Ethnomedicinal, Phytochemical and Pharmacological properties of Pistacia atlantica Desf. (Anacardiaceae): Review

 

Chahrazad Bakka*, Ouanissa Smara, Hocine Dendougui, Mohamed Hadjadj

Laboratory of Valorization and Promotion of Saharan Resources VPRS, Department of Chemistry,

Faculty of Mathematics and Material Sciences, University of Kasdi Merbah, Ouargla, Algeria.

*Corresponding Author E-mail: bakkachahrazad@gmail.com

Pistacia atlantica belongs to the Anacardiaceae family, it has been widely used in the Middle Eastern and Mediterranean areas since ancient times. Pistacia atlantica has been used for different diseases like stomach, pain, peptic ulcer, wounds, renal disorders, and coughs. This study aims to review its ethnobotanical characterization, traditional uses, phytochemistry, and pharmacological activities found in this plant. The data in this review article was based on electronic databases such as Web of Science, Springer, Yahoo search, Science Direct, PubMed, and Google Scholar for papers published from 2016 until March 2021 are considered. The results showed that Pistacia atlantica has many medicinal properties such as antioxidant, antidiabetic, anticancer, anti-inflammatory, and others. Phytochemical has shown the presence of numerous valuable compounds, including volatile compounds, fatty acids, phenolic compounds, and flavonoids.  In this regard, the ethnomedicinal, phytochemistry, biological, and pharmacological properties of Pistacia atlantica have been reviewed here.

 

 

INTRODUCTION:

Pistacia genus belonging to the Anacardiaceae family encompasses about twenty species, which include evergreen or deciduous species, shrubs, and small trees ranging from 5 to 15 m in height, living in arid and semi-arid regions¹. Most species P. vera, P. lentiscus, P. terebinthus, P. khinjuk, and P. atlantica are widely distributed in the Mediterranean and Middle Eastern areas², P. atlantica (wild pistachio) is the most economical species of Pistacia genus, found in Iran, wild pistachio grows in different countries like Pakistan, Greece, Turkey, and North Africa, also occurs from the canary islands to Pamir mountain³.

 

Only three review articles were found^1-3, which highlighted, in brief, the reported phytochemical and biological activities of P. atlantica.

 

Common vernacular names, botanical description, taxonomy, and distribution, pharmacological properties, as the article review presented by³ showed for the first time in the literature related four subspecies of Pistacia atlantica (atlantica, kurdica, cabulica, and mutica), collected all each subspecies for their botany, ethnobotany, phytochemistry, and pharmacology.

 

This review is aimed to contribute to the knowledge of the plant of growing interest, the wild pistachio (P. atlantica), by providing a botanical, and medicinal use, phytochemical, and pharmacological overview by focusing on data reported from 2016 to the 2021 year via papers on databases including Web of Science, PubMed, Scopus, and Google Scholar.

 

RESEARCH METHODOLOGY:

The review has been designed based on online databases including, Scopus, Science Direct, Pub Med, Elsevier, Google Scholar, Web of Science and Yahoo search, Springer, and Google Web ResearchGate for papers published between 2016 to 2021 years. By using different synonyms of the plant (Pistacia atlantica, wild pistachio, Atlas pistachio, P.atlantica Desf.), and consulting published research about the phytochemistry, traditional, medicinal uses, ethnobotanical and ethnobiological, pharmacological, qualitative and quantitative chemical, biological and clinical studies regarding P. atlantica, as the term used for the search which was as follows for English and French writings, the reported of this plant were presented, and chemical components and their structural formulae were drawn and verified from Chem Draw and Pubchem.

 

Taxonomy, Distribution, and Description of P. atlantica Desf:

Pistacia atlantica is one of Pistacia species belonging to the Anacardiaceae family, it has 4 sub-species are admitted (P. atlantica subsp. kurdica, P. atlantica subsp. atlantica, P. atlantica subsp. cabulica, P. atlantica subsp. mutica), and it is one of the tree species Irano-Touranian taxa, which is largely distributed in the Mediterranean region. The Mediterranean and the Irano-Turanian regions have many common taxa because they belong to the same climate type and are in contact since ancient geological times. P. atlantica occupies a wide variety of soils. It thrives well in poor and dry soils, in silty or clay soils. where it can colonize the rocky soils the roots insinuate and develop inside cracks, and where it can overcome many other species in a growing Competition⁴.

 

Pistacia atlantica is widely distributed across North Africa, the Canary Islands, and a section of Eurasia from the Iranian Plateau. In North Africa, P. atlantica occurs in isolated stands in Egypt and Libya, Morocco, Algeria, and Tunisia.

 

In Europe, P. atlantica is recorded from Greece (the East Aegean Islands and the Cyclades), Cyprus, Ukraine (Crimea), Turkey (Thrace), Serbia, and the Canary Islands.

 

In Asia, Pistacia atlantica is found from Northern and Western Pakistan to central and South Afghanistan, South and West Iran, the Southeast Caucasus, North Iraq, South Turkey, Syria, Lebanon, Jordan to Palestine. It reapers in the Canary Islands, the western limit of its wide distribution area. It is believed that P. atlantica originated in the Persian region (Iran) from where it has expanded to the Southwest of Europe, North Africa, and the Canary Islands^5,6.

Botanically, the trees of Pistacia atlantica are a spontaneous and woody species that can be reached over 10m in height⁷, leaves are imparipinnate, 5 -(9) leaflets, lanceolate, 26-70mm long, and 8-22mm wide. Panicles are extra-axillaries, petioles are winged, and flowers are dioecious and unisexual.

 

P. atlantica subsp. atlantica:

The leaves are deciduous, imparipinnate, terminal leaflet sessile, leaflets oblong-lanceolate, hairy with ciliated ribs and ciliated midrib, 3-5 Paired; rachis widely winged, wings exist along all of the rachides.

 

P. atlantica subsp. cabulica:

leaves deciduous, imparipinnate, terminal leaflet sessile, leaflets oblong-lanceolate, with ciliated midrib, ribs, and veins, 3-5 Paired; - rachis winged, wings exist along all of the rachides.

 

P. atlantica subsp. mutica:

leaves deciduous, imparipinnate, terminal leaflet sessile, leaflets oblong-ovate with ciliated midrib, ribs but rarely the veins, 2-4 (-5) Paired; rachis winged, wings exist between the two last pairs.

 

P. atlantica subsp. Kurdica:

Leaves deciduous, imparipinnate, terminal leaflet subsessile or petiolulated, leaflets oblong-ovate sometimes acuminate; rachis tightly winged, wings exist between the two last pairs.

 

Leaves and fruits of the three subspecies found in Iran. The Drupes are slightly broader, and then long in P. atlantica subsp. mutica, are globose, with equally long and broad in P. atlantica subsp. cabulica; and are depressed globose, 5-8 mm x 8-10 mm in P. atlantica subsp. Kurdica^7,8.

 

Medicinal, Traditional Uses of Pistacia atlantica Desf:

Pistacia atlantica is known by many vernacular names, in Arabic is called btom, bettam, botma. It is called tesemhalt and tismelelt in the Berber population of the Maghreb (Amazighs)⁸. In Persian, P. atlantica is known as Baneh, and in English Atlas mastic tree, in the Canary Islands Almacigo, and Turkish Melengic or Atlantik sakizi and Bittim. It is called Almacigo de canarias or Lengua de oveja in Spanish and in Italian is called Tremintos².

 

In Persian, The resin of P.atlantica is called Saqez. The Baneh have been mentioned as ripe fruits with delicious marrow². In Algeria, the fruits are called Elkhodiri and goddim khoddir for the green fruits or Kohhil for the black ones⁹.

 

Traditionally, different parts of P.atlantica have been used to treat various diseases, such as food consumption and cosmetics use. In Algeria, it is used in traditional medicines for various diseases such as stomach disease, diabetes, cold, vomiting, cough, irritations, and stress¹⁰. The oils of fruits are used as a food additive; the seeds are ground, mixed with grand dates, also the fruits are used for tanning and as fodder for cattle¹¹.

 

In Tunisia, traditionally P.atlantica has been used as a treatment for stomatitis, ophthalmic and digestive tract diseases¹².

