Rhamnus alaternus Plant: Comparison
Please note this is a comparison between Version 1 by Amine NEKKAA and Version 4 by Vivi Li.

Rhamnus alaternus, is a wild-growing shrub, belonging to the Rhamnaceae family. Widely distributed in the Mediterranean basin, R. alaternus is used in the usual medicine in numerous countries, mostly Tunisia, Algeria, Morocco, Spain, France, Italy, and Croatia. A large number of disorders including dermatological complications, diabetes, hepatitis, and goiter problems can be treated by the various parts of R. alaternus (i.e., roots, bark, berries, and leaves). Several bioactive compounds were isolated from R. alaternus, including flavonoids, anthocyanins, and anthraquinones, and showed several effects such as antioxidant, antihyperlipidemic, antigenotoxic, antimutagenic, antimicrobial, and antiproliferative.

  • Rhamnus alaternus
  • extraction processes
  • phytochemistry
  • ethnopharmacology
  • phytotherapy
  • toxicity
  • bioactive compounds

1. Introduction

Rhamnus species are considered as medicinal plants. Indeed, these sources of natural compounds possess pharmacological activities, and are used for their curative effects to treat some symptoms and diseases [1][2][3][4][5][6][7][1,2,3,4,5,6,7]. During the past few years, several studies highlighted the potential efficacy of Rhamnus species in many areas [8][9][10][11][8,9,10,11]. Among these naturally available species, the Rhamnus alaternus plant (R. alaternus) is commonly recognized as a 5-meter-tall shrub, and is distributed throughout the Mediterranean area [12][13][14][15][12,13,14,15] including North Algeria, Tunisia, and Morocco [16][17][16,17]. This plant widely grows in a Mediterranean climate with hot and dry summer and winter period is moderate to cold [14][18][19][14,18,19].
The Rhamnus alaternus plant, the so-called "Imlilesse or Safir" in the North of Algeria, has been traditionally used for a long time in various medicine areas as infusion notably for its gastric, hypotensive, purgative, laxative, diuretic, antihypertensive, hepatoprotective, and digestive effects and finally to treat dermatological complications [20]. Such biological activities would be related to the natural presence of beneficial compounds as evidenced by many experimental studies, that pointed out that R. alaternus contains important metabolites such as flavonoids, coumarins, glycosides, tannins, anthraquinones, and polyphenolic compounds [21][22][21,22]. Some of these molecules were isolated from Rhamnus alaternus using various extraction processes (i.e., maceration, decoction, hydrodistillation, soxhlet, ultrasonic extraction) and demonstrated various pharmacological properties including antihyperlipidemic, antioxidant, antigenotoxic, antiproliferative, and antimutagenic activities. Some biological activities, especially antibacterial and antiproliferative effects were reviewed elsewhere [8][20][22][23][24][8,20,22,23,24].

2. Botanical Data

2.1. Geographical Distribution

Common in wild, Rhamnus alaternus growths generally between evergreen shrubs of the Mediterranean region, especially in a climate with discontinuous rains during winter. With such characteristics, R. alaternus is a very important species of the Mediterranean basin, where it is well acclimated to high solar radiation [25][26][25,26]Rhamnus alaternus is widely distributed and grows naturally in a large part of the littoral and islands of the Mediterranean. In France, this plant is mainly found in the South departments such as Isère, Ardèche, Aveyron, Maine-et-Loire, in Vienne but also in Brittany [27]. In addition, this plant growths in Corsica, Algeria, and Northern Tunisia [22][28][29][30][22,28,29,30].

