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Phytochemistry Reviews

, Volume 17, Issue 4, pp 701–731 | Cite as

Genus Retama: a review on traditional uses, phytochemistry, and pharmacological activities

  • A. J. León-González
  • I. Navarro
  • N. Acero
  • D. Muñoz Mingarro
  • C. Martín-Cordero
Article

Abstract

Plants of the genus Retama (Fabaceae) are used in traditional medicine of the Mediterranean Basin as an emetic, purgative, and vermifuge. Certain Retama species are also employed to treat a multitude of disorders, including diabetes, hepatitis, jaundice, sore throat, skin diseases, joint pain, rheumatism, fever, and inflammation. This review deals with updated information on the distribution, botanical characteristics, ethnopharmacology, phytochemistry, pharmacological activities, and toxicity of the Retama species in order to support their therapeutic potential and to provide an input for future research prospects. The Retama species are mainly employed as ethnomedicinal remedies in Mediterranean countries, including Algeria, Egypt, Italy, Lebanon, Libya, Morocco, and Spain. Previous phytochemical studies show a complex composition, rich in carbohydrates (galactomannans), polyols (pinitol), fatty acids, phenolic compounds (genistein, daidzein) and alkaloids (retamine, lupanine). The pharmacological activity of their various extracts has been widely studied, revealing, among others, the anti-microbial, anti-inflammatory, and anti-diabetic effects of these species. The potential toxicity of these medicinal plants has also been discussed. Although recent experimental evidence confirms the pharmacological interest of this genus, further studies are necessary.

Keywords

R. monosperma R. raetam R. sphaerocarpa Quinolizidine alkaloids Isoflavones 

Abbreviations

GLC–MS

Gas liquid chromatography mass spectrometry

MIC

Minimum inhibitory concentration

RP-HPLC

Reversed phase high performance liquid chromatography

HCMV

Human cytomegalovirus

MSSA

Methicillin sensitive Staphylococcus aureus

MRSA

Methicillin resistant Staphylococcus aureus

ROS

Reactive oxygen species

DPPH

1,1-Diphenyl-2-picrylhydrazyl

IC50

50% inhibitory concentration

TAC

Total antioxidant capacity

AGEs

Advanced glycation end products

SOD

Superoxide dismutase

GPx

Glutathione peroxidase

MDA

Malondialdehyde

NSAID

Non-steroidal anti-inflammatory drug

LOX

Lipoxygenase

TNBS

Trinitrobenzene sulfonic acid

TNF-α

Tumour necrosis factor alpha

COX

Cyclooxigenase

iNOS

Inducible nitric oxide synthase

Introduction

Retama Raf. (Fabaceae) nomen conservandum, previously named Lygos Adanson, also known as rtem or ratam, constitutes a monophyletic taxon, and is comprised of four closely related endemic species of the Mediterranean Basin: R. monosperma (L.) Boiss., R. raetam (Forsk.) Webb., R. sphaerocarpa Boiss. and R. dasycarpa Coss. This genus is distributed over several climates and ecosystems including coastal dunes, maquis, and even deserts, since Retama species tolerate extreme drought conditions. The similarities between the phenotypic characteristics of those four species hinder their taxonomical determination. Species differ in banner colour, which is white in R. monosperma and R. raetam and yellow in R. sphaerocarpa and R. dasycarpa (Belmokhtar and Harche 2012; Boulila et al. 2009; Cardoso et al. 2013; Greuter et al. 1989).

Plants of the genus Retama are perennial and unarmed shrubs, with evergreen cladodes (photosynthetic stems), grow between 2 and 4 m in height, and are many-branched, with simple and deciduous leaves, which fall rapidly after emergence. Flowers in racemes include those of calyx urceolate, campanulate or turbinate, bilabiate, with white to yellow corolla. Stamens are monadelphous and the style is filiform and incurved. The fruit is an ovoid to globose legume, indehiscent or finally incompletely dehiscent along the ventral suture with one or two seeds (Heywood 1968; Villar et al. 2013).

Retama raetam, grows in Israel, and is believed to be the juniper of the Bible: in Kings 19:4–5, it is called rotem in the Hebrew singular; and in Job 30:4, it is called retamim in the plural (Hehmeyer and Schönig 2012).

Plants from the genus Retama have shown great homogeneity regarding their medicinal use (Bellakhdar 1997). They have traditionally been used by local people to treat several ailments, such as diabetes, rheumatism, and inflammation (Ali-Shtayeh et al. 1998; Abouri et al. 2012; Telli et al. 2016).

With the increasing interest in the exploration and exploitation of natural sources, a number of studies related to phytochemical and pharmacological aspects of Retama spp. have been conducted on R. monosperma, R. raetam, and R. sphaerocarpa. In roots, flowers, seeds and cladodes, the presence of carbohydrates, fatty acids, phenolic compounds as phenolic acids, flavonols, flavones, flavanones, chalcones, aurones, isoflavones and phenylpropanoids, terpenes, steroids and alkaloids has been described.

Indeed, most of the traditional uses of Retama spp. have been substantiated by pharmacological studies.

The literature reveals that Retama spp. shows several biological activities, including antibacterial (Hammouche-Mokrane et al. 2017), anti-inflammatory (González-Mauraza et al. 2014), antioxidant (El-Toumy et al. 2011), anti-proliferative (Belayachi et al. 2013) anti-ulcer (El-Toumy et al. 2011), anti-viral (Edziri et al. 2008), and hepatoprotective activities (Omara et al. 2009b; Koriem et al. 2010).

In this review, the traditional uses, chemical constituents, pharmacological activities and toxicology of the Retama genus are highlighted. A critical evaluation of pharmacological studies in terms of their relation to ethnopharmacology is also provided.

Ethnobotany of Retama spp.

Origin and geographic distribution

Fabaceae is a widely distributed family of flowering plants with 730 genera and 19,400 species divided into three subfamilies: namely Faboideae, Mimosoideae, and Caesalpinioideae (Kirkbride et al. 2003). The Retama genus belongs to the family Fabaceae, subfamily Faboideae, tribu Genisteae and comprises four species that are mainly distributed in the Mediterranean Basin (Greuter et al. 1989) (Table 1). R. sphaerocarpa is largely distributed throughout the Iberian Peninsula and North Africa. R. monosperma is native to the coastal sandy areas of SW Spain and NW of Africa. R. dasycarpa is restricted to the Atlas Mountains in Morocco. R. raetam has an amphi-Mediterranean distribution. R. raetam subsp. gussonei is endemic to Sicily.
Table 1

Species of the Retama genus

Retama species

(Accepted names)

Synonyms

Country

R. monosperma (L.) Boiss.

Genista monosperma (L.) Lam.; Lygos monosperma (L.) Heywood; Retama monosperma subsp. monosperma; Retama rhodorhizoides Webb & Berthel.; Spartium monospermum L.

Spain, Portugal, Morocco, Algeria, Egypt

R. raetam (Forsk.) Webb.

Genista monosperma; Genista raetam Forssk.; Lygos raetam (Forssk.) Heywood; Retama duriaei (Spach) Webb; Retama raetam subsp. Raetam; Retama raetum (Forssk.) Webb]

Morocco, Algeria, Tunisia, Libya, Egypt, Sicily, Jordan, Israel, Lebanon, Palestina

Retama raetam subsp. gussonei (Webb) Greuter

Lygos raetam subsp. gussonei (Webb) Heyw.

Retama gussonei Webb

Retama gussonii Webb

Sicily

R. sphaerocarpa Boiss.

Lygos sphaerocarpa (L.) Heywood

Spain, Portugal, Morocco, Algeria, Tunisia

R. dasycarpa Coss.

 

SW Morocco

Synonyms and worldwide distribution (GBIF 2017; Greuter et al. 1989; Sequeira et al. 2011; The Plant List 2017)

Studies on genetic diversity and relationships among and within three populations of R. raetam collected in different habitats in southern Tunisia were conducted by Abdellaoui et al. (2014). Research indicates that most variation occurred within populations and that genetic differentiation had occurred between populations. These findings are crucial for a better understanding of the adaptive strategy of this plant in this geographical area and to help in the creation of an effective strategy to protect this important species.

Economic relevance

The most commonly used species in North Africa is R. raetam, and thus the one with major economic relevance. This specie is widely utilized by local population for construction and ornamental purposes, and for healing or ameliorating several diseases (Barakat et al. 2013). Retama plant species are also used in pastures to provide shade and shelter for animals, especially on hot dry days (Obón et al. 2011; Barakat et al. 2013).

Agro-climatic preference

The Retama genus occupies a wide range of habitats. The plants of this genus grow preferably in coastal areas and deserts. They are plants that resist winter low temperatures and summer extreme hot. Retama spp. could grow up in low fertility and drought soils (Muñoz Vallés et al. 2013; Barakat et al. 2013).