 

In Iranian traditional medicine, Pistacia atlantica is used as a demulcent, carminative, stomach, diuretic, wound healing, liver and kidneys tonic, also used in the treatment of the gastrointestinal disorder, visceral inflammation, motion sickness, joint pains, and toothache diseases¹³. The resin of P. atlantica is used to treat gastrointestinal disorders like diarrhea, peptic ulcer, dyspepsia, as well as liver diseases, and skin wounds¹⁴. P. atlantica oil can be used in food, and cosmetics; also the resin is used in the food industry to prepare chewing gum^15,16. It’s used to gum disease, clear the mouth, strengthen teeth, relieving, and abdominal pain, improve memory, and reduce stress¹⁷.

 

In Morocco, P. atlantica has important for is known as the source of mastic gum, an exudate that strengthens gums, chills, and stomach diseases, and the decoction of its leaves is used to treat eye infection¹⁸.

 

Phytochemistry of Pistacia atlantica Desf:

Essential oils:

Essential oil is one of the numerous metabolites, that can be isolated from galls, leaves, and fruits (ripe and unripe), leaf-buds, twigs, flowers, resin, and gum of P. atlantica. The essential oils composition % of P. atlantica is listed in table.1. The main ingredients of the essential oils reported by hydrodistilled in Clevenger type, Soxhlet method¹⁵, and were analyzed by using gas chromatography (GC) and gas chromatography coupled to mass spectrometry (GC-MS). In general, the highest amounts of the compounds of the essential oil were monoterpenes hydrocarbons, oxygenated monoterpenes, sesquiterpenes hydrocarbons, and oxygenated sesquiterpenes. Wherever, the major common compounds were α-pinene, Myrcene, and Limonene, Terpinene-4-ol.

 

Fatty acids:

Pistacia atlantica is rich in sours of fatty acids (unsaturated). Leaf, fruit, seed, gall oils were identified by using chromatographic techniques including GC/FID and GC/MS. Twelve fatty acids were detected by GC/FID isolated to leaf oil collected from Laghouat, Algeria. The major fatty acid detected was Linolenic acid (41.73% of TFA)¹⁹. On other hand, The Fruits oils were extracted with hexane, esterified, and then analyzed by gas chromatography. Oleic acid, linoleic acid, and palmitic acid were the major fatty acid composition identified¹⁹. In the seeds of P. atlantica, the fatty acids of the seed oil (collected from Sidi Bouzid, Tunisia) were extracted by using three methods as already mentioned higher. The supercritical CO₂ assay was the most powerful with an extraction rate of 25% compared to extraction by hexane (7.9%) or by pressing (5.3%). The three extraction methods give similar fatty acid compositions, the most abundant were oleic acid (55.4-56.4%), followed by linoleic acid (28.50-29.63%). Palmitic (11.2-11.6%) and stearic acids (2.3-2.4%) were the main saturated fatty acids²⁰. The oil of seeds (Djelfa-Algeria) was extracted by using a soxhlet method and analyzed by GC/MS, the major fatty acids were oleic (39-49%), linoleic (23.6-31%), palmitic acids (21.3-26.6%)¹⁵.

 

Table.1: Major Chemical composition isolated from the essential oil of P. atlantica Desf.

Name of compound	Structure	Composition %	Part used	Region	References
α-pinene		6.8 10.8 18.4 18.5 19.2 30 30 32.48 46.05 47.7 64.8-15.4 79.76 81.6 93.17	Aerial parts Ripe fruit Leaves Oleoresin Leaves Hull Flowers Fruits Seeds Fruits Leaf Gum Gum Oleoresin	Algeria (Tiaret) Iran Algeria Iran (Oramanat) Kurdistane Iran (Awraman) Algeria Iran   Iran (Kermanshah)   Kurdistane Algeria (Mascara) Iraq (Halabja) Kurdistane Iran(Kermanshah)	21 22 23 24 25 26 23 27 28 25 29 30 25 31
β-pinene		1.69 4.7 29.38	Oleoresin Hulls Oleoresin	Iran(Kermanshah) Iran (Awraman) Iran (Oramanat)	31 26 24
Myrcene		5.4 7.36 10.235 16.10 41.4	Hull Oleoresin Seeds Fruit fruit	Iran (Awraman) Iran (Oramanat) Iran (Kermanshah) Kurdistane Iran	26 24 28 25 27
Camphene		4.12 5.7	Hulls Oleoresin	Iran (Awraman) Iran (Oramanat)	26 24
Limonene		3.8 4.66 5.9 8.75 8.835 8.9	Hulls Fruits Leaves Fruits Seeds Flowers	Iran (Awraman) Iran Algeria Kurdistane Iran (Kermanshah) Algeria	26 27 23 25 28 23
Terpinene-4-ol		4.1 4.9 16.1-34.7 35.6	Hull Fruit Leaf Aerial parts	Iran (Awraman) Kurdistane Algeria (Mascara) Algeria(Tiaret)	26 25 29 21
Germacrene		6.2 6.2 19-24.5	Aerial parts Leaf Leaf	Algeria (Tiaret) Algeria Algeria (Mascara)	21 23 29
α-phellandrene		8.9 11	Leaves Flowers	Algeria	23
β-phellandrene		13.4	Flowers	Algeria	23
Elemene		7.5	Leaves	Algeria Algeria (Tiaret)	23 21
γ-Gurjunene		10	Leaves	Algeria	23
β-citral		7	hull	Iran (Ilam)	22
Trans-pinocarveol		7.15	Oleoresin	Iran (Oramanat)	24
E-caryophyllene		23	Leaves	Algeria (Mascara)	29
Bromyl acetate		8.5	hull	Iran (Awraman)	26

 

Phenolic compounds:

Wild pistachio (P. atlantica) is known to be a rich source of phenolic compounds (such as phenolic acid, flavonoids, and tannin). They had been isolated and identified in different parts of the plant (seeds, stem, resin, gum, leaf, fruit, hull, root) by using various methods. The quantification of different types of phenolic classes and the total content of it, and the isolated phenolic are shown in table.2, and table.3.

 

The methanolic extract of P. atlantica subsp. mutica hulls showed the presence of twenty-one phenolic compounds, identified by HPLC-DAD, LC-MS, and ¹H NMR. The main identified compounds were luteolin, gallic acid, O-galloylisoquercitin, quercitin 3-rutinoside, and caffeoylequercetine³². Also, twenty-seven phenolic compounds were identified by Khallouki et al from methanolic extracts of P. atlantica Desf, fruits namely gallic acid, galloyl quinate, galloyl glucoside digalloyl uinate-1, digalloyl quinate-2, methyl gallate, digalloyl lucoside, trigalloyl glucoside, tetragalloyl glucoside-1, etragalloyl glucoside-2, pentagalloyl glucoside, 2-O-alloyl quercetin-3-O-glucoside, quercetin-3-O-hamnogalactoside, quercetin-3-O-galactoside, luteolin, uteolin-4-O-glucoside, 2-O-galloyl-luteolin-4-O-lucoside, quercetin-3-O-glucuronide, kaempferol-3-O-lucoside, eriodictyol, apigenin, ellagic acid, ellagic acid iglucoside, ellagic acid glucoside, methyl ellagic acid lucoside, and ellagic acid³³.

The leaf, buds, and root of P. atlantica were extracted with the hydro-methanolic mixture and then partitioned with solvents of increasing polarity. From the ethyl acetate and butanol extracts fractions were identified ten phenolic compounds, namelytannic acid, rutin, gallic acid, vanillic acid, ρ-coumaric acid, catechin, syringic acid, ferulic acid, quercetin and naringenin [34]. Benamar et al[35] led to identifying 14 gallic acid derivatives by using high-pressure liquid chromatography (HPLC)-diode array detecter (DAD)-UV and HPLC-atmospheric pressure ionization (API) electrospray (ES)-mass spectrometry (MS) analysis, in three fractions of P. atlantica leaves (aqueous, ethyl acetate, butanol), rutin and myricetin-galloylhexoside, quercetin-O-gallate. These results indicated that the ethyl acetate was rich in phenolic compounds.

 

Amri et al confirmed the presence of gallic acid derivatives and glycosylated, heterosides flavonoids in the methanolic extract of P. atlantica leaves³⁶.

 

From CHCl₃, ethyl acetate, and butanol extracts of P. atlantica leaf and stem were identified twenty-two phenolic compounds by using HPLC-TOF/MS analysis. In particular, gallic acid and rutin were the main compounds detected. Cichoric, gentisic, vanillic, protocatechuic and rosmarinic acids as well as catechin and quercetin were also identified¹⁰.