2.2. Botanical Description

In North Africa, Rhamnus alaternus has several names such as Am’lile’ce, M’lila, Soitfaïr, Oud El-khir, or Safir, and is commonly known as Meliles in Berber language [31][32][33][31,32,33]R. alaternus is also called Buckthorn in English, Nerprun in French, Kreülzdorn in German, Aladierna, Cosco Unia, or Sanguino de Andalucia in Spanish, and Alaterno or Legno Puzzo in Italian [34]. Concerning its botanical classification, R. alaternus belongs to the Magnoliophyta division, the Magnoliopsida class, the Rhamnales order, the Rhamnaceae family, the Reynosia Genus and the Rhamnus alaternus species [35]. In addition, this plant has various synonyms including R. a. var angustifolia DC, R. a. var balearica DC, R. a. var hispanica DC, and R. a. var vulgaris DC [36]R. alaternus is a small shrub of about 5-meter-tall (Figure 1A–D). Its flowers are fecundated by insects or with the help of wind [37][38][37,38] and get yellow-green from January until the end of April (Figure 1E), with a top in mid-February [39]. Then puffy and black fruits are produced, and mature between late spring and early summer, each one containing between 2 and 5 red berry seeds with on average 2.5 mm width, 4.6 mm length, and 9.1 mg weight as maximum (Figure 1F) [38][40][38,40]. Seeds are surrounded within a pericarp, which opens up once dried [38], and represents an important trophic source for birds and small mammals [41]. Usually germinated in 3 to 4 weeks between 7.5 and 24 °C, the seeds remain viable for several years in storage [40].
Figure 1.
Rhamnus alaternus
 plant with a focus on its different aerial parts: (
) leaves, (
) stem, (
) pods, (
) flowers, and (
) berries.

3. Phytochemistry

3.1. Generalities

The phytochemical investigations of Rhamnus alaternus extracts led to the isolation of various classes of natural bioactive compounds, and evidenced the richness in secondary metabolites of this medicinal plant. These bioactive compounds included flavonoids, tannins, anthraquinones, anthocyanins, anthocyanidins, and other compounds [42][43][48,72], isolated from various parts of R. alaternus such as barks, leaves, roots, and berries extracts. The investigation of these compounds was limited to qualitative studies. The most important classes of phytochemicals identified in R. alaternus are summarized (Table 12) with their main chemical compounds, whose structures are presented in Supplementary Data (supplementary could be found in https://www Supplementary Data.mdpi.com/2076-3921/10/2/300#supplementary). Each class of compounds is reviewed hereafter.
Table 12.
 Compounds isolated from 
Rhamnus alaternus.
Compound Class Compound Compound Number * Reference
Flavonoids Quercetin-3-O-rhamninoside 1 [42][44][48,55]
Kaempferol-3-O-rhamninoside 2 [44][55]
Quercetin-4′-O-rhamninoside 3 [44][55]
Kaempferol-4′-O-rhamninoside 4 [44][55]
Rhamnetin-3-O-rhamninoside 5 [44][55]
Rhamnocitrin-3-O-rhamninoside 6 [44][55]
Rhamnocitrin-4′-O-rhamninoside 7 [44][55]
Kaempferol 8 [21][23][42][44][45][21,23,47,48,55]
Quercetin 9 [21][23][44][21,23,55]
Isorhamnetin 10 [21][44][21,55]
Rhamnetin 11 [21][44][21,55]
Rhamnazin 12 [44][55]
Kaempferol-3-O-isorhamninoside 13 [23][24][46][23,24,50]
Rhamnocitrin-3-O-isorhamninoside 14 [24][46][24,50]
Rhamnetin-3-O-isorhamninoside 15 [46][50]
Anthraquinones Emodin 16 [8][45][47][8,47,56]
Rhein 17 [8][48][8,57]
Chrysophanol 18 [8]
Physcion 19 [8][48][8,57]
1,4,6,8 tetrahydroxy-3 methyl anthraquinone 20 [16]
1,2,6,8 tetrahydroxy-3 methyl anthraquinone 8-O-β-D-glucopyranoside 21 [16]
1, 6 dihydroxy-3 methyl 6 [2′-Me (heptoxy)] anthraquinone    
Physcion-3-O-β-rutinoside 22 [16]
Emodin-6O-α-L-rhamnopyranoside 23 [16]
β-sitosterol 24 [16]
β-sitosterol-3-O-β-D-glycopyranoside 25 [16]
  26 [16]
Anthocyanins Cyanidin 3-rutinoside 27 [18]
Petunidin 3-rutinoside 28 [18]
Delphinidin 3-rutinoside 29 [18]
Pelargonidin 3-rutinoside 30 [18]
Peonidin 3-rutinoside 31 [18]
Malvidin 3-rutinoside 32 [18]
Delphinidin 3-glucoside 33 [18]
Cyanidin 3-glucoside 34 [18]
Petunidin 3-glucoside 35 [18]
Pelargonidin 3-glucoside 36 [18]
Peonidin 3-glucoside 37 [18]
Malvidin 3-glucoside 38 [18]
Delphindin 39 [18]
Cyandin 40 [18]
Petunidin 41 [18]
Pelagonidin 42 [18]
Peonidin 43 [18]
Malvidin 44 [18]
* These numbers refer to the chemical structures plotted in Supplementary Data (Figure S2) Supplementary Data (Figure S2).