Ethnopharmacological uses

Plants belonging to Retama genus have been used traditionally for the treatment of different diseases in many parts of Mediterranean Basin, especially in North Africa and the Middle East (Table 2). Literature revealed that R. raetam is the most widely used species.
Table 2

Ethnopharmacological uses of Retama spp. Species, common name, part of the plant that is used in each case, preparation, via of administration and Country

Species

Common name

Plant part

Traditional use

Preparation

Administration and application area

Country/Province

References

R. monosperma (L.) Boiss

Retam, Rtem

Cladodes

Emetic

Powdered and mixed with honey

Oral

Morocco

Bellakhdar (1997)

  

Cladodes

Purgative,Vermifuge

Decoction

Rectal washings

Morocco

Bellakhdar (1997)

 

Tillugwît, îllugwî, Allugû, Talggût (berbère)

Cladodes

Prevention of hydrophobia (rabies)

Decoction

Oral

Algeria

Helmstädter (2016)

R. raetam (Forsk.) Webb.

R’tam, Retam, Rataym

Cladodes

Emetic

Powdered and mixed with honey

Oral

Morocco

Bellakhdar (1997)

  

Cladodes

Purgative,Vermifuge

Decoction

Rectal washings

Morocco

Bellakhdar et al. (1991) and Bellakhdar (1997)

  

Cladodes

Healing in circumcisions

Antiseptic and sedative in local wound care, wound and skin ulcers, vulnerary

Powered

Cataplasm

Morocco (Tissint)

Bellakhdar et al. (1991) and Bellakhdar (1997)

  

Cladodes

Antipruritic and Scabies

Decoction

Liniments

Morocco (Marrakech)

Bellakhdar et al. (1991) and Bellakhdar (1997)

  

Cladodes, Flowers

Abortive

Infusion

Oral

Morocco

Abouri et al. (2012) and Bellakhdar (1997)

  

Roots

Abortive

Decoction

Vaginal washings

Morocco (Sahara)

Bellakhdar (1997)

 

Rtem

Roots

Diphtheria

NS

NS

Morocco (Sahara)

Mouhajir 2002

  

Cladodes, Flowers

Skin disease

Decoction

External use

Morocco (Taounate, Tata)

Bellakhdar et al. (1991), El-Hilaly et al. (2003) and Abouri et al. (2012)

  

Cladodes

Rheumatism

Infusion

Oral

Morocco (Tata)

Abouri et al. (2012)

  

Cladodes

Scorpion bite, wounds healing

Cataplasm

External use

Morocco (Tata)

Abouri et al. (2012)

 

Retam

Cladodes

Rheumatism, Scorpion sting, Skin wounds

NS

NS

Algeria (Ouargla)

Ould El Hadj et al. (2003)

  

Cladodes

Healing in skin diseases, inflamed eyes, diarrhea, fever

NS

 

Algeria (Ouanougha)

Rebbas et al. (2012)

  

Cladodes

Treat stomachache

Infusion

Oral

Algeria

Rebbas et al. (2012)

  

Cladodes

Skin wounds, back pain

Powdered and mixed with olive oil

External use

Algeria

Rebbas et al. (2012)

  

Fruits, seeds

Diabetes

Decoction, Infusion

Oral

Algeria (Ouargla)

Telli et al. (2016)

  

Cladodes

Eczema

Decoction

External use

Algeriaç (M’Sila)

Boudjelal et al. (2013)

 

Rtam

Cladodes

Scabies

NS

Poultice

Tunisia

Viegi and Ghedira (2014)

 

Ratam

NS

Diabetes, sinusitis

NS

NS

Libya (Al-Jabal Al-Akhder)

El-Mokasabi (2014)

  

Cladodes

Aching joints, back pain and skin bruise

Decoction

Bath

Israel

Said et al. (2002)

 

Retem

Cladodes

Fractures and burns

Decoction

Poultice

Jordan

Hudaib et al. (2008)

 

Retem

Cladodes

Joint aches

Decoction

Bath

Lebanon

El-Beyrouthy et al. (2008)

 

Ratame

Cladodes, seeds

Antiinflammatory, treat inflamed eyes and sore throat, antirheumatic, treat infertility, treat paralysis

NS

Poultice

Palestine

Ali-Shtayeh et al. (1998)

  

Cladodes, seeds

Analgesic, treat stomachache

NS

Oral

Palestine

Ali-Shtayeh et al. (1998)

 

Ratam, rotem hamidbar

Cladodes

Hepatitis, jaundice

Infusion

Internal use

Yemen

Hehmeyer and Schönig (2012)

 

Ratam, Ratama

Cladodes,Flowers

Syphilis, women infertility

Decoction

External use

Middle –East

Yaniv and Dudai (2014)

R. sphaerocarpa Boiss.

R’tam, Retam, Algu

Cladodes

Emetic

Powdered and mixed with honey

Oral

Morocco

Bellakhdar (1997)

  

Cladodes

Purgative,Vermifuge

Decoction

Rectal washings

Morocco

Bellakhdar (1997)

 

Rtem

Root

Diabetes

Decoction

Internal use

Morocco (Errachidia)

Tahraoui et al. (2007)

 

Rtem

Roots

Diphtheria

NS

NS

Morocco (Sahara)

Mouhajir 2002

  

NS

To cure rabies

NS

NS

Algeria

Louaar et al. (2005)

 

Retama de flor amarilla

Cladodes

Joint aches

Crushed with salt, vinegar or ash

Poultice

Spain

Benítez Cruz (2007)

  

Fruits

Diarrhoea

Fresh ingested

Oral

Spain

Benitez et al. (2010)

  

Flowers

Liver disease

Infusion

Oral

Spain

Benítez Cruz (2007) and Benitez et al. (2010)

  

Cladodes

Fever

Infusion/Decoction

Oral

Spain

Benítez Cruz (2007) and Benitez et al. (2010)

  

Flowers

Contusion, pain

Cataplasm

Topic

Spain

Benitez et al. (2010)

  

Cladodes

Luxation

No preparation

Topic

Spain

Benitez et al. (2010)

  

Flowers

Healing wounds skin

Crushed with water

Poultice

Spain

Benítez Cruz (2007)

  

Cladodes, Flowers

Rheumatism, warts, Healing, Diabetes

Decoction

Oral and external use

Spain

Benítez Cruz (2007)

R. dasycarpa Coss.

Algu

Seeds

Urological, nephrological disease

 

Oral

Morocco (Atlas Mountains)

Teixidor-Toneu et al. (2016)

NS not specified

R. raetam has a long history of use by desert Berbers and in Jewish traditional medicine, where it is used as a treatment for several diseases. Plant parts such as cladodes, fruits, seeds and roots are involved in different traditional remedies.

R. raetam (Forsk.) Webb. (commonly known in English as white broom or white weeping broom) grows in countries of North Africa such as Morocco, Algeria, Tunisia, Libya, and Egypt, and in certain Middle Eastern countries, such as Lebanon, Palestine, Jordan and Israel. The cladodes (photosynthetic stems), flowers, seeds and roots are employed such a powder, in an infusion or decoction for external use such as a cataplasm or poultice, as a bath, or in oral use.

The Moroccan pharmacopoeia has been developed and enriched by knowledge from several ethnic groups that migrated to Morocco from many areas, including Arabs from the Middle East, Andalusians from Spain, and Jews from Europe (Tahraoui et al. 2007). In Morocco, powdered cladodes from R. raetam, R. monosperma and R. sphaerocarpa, mixed with honey, are orally administered as an emetic, and a decoction of cladodes constitutes a useful enema utilized as purgative and vermifuge. In Tissint, powdered cladodes and flowers of R. raetam are employed for their healing properties in circumcision, and as a vulnerary, antiseptic and sedative in local wound care, skin ulcers and infected pimples. In Marrakech, R. raetam crushed with milk or butter is used with the same indications, while decoctions are applied in frictions to relieve pruritus, and human and animal scabies (Bellakhdar et al. 1991; Bellakhdar 1997). Roots are employed as enemas or as an abortifacient by fumigation. An infusion of cladodes and flowers taken orally is also used as an abortive medicine, however it is widely known that a considerable risk of poisoning exists. In Sahara, roots are employed in diphtheria and cladodes as fire spikes in neuralgias such as sciatica neuralgia. In Tata, a south-eastern Moroccan province that borders Algeria, this plant is commonly used for the treatment of scorpion bites, skin diseases, wounds healing, and rheumatism. In Algeria it is prescribed to relieve inflamed eyes, fever, stomach-ache, back pain and diarrhoea (Abouri et al. 2012; Mouhajir 2002; Bellakhdar 1997). The Ouargla region includes the most popular oasis in the Algerian Sahara in south-eastern Algeria where a decoction or infusion of fruits and seeds from R. raetam is used for the treatment of diabetes (Telli et al. 2016). In the Al-Jabal Al-Akhdar region of Libya, it is also recommended for the treatment of diabetes and sinusitis (El-Mokasabi 2014). In Tunisia, this is externally dispensed in scabies as a poultice (Viegi and Ghedira 2014).

In the Middle East, a decoction of cladodes and flowers of R. raetam is used to treat syphilis and female infertility (Yaniv and Dudai 2014). In Israel, a decoction of cladodes is employed as a bath for joint pain, back pain and skin bruising (Said et al. 2002). Jordan is a relatively small country, and it is characterized by a weak biodiversity. The inhabitants of the Mujib area use R. raetam on fractures and burns as a poultice, mainly for animals. A decoction of cladodes is made to treat burns (Hudaib et al. 2008). In Lebanon, this plant is also employed for joint pain (El-Beyrouthy et al. 2008). In Palestine, it is prescribed against eye inflammation, sore throat, rheumatism, infertility, paralysis, and stomach ache (Ali-Shtayeh et al. 1998). In Yemen, traditional medicinal uses of this plant have been introduced from Israeli and Yemenite Jews; these populations use an infusion as a remedy for hepatitis and jaundice (Hehmeyer and Schönig 2012).

R. monosperma (in Spanish known as Retama de olor, Retama blanca and in English as White bridal broom) is native to the coastal sandy areas of SW Spain, NW Morocco, Algeria and Egypt. The Algerian Berbers use an extract from cladodes for the prevention of hydrophobia (rabies) (Helmstädter 2016).

A decoction of R. sphaerocarpa roots is used in the Errachidia province of Morocco, in the treatment of diabetes (Tahraoui et al. 2007). In the Sahara, roots are employed as a diphtheria remedy (Mouhajir 2002). In Algeria, it is used to cure rabies (Louaar et al. 2005). In the western part of the province of Granada (Andalusia, southern Spain), an infusion or decoction of cladodes and flowers is applied as a poultice or cataplasm to relieve joint pains, contusions, and luxations, and the for the healing of skin wounds and warts. Moreover, in oral administration, a decoction of cladodes and flowers is used in the treatment of diabetes and fever; the fresh ingestion of fruits is employed to stem diarrhoea; and an infusion of flowers to treat liver diseases (Benítez Cruz 2007; Benitez et al. 2010).