 

 

Table.2 Quantitative analysis of phenolic contents

Phytochemicals	Plant part used	Region	Type of extraction / or extract	Value	Quantitative method	Ref.
Total phenolic content TPC	Leaves	Algeria	Aceton/Water (7:3, v:v)	79-258 mg GAE / g DM	UV-Vis	37
		Algeria (Telmcen)	Crude extract	255.789±4.7333 mg GAE / g DM	UV-Vis	34
		Algeria (Naama)	Aqueos extract	421.01±8.92 mg GAE / g DE	UV-Vis	35
			EtOAc	514.81±2.10 mg GAE / g DE	UV-Vis	35
			n-BuOH	376.34±3.43 mg GAE / g DE	UV-Vis	35
	Gum	Iraq	Extude gum extract	147.11 ±0.25 mg GAE / g extract	UV-Vis	13
	Fruits	Algeria (Telmcen)	Crude extract	205.219±9.974 mg GAE / g DM	UV-Vis	34
		Iraq	Ethanol	5.20 mg GAE / g extract	UV-Vis	38
	Stems	Algeria (Telmcen)	Crude extract	90.727±7.360 mg GAE / g DM	UV-Vis	34
	Buds	Algeria (Telmcen)	Crude extract	233.946±6.205 mg GAE / g DM	UV-Vis	34
	Internal trunks barks	Algeria (Telmcen)	Crude extract	131.449±18.972 mg GAE / g DM	UV-Vis	34
	External trunks barks	Algeria (Telmcen)	Crude extract	6.236±0.081 mg GAE / g DM	UV-Vis	34
	Roots	Algeria (Telmcen)	Crude extract	35.603±2.256 mg GAE / g DM	UV-Vis	34
		Iraq	Ethanol	5.05 mg GAE / g extract	UV-Vis	38
	Epicarp	Algeria	MeOH	0.21-94.15 mg GAE / g FW	UV-Vis	16
	Seed	Algeria	MeOH	5.64-16.39 mg GAE / g FW	UV-Vis	16
Total flavonoid content TFC	Leaves	Algeria	Aceton/Water (7:3, v:v)	0.65-2.81 mg QE / g DM	UV-Vis	37
		Algeria (Telmcen)	Crude extract	22.683±0.693 mg CE / g DM	UV-Vis	34
		Algeria (Naama)	Aqueous extract	44.81±1.31 mg CE / g DE	UV-Vis	35
			EtOAc	126.43±1.31 mg CE / g DE	UV-Vis	35
			n-BuOH	103.77±1.07 mg CE / g DE	UV-Vis	35
	Stems	Algeria (Telmcen)	Crude extract	9.466±0.305 mg CE / g DM	UV-Vis	34
	Buds	Algeria (Telmcen)	Crude extract	24.623±0.252 mg CE / g DM	UV-Vis	34
	Internal trunks barks	Algeria (Telmcen)	Crude extract	21.805±0.664 mg CE / g DM	UV-Vis	34
	External trunks barks	Algeria (Telmcen)	Crude extract	1.69±0.050 mg CE / g DM	UV-Vis	34
	Roots	Algeria (Telmcen)	Crude extract	17.02±0.280 mg CE / g DM	UV-Vis	34
		Iraq	Ethanol	0.68 mg QE / g extract	UV-Vis	38
	Gum	Iraq	Extude gum extract	45.55±3.2 mg RE /g extract	UV-Vis	13
	Epicarp	Algeria	MeOH	23.6-459.86 mg QE / g FW	UV-Vis	16
	Seed	Algeria	MeOH	13.82-45.08 mg QE / g FW	UV-Vis	16
Total tannins content TTC	Leaves	Algeria	Aceton/Water (7:3, v:v)	0.32-3.15 mg CE / g DM	UV-Vis	37
Flavonols content	fruits	Algeria (Telmcen)	Crude extract	3.291±0.087 mg QE / g DM	UV-Vis	34
	Leaves	Algeria (Telmcen)	Crude extract	1.539±0.015 mg GAE / g DM	UV-Vis	34
	Stems	Algeria (Telmcen)	Crude extract	2.538±0.136 mg GAE / g DM	UV-Vis	34
	Buds	Algeria (Telmcen)	Crude extract	8.942±0.208 mg GAE / g DM	UV-Vis	34
	Internal trunks barks	Algeria (Telmcen)	Crude extract	5.139±0.176 mg GAE / g DM	UV-Vis	34
	External trunks barks	Algeria (Telmcen)	Crude extract	0.788±0.005 mg GAE / g DM	UV-Vis	34
	Roots	Algeria (Telmcen)	Crude extract	1.497±0.0149 mg GAE / g DM	UV-Vis	34
Gallic acid	Leaf		MeOH	51.54±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
			CHCl3	0.58±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
		Algeria (Bechar)	EtOAc	3869.07±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	3990.42±0.39 mg phenolic / kg plant	HPLC-TOF/MS	10
		Algeria (Telmcen)	Crude extract	709.37 µg/ g DM	HPLC	34
		Algeria (Naama)	EtOAc	N.D.	HPLC-DAD-UV	35
	Buds	Algeria (Telmcen)	EtOAc	1166.22 µg/ g DM	HPLC	34
			n-BuOH	27.27 µg/ g DM	HPLC	34
	Stem	Algeria (Bechar)	CHCl3	21.75±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	1517.17±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
	Roots	Algeria (Telmcen)	Crude extract	600.02 µg/ g DM	HPLC	34
			EtOAc	6.56 µg/ g DM	HPLC	34
			n-BuOH	592.36 µg/ g DM	HPLC	34
	Epicarp	Algeria	MeOH	0.04-48.8 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	1.27-6.44 mg / g FW	HPLC	16
	Hull	Iran	MeOH	9.84 % W/W pure compound/ weight of extract	HPLC-DAD	32
	Fruits	Morocco	MeOH	3.95 g/kg W	HPLC-DAD	33
Ascorbic acid	Leaves	Algeria (Telmcen)	Crude extract	135.06 µg/ g DM	HPLC	34
	Buds	Algeria (Telmcen)	Crude extract	600.10 µg/ g DM	HPLC	34
			n-BuOH	133.14 µg/ g DM	HPLC	34
	Roots	Algeria (Telmcen)	Crude extract	2.02 µg/ g DM	HPLC	34
			EtOAc	0.90 µg/ g DM	HPLC	34
			n-BuOH	1.41 µg/ g DM	HPLC	34
p-coumaric acid	Buds	Algeria (Telmcen)	Crude extract	680.21 µg/ g DM	HPLC	34
	Epicarp	Algeria	MeOH	0.03-0.28 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.03-0.16 mg / g FW	HPLC	16
	Leaf	Algeria (Bechar)	EtOAc	8.009±0.15 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	EtOAc	1.514±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
Gentisic acid	Leaf	Algeria (Bechar)	MeOH	51.54±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	1517.17±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
	stem	Algeria (Bechar)	CHCl3	21.75±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	1517.17±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
Catechin	Leaf	Algeria (Bechar)	CHCl3	21.75±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	1517.17±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
		Algeria (Telmcen)	Crude extract	256.14 µg/ g DM	HPLC	34
			EtOAc	198.31 µg/ g DM	HPLC	34
			n-BuOH	851.42 µg/ g DM	HPLC	34
	Buds	Algeria (Telmcen)	Crude extract	5.03 µg/ g DM	HPLC	34
			EtOAc	1.02 µg/ g DM	HPLC	34
			n-BuOH	0.69 µg/ g DM	HPLC	34
	Roots	Algeria (Telmcen)	Crude extract	275.64 µg/ g DM	HPLC	34
			EtOAc	8.32 µg/ g DM	HPLC	34
	Stem	Algeria (Bechar)	EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	1517.17±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
4-hydroxybenzoic acid	leaf	Algeria (Bechar)	MeOH	51.54±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	EtOAc	2804.84±0.35 mg phenolic / kg plant	HPLC-TOF/MS	10
Chlorogenic acid	Leaf	Algeria (Bechar)	MeOH	2.288±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			CHCl3	0.41±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	CHCl3	0.594±0.01mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	15.84±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
Protocatechuic acid	Leaf	Algeria (Bechar)	MeOH	1.187±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			CHCl3	0.194±0.015 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	42.58±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10]
			n-BuOH	29.49±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	CHCl3	0.419±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	44.117±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	7.299±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
