with IC50 = 10.1 μg/mL (3D7 strain) and 8.4 μg/mL (W2 strain). The dichloromethane extract was selected for in vivo tests in infested mice at doses of 50 mg/Kg and 200 mg/Kg. In accordance with the in vitro test, P. arguta extract exhibited an antimalarial activity. Indeed, when tested at 50 mg/Kg and 200 mg/Kg, the extract inhibited the parasitaemia in mice at 75.5% and 86.7%. Compared to the negative control, after seven days post-infection the extract showed a good activity (60% viability). Later on, the same authors investigated the antiplasmodial, anti-inflammatory and cytotoxic activities of P. arguta and P. dentata methanol and dichloromethane extracts (Jonville et al., 2011). The antiplasmodial assays were performed on Plasmodium falciparum 3D7 strain. P. arguta showed the same activity as described in 2008, and a low selectivity index: SI = 2.4 for the dichloromethane extract and SI = 1.9 for the methanol extract. In addition, P. dentata dichloromethane and methanol extracts displayed a strong antiplasmodial activity with IC50 = 7 μg/mL and 15 μg/mL respectively. Both extracts exhibited a higher selectivity index (SI = 7.8 for the dichloromethane extract and SI = 8.3 for methanol extract) compared to P. arguta extracts.

Pink et al., (2005) reported that in a screening campaign of antiparasite hits, a selective extract should be at least tenfold more active against a parasite than a mammalian cell line. Thus, we can consider that these two species display a moderate selectivity index and appear to be promising plants for discovering new antiplasmodial agents. The three species evaluated for antiplasmodial activity seem to be significantly active against P. falciparum. This may imply that the genus Psiadia, or at least these three species, contain similar compounds that are responsible for the antiplasmodial activity. The chemical composition of these three species revealed the presence of phenolic compounds in the crude extracts. Besides, several terpenoids have been isolated in P. punctulata. These classes of compounds may be related to the antiplasmodial activity considering that terpenes and flavonoids displayed a wide range of biological properties. The antiparasitic potential of terpenes and flavonoids have been reported in the literature (Batista et al., 2009; Bero et al., 2009; Cavalcanti et al., 2017; Kaur et al., 2009; Nogueira and Lopes, 2011; Zakaria et al., 2012).

5.5. Antileishmanial Githinji et al. (2010) investigated the antileishmanial potential of the methanol and water extracts of P. punctulata leaves and stem bark. The assays were performed in vitro on Leishmania major promastigotes (Strain IDU/KE/83 = NLB-144) and infected mouse peritoneal macrophages. P. punctulata extracts was tested in vitro against Leishmania major promastigotes and amastigotes and displayed a low activity. Thus P. punctulata methanol and water extracts can be considered as non-active against Leishmania major. The methanol extract of the aerial parts of P. punctulata was tested against Leishmania infantum amastigotes (MHOM/MA(BE)/67) (Abdel-Sattar et al., 2010). The parasite was in culture in primary peritoneal mouse macrophages. The extract exhibited a low activity against Leishmania infantum with IC50 = 32.46 μg/mL compared to the positive control miltefosin with an IC50 = 0.065 μg/mL. In comparison to other plant extracts that have been evaluated for their antileishmanial potential, P. punctulata methanol extract appeared to have a moderate activity. Recent studies showed the potential of several plant crude extracts against Leishmania major and Leishmania infantum: Isolona hexaloba (Musuyu Muganza et al., 2015), Casearia sylvestris, Piptocarpha macropoda, Cymbopogon citratus (Antinarelli et al. 2015), Ricinus communis and Azadirachta indica (Jumba et al., 2015) and IC50 values were below 10 μg/mL. 5.6. Antitrypanosomal Abdel-Sattar et al. (2010) screened the antitrypanosomal activity of 51 plants from the western region of Saudi Arabia. The methanol extracts of the aerial parts of each plant were tested against the suramin-sensitive Trypanosoma brucei brucei (Squib-427 strain) and nifurtimox-sensitive Trypanosoma cruzi (Tulahuen CL2 strain). Among plants tested, P. punctulata showed a strong activity against both parasites with IC50 values less than 0.25 μg/mL. 5.7. Anticancer P. punctulata has been investigated for antiproliferative activity on human cancer cell lines: human urinary bladder carcinoma cells 5637 (ATCC HTB-9) and human breast cancer cells MCF-7 (ATCC HTB-22) (Mothana et al., 2011). The aqueous extract showed a very weak activity on 5637 and MCF-7 cells and the methanol extract displayed a low activity on 5637 and MCF-7 cells. Psiadin, a terpene isolated from the aerial parts of P. punctulata, has been evaluated for a potential antiproliferative activity. The compound displayed anticancer effects on colorectal and hepatocellular cancer cells (Orabi et al., 2015). In their screening of potential activities of plants from Reunion Island, Jonville et al. (2011) measured the antiproliferative effect of methanol and dichloromethane extracts on different cancer cell lines: human lung carcinoma A-549 (ATCC #CCL-185) and human colorectal adenocarcinoma DLD-1 (ATCC #CCL-221). Results showed that both extracts of Psiadia arguta are active on the DLD-1 and A-549 cell lines. In contrast, Psiadia dentata methanol extract showed a lower antiproliferative effect and the dichloromethane extract displayed a significant antiproliferative effect on human lung carcinoma cells (A-549).