R. dasycarpa is an endemic plant of the high Atlas Mountains used by the Ishelhin people, a southern Moroccan Amazigh (Berber) ethnic group, in urological and nephrological diseases (Teixidor-Toneu et al. 2016).

Chemical constituents of Retama spp.

Alcohols and aldehydes

The main component of the essential oil from R. raetam flowers is nonanal or pelargonaldehyde. Aldehydes are highly aromatic compounds: octanal (caprylic aldehyde), dodecanal (lauraldehyde) and undecanal have also been identified (Touati et al. 2015).

Cyclitols

Pinitol has been isolated from cladodes and quantified in R. raetam (1.8%), R. sphaerocarpa (1.9%) and R. monosperma, which has the highest concentration (2.3%) of this compound (González-Mauraza et al. 2016). Quinic acid was identified as one the main components in seeds and cladodes of R. sphaerocarpa (Touati et al. 2017).

Polysaccharides

Two homogeneous galactomannans were isolated from seeds of Libyan R. raetam (Ishurd et al. 2004).

Fatty acids

The chemical analysis of seeds and cladodes from R. monosperma led to the identification of 11 saturated (2.3% w/w) and 5 unsaturated fatty acids (El-Hamdani and Fdil 2015). Similarly, Touati et al. (2015) identified 14 fatty acids and quantified 2.3% w/w of saturated fatty acids and 14% of unsaturated fatty acids from R. sphaerocarpa seeds and cladodes (Table 3).
Table 3

Phytochemical composition of different parts of each Retama species

Phytochemical clasiffication

Part of plant

Plant species

References

Minerals

   

 Al, Ba, Cd, Cu, Fe, Mg, Pb,Zn, Mn, Ca, K, Na, P

Cladodes, Seeds

R. monosperma

El-Hamdani and Fdil (2015)

Alkanes

   

 Pentacosane

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 Hexacosane

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 Heptacosane

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

Acids

   

 Hexadecanoic acid

Flowers

R. monosperma

Derhali et al. (2016)

Aldehydes

   

 Nonanal (Pelargonaldehyde)

Flowers

R. raetam

Edziri et al. (2010)

 Octanal (Caprylic aldehyde)

Flowers

R. raetam

Edziri et al. (2010)

 Dodecanal (Lauraldehyde)

Flowers

R. raetam

Edziri et al. (2010)

 Undecanal

Flowers

R. raetam

Edziri et al. (2010)

Alcohols

   

 Hexadecan-1-ol

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

 Octadec-9-en-1-ol

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

 Octadec-1-ol

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

 Eicosan-1-ol

Cladodes

R. sphaerocarpa

Touati et al. (2015)

 Docosan-1-ol

Cladodes

R. sphaerocarpa

Touati et al. (2015)

 Tetracosan-1-ol

Cladodes

R. sphaerocarpa

Touati et al. (2015)

 Octacosan-1-ol

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

Cyclitols

   

 Pinitol

Cladodes

R. monosperma, R. sphaerocarpa, R. raetam

González-Mauraza et al. (2016)

 Quinic acid

Cladodes

R. sphaerocarpa

Touati et al. (2017)

Polysaccharides

   

 Galactomannans

Seeds

R. raetam

Ishurd et al. (2004)

 Xilo-gluco-4-O-methyl-α-D-glucopyranosyluronic acid

Seeds

R. raetam

Wu et al. (2006)

Fatty acids

   

Saturated

   

 Lauric acid

Cladodes, seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Myristic acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Pentadecanoic acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Margaric acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Stearic acid

Cladodes, Seeds, Flowers

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015), Touati et al. (2015) and Derhali et al. (2016)

 Arachidic acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Heneicosanoic acid

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

 Behenic acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Tricosanoic acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Lignoceric acid

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Pentacosanoic acid

Cladodes

R. monosperma

El-Hamdani and Fdil (2015)

 Palmitic acid

Cladodes, Seeds

R. monosperma

El-Hamdani and Fdil (2015)

Unsaturated

   

 Palmitoleic acid (omega 7)

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Oleic acid (omega 9)

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Elaidic acid (omega 9)

Cladodes, Seeds

R. sphaerocarpa

Touati et al. (2015)

 Linolelaidic acid (omega 6)

Cladodes, Seeds

R. monosperma, R. sphaerocarpa

El-Hamdani and Fdil (2015) and Touati et al. (2015)

 Linoleic acid (omega 6)

Cladodes, Seeds

R. monosperma

El-Hamdani and Fdil (2015)

 Linolenic acid (omega-3)

Cladodes, Seeds

R. monosperma

El-Hamdani and Fdil (2015)

Phenolic compounds

   

Phenolic alcohols

   

 Resorcinol

Cladodes

R. raetam

Mariem et al. (2014)

 Tyrosol

Cladodes

R. sphaerocarpa

Touati et al. (2015)

Phenolic acids

   

 Hydroxybenzoic acids

   

  Gallic acid

Cladodes, seeds

R. raetam

Mariem et al. (2014)

  Protocatechuic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Ferulic acid

Cladodes

R. sphaerocarpa

Touati et al. (2017)

  Homoprotocatechuic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Salycilic acid

Cladodes

R. raetam

Mariem et al. (2014)

  p-Hydroxybenzoic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Vainillic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Gentisic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Syringic acid

Cladodes

R. raetam

Mariem et al. (2014)

  Piscidic acid

Stems

R. sphaerocarpa

Touati et al. (2017)

Hydroxycinnamic acids

   

 trans-Cinnamic acid

Cladodes

R. raetam

Mariem et al. (2014)

 Caffeic acid

Cladodes

R. raetam

Mariem et al. (2014)

 Ferulic acid

Cladodes

R. raetam, R. sphaerocarpa

Mariem et al. (2014) and Touati et al. (2015)

 p-Coumaric acid

Cladodes; seeds

R. raetam, R. sphaerocarpa

Djeddi et al. (2013), Mariem et al. (2014) and Touati et al. (2017)

 o-Coumaric acid

Cladodes

R. raetam

Mariem et al. (2014)

Phenylpropanoids

   

 Chlorogenic acid

Cladodes

R. raetam

Mariem et al. (2014)

 Rosmarinic acid

Cladodes

R. raetam

Mariem et al. (2014)

Flavonoids

   

 Flavonols

   

  Quercetin

Cladodes, Seeds

R. raetam, R. sphaerocarpa

El Sherbeiny et al. (1978) and Touati et al. (2017)

  Quercetin 3,7-di-O-β-glucoside.

 

R. sphaerocarpa

Louaar et al. (2005)

  Rhamnazin (Quercetin 3′,7-dimethylether)

Cladodes

R. sphaerocarpa

López-Lázaro et al. (1999)

  Rhamnazin-3-O-β-glucopyranosyl-(1→5)-α-arabinofuranoside

Cladodes

R. sphaerocarpa

Martín-Cordero et al. (1999)

  Rhamnazin 3-O-β-D-glucopyranosyl-(1–>5)-[β-D-apiofuranosyl(1–>2)]-α-L-arabinofuranoside (Retamatrioside)

Cladodes

R. sphaerocarpa

Martín-Cordero et al. (2000a)

  Kaempferol

Cladodes, Seeds

R. raetam

El Sherbeiny et al. (1978), Djeddi et al. (2013) and Mariem et al. (2014)

  Kaempferol-7-glucoside

Seeds

R. raetam

El Sherbeiny et al. (1978)

  Isorhamnetin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

  Morin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

  Galangin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

 Flavononols

   

  Taxifolin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

 Flavones

   

  Luteolin

Cladodes, seeds

R. raetam, R. sphaerocarpa

Abdalla and Saleh (1983), Djeddi et al. (2013), Mariem et al. (2014) and Touati et al. (2017)

  Luteolin-di-O-rhamnoside

Claodes, seeds

R. sphaerocarpa

Touati et al. (2017)

  Luteolin 4′-O-neohesperidoside

Cladodes

R. raetam

Kassem et al. (2000)

  Orientin (Lutexin, Luteolin 8-C-glucoside)

Cladodes

R. raetam, R. sphaerocarpa

Abdalla and Saleh (1983) and Touati et al. (2017)

  Orientin-4′-glucoside

Cladodes

R. raetam

Abdalla and Saleh (1983)

  Apigenin

Cladodes, Seeds

R. raetam, R. sphaerocarpa

El Sherbeiny et al. (1978), Mariem et al. (2014) and Touati et al. (2017)

  Apigenin 8-C-glucoside (vitexin)

Cladodes

R. sphaerocarpa

Louaar et al. (2005)

  Apigenin-7-glucoside

Cladodes

R. raetam

Abdalla and Saleh (1983)

  Apigenin 6,8-di-C-glucoside (vicenin-2)

Cladodes, seeds

R. raetam, R. sphaerocarpa

Louaar et al. (2005), El Sherbeiny et al. (1978) and Abdalla and Saleh (1983)

  Chrysoeriol (3′-Methoxyapigenin)

Cladodes

R. raetam

Abdalla and Saleh (1983)

  Scutellarein (6-Hydroxyapigenin)

Cladodes

R. raetam

Djeddi et al. (2013)

 Prenylated flavones

   

  Licoflavone C

Cladodes

R. raetam

Xu et al. (2015)

 Isoprenylated flavones

   

  Ephedroidin

Cladodes

R. raetam

Kassem et al. (2000) and Xu et al. (2015)

 Furanoflavones

   

  Retamasins A

Cladodes

R. raetam

Xu et al. (2015)

  Retamasins B

Cladodes

R. raetam

Xu et al. (2015)

  Atalantoflavone

Cladodes

R. raetam

Xu et al. (2015)

  5,4′-dihydroxy-(3″,4″-dihydro-3″,4″-dihydroxy)-2″,2″-dimethylpyrano-(5″,6″:7,8)-flavone

Cladodes

R. aetam

Kassem et al. (2000)

 Flavanones

   