Caffeic acid	Stem	Algeria (Bechar)	EtOAc	1.437±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10]
			n-BuOH	0.648±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
	Epicarp	Algeria	MeOH	0.02-0.39 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.02-0.03 mg / g FW	HPLC	16
	hull	Iran	MeOH	0.5% W/W	HPLC-DAD	32
Vanillic acid	Leaf	Algeria (Bechar)	EtOAc	5.76±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	27.01±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
	Buds	Algeria (Telmcen)	Crude extract	100.62 µg/ g DM	HPLC	34
			EtOAc	59.45 µg/ g DM	HPLC	34
			n-BuOH	42.32 µg/ g DM	HPLC	34
	Epicarp	Algeria	MeOH	0.02-0.82 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.03-0.09 mg / g FW	HPLC	16
	Stem	Algeria (Bechar)	CHCl3	1.855±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	23.999±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	41.403±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
Cichoric acid	Leaf	Algeria (Bechar)	EtOAc	1598.9±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	381.88±0.16 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	CHCl3	0.268±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	315.32±0.15 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	22.72±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
Rutin	Leaf	Algeria (Bechar)	MeOH	0.784±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	22.75±0.04 mg phenolic / kg plant	HPLC-TOF/MS	10
			MeOH	1632.27±0.25 mg phenolic / kg plant	HPLC-TOF/MS	10
		Algeria (Telmcen)	Crude extract	21.95 µg/ g DM	HPLC	34
		Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
	Buds	Algeria (Telmcen)	n-BuOH	7.87 µg/ g DM	HPLC	34
	Stem	Algeria (Bechar)	CHCl3	0.874±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	10.649±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	337.85±0.15 mg phenolic / kg plant	HPLC-TOF/MS	10
	Leaves	Iran	MeOH	Detected	HPLC-DAD, LC.MS	39
	Epicarp	Algeria	MeOH	0.07-1.51 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.4-1.13 mg / g FW	HPLC	16
	Fruit	Morocco	MeOH	1.22 g/kg DW	HPLC-DAD	33
	hull	Iran	MeOH	0.34% W/W	HPLC-DAD	32
5,4-dihydroxi-3,3-dimithoxi-6,7-methylene-dioxiflavone	hull	Iran	MeOH	0.34% W/W	HPLC-DAD	32
Ferulic acid	Stem	Algeria (Bechar)	CHCl3	0.687±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	3.134±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
	Leaves	Algeria (Telmcen)	Crude extract	1050.32 µg/ g DM	HPLC	34
			EtOAc	188.67 µg/ g DM	HPLC	34
			n-BuOH	151.37 µg/ g DM	HPLC	34
	Buds	Algeria (Telmcen)	Crude extract	1376.62 µg/ g DM	HPLC	34
			EtOAc	26.97 µg/ g DM	HPLC	34
			n-BuOH	84.24 µg/ g DM	HPLC	34
	Roots	Algeria (Telmcen)	Crude extract	9.07 µg/ g DM	HPLC	34
			EtOAc	1.61 µg/ g DM	HPLC	34
			n-BuOH	1.06 µg/ g DM	HPLC	34
Syringic acid	Leaves	Algeria (Telmcen)	Crude extract	25.36 µg/ g DM	HPLC	34
			EtOAc	12.51 µg/ g DM	HPLC	34
			n-BuOH	42.24 µg/ g DM	HPLC	34
	Buds	Algeria (Telmcen)	Crude extract	20.14 µg/ g DM	HPLC	34
			EtOAc	11.64 µg/ g DM	HPLC	34
	Roots	Algeria (Telmcen)	Crude extract	64.80 µg/ g DM	HPLC	34
			EtOAc	25.49 µg/ g DM	HPLC	34
			n-BuOH	83.59 µg/ g DM	HPLC	34
Hesperidin	Stem	Algeria (Bechar)	n-BuOH	1.578±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
Apigenin7-O-glucoside	Leaf	Algeria (Bechar)	MeOH	0.748±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
Rosmarinic acid	Leaf	Algeria (Bechar)	CHCl3	18.5±0.03 mg phenolic / kg plant	HPLC-TOF/MS	10
			EtOAc	1.35±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	EtOAc	0.50±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
			n-BuOH	53.826±0.02 mg phenolic / kg plant	HPLC-TOF/MS	10
Quercetin	Leaf	Algeria (Bechar)	EtOAc	66.72±0.09 mg phenolic / kg plant	HPLC-TOF/MS	10
		Algeria (Telmcen)	Crude extract	325.12 µg/ g DM	HPLC	34
			EtOAc	106.64 µg/ g DM	HPLC	34
			n-BuOH	21.90 µg/ g DM	HPLC	34
	Buds	Algeria (Telmcen)	EtOAc	17.65 µg/ g DM	HPLC	34
	Roots	Algeria (Telmcen)	Crude extract	6.25 µg/ g DM	HPLC	34
		Algeria (Telmcen)	n-BuOH	5.39 µg/ g DM	HPLC	34
	Stem	Algeria (Bechar)	EtOAc	36.098±0.05 mg phenolic / kg plant	HPLC-TOF/MS	10
	Fruit	Morocco	MeOH	0.54 g/kg DW	HPLC-DAD	33
Narnigenin	Stem	Algeria (Bechar)	EtOAc	0.290±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
	Epicarp	Algeria	MeOH	0.07-1.51 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.07-0.3 mg / g FW	HPLC	16
Kaempferol	Leaf	Algeria (Bechar)	EtOAc	2.94±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	EtOAc	0.336±0.01 mg phenolic / kg plant	HPLC-TOF/MS	10
	Hull	Iran	MeOH	46.53% W/W	HPLC-DAD	32
Cinnamic acid	Leaf	Algeria (Bechar)	MeOH	4.17±0.00 mg phenolic / kg plant	HPLC-TOF/MS	10
	Stem	Algeria (Bechar)	n-BuOH	24.458±0.04 mg phenolic / kg plant	HPLC-TOF/MS	10
Myricetin 3-O- rutinoside	Leaves	Iran	MeOH	Detected	HPLC-DAD, LC-MS	39
Isoquercetin	Leaves	Iran	MeOH	Detected	HPLC-DAD, LC-MS	39
Kaempferol-3-O-rutinoside	Leaves	Iran	MeOH	Detected	HPLC-DAD, LC-MS	39
	Fruit	Morocco	MeOH	1.05g/kg DW	HPLC-DAD	33
Vanillin	Epicarp	Algeria	MeOH	0.02-0.09 mg / g FW	HPLC	16
	Seed	Algeria	MeOH	0.02-0.11 mg / g FW	HPLC	16
Quinic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
Galloyl quinic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Digalloyle quinic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Methyl gallate	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
	Fruit	Morocco	MeOH	1 g/kg DW	HPLC-DAD	33
Digallic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
Trigalloyl quinic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Trigallic acid	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
Methyl digallate	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Myricetin	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
galloyl hexoside			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Quercetin-O-gallate	Leaves	Algeria (Naama)	Aqueous extract	Detected	HPLC-DAD-UV	35
			EtOAc	Detected	HPLC-DAD-UV	35
			n-BuOH	Detected	HPLC-DAD-UV	35
Glucogallin	Leaves	Algeria (Naama)	n-BuOH	Detected	HPLC-DAD-UV	35
Tetragalloyl quinic acid	Leaves	Algeria (Naama)	n-BuOH	Detected	HPLC-DAD-UV	35
Galloyl glucoside	Fruit	Morocco	MeOH	0.75 g/kg DW	HPLC-DAD	33
Ellagic acid	Fruit	Morocco	MeOH	0.25 g/kg DW	HPLC-DAD	33
Luteolin	Fruit	Morocco	MeOH	3.18 g/kg DW	HPLC-DAD	33
Pentagalloyl glucoside	Fruit	Morocco	MeOH	5 g/kg DW	HPLC-DAD	33
Digalloyl quinate-1	Fruit	Morocco	MeOH	1 g/kg DW	HPLC-DAD	33