5.8. Cytotoxicity and toxicity The cytotoxicity of P. punctulata methanol extract was evaluated in vitro on human embryonic lung fibroblasts (MRC-5) and the extract exhibited a high cytotoxicity effect. The evaluation of cytotoxicity of P. arguta and P. dentata extracts were performed in vitro on human normal fibroblasts (Jonville et al., 2008, 2011). P. arguta extracts were considered as cytotoxic with IC50 = 24 and 43 μg/mL for dichloromethane and methanol extracts, respectively. When tested in vivo, the dichloromethane extract displayed a slight toxicity; on day 15 post-infected the viability of the mice was 0% in comparison to positive control (viability of 80 and 100%). Moreover, P. dentata showed moderate cytotoxicity on human fibroblast with IC50 = 55 and 125 μg/mL for dichloromethane and methanol extract respectively. Both species extracts demonstrated slight cytotoxicity in vitro and P. arguta showed a low toxicity in vivo. Owing to their pharmacological effects (antimicrobial, anti-inflammatory and antiplasmodial activities), P. arguta and P. dentata deserve to be explored for characterisation of active compounds. The cytotoxicity and toxicity may not be related to biologically active molecules. 6. Conclusions and perspectives This review summarised the botany, traditional uses, phytochemistry and pharmacology of species of the genus Psiadia. Major ethnomedicinal uses that are common among different countries are for respiratory disorders (cough, asthma, bronchitis and pulmonary infections). To a certain extent some traditional uses of Psiadia species have been scientifically validated and supported by pharmacological studies. Results obtained on the antimicrobial activity of Psiadia species extracts showed a good correlation with the reported usages of these plants in traditional medicine as expectorants, for treatment of bronchitis and pulmonary infections. According to literature information, only a few species of the genus have been studied, and little data are available. Current knowledge of Psiadia species contains several gaps, which require more investigation. These gaps include: 1) A chemotaxonomic study is clearly lacking on the genus Psiadia. Indeed, taxonomic and molecular phylogenetic studies have been performed on Psiadia species from Mascarene Islands and each study defined different groupings of species based on morphological and genetic aspects (Bosser et al., 1993; Strijk et al., 2012). It could be interesting to combine these results with those of a chemotaxonomic study to see if there is any correlation between chemical profile and genetic or morphological aspects. To date only five species have been investigated for their phytochemical composition and 73 compounds have been isolated, including flavonoids, coumarins, hydroxycinnamic acids and terpenes. Among the isolated molecules, flavonoids and diterpenes are classes of compounds mostly represented. Several new flavonoids (5,7-dihydroxy-2’,3’,4’,5’-tetramethoxyflavone (22), 5,4’-dihydroxy-7,2’,3’,5’-tetramethoxyflavone (23) and 5,7,4’-trihydroxy-2’,3’,5’-trimethoxyflavone (24)) and terpenes (name of compound not available (63), name of compound not available (64), ciliaric acid (65), 6α,18,19ent-trachylobantriol (66) and 2α,17,18-ent-trachylobantriol (67)) have been identified, and appear to be exclusive to the genus. These compounds may be considered to be taxonomic markers of the genus. Flavonoids 22, 23 and 24 were identified in P. punctulata; terpenes 63, 64 and 65 in P. altissima and terpenes 66 and 67 in P. anchusifolia. However, phytochemical investigations on more Psiadia species are required in order to confirm the possibility of using these compounds as chemotaxonomic markers. Moreover, a combination of genetic, morphological and chemical markers will reduce confusion between species. 2) Pharmacological studies conducted on the genus Psiadia have indicated that a few species possess several biological activities, including antimicrobial, antiplasmodial, antiviral and anti-inflammatory. However, measured activities and ethnomedicinal uses are not always in agreement. Indeed, almost all activity measurements have been carried out on polar or apolar extracts, while aqueous extracts are traditionally used for treatment of ailments. However, P. arguta aqueous extract has an antimicrobial effect and displays a moderate topical and oral anti-inflammatory activity in vivo. Those results can be related to some traditional uses such as treatment of abscesses, pulmonary infections and abdominal pains. It should be stated that most pharmacological studies have