  Naringenin

Cladodes, Seeds

R. raetam, R. sphaerocarpa

El Sherbeiny et al. (1978), Mariem et al. (2014) and Touati et al. (2017)

 Isoflavones

   

  Genistein

Cladodes, Seeds

R. monosperma, R. raetam

Harborne (1969), El Sherbeiny et al. (1978) and Djeddi et al. (2013)

  6-Hydroxygenistein

Cladodes

R. raetam

Djeddi et al. (2013)

  Genistin (Genistein-7-glucoside)

Cladodes

R. sphaerocarpa

López-Lázaro et al. (1998) and Louaar et al. (2005)

  5-methoxy-Genistein

Cladodes

R. monosperma, R. raetam

Harborne (1969)

  Genistein 8-C-glucoside

Cladodes

R. sphaerocarpa

Louaar et al. (2007)

  Genistein-7-O-xylosyl- 8-C-glucoside

Cladodes

R. sphaerocarpa

Akkal et al. (2010)

  Daidzein

Cladodes, Seeds

R. monosperma, R. raetam

Harborne (1969), El Sherbeiny et al. (1978) and Abdalla and Saleh (1983)

  Daidzein-7-glucoside (Daidzin)

Cladodes

R. sphaerocarpa

López-Lázaro et al. (1998)

  6′-methoxypseudobaptegenin

Cladodes

R. sphaerocarpa

Louaar et al. (2007)

  6′-methoxypseudobaptigenin   7-O-β-glucoside

Cladodes

R. sphaerocarpa

López-Lázaro et al. (1998)

  Biochanin A

Cladodes

R. raetam

Djeddi et al. (2013)

  Pratensein (3′-hydroxy-biochanin A)

Cladodes

R. raetam

Djeddi et al. (2013)

  3′-O-Methylorobol

Cladodes

R. raetam

Djeddi et al. (2013)

  Calycosin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

  Puerarin

Cladodes

R. sphaerocarpa

Touati et al. (2017)

 Furanoisoflavones

   

  Derrone

Cladodes

R. raetam

Xu et al. (2015)

  5″-Hydroxy-Derrone

Cladodes

R. raetam

Xu et al. (2015)

 Dihydrochalcones

   

  Phloretin

Cladodes, seeds

R. sphaerocarpa

Touati et al. (2017)

 Aurones

   

  6,4′-dihydroxyaurone (Hispidol)

Seeds

R .raetam

El Sherbeiny et al. (1978)

  Hispidol-6-glucoside

Seeds

R. raetam

El Sherbeiny et al. (1978)

Terpenoids

   

Monoterpenes

   

 Oxygenated monoterpenes

   

  β-Linalool

Flowers

R. raetam

Edziri et al. (2010) and Awen et al. (2011)

  α-Terpineol

Flowers

R. raetam

Edziri et al. (2010) and Awen et al. (2011)

  cis-linalool oxide

Flowers

R. raetam

Awen et al. (2011)

  Ethyl linalool

Flowers

R. raetam

Awen et al. (2011)

  Linalyl acetate

Flowers

R. raetam

Edziri et al. (2010)

  2-Decen-1-ol

Flowers

R. raetam

Awen et al. (2011)

  Isobornyl thiocyano acetate

Flowers

R. raetam

Awen et al. (2011)

  Geraniol

Flowers

R. raetam

Edziri et al. (2010)

  Geraniol formate

Flowers

R. raetam

Awen et al. (2011)

  Geranyl acetate

Flowers

R. raetam

Edziri et al. (2010)

  Citronellal

Flowers

R. raetam

Edziri et al. (2010)

  Neral (Citral)

Flowers

R. raetam

Edziri et al. (2010)

  Nerol

Flowers

R. raetam

Edziri et al. (2010)

  Geranial

Flowers

R. raetam

Edziri et al. (2010)

  Geraniol

  

Edziri et al. (2010)

 Non-oxygenated monoterpenes

   

  cis-β-Ocimene

Flowers

R. raetam

Awen et al. (2011)

  Limonene

Flowers

R. raetam

Awen et al. (2011)

  Terpinolene

Flowers

R. raetam

Edziri et al. (2010) and Awen et al. (2011)

  α-Pinene

Flowers

R. raetam

Edziri et al. (2010)

  β-Pinene

Flowers

R. raetam

Edziri et al. (2010)

  α-Thujene

Flowers

R. raetam

Edziri et al. (2010)

  Camphene

Flowers

R. raetam

Edziri et al. (2010)

  Sabinene

Flowers

R. raetam, R. monosperma

Edziri et al. (2010) and Derhali et al. (2016)

  Myrcene

Flowers

R. raetam

Edziri et al. (2010)

  α-Terpinene

Flowers

R. raetam

Edziri et al. (2010)

  Limonene

Flowers

R. raetam

Edziri et al. (2010)

  p-Cymene

Flowers

R. raetam

Edziri et al. (2010)

  γ-Elemene

Flowers

R. raetam

Edziri et al. (2010)

  Santolinatriene

Flowers

R. monosperma

Derhali et al. (2016)

Sesquiterpenes

   

 Nerolidol acetate

Flowers

R. raetam

Awen et al. (2011)

 α-Humelene (α-Caryophyllene)

Flowers

R. raetam

Edziri et al. (2010)

 β-Caryophyllene

Flowers

R. raetam, R. monosperma

Edziri et al. (2010) and Derhali et al. (2016)

 Farnesol

Flowers

R. raetam

Edziri et al. (2010)

Diterpenes

   

 Carnosic acid

Cladodes

R. raetam

Mariem et al. (2014)

 Phytol

Cladodes

R. monosperma

Derhali et al. (2016)

Triterpenes

   

 β-Amyrin

Caldodes

R. sphaerocarpa

Touati et al. (2015)

Nor-isoprenoids

   

 β-Damascenone

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 β-Damascone

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 Theaspirane A

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 Theaspirane B

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 β-Ionone

Flowers

R. monosperma

Derhali et al. (2016)

 β-Damascenone

Flowers, cladodes

R. monosperma

Derhali et al. (2016)

 β-Sitosterol

Cladodes, Seeds

R. monosperma, R. sphaerocarpa, R. raetam

El Sherbeiny et al. (1978), Belayachi et al. (2014) and Touati et al. (2015)

 Stigmasterol

Cladodes, seeds

R. monosperma, R. sphaerocarpa

Belayachi et al. (2014) and Touati et al. (2015)

 Campesterol

Cladodes,seeds

R. monosperma, R. sphaerocarpa

Belayachi et al. (2014) and Touati et al. (2015)

Alkaloids

   

Bipyperydine

   

 Ammodendrine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 N-Formylammodendrine

Cladodes

R. monosperma

El-Shazly et al. (1996)

 Dehydroammodendrine

Cladodes

R. monosperma

El-Shazly et al. (1996)

Quinolizidine

  

El-Shazly Et Al. (1996)

 Epilupinine

Cladodes

R. sphaerocarpa

El-Shazly et al. (1996)

 Sparteine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 α-Isosparteine

Cladodes

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 β-Isosparteine

Cladodes, fruits, flowers, roots

R. monosperma, R. raetam

El-Shazly et al. (1996)

 11,12-Dehydrosparteine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

El-Shazly et al. (1996)

 17-Oxosparteine

Stems, flowers

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 Lupanine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 α-Isolupanine

Cladodes

R. monosperma, R. sphaerocarpa

El-Shazly et al. (1996)

 5,6-Dehydrolupamine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

 12α-Hydroxylupanine

Cladodes

R. sphaerocarpa, R. raetam

El-Shazly et al. (1996) Abdel-Halim et al. (1992)

 6 α-Hydroxylupanine

Cladodes

R. raetam

Abdel-Halim (1995)

 Retamine

Cladodes, fruits, flowers, roots

R. monosperma, R. sphaerocarpa, R. raetam

Martín-Cordero et al. (1991) and El-Shazly et al. (1996)

Phenolic compounds

Isoflavones

In R. sphaerocarpa, R. monosperma, and R. raetam, isoflavones, such as genistein, genistin, daidzin, and daidzein and other isoflavones, such as biochanin A, 6′-methoxypseudobaptegenin and puerarin, have been isolated and identified (López-Lázaro et al. 1998; Djeddi et al. 2013; Abdalla and Saleh 1983). Two new furanoisoflavones have been isolated from R. raetam cladodes derrone and 5″ hydroxyl-derrone (Xu et al. 2015).

Dihydrochalcones and aurones

Phloretin belongs to the chemical group of dihydrochalcones, found in apple trees and pear trees (Huang et al. 2016). Hispidol has been isolated for the first time in soybean seedlings (Soja hispida) and could originate from the oxidative cyclization of chalcone, which is an intermediate step in aurone biosynthesis (Wong 1966).

Terpenoids

Monoterpenes

The essential oil of R. monosperma cladodes is rich in hydrocarbons, mainly: alkanes (31.8%), norisoprenoids (25.4%) oxygenated diterpenes (11.6%) and oxygenated sesquiterpenes (10.5%). Flower oil revealed the presence of alkanes (25.8%), fatty acids (56.7%) and norisoprenoids (3.1%) as the main subclasses. Hexadecanoic acid was the main compound in the essential oil of flowers (0 - 30.6%) while heptacosane was in the essential oil of cladodes (13%). The ionones and damascones showed low presence in flower oil in contrast to branch oil. The pleasant aroma of R. monosperma during full flowering is due to the presence at significant levels of norterpenoids. The main components in the essential oil of R. raetam flowers are β-linalool, nonanal and α-humulene (Edziri et al. 2010).

Triterpenes

Touati et al. (2015) reported the identification and quantification from cladodes of triterpene β-amyrin (0.06%).

Steroids

Belayachi et al. (2014) and Touati et al. (2015) identified β-sitosterol, stigmasterol and campesterol from the cladodes and seeds of R. monosperma and R. sphaerocarpa. Touati et al. (2015) quantified total phytosterols in R. sphaerocarpa (2.5%). El Sherbeiny et al. (1978) identified β-sitosterol, a phytosterol in R. raetam.