 

Hussein et al led to isolated, and identified new polyphenolics from P. atlantttica leaf, by using conventional methods, spectroscopic analysis, including 1D- and 2D-NMR, ESI-MS, and HRESI MS. The ethyl acetate extracts showed a complicated mixture of phenolic acids and gallotannines identified for the first time from this plant as polyphenolic acid, ellagic acid,3,3’- dimethoxyellagicacid, and gallotannines, namely: gallic acid, 1,2,3,4,6-Penta-O-galloyl-ß-4C1-glupyranose, 1,6-digalloylglucopyranose, 1,3- digalloylglucopyranose, 2,3-digalloyl-glucopyranose and 2,3,6-trigalloylglucopyranose respectively⁴⁰.

 

Ahmed et al reviewed all the isolated phenolic compounds until 2020, which led to the collection of isolated phenolics from P. atlantica, namely gallic acid, methyl gallate, quinic acid, galloy quinic acid, digalloyl quinic acid, and digallic acid. A new flavonoid isolated from leaf and twigs, the compounds 3-methoxy-carpachromene, and methyl ester gallic acid were isolated from methanolic extract leaves, in the ethyl acetate fraction, and crude extract from stocks of P. atlantica two flavoinds were isolated (transilitin, and dihydro-luteolin). A new derivative of hispolone and hispidin methyl 5-(3,4-dihydroxyphenyl)-3-hydroxypenta-2,4-dienoate was isolated from P. atlantica³.

 

Table.3 phenolic compounds isolated and characterized from P. atlantica

Name of compounds isolated	Structures	Solvent extracts	Plant part	Region	Ref
Gallic acid		Methanol	Leaves	Algeria	3
Digallic acid		ethyl acetate	leaves	Libya	40
Methyl gallate		ethyl acetate	leaves	Libya	40
Quinic acid		ethyl acetate	leaves	Libya	40
ellagic acid		ethyl acetate	leaves	Libya	40
3,3’- dimethoxyellagic acid		Ethyl acetate	leaves	Libya	40
1,6-digalloylglucopyranose		Ethyl acetate	leaves	Libya	40
1,3-digalloylglucopyranose		Ethyl acetate	leaves	Libya	40
2,3-digalloyl-glucopyranose,nilocitin		Ethyl acetate	leaves	Libya	40
2,3,6-trigalloylglucopyranose		Ethyl acetate	leaves	Libya	40
2,3-di-Ogalloyl- 4,6-O-hexahydroxydiphenoyl-(α/β)- 4C1-glucopyranose		Ethyl acetate	leaves	Libya	40
1,3-di-O-galloyl-β-D-4C1-glucopyranose		Ethyl acetate	leaves	Libya	41
3-methoxycarpchromene		/	Leaves and twigs	/	3
Galloylquinic acid		/	/	/	3
Digalloylquinic acid		/	/	/	3
Methyl 5-(3,4-dihydroxyphenyl)-3-hydroxypenta-2,4-dienoate		MeOH	Fungus	Algeria	3
6-(3,4-dihydroxyphenyl)-4-hydroxy-3,4-hexadien-2-one		MeOH	Fungus	Algeria	3

 

Pharmacological properties and Safety Evaluation P. atlantica Desf.

Antioxidant effect:

The different parts of P. atlantica plant are known as an excellent source of natural antioxidants^42,43. The antioxidant of the tannin extract of leaves, roots internal, and external trunk barks of P. atlantica (Telmcen, Algeria) were shown a good radical scavenging activity DPPH (IC₅₀ of 0.124±0.001, 0.304±0.001, and 0.440±0.001 mg/ml, respectively), β-carotene bleaching inhibition with values 0.313±0.009, 0.094±0.006 and 0.131±0.002 respectively, and in FRAP method the ferric reducing power given values with 0.021±0.001, 0.154±0.001 and 0.170±0.005mg/ml respectively [44]. In other studies, the same methods were applied for twenty-one methanolic extracts of seven parts of P. atlantica (leaf, fruit, stems, roots, buds, external and internal trunk barks) in the same region, the best antioxidant activity was registered at the leaves and buds, values of EC₅₀ for DPPH ranged from 0.052 to 5.712mg/ml, and 0.015 to 3.141mg/ml for FRAP, and in β-carotene method ranged from 0.068 to 5.021mg/ml³⁴. The ethyl acetate extract of P. atlantica leaves were collected monthly from April to October in two Algerian sites (Laghouat, Ain-oussera), the values of DPPH and FRAP assays varied between 262±18 and 675±25mg AAE/g DW, and 259±16 to 983mg AAE/g DW respectively³⁷. The essential oil (EO) of Algerian P. atlantica leaf and flower had significantly a good antioxidant potent on three assays: β-carotene-linoleic acid, ABTS, DPPH with values (17±0.3, 19.1±1.7 µg/ml), (4.7±0.2, 65±0.54µg/ml) and (23.9±0.3, 28±0.3 µg/ml) respectively²³. The antioxidant activity of ethanol, methanol, and water extracts of Iranian P. atlantica leaves on DPPH assay indicated that the aqueous phase had the highest scavenging DPPH with a value of 5.87mg/ml than other extracts⁴⁵. The DPPH scavenging activity assay on leaves P. atlantica (Iran) had exhibited an highest antioxidant effect with two fractions (Ethyl acetate: IC₅₀ = 1.54±0.12µg/ml, Chloroform: IC₅₀ = 3.4±0.11µg/ml) compared with a standard reference BHT (IC₅₀ = 33.5±3.67µg/ml)⁴⁶. The hydro-alcoholic extract of hulls P. atlantica had shown moderate antioxidant potent with IC₅₀ = 75µg/ml in DPPH method²⁶. The EO of P. atlantica (Saida, Algeria) appeared that the leaf had a high antioxidant power⁴⁷. The antioxidant activity of P. atlantica (Iran) kernel oil PAKO tested on FRAP, DPPH radical-scavenging. In DPPH radical-scavenging assay, the EC₅₀ values of PAKO were determined as 38.9 mg/ml, In the FRAP assay PAKO (364 mmol/l)⁴⁸. The essential oil of Iranian P. atlantica had shown a dose-dependent and scavenging activity in DPPH assay with a value of 48.64 ±0.84 % and ABTS with value 85.92±1.30% at concentration 4 mg/ml⁴⁹. The fruit of P. atlantica (Iraq) had shown that fruit exhibited a strong antioxidant effect than root extract (30.93 %, and 24.55 % respectively in the DPPH test)³⁸.The different extracts of P. atlantica leaves and stems were demonstrated a good antioxidant for DPPH and FRAP scavenging activity with values ranging from 0.99±0.12 to 9.41±0.08µg/ml, and 1.52±0.02 to 4.70±0.47µg/ml respectively¹⁰. Ethyl acetate leaves extract of P. atlantica (Libya)had shown an effect scavenging of DPPH with IC₅₀ value 8.41±0.24µg/ml⁴¹. The different extract of P. atlantica leaves and fruit (Mesaad, Algeria) had shown an exhibit antioxidant activity in DPPH assay, the best activity was registered in the crude and ethyl acetate extract of leaves with IC₅₀ values 0.0273±0.001, and 0.0419±0.001mg/ml respectively, in total antioxidant capacity and FRAP assay, the values varied between 21.572±0.05 to 2319,238±0.57mM, and 48.6±0.5 to 3652.285±1.91mM respectively, it was showed a high antioxidant activity in the different extract⁵⁰. P. atlantica (Morocco) had exhibited a good antioxidant effects on FRAP, DPPH assays registered in the butanolic and ethyl acetate with EC₅₀ = 0.02 and 0.03mg/ml, and IC₅₀ = 0.08 and 0.04mg/ml⁵¹. The hull`s EO of P. atlantica (Iran) had a potent antioxidant on FRAP, and DPPH tests with values 6.24mg/ml, and IC₅₀ =25.2mg/ml respectively²². The antioxidants activity (DPPH, ABTS, FRAP) of galls of P. atlantica (Algeria) had showed an antioxidant inhibitory activity⁵². The ethyl acetate of P. atlantica leaf had an antioxidant activity with IC₅₀ of 1.54±0.12mg/ml in DPPH assay⁵³. Roots of P. atlantica (Tunisia) had an antioxidant activity presented in DPPH with IC₅₀ of 246.84±13.79µg/ml, and in FRAP with IC₅₀ of 617.42±36µg/ml [12].