been performed on crude extracts and few activity-guided isolations have been conducted. According to pharmacological data on crude extracts, biological activities that have promising results are antimicrobial, antiparasitic (antiplasmodial and antitrypanosomal), anticancer and anti-inflammatory activities. These activities have been screened in vitro on biological models and further experiments should be performed in order to identify the active compounds. As stated before, these biological properties may be related at least to terpenes and flavonoids that have been identified in the genus Psiadia. Isolated diterpenes should be tested for their pharmacological properties considering that terpenoids display a wide range of pharmacological properties including antiparasitic activities (Ludwiczuk et al., 2017; Mbaveng et al., 2014; Nevzorova et al., 2017; Šarac et al., 2014). Based on pharmacological results, the most promising species for further investigations are P. punctulata, P. dentata and P. arguta. Indeed, P. punctulata extract exhibited a strong antitrypanosomal activity in vitro with IC50 = 0.25 μg/mL. Compared to other tests performed on this extract (antimicrobial, antileishmanial, antiplasmodial and anticancer effects), this species has a high antitrypanosomal activity, which implies that it has a selective activity. Thus, P. punctulata provides convincing evidence for further investigations in order to characterise its active compounds and to perform in vivo experiments for preclinical validation. Furthermore, P. dentata and P. arguta show antimicrobial, anti-inflammatory, antiplasmodial and anticancer effects. Extracts of P. dentata displayed a high selectivity index. In in vivo experiments, Psiadia arguta crude extracts have shown promising results for antiinflammatory and antiplasmodial assays, which are the first steps in preclinical validation. In addition, this species shows high antimicrobial activities. For both species, bioactive molecules should be determined using bioactivityguided isolation strategies. More systematic research is required to reveal the active molecules in those species and rigorous investigations into the isolated compounds in in vivo experiments in clinical trials are required. As demonstrated above, a great deal of information on the chemistry of the genus Psiadia is scattered through literature and many gaps remain. Phytochemical and pharmacological data have supplied some evidence for the therapeutic potential of some Psiadia species. A few investigations on biological activities of Psiadia spp. have been carried out in vivo on animal models but no further research on clinical assays has been completed. Thus, further research should highlight the isolation of bioactive compounds of P. arguta, P. dentata and P. punctulata. These studies should be combined with investigations into pharmacological effects in vivo, identifying the mechanisms of action, toxicology and clinical applications in assessing the efficacy of isolated molecules. Furthermore, the genus Psiadia has a high level of endemism on Madagascar and Mascarene islands. Therefore, there is a high possibility of isolation of new active compounds. Acknowledgements: Financial support from the Conseil Régional of La Réunion Island is gratefully acknowledged. References: A. Al-Yahya, M., S. Hifnawy, M., S. Mossa, J., S. El-Feraly, F., R. McPhail, D., T. McPhail, A., 1987. X-ray structure of psiadiarabin, a flavone from Psiadia arabica. Phytochemistry 26, 2648–2649. doi:10.1016/S00319422(00)83901-1 Abdel-Sattar, E., Maes, L., Salama, M.M., 2010. In vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease. Phytother. Res. PTR 24, 1322–1328. doi:10.1002/ptr.3108 Abou-Zaid, M.M., El-Karemy, Z., EI-Negoumy, S.I., Altosaar, I., Saleh, N.A.M., 1991. The flavonoids of Psiadia punctulata. Bull. Chem. Soc. Ethiop. 5. doi:10.4314/bcse.v5i1. Ameenah Gurib-Fakim, C.B., 1995. Chemical composition of the essential oils of Psiadia lithospermifolia (Lam.) Cordem. and P. viscosa (Lam.) A. J. Scott of the Asteraceae Family. J. Essent. Oil Res. 7, 533–535. doi:10.1080/10412905.1995.9698579 Andriamanantoanina, H., Mananjarasoa, E., Ramaroson, L., Casabianca, H., Grenier-Loustalot, M.F., 2004. Composition and antimicrobial activity of the leaf of Psiadia lucida (Cass.) Drake (Asteraceae). J. Essent. Oil Res. 16, 623–625. doi:10.1080/10412905.2004.9698811 Antinarelli, L.M.R., Pinto, N.C., Scio, E., Coimbra, E.S., Antinarelli, L.M.R., Pinto, N.C., Scio, E., Coimbra, E.S., 2015.

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The genus Machaerium (Fabaceae): taxonomy, phytochemistry, traditional uses and biological activities.

Genus Tinospora: Ethnopharmacology, Phytochemistry, and Pharmacology.

Jatropha gossypiifolia L. (Euphorbiaceae): A Review of Traditional Uses, Phytochemistry, Pharmacology, and Toxicology of This Medicinal Plant.

Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)--a review of their phytochemistry, pharmacology, toxicology and traditional use.

Citrullus colocynthis (L.) Schrad (bitter apple fruit): a review of its phytochemistry, pharmacology, traditional uses and nutritional potential.

Ethnomedicinal uses, phytochemistry and pharmacological properties of the genus Boerhavia.

Traditional Uses, Phytochemistry, and Bioactivities of Cananga odorata (Ylang-Ylang).

Medicinal uses, phytochemistry and pharmacology of Picralima nitida (Apocynaceae) in tropical diseases: a review.

Phytochemistry, pharmacology and ethnomedicinal uses of Ficus thonningii (Blume Moraceae): a review.

Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities.

Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review.

A review on ethnobotany, phytochemistry and pharmacology of plant genus Caralluma R. Br.