Alkaloids

El-Shazly et al. (1996) reported the presence of 31 bipiperydine and quinolizidine alkaloids by GLC-MS in different plant parts (cladodes, roots, fruit, and seeds) of three Retama species: R. monosperma, R. sphaerocarpa, and R. raetam (Table 3). The bipiperydine alkaloid ammodendrine, which shares part of the biosynthetic pathway with quinolizidine alkaloids, was detected in the three species. Alkaloidal profiles of these Retama species are rather similar; typical for Retama is the occurrence of retamine, which is uncommon in other Fabaceae, although it appears in relatively higher concentrations in R. sphaerocarpa and R. raetam than in R. monosperma. The tetracyclic quinolizidine alkaloids (sparteine, lupanine and retamine) represent the major components of roots and cladodes. The α-pyridone alkaloids, such as cytisine, methylcytisine and anagyrine, derive from the tetracyclic alkaloid lupanine and were detected in high concentrations in flowers and seeds. These results have been confirmed by various authors (Table 3).

Pharmacological activity

Antibacterial and antifungal activity

Many studies have focused on the antibacterial activity of Retama spp. extracts; in the majority of instances this activity was evaluated by means of the disc diffusion method, measuring the diameter of inhibition zones, or by determining the minimum inhibitory concentration (MIC).

The methanol-water (50:50) polyphenol-rich extract of R. sphaerocarpa stems exerted a significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa bacterial strains. The major components of this polyphenol-rich extract were piscidic and quinic acids and the flavonoid morin (Touati et al. 2017).

The alkaloid extracts obtained from seeds, leaves and stems of R. monosperma were tested against Aspergillus niger, Candida albicans and Candida tropicalis. The antifungal activity of the leaves and stems was related to their higher content of sparteine, ammodendrine and anagyrine, whereas no activity was observed on seed extract, with a major content of cytisine and its derivatives (El-Hamdani et al. 2016).

The aqueous and ethanolic extracts of the aerial parts of Palestinian R. raetam did not affect the viability of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa or the yeast Candida albicans (Ali-Shtayeh et al. 1998). However, the ethyl acetate extract of aerial parts of R. raetam from Tunisia, rich in flavonoids, tannins and alkaloids, showed significant antibacterial activity against Gram-positive microorganisms, especially methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA, MRSA), thereby suggesting that the use of intermediary polarity solvents is necessary for the extraction of bioactive components with antibacterial activity (Edziri et al. 2007). This hypothesis is also supported by Mariem et al. (2014), who observed that the moderately polar fraction of Tunisian R. raetam shoots, obtained after ethyl acetate extraction, not only exerted the highest antibacterial activity, especially against E. coli and B. cereus, but also presented the highest polyphenol content, whereby syringic acid and coumarin were the most abundant compounds detected by RP-HPLC.

The results obtained with extracts from the flowers of R. raetam are along the same lines, since the most active extracts from the flowers of Tunisian R. raetam were those obtained with ethyl acetate and butanol, rather than with methanol and chloroform. Butanol extract exerts high activity, with MICs in the range of 0.256–0.512 mg ml−1 against Gram-positive bacteria, including Bacillus subtilis, Enterococcus faecium, Streptococcus spp., Corynebacterium spp., MSSA, and MRSA. This capacity of the extracts was correlated with a higher content on total polyphenols and flavonoids; whereas the ethyl acetate extract of the flowers, with appreciable activity against Gram-positive bacteria and the ability to inhibit the cytopathic effect of human cytomegalovirus (HCMV) strain, presented the highest tannin content (Edziri et al. 2008). Two isolated flavonoids from the ethyl acetate extract of R. raetam flowers, namely licoflavone C and derrone, exerted good antibacterial activity against E. coli and Pseudomonas aeruginosa and significant antifungal activity against Candida species (Edziri et al. 2012).

Two separate studies focused on the chemical composition and antimicrobial activity of the essential oils obtained by the Clevenger apparatus from the flowers of R. raetam collected in Tunisia and Libya, respectively. The Tunisian essential oil was rich in oxygenated monoterpenes (59.73%) and sesquiterpene hydrocarbons (32.39%), whereby the major detected components were nonanal, α-humulene, acetaldehyde, and linalool, and this oil exerted a moderate antibacterial and antifungal activity, with MICs in the range between 0.625 and 5 mg ml−1 (Edziri et al. 2010). The Libyan essential oil presented a similar composition in oxygenated monoterpenes (62.0%) and a MIC of 3 and 6 mg ml−1 against S. aureus and S. pyogenes, respectively, whereas the isolated compound linalool presented MICs of 250 and 375 μg ml−1, respectively (Awen et al. 2011).

Taken together, the studies focused on the antibacterial activity of Retama spp., mainly R. raetam, support the ethnopharmacological use of this plant in the treatment of infectious diseases. Notably, the studied extracts exerted significant activity against pathogens responsible for skin and soft-tissue infections, such as S. aureus and S. pyogenes. These results justify the use of this plant in traditional medicine, which is included in the special medicinal herbal powder (locally named rshush, rishush, or dhrur) used in Bedouin indigenous medicine in the Middle East for the healing of the skin after circumcision (Abu-Rabia 2015). The antibacterial activity of Retama spp. has been related to the presence of polyphenols, alkaloids and essential oils; however, further research is necessary in order to determine the main active principles and their mechanism of action, as well as the optimization of the extraction methods in order to obtain extracts of a more standardized nature.

Antioxidant and chemoprotective activity

High levels of reactive oxygen species (ROS) are involved in the development of the majority of chronic diseases, including cancer and neurodegenerative and cardiovascular diseases, due to their ability to damage biomolecules by inducing lipid peroxidation or DNA oxidation, and to modulate redox-sensitive pathways involved in the pathogenesis of these diseases (Valko et al. 2007). Natural products, including polyphenols, are known to exert antioxidant properties, by means of ROS scavenging, chelating transition metals, or modulating the activity of redox-sensitive enzymes (León-González et al. 2015).

Numerous studies have evaluated the antioxidant activity of Retama spp. extract, as summarized in Table 4. Most of these studies determined the anti-radical activity in vitro against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical via a spectrophotometric method and expressed it as IC50 values, thereby indicating the concentration of extract required to scavenge 50% of the DPPH radical. The IC50 results ranged between 25 and > 1000 μg ml−1, which correspond to the methanol extract of R. raetam seeds (Tlili et al. 2015) and the aqueous extracts of R. raetam (Djeddi et al. 2013), respectively. This variability could be correlated with the alternative extraction methods and/or the part of the plant or species employed in each study. The lower antioxidant activity of aqueous extracts suggests that the use of more intermediate polarity solvents, such as hydro-alcoholic mixtures or ethyl acetate, is more effective for the extraction of Retama spp. antioxidant molecules.
Table 4

Main biological activities of Retama spp. Species, part of the plant that was analysed, extract type, test system, and effects are summarized

Activity

Extracts

Test systems

Effects

Study

Dosage

Species

Plant part

References

Analgesic

Isolated flavonoids (3-methylorobol, Biochamin A)

Acetic acid induced writhing behavior in mice

86.2% and 75.23% inhibition

In vivo

1 mg kg−1

R. raetam

Aerial parts

Djeddi et al. (2013)

Anti-anxiety

MeOHE

Elevated plus-maze test in mice model

The extract enhances ambulatory movement at a dosage of 250 mg kg−1, but decrease it at higher doses. Anxiolytic at lowest doses and anxiogenic athighest doses

In vivo

125, 250 and 375 mg kg−1

R. raetam

Aerial parts

Al-Tubuly et al. (2011)

Antihypertensive/Diuretic

AE

Normotensive and hypertensive animal model. Oral administration

Lowered systolic blood pressure in spontaneous hypertensive rats by 26.5 mmHg from 7 days (increased Na+,K+,and Cl excretion). Enhancement of glomerular filtration rate

In vivo

20 mg kg−1 body weight day−1 p.o. for 3 weeks

R. raetam

Leaves

Eddouks et al. (2007)

AE

Wistar rats (urinary excretion, clearance of creatinine, plasma osmolality). Intravenously administration.

Elevation of Glomerular filtration rate, a significant decrease of osmolarity and a significant diuretic effect in normal rats. Reduction of blood pressure

In vivo

5 mg kg−1 body weight. h i.v.

R. raetam

Aerial parts

Maghrani et al. (2005b)

Anti-inflammatory

MeOHF

EtOAcF

Monocytes from healthy human donors

Inhibition 80–100% against the activation of TNF-α signalling

In vitro

10 μg ml−1

R. sphaerocarpa

Cladodes

Bremner et al. (2009)

AE

Wistar rats (Extension of colon lesion)

(Colonic weight length ratio)

This extract significantly attenuated the extend and severity of the colonic injury against control TNBS.

0.18 and 0.19 mg cm-1 at 9 and 18 mg kg−1 respectively against the negative control TNBS (0,26 mg cm-1)

In vivo

9 and 18 mg kg−1 p.o.