 

Antibacterial, antimicrobial and antiviral, antifungal effects:

The aqueous extract leaf of P. atlantica has been an effect inhibitory bacterial against two streptococcus species pathogens namely S. mutans, and S. mitis by using disc diffusion technique with inhibition zones of 19 mm and 25mm respectively for S. mutans, and S. mitis, the MIC and MBC values were 60 and 90 µg/ml for S. mutans, 75 and 110µg/ml for S. mitis⁵⁴. The essential oil of P. atlantica fruits against 6 bacterial pathogens had large antibacterial effects on two types of bacterial (gram-positive and gram-negative bacteria)^49. The P. atlantica gum essential oil extracted was investigated as an effective antibacterial against Porphyromonas gingivalis by using two-fold serial dilution methods³⁰. The ethanolic and aqueous extracts of P. atlantica aerial parts exhibited an antimicrobial effect against gram-negative bacteria (E. coli, S. typhimurium, A. hydrophila, P. aeruginosa) and gram-positive bacteria (S. aureus, L. monocytogenes, B. cereus)⁵⁵. The gum of P. atlantica has shown a strong antibacterial activity compared to common antibiotics⁵⁶. The effect of essential oils of P. atlantica fruits on antimicrobial properties of gelatin-carboxymethyl cellulose film had significantly inhibited the growth of E. coli, S. enteica, which the higher concentration of EO inhibited bacteria growth⁵⁷. The leaves extracts of P. atlantica showed an inhibitory effect against pathogenic microorganisms: S. aureus, B. subtilis, E. coli, P. aerogenasa; Candida albicans. The ethyl acetate extracts showed a sensitizing effect against S. aureus with a 20mm inhibition zone, while the methanolic extract an effect against B. subtilis with a 19.5 mm inhibition zone⁴¹. The ethanol (EE), methanol (ME), and water (AE) extracts of P. atlantica leaf were evaluated for their antimicrobial activity against six bacterial (three Gram-positive, three Gram-negative) and one yeast by using an assay for minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) using disc diffusion method. The results showed to be effective against the entire organism test with Gram-positive strains being more sensitive than Gram-negative strains. Also, the AE extract was the most effective against the examined bacteria, and yeast species, Among the examined microorganisms, Candida albicans and S. faecium were found to be the most sensitive and resistant, respectively⁴⁵. The antimicrobial activity of P. atlantica resin as an intracanal medicament in failed root canal on Enterococcus fecalis in extracting teeth was investigated by the minimal inhibitor concentration (MIC) of resin which it was 5x10-3mg/ml. conclude that the P. atlantica dose-dependently increased zone inhibition diameter while the colony-forming unit (CFU) of treated teeth with resin was significantly reduced⁵⁸. The EO of P. atlantica leaf was investigated for their antimicrobial effect against two bacterial strain of origin clinical, which it showed an inhibition zone against S. auereus with 8-12mm, and 12-14mm zone inhibition against C.albicans, and in the MIC of 52mg/ml, and 257 mg/ml respectively⁵⁹.

 

The P. atlantica gum has an antifungal effect against the growth of Aspergillus parasiticus with the minimum inhibitory concentration MIC at 125mg/ml⁶⁰.

 

Effect on memory:

On memory effect, the hydro-alcoholic extract of P. atlantica has been an effect to improve the memory by immolihibization stress of male rate at the spatial memory compared to fluvoxamine drug⁶¹.

 

Anti-diabetic and hypoglycemic effect:

Anti-diabetic effect of Pistacia atlantica has been reported⁶², the leaves of P. atlantica significantly have inhibitory activities against to α-amylase, and α-glucosidase (enzymes linked to type 2 diabetes)⁶³. The EO gum of P. atlantica on the expression of an antioxidant enzyme in diabetic rats (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) resulted that the EO could be an agent protective against diabetic diseases²⁴. The methanolic and lipid extracts from galls were shown inhibitory activity against the α-amylase enzyme⁵². The fruit extract of P. atlantica has been significantly effective administered orally, to histomorphological and blood glucose levels changes in the ovaries of the rats with streptozotocin-induced diabetes⁶⁴. The administration of essential oil (EO) and hydroalcoholic extract of P. atlantica in STZ-induced diabetic mice for 3 consecutive weeks showed a significantly important effect on hyperlipidemia, oxidative stress, and inflammatory response in diabetic mice⁶⁵.

 

Anti-cholinesterase effect:

In the different extracts of P.atlantica stem and leaves, the anti-cholinesterase activity against Butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes has been inhibited by the P.atlantica extracts in a dose-dependent manner, which the Ethyl acetate extract exhibited the highest inhibitory potent on AChE and BChE enzymes¹⁰. The aqueous and ethyl acetate extracts of P.atlantica leaf gave a good effect inhibitory of acetylcholinesterase (AChE)³⁵. The EO of P. atlantica flower and leaf have been shown a good anticholinesterase activity with IC₅₀ 20.5 mg/ml, and 18.5 mg/ml respectively²³.

 

Wound healing:

Wound healing is a process of the being inflammatory response, Pistacia atlantica has one of the useful and important medicinal plants used for wound healing treatment⁶⁶. the essential oil of P. atlantica has been reported as having significant a topical wound healing effect in rats⁶⁷. The effectiveness of the hydro-alcoholic extract of P. atlantica mastic on wound healing showed an appropriate effect by using a topical cream, the healing activity was evaluated by histological examination on day twenty-one⁶⁸. The EO extracted from the P. atlantica gum has been a good wound healing, histological was evaluated conducted on 15 Wistar rats on an experimental gel³⁰. To investigate the healing potential of EO of P. atlantica, the experimental study was evaluated by using 24 mice. Which was applied topically twice a day for twenty-one days, the process of wound healing was evaluated by using immunohistological and histological methods, which resulted in the EO extract being involved in the burn wound healing effect of NF⁶⁹. The wound healing activity of topical co-administration of hulls of P. atlantica hydro-ethanolic extract in streptozotocin-induced mice diabetic significantly indicated the beneficial effect on fuel-thickness wound healing activity⁷⁰. The EO extract of P. atlantica hulls was treated by oral mucositis in hamsters golden was demonstrated dose-dependent healing promotion in the groups receiving active gel⁷¹.

 

Anti-inflammatory effect:

The literature studies indicated that P. atlantica has a strong anti-inflammatory activity. The methanolic extract of P. atlantica leaves was determined by the reduction of carrageenan-induced hind paw edema in mice, which permitted a significant reduction of the edema at h3 and 6 in a dose-dependent manner of 100 and 250 mg/kg [36]. P. atlantica leaves hydroethanolic extract showed an effect anti-inflammatory⁷². The anti-inflammatory activity of P.atlantica leaf and fruit was evaluated by the inhibition of protein denaturation method (Bovine serum and egg albumin method), and the results showed a strong inhibition compared with a standard drug Diclofenac Sodium⁷³.

 

The anti-inflammatory activity of gum the P. atlantica on an experimental in BALB/c mice with asthma, the dose of the extract have a significant decrease in several BALF eosinophilic cells and levels of anti-ovalbumin IgE, and cytokine levels, which significantly increased in a dose-dependent manner compared to the un-treated asthma group⁷⁴. The hydro-alcoholic extract of P. atlantica leaf has been effective in the treatment of Oral mucositis (OM)⁷⁵. P. atlantica has been shown significantly anti-inflammatory in an animal model⁷⁶. The aqueous extract of P. atlantica aerial parts was exhibited a high analgesic effect in the writhing test and tail immersion, and have also an effect inhibitory on the rat paw edema induced by experimental trauma and carrageenin which showed a great anti-inflammatory activity (93.01%, and 88.99% in dose 200 mg/kg, and 400 mg/kg respectively)⁷⁷. By the granuloma method( the cotton pellet), the ethanolic and water extract of P. atlantica was tested for anti-inflammatory potent in the swiss albino rats; the extracts exhibited a significant dose-dependent activity compared with the indomethacin standard drug⁷⁸.

 

Anti-cancer and cytotoxicity effect:

The ethanolic extract of P. atlantica leaves significantly inhibited the proliferation of AGS and Hela, HDFs cells with IC₅₀ values of 382.3 µg/m, 332.3µg/m, and 896.3 µg/m respectively. This activity was evaluated by MTT assay 48 hours after treatment, which results that the P. atlantica can be suppressing the proliferation of gastric carcinoma and cervical cancer cells⁷⁹. The resin of P. atlantica sup. kurdica has significant cyto/genotoxic effects on noncancerous and cancerous cell lines⁸⁰. The aerial parts of P. atlantica extracts showed significant antiproliferative activity against HeLa cell lines, and the best antiproliferative activity was obtained for the methanol and EtOAc extracts¹⁰. The anti-proliferative effects of fruit extract on cancer cell lines were designed to evaluate the cytotoxic effects of P. atlantica fruit ethanolic extract on KB and human gingival fibroblast cell lines (HGF). The IC₅₀ after 24 and 48 hours of treatment were respectively 2.6 and 1 mg/mL for the KB cell line, and 1.5 and 1.6 mg/mL for the HGF cell. During 48 hours fruit extract induced apoptosis without significant necrosis, in a time- and dose-dependent manner⁸¹. The cytotoxicity of the gum extract of P. atlantica was treated by using an MTT assay on MCF-7 (human breast cancer cells), given that gum extract at 100 µg/ml significantly induced cell damage, increased P53 protein level, and activated caspase3, which induced that plant has been a potent modality to treat cancer⁸².