3.2. Flavonoids

Flavonoids, whose skeleton is based on about 15-carbon and is composed of two benzene rings [49][50][73,74], gather the bioactive compounds with low molecular weight (286–610 g/mol).
These flavonoids are the most active constituents of Rhamnus alaternus. Among these isolated compounds, literature reports quercitin-3-0-rhamninoside, kaempferol-3-0-rhamninoside, quercitin-4’-0-rhamninoside, kaempferol-4’-0-rhamninoside, rhamnetin-3-0-rhamninoside, rhamnocitrin-3-0-rhamninoside, and rhamnocitrin-4’-0-rhamninoside (Figure S2(1Figure S2(1)–(7))–(7)), identified from green fruits of Rhamnus alaternus [44][55]. Other flavonols —including quercitin, kaempferol, isorhamnetin, rhamnetin, rhamnazin (Figure S2(8Figure S2(8)–(12))–(12))—were extracted by maceration, from methanolic and aqueous extracts from Algerian Rhamnus alaternus barks [21][44][21,55]. More, flavonols such as kaempferol 3-0-β-isorhamninoside, rhamnocitrine 3-0-β-isorhamninoside, and rhamnetin-3-0-isorhamninoside (Figure S2(13Figure S2(13)–(15))–(15)) were also isolated from Rhamnus alaternus’s leaves by Soxhlet extraction method [24][46][24,50]. Furthermore, other valuable bioactive compounds were isolated from R. alaternus’ leaves such as kaempferol 3-O acetyl-rhamnoside and quercetin-3-rhamnoside [23][42][23,48].

3.3. Anthraquinone Compounds

Anthraquinones are aromatic organic compounds with the 9,10-anthracenedione core [51][75]. These ones, including three new Anthraquinones, were isolated from the extracts of various parts collected from Rhamnus alaternus (i.e., leaves, barks, and roots). Among anthraquinones, rhein, chrysophanol, and physcion (Figure S2(17Figure S2(17)–(19))–(19)) were also isolated from the bark extract of R. alaternus by ultrasonic extraction [8]. Furthermore, 1,4,6,8 tetrahydroxy-3 methyl anthraquinone 1-O-β-D-glucopyranosyl-4,6-di-O-α-L-rhamnopyranoside, 1,2,6,8 tetrahydroxy-3 methyl anthraquinone 8-O-β-D-glucopyranoside and 1, 6 dihydroxy-3 methyl 6 [2′-Me (heptoxy)] anthraquinone (Figure S2(20Figure S2(20)–(22))–(22)) were identified from various parts of Rhamnus alaternus such as leaves, bark and roots [16].

3.4. Anthocyanin Constituents

Anthocyanins are structurally related to anthocyanidins (parent class of flavonoids) and are also derived from the 2-phenylbenzopyrilium ion [52][53][76,77].
The extracts of Rhamnus alaternus’ berries showed many compounds of high nutritional values and were rich in diverse anthocyanins and anthocyanidins constituents, such as delphinidin 3-rutinoside, delphinidin 3-glucoside, delphinidin, cyanidin 3-rutiniside, cyanidin 3-glucoside, cyanidin, pelargonidin 3-rutinoside, pelargonidin 3-glucoside, pelargonidin, petunidin, peonidin, and malvidin [18] (Figure S2(27Figure S2(27)–(44))–(44)).
A review on this plant was recently published by Nekkaa and co-workers in 2021 with the corresponding reference of Antioxidant journal [54].