R. monosperma

Cladodes

González-Mauraza et al. (2014)

HEtOHE

%-Lipoxygenase enzyme inhibition assay

IC50: 0.421 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

Antimicrobial

EtOAcE

Bacillus subtilis, Streptococcus agalactiae, Streptococcus pyogenes, Enterococcus faecium, Staphylococcus aureus (MSSA), and Staphylococcus aureus (MRSA)

MICs : 0.256–1.25 mg ml−1

In vitro

0.1 μg ml−1 up to 2 mg ml−1

R. raetam

Flowers

Edziri et al. (2008)

MeOHE

Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi

An Inhibition zone diameter at 14–19 mm

In vitro

150 μg ml−1 disc

R. raetam

Leaves

Alghazeer et al. (2012)

EtOAcF

Bacillus cereus ATCC 14579, Escherichia coli ATCC 85218

An Inhibition zone diameter equal to 12 mm

In vitro

300 μg ml−1

R. raetam

Cladodes

Mariem et al. (2014)

Essential oil

Staphylococcus aureus ATTC 27950, Streptococcus faecalis ATCC 29212

MICs: 2.5 and 0.625 mg ml−1 respectively

In vitro

0.625–5 mg ml−1

R. raetam

Flowers

Edziri et al. (2010)

Essential oil

Staphylococcus aureus, Streptococcus pyogenes

MICs: 250 and 375 μg ml−1 for isolated compunds

3–6 mg ml−1 essential oil

In vitro

Up to 6 mg ml−1

R. raetam

Flowers

Awen et al. (2011)

Flavonoids isolated from EtOAcE (licoflavone C and darrone)

Escherichia coli

Pseudomonas aeruginosa

Candida sp

MICs: 7.81–15.62 81 μg ml−1 for bacteria

7.81 μg ml−1 for fungi

In vitro

0.125 μg ml−1 up to 250 μg ml−1

R. raetam

Flowers

Edziri et al. (2012)

HMeOHE

Staphylococcus aureus ATCC 25923, L. innocua CLIP 74915, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 2785

Inhibition zone diameter S. aureus: 11.17 mm (cladodes); P. aeruginosa: 10.23 mm

In vitro

20 μl at 3 mg ml−1 per disk ml−1

R. sphaerocarpa

Cladodes

Touati et al. (2017)

EtOAcE

Bacillus subtilis, Enterococcus faecium, Enterococcus fecalis, Streptococcus agalactiae, Streptococcus pyogenes, Corynebacterium spp, Staphylococcus aureus (MSSA), and Staphylococcus aureus (MRSA), Acinetobacter beumannii, Erratia marcescens, Escherichia coli, Klebsiella pneumonia, Candida albicans, C. glabrata, C. parapsilosis, C. kreusei

MIC less than 1 mg ml−1 for Gram-positive bacteria, especially MSSA, MRSA and Streptococcus spp.

Low antifungal activity

In vitro

1 μg ml−1 up to 10 mg ml−1

R. raetam

Aerial parts

Edziri et al. (2007)

Acid-base alkaloids purification from a MeOHE extract

Aspergillus niger, Candida albicans, Candida tropicalis

An Inhibition zone diameter at 125 μg ml−1 10.1, 9.66 and 8.10 mm respectively for stems; 9.66; 9.33; 7,01 mm for leaves

In vitro

31,25 μg ml−1 up to 500 μg ml−1

R. monosperma

StemLeaves

Flowers

Seeds

El-Hamdani et al. (2016)

Anti-osteoporosis

HMeOHE

Dexamethasone induced osteoporosis in rats

Increase in alkaline phosphatase activity

Amelioration of the imbalance between bone resorption and formation

In vivo

30 mg kg−1, 3 months

R. raetam

Seeds

Omara et al. (2009a)

Antioxidant

AE

DPPH, Hydrogen peroxide scavenging activity

Low free radical scavenging activity, good hydrogen peroxide scavenging activity flowers: 54%; stems 53%)

In vitro

100–1000 mg L-1

R. raetam

Roots

Stems

Flowers

Fruits

Djeddi et al. (2013)

HEtOHE

Indometacin administred reduced significantly SOD, CAT, GST

SOD, CAT, GST increased by the extract

In vivo

25 mg kg−1

R. raetam

Seeds

El-Toumy et al. (2011)

HMeOHE

Gavage of 7.2 mg kg−1 per day of Formalin for two weeks

This extract cancels out the formalin mediated increase in red blood cells count, hemoglobin content, serum glucose, SOD and GPX.

In vivo

20 mg kg−1 day−1 for 3 weeks

R. raetam

Seeds

Koriem et al. (2010)

HMeOHE

ABTS, Reduction power, DPPH

ABTS IC50: 125.62 μg ml−1; Reduction power:1.25 mg ml−1; DPPH IC50: 252.03 μg ml−1;

In vitro

 

R. sphaerocarpa

Cladodes

Touati et al. (2017)

HEtOHE

TBARS

IC50: 1.05 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

HEtOHE

DPPH

IC50: 0.477 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

HEtOHE

OH scavenging activity

IC50: 0.144 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

HEtOHE

Chelating metal ions

IC50: 0.134 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

HEtOHE

ABTS

IC50: 0.237 mg ml−1

In vitro

 

R. raetam

Aerial parts

Miguel et al. (2014)

MeOHE

DPPH test, TAC and Reduction power assay

IC50: 25 μg gallic acid equivalents ml−1; 70.5 mg gallic acid equivalents ml−1; EC50: 78.10 μg ml−1 respectively

In vitro

 

R. raetam

Seeds

Tlili et al. (2015)

MeOHE

DPPH test

IC50: 40 μg ml−1

In vitro

0.03 up to 3.13 mg ml−1

R. raetam

Leaves

Alghazeer et al. (2012)

MeOHE

ORAC, TEAC, DPPH, FRAP, Antiglycation capability

7.3 mmol Trolox equivalent g-1 extract, 0.4 mmol Trolox equivalent g-1 extract, 0.24 mmol Trolox equivalent g-1 extract, 0.2 mmol Fe2 g-1 extract, respectively. IC50 of AGEs inhibition: 40.32 μg ml−1

In vitro

5 μg ml−1 up to 100 μg ml−1

R. sphaerocarpa

Fruits

Boussahel et al. (2017)

AE

ORAC, TEAC, DPPH, FRAP, Antiglycation capability

4.03 mmol Trolox equivalent g-1 extract, 0.3 mmol Trolox equivalent g-1 extract, 0.16 mmol Trolox equivalent g-1 extract, 0.7 mmol Fe2+ g-1 extract, respectively. IC50 of AGEs inhibition: 249.86 μg ml−1

In vitro

50 μg ml−1 up to 400 μg ml−1

R. sphaerocarpa

Fruits

Boussahel et al. (2017)

MeOHE

TBA test

IC50: 0.122%(w/v)

In vitro

0.005% w/v up to 0.5% w/v

R. raetam subsp. gussonei

Seeds

Conforti et al. (2004)

MeOHE

TBA test

IC50: 0.59% (w/v)

In vitro

0.005% w/v up to 0.5% w/v

R. raetam subsp. gussonei

Leaves

Conforti et al. (2004)

EtOAcF

DPPH test

EC50: 150 μg ml−1

In vitro

 

R. monosperma

Seeds

Belmokhtar and Harche (2014)

EtOAcF

DPPH test

IC50: 166 μg ml−1

In vitro

1 µg ml−1 up to 100 µg ml−1

R. sphaerocarpa

Cladodes

León-González (2012)

EtOAcF

DPPH test

IC50: 400 μg ml−1

In vitro

0,1 μg ml−1 up to 2 mg ml−1

R. raetam

Flowers

Edziri et al. (2008)

EtOAcF

DPPH test

IC50: 33.5 μg ml−1

In vitro

 

R. raetam

Cladodes

Mariem et al. (2014)

EtOAcF

ABTS assay

EC50: 500 μg ml−1

In vitro

 

R. raetam

Cladodes

Mariem et al. (2014)

Essential oil

DPPH test

EC50: 800 μg ml−1

In vitro

 

R. raetam

Flowers

Edziri et al. (2010)

Antiulcer

HEtOHE

Gastroprotective effect of ulcers induced by Indometacin

76% protection compared to Ranitidine (85%)

In vivo

25 mg kg−1

R. raetam

Seeds

El-Toumy et al. (2011)

Antiviral

MeOHE

Ability of the extract to inhibit the cytopathic effect of human cytomegalovirus (HCMV) strain AD-169

IC50: 250 μg ml−1

In vitro

0,1 μg ml−1 up to 2 mg ml−1

R. raetam

Flowers

Edziri et al. (2008)

Cytotoxic

DCMEF

MTT assay: SiHa cervical carcinoma and HeLa cervix carcinoma

IC50: 15 and 21 μg ml−1

In vitro

5 up to 80 μg ml−1

R. monosperma

Leaves

Merghoub et al. (2011)

DCMEF

Apoptosis induction: annexin V and propidium iodide stain in SiHa and HeLa cell lines

28.34% early apoptosis in SiHa; 57.68% in HeLa.

Reduction of mitochondrial membrane potential, increase in ROS levels, activation of Caspase 3 and a decrease in Bcl2 expression

In vitro

20 μg ml−1

R. monosperma

Leaves

Merghoub et al. (2011)

EtOAcE

MTT assay: SiHa cervical carcinoma and HeLa cervix carcinoma

IC50: 28 and 77 μg ml−1

In vitro

5 up to 80 μg ml−1

R. monosperma

Leaves

Merghoub et al. (2011)

MeOH

SRB assay: large lung carcinoma cell (COR-L23)

IC50:40 μg ml−1

In vitro

1,5, 10, 20, 30, 50, 100, 150 μg ml−1

R. raetam subsp. gussonei

Leaves

Conforti et al. (2004)

MeOH

SRB assay: large lung carcinoma cell (COR-L23)

IC50:150 μg ml−1

In vitro

1,5, 10, 20, 30, 50, 100, 150 μg ml−1

R. raetam subsp. gussonei

Seeds

Conforti et al. (2004)

HE

Cell Titer –Glo Luminiscent assay: Leukemic T-cell lymphoblast (Jurkat cell line)

IC50: 34.44 μg ml−1

Cell cycle arrest, activation of Caspase 3, 7, 8, and 9. increase in Fas L level

In vitro

0 up to 50 μg ml−1

R. monosperma

Leaves

Belayachi et al. (2014)

HEXE

Cell Titer –Glo Luminiscent assay: Lymphocyte cells (Jurkat)

IC50: 34.44 μg ml−1

In vitro

1 μg ml−1 up to 50 μg ml−1

R. monosperma

Leaves

Belayachi et al. (2013)

MeOHE

Cell Titer –Glo Luminiscent assay: Lymphoblast cells (Jeko-1)