 

Toxicological effect:

In an acute toxicity study, the scolicial effects of the hydroalcoholic extracts of leaf and fruit of Pistacia atlantica on protoscolices of hydatid cyst were significant that had strong scolicial effects in 360 min, at a concentration of 1% (mg/ml). the mortality rate gives 99.09±1.27 for fruit and 92.5±6.6 for the leaf⁸³. The methanolic extract of P. atlantica fruits proved to be safe with no significant toxicity, its levels for LD₅₀ of the intraperitoneal injection was 2.43 g/kg and the maximum non-fatal dose was 1.66 g/kg²⁷. Another study results that the methanolic extract of the fruit gives the LD₅₀ value was 1.66 g/kg and the maximum non-fatal dose was 0.93g/kg, thus according to the toxicity classification of P.atlantica fruits extract had no significant toxicity against male NIH mice⁸⁴. The aqueous extract of the green seeds of P. atlantica was investigated in groups of Sprague-Dawley rats at oral doses of 200, 400, and 800 mg/kg body weight. After 14 days, there was no significant difference in behavior, which that indicating that aqueous P. atlantica seed extract causes some hepatoxicity and nephrotoxicity in rats⁸⁵.

 

CONCLUSIONS:

The focus of this review is to provide and highlight the ethnomedicinal uses, phytochemistry, and pharmacological activities of P. atlantica covering literature daring 2016 to 2021; traditionally different parts of P. atlantica have been employed in the treatment of various diseases like stomach diseases, pain, peptic ulcer, and inflammation in different geographical location.

 

Pharmacological, P. atlantica was reported to emphasize its antioxidants, antibacterial, antiviral, antidiabetic, toxicological effects, anticancer, wound healing, and anticholinesterase activities, the diverse uses of P. atlantica of its phytochemical and pharmacological properties indicated that have therapeutic potential. However, most pharmacological activities have been investigated in vitro rather than in vivo models, there is a need for clinical evaluation of crude extract and compounds isolated from P. atlantica using in vivo models, and especially isolated compounds in vitro and in vivo.

 

Phytochemical, in different parts of P. atlantica many classes of chemical compounds have been identified namely phenols, flavonoids, tannin, fatty acids, and volatile compounds. The over 50 phenolic compounds were identified and isolated, and very few isolated compounds (22 compounds). P. atlantica appears to be an important plant species for the isolation of bioactive metabolites with potential application in medicine as pharmaceutical drugs.

 

FUNDING:

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

 

CONFLICTS OF INTEREST:

The authors declare no conflict of interest is associated with this work.

 

REFERENCES:

1.      A. Rauf, S. Patel, G. Uddin, B.S. Siddiqui, B. Ahmad, N. Muhammad, Y.N. Mabkhot, T.B. Hadda, Phytochemical, ethnomedicinal uses and pharmacological profile of genus Pistacia, Biomedicine & Pharmacotherapy, 86 (2017) 393-404.

2.      F. Mahjoub, K.A. Rezayat, M. Yousefi, M. Mohebbi, R. Salari, Pistacia atlantica Desf. A review of its traditional uses, phytochemicals and pharmacology, Journal of medicine and life, 11 (2018) 180.

3.      Z.B. Ahmed, M. Yousfi, J. Viaene, B. Dejaegher, K. Demeyer, Y. Vander Heyden, Four Pistacia atlantica subspecies (atlantica, cabulica, kurdica and mutica): A review of their botany, ethnobotany, phytochemistry and pharmacology, Journal of Ethnopharmacology, (2020) 113329.

4.      E.Z.-B. Asma, Taxonomic and botanical retrospective review of Pistacia atlantica Desf.(Anacardiaceae), Arabian Journal of Medicinal and Aromatic Plants, 5 (2019) 47-77.

5.      A. Labdelli, R. De La Herrán, R. Arafeh, F. Resentini, L. Trainotti, Y. Halis, A. Adda, O. Merah, Genetic Variation in Damaged Populations of Pistacia atlantica Desf, Plants, 9 (2020) 1541.

6.      H. Rankou, S. M'SOU, R. Ait Babahmad, A. Ouhammou, M. Alifriqui, G. Martin, Pistacia atlantica, in, The IUCN Red List of Threatened Species, 2018.

7.      M. Amara, M. Bouazza, K. Errouane, M. Kaid-Harche, D. Nafil, R. Pascalau, L. Smuleac, M.G. Al-Saghir, Systematic Position of Pistacia atlantica Desf. Subsp. atlantica in North-West Algeria: Anatomy and Biometry of Leaves, Advanced Research in Life Sciences, 4 (2020) 48-53.

8.      A. El Zerey-Belaskri, H. Benhassaini, Morphological leaf variability in natural populations of Pistacia atlantica Desf. subsp. atlantica along climatic gradient: new features to update Pistacia atlantica subsp. atlantica key, International journal of biometeorology, 60 (2016) 577-589.

9.      A. El Zerey-Belaskri, T. Ribeiro, M.L. Alcaraz, W.E. Zerey, S. Castro, J. Loureiro, H. Benhassaini, J.I. Hormaza, Molecular characterization of Pistacia atlantica Desf. subsp. atlantica (Anacardiaceae) in Algeria: Genome size determination, chromosome count and genetic diversity analysis using SSR markers, Scientia Horticulturae, 227 (2018) 278-287.

10.    I. Achili, A. Amrani, C. Bensouici, F. Gül, M. Altun, I. Demirtas, D. Zama, F. Benayache, S. Benayache, Chemical constituents, antioxidant, anticholinesterase and antiproliferative effects of Algerian Pistacia atlantica Desf. extracts, Recent patents on food, nutrition & agriculture, 11 (2020) 249-256.

11.    M.D. Miara, I. Teixidor-Toneu, T. Sahnoun, H. Bendif, M.A. Hammou, Herbal remedies and traditional knowledge of the Tuareg community in the region of Illizi (Algerian Sahara), Journal of Arid Environments, 167 (2019) 65-73.

12.    M.B. Hmed, H. Alimi, F. Guesmi, F. Elatrech, N. Zouari, Y. Chtourou, R.B. Salem, G. Rigane, S. Cherif, Pistacia atlantica Desf. roots extract: LC-ESI-MS Analysis, antioxidant activity and gastroprotective effect on experimentally-induced ultrastructural gastric ulcers in mice, Ultrastructural Pathology, (2021) 1-10.

13.    H.S. Rahman, Phytochemical analysis and antioxidant and anticancer activities of mastic gum resin from Pistacia atlantica subspecies kurdica, OncoTargets and therapy, 11 (2018) 4559.

14.    P. Gharazi, S. Momtaz, Z. Rezaei, M. Rahimifard, M. Baeeri, A. Abdollahi, M. Abdollahi, K. Zare, M.H. Farzaei, Protective effect of a formulation containing Pistacia atlantica oleo-gum-resin and honey on experimental model of acetic acid-induced colitis in rats, Research Journal of Pharmacognosy, 8 (2021) 37-49.

15.    A. Labdelli, K. Zemour, V. Simon, M. Cerny, A. Adda, O. Merah, Pistacia atlantica Desf., a source of healthy vegetable oil, Applied Sciences, 9 (2019) 2552.

16.    A. Labdelli, A. Rebiai, M. Tahirine, A. Adda, O. Merah, Nutritional content and antioxidant capacity of the seed and the epicarp in different ecotypes of Pistacia atlantica desf. subsp. atlantica, Plants, 9 (2020) 1065.

17.    H.M. Ahmed, Traditional uses of Kurdish medicinal plant Pistacia atlantica subsp. kurdica Zohary in Ranya, Southern Kurdistan, Genetic Resources and Crop Evolution, 64 (2017) 1473-1484.

18.    G. Hajjaj, A. Bahlouli, K. Sayah, M. Tajani, Y. Cherrah, A. Zellou, Phytochemical screening and in vivo antipyretic activity of the aqueous extracts of three Moroccan medicinal plants, Pharm. Biol. Eval., 4 (2017) 188-192.

19.    M. Chelghoum, H. Guenane, M. Harrat, M. Yousfi, Total Tocopherols, Carotenoids, and Fatty Acids Content Variation of Pistacia atlantica from Different Organs’ Crude Oils and Their Antioxidant Activity during Development Stages, Chemistry & Biodiversity, 17 (2020) e2000117.