IC50: 21.47 μg ml−1

In vitro

1 μg ml−1 up to 50 μg ml−1

R. monosperma

Leaves

Belayachi et al. (2013)

DCMF

Cell Titer –Glo Luminiscent assay: Lymphoblast cells (Jeko-1), Lymphocyte cells (Jurkat)

IC50: 24 .77 μg ml−1 and 9.12 μg ml−1 respectively

In vitro

1 μg ml−1 up to 50 μg ml−1

R. monosperma

Leaves

Belayachi et al. (2013)

EtOAcF

Cell Titer –Glo Luminiscent assay: Lymphoblast cells ((Jeko-1), Lymphocyte cells (Jurkat)

IC50: 12.01 and 20.22 μg ml−1 respectively

In vitro

1 μg ml−1 up to 50 μg ml−1

R. monosperma

Leaves

Belayachi et al. (2013)

TCMF

SRB assay: human renal adenocarcinoma (TK-10); human breast adenocarcinoma (MCF-7): human melanoma (UACC-62)

IC50: 87, 76 and 42 μg ml−1 respectively

In vitro

25 μg ml−1 up to 250 μg ml−1

R. sphaerocarpa

Aerial parts

López-Lázaro et al. (2000)

EtOAcF

SRB assay: human renal adenocarcinoma (TK-10); human breast adenocarcinoma (MCF-7): human melanoma (UACC-62)

IC50: 49, 52 and 36 μg ml−1 respectively

In vitro

25 μg ml−1 up to 250 μg ml−1

R. sphaerocarpa

Aerial parts

López-Lázaro et al. (2000)

BuOHF

SRB assay: human renal adenocarcinoma (TK-10); human breast adenocarcinoma (MCF-7): human melanoma (UACC-62)

IC50: >250, 51 and 65 μg ml−1 respectively ml−1

In vitro

25 μg ml−1 up to 250 μg ml−1

R. sphaerocarpa

Aerial parts

López-Lázaro et al. (2000)

Hypolipidaemic

AE

STZ rats

This extract exhibited long term cholesterol and triglycerides lowering activities in normal and streptozotocin

In vivo

20 mg kg−1

R. raetam

Cladodes

Maghrani et al. (2004)

HMeOHE

Gavage of 7,2 mg kg−1 per day of Formalin for two weeks

This extract decrease serum cholesterol levels

In vivo

20 mg kg−1 day−1 for 3 weeks

R. raetam

Seeds

Koriem et al. (2010)

Hypoglycaemic

AE

STZ rats

This extract induced a significant hypoglycaemic effect both in normal an streptozotocin diabetic rats (STZ). This effect was more pronounced in STZ than normal rats. This effect was greater than metformin. No effect in insulin levels

In vivo

20 mg kg−1

R. raetam

Leaves

Maghrani et al. (2003)

MeOHE

STZ rats

This extract at 250 or 500 mg kg−1 significantly lowered blood glucose levels at the 3rd and 1st week of treatment, respectively. Increase of insulin levels. Inhibition of glucose intestine absorption

In vivo

100, 250, 500 mg kg−1

R. raetam

Fruits

Algandaby et al. (2010)

Hepatoprotective

AE

Carbon tetrachloride induced liver damage in rats

Reduce histopathological alterations. Restore enzyme serum levels (aspartate and alanine aminotransferase, alkaline phosphatase

In vivo

20 and 40 mg kg−1 for 2, 3 or 4 weeks

R. raetam

Seeds

Omara et al. (2009b)

HMeOHE

Liver and kidney toxicity induced bay formalin

Diuresis, Decrease in cholesterol levels, reduce hyperglucemia, antioxidant properties, reverse of histopathological laterations, restore lvier enzimes serum levels

In vivo

100 or 20 mg kg−1 for 2 weeks

R. raetam

Seeds

Koriem et al. (2010)

AE aquous extract, BuOHF buthanol fraction, EPE ether petroleum extract, DCMEF dichloromethane fraction, EtOAcE ethyl acetate extract, EtOAcF ethyl acetate fraction, HEtOHE H2O: ethanol extract; HMeOHE H2O: methanol extract, MeOHE methanol extract, MeOHF methanol fraction, TCMF trichloromethane fraction

Belmokhtar and Harche (2014) determined the antioxidant capacity of the R. monosperma 70% aqueous methanol extracts of seeds, stems and flowers and of their fractions (toluene, chloroform, ethyl acetate, and butanol) by means of the DPPH and the phosphomolybdenum total antioxidant capacity (TAC) assays. Results showed that the ethyl acetate fractions were the most active for each part and that the extract from the ethyl acetate seeds presented the highest antioxidant capacity from among all the plant parts (DPPH IC50, 150 μg ml−1). A linear regression analysis showed a significant Pearson’s coefficient of correlation between flavonoid content and the DPPH and TAC values, which suggests they are major contributors to the antioxidant activities (Belmokhtar and Harche 2014).

In another study, Boussahel et al. (2017) reported the antioxidant and antiglycative properties of methanol and aqueous R. sphaerocarpa fruit extracts. The methanol extract presented a higher content on flavonoids, including the isoflavones daidzein and genistein. This extract exerted a noticeable antioxidant activity in the chemical assays performed, especially in the oxygen radical-absorbance capacity assay (ORAC), which suggests that the antioxidants of R. sphaerocarpa fruit are more soluble in organic solvents than in water, and that they predominantly act as hydrogen atom transfers. The methanol extract also induced a major decrease in the formation of advanced glycation end products (AGE), which are related with oxidative stress, inflammation and insulin resistance, which suggests that this flavonoid-rich extract is able to prevent the reactions between reducing sugars and proteins that lead to non-enzymatic glycation or browning.

The chemoprotective effect of the aqueous methanol extract of R. raetam seeds against the damage induced by formalin, indomethacin and cadmium chloride has been studied in various in vivo models. Formalin is a mixture of formaldehyde and methanol that mimics the effects of pollutants on humans. Formalin induced blood, liver and kidney toxicity in Sprague Dawley albino rats, by inducing a high increase in serum glucose, transaminases, bilirubin, urea, creatinin, red blood cells, and hemoglobin, an increase in white blood cells, and in liver and kidney dysfunction. The administration of R. raetam seed extract restored liver and kidney injuries and blood parameters to the normal levels, also increasing the blood levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) and lowering lipid peroxidation (malondialdhyde (MDA) in serum (Koriem et al. 2010). Similar results were obtained by this extract against the kidney and liver toxicity induced by cadmium chloride (Koriem et al. 2009). Furthermore, treatment with 25 mg kg−1 indomethacin, a non-steroidal anti-inflammatory drug (NSAID), induced severe gastric damage to male albino rats due to the lipid peroxidation of the membranes. The administration of 25 mg kg−1 R. raetam seed extract significantly reduced the ulcer area and the gastric MDA levels, whereas it increased the levels of antioxidant enzymes SOD and GPx, thereby exerting a gastroprotective effect comparable to the histamine-2 (H2) blocker ranitidine (El-Toumy et al. 2009).

Analgesic and anti-inflammatory activity

Although there is no a specific ethnobotanical use of Retama spp. as an anti-inflammatory, they are used in the treatment of ailments that involved inflammation. For example, R. sphaerocarpa crushed shoots, are traditionally applied as a poultice to the skin to treat rheumatism or as analgesic for menstrual pain in Southern regions of Spain (Obón et al. 2011; Martínez-Lirola et al. 1997; Rivera et al. 1994). The anti-inflammatory activity was confirmed in vitro, as pre-incubation of human monocytes with different R. sphaerocarpa extract fractions for 30 min before stimulation with LPS (10 ng ml−1) significantly prevented the release of the inflammatory cytokine tumour necrosis factor-alpha (TNF-α) (Bremner et al. 2009). The methanol and ethyl acetate fractions were the most active.

Lipoxygenase (LOX) is an enzyme that catalyses the reaction of fatty acids to hydroperoxides, which can be converted into other products that play a key role in the inflammatory process; the molecules that inhibit LOX are thus considered to have anti-oxidant and anti-inflammatory properties (Steinhilber 1999). Miguel et al. (2014) studied the capacity of various medicinal plants to inhibit LOX, showing that R. raetam extract significantly inhibited this enzyme and that this anti-inflammatory activity was correlated with the free radical scavenging capacity (Miguel et al. 2014).

The anti-inflammatory activity of R. monosperma was evaluated in vivo in a murine Crohn’s disease model, by intra-colonic administration of trinitrobenzene sulfonic acid (TNBS) in rats. Oral administration of this extract significantly prevented the TNBS-induced intestinal damage and increased the production of colonic mucus. This action was due, at least in part, to a decreased neutrophil infiltration and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) overexpression. The mechanism of action probably involves a reduction of p38 mitogen-activated protein kinase activation, thus preventing the inhibitory protein IκB degradation in colonic mucosa (González-Mauraza et al. 2014).

The anti-inflammatory effect of R. raetam extracts must be mediated by the presence of the isoflavones, including genistein, 6-hydroxygenistein, 3′-O-methylorobol, pratensein, and biochanin, since Djeddi et al. (2013) showed that 1 mg kg−1 of these isolated compounds significantly reduced the amount of abdominal writhing induced by intra-peritoneal acetic acid injection. They suggested that these active components might inhibit the cyclo-oxygenase or other enzymes involved in the synthesis or release of inflammatory prostaglandins (Djeddi et al. 2013).

Anticancer activity

Even though no species of the genus Retama are traditionally used to treat cancer, several studies have tested the cytotoxic activity of crude extracts, fractions and isolated compounds.

In a screening of anticancer plant materials from Moroccan folk medicine, the methanol extract of R. monosperma aerial parts exerted an IC50 of almost 100 μg ml−1 against both SiHa and HeLa cell lines, from human cervical cancer (Merghoub et al. 2009, 2011). This crude extract was further fractionated, whereby the dichloromethane fraction was the most active, and presented an IC50 of 14.57 ± 4.15 μg ml−1 and 21.33 ± 7.88 μg ml−1 against SiHa and HeLa cell lines, respectively. The cytotoxic activity was mediated by the induction of caspase-dependent apoptosis, which involved an increase in ROS production and depolarization of mitochondrial membrane potential (Benbacer et al. 2012). The dichloromethane fraction also exerted significant activity against Jurkat (acute T cell leukemia) and JeKo-1 (non-Hodgkin lymphoma) (Belayachi et al. 2013). This activity was correlated to the presence of alkaloids, quantified by GC/MS (Benbacer et al. 2012). Furthermore, the hexane extract obtained by Sohxlet of R. monosperma aerial parts was tested against a panel of cancer and non-transformed cell lines and exerted a dramatic decrease in the cell viability of Jurkat cells, with almost no effect in the other tested cell lines. Induction of apoptosis was observed, accompanied by cell-cycle arrest, DNA damage induction, and the activation of the JNK/Fas-L/caspase 8/caspase 3 pathway. However, in this study, the chemical analysis by GC/MS revealed a major composition in α-linoleic acid (13.97%), stigmasterol (10.34%), β-sitosteryl (7.92%) and campesterol (11.09%) (Belayachi et al. 2014).

The methanol extract from the Italian endemism R. raetam subsp. gussonei exerted a cytotoxic activity against large lung carcinoma cell (COR-L23, IC50: 40 μg ml−1), along with antioxidant activity (Conforti et al. 2004).

Genistin, daidzin and 6′-methoxypseudobaptigenin-7-O-β-glucoside, are glucosylated isoflavons isolated from R. sphaerocarpa cladodes that have the ability to stabilize topoisomerase II-DNA cleavage complex, by acting as topoisomerase II poisons (Martín-Cordero et al. 2000b). Even though genistin is not a potent topoisomerase II poison, this ability could explain, at least in part, this flavonoid cytotoxic activity over the TK-10 cell line (IC50 27 µM) (López-Lázaro et al. 2000).

Effect on the cardiovascular system

Aqueous extracts of R. raetam leaves exhibit antihypertensive and diuretic effects on hypertensive rats, by increasing sodium, potassium and chloride excretion, as well as acting as an enhancement of the glomerular filtration rate. On the other hand, the diuretic action in normotensive rats induces a significant increase on urinary potassium elimination (Eddouks et al. 2007).

Along the same lines, the intravenous administration of aqueous extracts of aerial parts of the same species showed a diuretic effect in normal rats. Again, a rise in the glomerular rate was detected, but in this case a significant decrease of urinary osmolality was found. The authors suggest that R. raetam metabolites could act synergistically or individually as angiotensin-converting enzyme inhibitors. This enzyme converts angiotensin I into angiotensin II. Angiotensin II is a powerful vasoconstrictor which causes an elevation of blood pressure. Thus, inhibition of this enzyme is a key way to reduce hypertension (Maghrani et al. 2005a; Patten et al. 2016).

Hypoglycemic activity

Aqueous leaf extract of R. raetam was able to reduce blood glucose levels with an extra-pancreatic mechanism, since plasma insulin levels remained unaffected. It is suggested that the extract inhibited renal glucose reabsorption as evidenced by the increased glycosuria. The inhibition of sodium-glucose symporters located in the proximal renal tubule should be involved in the mechanism of action. However, other mechanisms could explain these results, such as the stimulation of glucose uptake by muscle or adipose tissues, correction of insulin resistance, inhibition of endogenous glucose production, and a rise in glucogenogenesis (Maghrani et al. 2003). The same results have been found with the intravenous administration of a decoction of the whole plant (Maghrani et al. 2005b). In addition, orally administrated aqueous extract exhibits lipid (cholesterol and triglycerids) and body-weight lowering activities in both normal and severe hyperglycemic rats (Maghrani et al. 2004); this fact links with an interesting application of the extract in atherosclerosis and cardiac disease.

These results are not in accordance with those of Algandaby et al. (2010), who orally administrated a methanolic extract of R. raetam fruit. Results showed a significant extract capacity to reduce blood glucose levels. However, in this case, an increase in serum insulin levels was detected. Furthermore, in vitro studies demonstrated that the extract was capable of inhibiting glucose absorption by rat isolated intestine. No effect was detected in vitro over gluconeogenesis or glycogenolysis or on skeletal muscle glucose uptake (Algandaby et al. 2010).

The antidiabetic effect of these extracts is attributed to quinolizidine alkaloids such as methylcytisine, lupanine and sparteine (Abdel Halim et al. 1997), but also to flavonoids such as chrysin and, mainly, quercetin (Lukačínová et al. 2008).

The antioxidant ability of flavonoids as free radical scavengers or metal chelators could help to preserve β-cells from ROS deleterious effects in islet of Langerhans. On the other hand, alkaloids block ATP-sensitive potassium channels present in β-cells, with subsequent insulin release. Differences in the mechanisms of action between alkaloids and flavonoids should explain the discrepancies between the aforementioned studies, since they use different extraction procedures.

It should also be borne in mind that Retama spp. is rich in pinitol (González-Mauraza et al. 2016). This compound has been reported to possess insulin-like properties since it is able to regulate the insulin-mediated glucose uptake in liver through translocation and activation of the PI3 K/Akt signalling pathway (Gao et al. 2015).

Effect on the nervous system

The methanol extract of aerial parts of R. raetam affects ambulatory and non-ambulatory movements in a dose-dependent way: no effect is detected with a dose of 125 mg kg−1 body weight; an increment-only ambulatory movement is detected with a dose of 250 mg kg−1 body weight; and a decrease in both movements is detected in mice after treatment with a dose of 375 mg kg−1 body weight. These results could be explained by the fact that certain alkaloids, in small doses, stimulateliver the brain, as does, for example cytisine, although in high doses, it can cause the inhibition of locomotor activity. In addition, high concentrations of methylcytisine produce a sedative effect (Al-Tubuly et al. 2011). Depending on the dose, the extract is anxiolytic at lower doses, has no effect at moderate doses, and is anxiogenic at higher doses, whereby an activity pattern similar to that triggered by nicotine is presented, which points to alkaloids as the metabolites responsible for the extract effect over central nervous system. Finally, different doses affect the onset of sleep and sleep duration in different ways (Al-Tubuly et al. 2011).

Effect on bone metabolism

A methanol:water (7:3) extract of R. raetam seeds had demonstrated efficacy in the protection and treatment of osteoporosis. This extract, probably due to phenolic compounds such as genistein, improved bone-tissue architecture in the form of regularity of inner and outer bone-tissue surfaces. With the increase in R. raetam treatment, the number and activity of the osteocytes also rise, as does the bone-tissue regeneration, due to an improved imbalance between bone formation and resorption. Omara et al. (2009a) concluded that this plant could be useful in the prevention of bone loss in postmenopausal women as an alternative to hormone replacement therapy.

Hepatoprotective effect

Aqueous seed extract of R. raetam is also active as a hepatoprotective agent in reducing histopathological alterations induced by CCl4 in the liver. This extract could also reverse increased pathological serum levels of aspartate and alanine aminotransferases and alkaline phosphatase (Omara et al. 2009b). Koriem et al. (2010) found similar results for formalin -induced liver, blood and kidney toxicity. This study is particularly interesting since the effects of formalin in rats are similar to those of several environmental pollutants in humans. The capability of the extract to increase diuresis, to decrease serum cholesterol and the hyperglucemia caused by formalin, its antioxidant and chelating activities, as well as its ability to restore serum levels of liver enzymes, and to reverse histopathological alterations, make this extract a promising treatment of environmental toxicity in humans (Koriem et al. 2010).

Conclusion

Retama spp. is a plant that grows almost exclusively in the Mediterranean Basin. Its ability to grow on dry soil and to withstand extreme temperatures facilitates its cultivation. Throughout history, these species have been used in traditional medicine by several cultures from the Mediterranean area and many of these activities have been demonstrated to be in use today. Their hypoglycemic effect and their antioxidant capacity are worthy of note, as is their diuretic activity associated with blood-pressure-lowering bioactivity. For this reason, these plants, especially R. raetam, the most commonly studied species, represent a major source of active principles. In this regard, the presence at Retama spp. of high concentrations of pinitol, quinolizidine alkaloids and isoflavones should be highlighted. These compounds are responsible for the majority of the pharmacological activities of the plant. However, the existence of toxic effects of the plant, such as respiratory failure and depression of the central nervous system, has been detected (Schmid et al. 2006). Repeated administration of the methanolic extract of R. raetam has a low nephrotoxic subacute toxicity potential, while it might have hepatotoxic, nephrotoxic, and mutagenic effects at higher doses (Algandaby 2015). Certain flavonoids have been pointed out as being responsible for the poisoning of livestock by ingestion of R. raetam (El-Bahri et al. 1999). For this reason, toxicological research is needed to study the adverse effects of these plants before they can be recommended for clinical use. In addition, certain molecular and cellular mechanisms of action must first be thoroughly investigated and elucidated.

Notes

Acknowledgements

Authors express their gratitude to Fundación Universitaria San Pablo-CEU and Banco de Santander for the financial support (PPC 20/2015).

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • A. J. León-González
    • 1
    • 2
  • I. Navarro
    • 3
  • N. Acero
    • 4
  • D. Muñoz Mingarro
    • 5
  • C. Martín-Cordero
    • 2
  1. 1.Maimonides Institute of Biomedical Research of Cordoba (IMIBIC)CórdobaSpain
  2. 2.Department of PharmacologyFaculty of Pharmacy, Seville UniversitySevilleSpain
  3. 3.Department of Physical ChemistryFaculty of Pharmacy, Seville UniversitySevilleSpain
  4. 4.Pharmaceutical and Health Sciences DepartmentSan Pablo-CEU University, CEU UniversitiesBoadilla del Monte, MadridSpain
  5. 5.Chemistry and Biochemistry DepartmentSan Pablo-CEU University, CEU UniversitiesBoadilla del Monte, MadridSpain

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