20.    M. Gharsallaoui, H. Azouzi, A. Chelli-Chaabouni, M. Ghrab, J. Condoret, M. Ayadi, S. Gabsi, Extraction methods of seed oil and oil quality of Pistacia atlantica grown in dry land, in: Options Méditerranéennes. Series A: Mediterranean Seminars, ENA, École Nationale d'Agriculture de Meknès (Morocco); CIHEAM-IAMZ …, 2016.

21.    T. Leila, M.E.A. Dib, B. Tabti, C. Jean, A. Muselli, Insecticidal Activity of Essential Oils of Pistacia atlantica Desf. and Pistacia lentiscus L. Against Tribolium confusum Dul, Journal of Applied Biotechnology Reports, 7 (2020) 111-115.

22.    S.-M. Hasheminya, J. Dehghannya, Composition, phenolic content, antioxidant and antimicrobial activity of Pistacia atlantica subsp. kurdica hulls’ essential oil, Food Bioscience, 34 (2020) 100510.

23.    I. Labed-Zouad, M. Ferhat, M. Öztürk, I. Abaza, S. Nadeem, A. Kabouche, Z. Kabouche, Essential Oils Composition, Anticholinesterase and Antioxidant Activities of Pistacia atlantica Desf, Rec Nat Prod, 11 (2017) 411-415.

24.    S. Bagheri, M.M. Sarabi, P. Khosravi, R.M. Khorramabadi, S. Veiskarami, H. Ahmadvand, M. Keshvari, Effects of Pistacia atlantica on oxidative stress markers and antioxidant enzymes expression in diabetic rats, Journal of the American College of Nutrition, 38 (2019) 267-274.

25.    A. Sadeghi, M. Pourya, G. Smagghe, Insecticidal activity and composition of essential oils from Pistacia atlantica subsp. kurdica against the model and stored product pest beetle Tribolium castaneum, Phytoparasitica, 44 (2016) 601-607.

26.    S.M. Nachvak, S. Hosseini, A. Nili-Ahmadabadi, D. Dastan, M. Rezaei, Chemical composition and antioxidant activity of Pistacia atlantica subsp. Kurdica from Awraman, Journal of Reports in Pharmaceutical Sciences, 7 (2018) 222-230.

27.    H. Mahmoudvand, F. Kheirandish, M. Ghasemi Kia, A. Tavakoli Kareshk, M. Yarahmadi, Chemical composition, protoscolicidal effects and acute toxicity of Pistacia atlantica Desf. fruit extract, Natural product research, 30 (2016) 1208-1211.

28.    N. Yarahmadi, M. Hojjatoleslamy, L. Sedaghat Boroujeni, Different drying methods of Pistacia Atlantica seeds: Impact on drying kinetics and selected quality properties, Food Science & Nutrition, 8 (2020) 3225-3233.

29.    A. El Zerey-Belaskri, C. Cavaleiro, A. Romane, H. Benhassaini, L. Salgueiro, Intraspecific chemical variability of Pistacia atlantica Desf. subsp. atlantica essential oil from Northwest Algeria, Journal of EssEntial oil rEsEarch, 29 (2017) 32-41.

30.    S.H. Azeez, S.M. Gaphor, Evaluation of antibacterial effect against Porphyromonas gingivalis and biocompatibility of essential oil extracted from the gum of Pistacia atlantica kurdica, BioMed research international, 2019 (2019).

31.    Z. Memariani, M. Sharifzadeh, M. Bozorgi, M. Hajimahmoodi, M.H. Farzaei, M. Gholami, F. Siavoshi, P. Saniee, Protective effect of essential oil of Pistacia atlantica Desf. On peptic ulcer: role of α-pinene, Journal of Traditional Chinese Medicine, 37 (2017) 57-63.

32.    M. Rezaie, R. Farhoosh, N. Pham, R.J. Quinn, M. Iranshahi, Dereplication of antioxidant compounds in Bene (Pistacia atlantica subsp. mutica) hull using a multiplex approach of HPLC–DAD, LC–MS and 1H NMR techniques, Journal of pharmaceutical and biomedical analysis, 117 (2016) 352-362.

33.    F. Khallouki, A. Breuer, E. Merieme, C.M. Ulrich, R.W. Owen, Characterization and quantitation of the polyphenolic compounds detected in methanol extracts of Pistacia atlantica Desf. fruits from the Guelmim region of Morocco, Journal of pharmaceutical and biomedical analysis, 134 (2017) 310-318.

34.    F. Toul, N. Belyagoubi-Benhammou, A. Zitouni, F. Atik-Bekkara, Antioxidant activity and phenolic profile of different organs of Pistacia atlantica Desf. subsp. atlantica from Algeria, Natural product research, 31 (2017) 718-723.

35.    H. Benamar, A. Marouf, M. Bennaceur, Phytochemical composition, antioxidant and acetylcholinesterase inhibitory activities of aqueous extract and fractions of Pistacia atlantica subsp. atlantica from Algeria, Journal of Herbs, Spices & Medicinal Plants, 24 (2018) 229-244.

36.    O. Amri, A. Zekhnini, A. Bouhaimi, S. Tahrouch, A. Hatimi, Anti-inflammatory activity of methanolic extract from Pistacia atlantica desf. leaves, Pharmacognosy Journal, 10 (2018).

37.    Z. Ben Ahmed, M. Yousfi, J. Viaene, B. Dejaegher, K. Demeyer, D. Mangelings, Y. Vander Heyden, Seasonal, gender and regional variations in total phenolic, flavonoid, and condensed tannins contents and in antioxidant properties from Pistacia atlantica ssp. leaves, Pharmaceutical biology, 55 (2017) 1185-1194.

38.    N. Tahir, J. Ahmed, H. Azeez, W. Palani, D. Omer, Phytochemical, antibacterial, antioxidant and phytotoxicity screening of the extracts collected from the fruit and root of wild mt. Atlas mastic tree (Pistacia atlantica subsp. Kurdica), Applied ecology and environmental research, 17 (2019) 4417-4429.

39.    H. Kordbacheh, F. Eftekhar, S. Ebrahimi, Anti-quorum sensing activity of Pistacia atlantica against Pseudomonas aeruginosa PAO1 and identification of its bioactive compounds, Microbial pathogenesis, 110 (2017) 390-398.

40.    S.A.A. Hussein, A. El-Mesallamy, S.O. Othman, A.e.-M.M. Soliman, Identification of Novel Polyphenolic Secondary Metabolites from Pistacia Atlantica Desf. and Demonstration of their Cytotoxicity and CCl4 induced Hepatotoxicity in Rat, Egyptian Journal of Chemistry, 63 (2020) 117-127.

41.    S. Othman, M. El-Hashash, S. Hussein, A. El-Mesallamy, S. Rizk, F.A. Elabbar, Phenolic Content as Antioxidant and Antimicrobial Activities of Pistacia atlantica Desf.(Anacardiaceae) Extract from Libya, Egyptian Journal of Chemistry, 62 (2019) 21-28.

42.    Z.B. Ahmed, M. Yousfi, J. Viaene, B. Dejaegher, K. Demeyer, D. Mangelings, Y. Vander Heyden, Antioxidant activities of Pistacia atlantica extracts modeled as a function of chromatographic fingerprints in order to identify antioxidant markers, Microchemical journal, 128 (2016) 208-217.

43.    A.A. Hatamnia, A. Rostamzad, M. Hosseini, N. Abbaspour, R. Darvishzadeh, P. Malekzadeh, B.M. Aminzadeh, Antioxidant capacity and phenolic composition of leaves from 10 Bene (Pistacia atlantica subsp. kurdica) genotypes, Natural product research, 30 (2016) 600-604.

44.    F. Toul, N. Belyagoubi-Benhammou, A. Zitouni, N. Ghembaza, F. Atik-Bekkara, T.A. Imama, IN-VITRO ANTIOXIDANT EFFECTS OF TANNIN EXTRACTS OF PISTACIA ATLANTICA, International Journal of Pharmaceutical Sciences and Research, 7 (2016) 121.

45.    H. Barzegar, M. Hojjati, M. Panahi, Antioxidant and antimicrobial activity of different extracts of Pistacia atlantica leaf, (2017).

46.    S. Alidadi, M.-T. Moradi, M. Asadi-Samani, Z. Lorigooini, Antioxidant potential and total phenolic compounds of extracts and fractions of Pistasia atlantica, Int J Pharm Clin Res, 9 (2017) 293-297.

47.    A. Fatima, T. Mohamed, A. Abdelkader, T.A. Faiza, Phytochemical screening and evaluation of the antioxidant activity of essential oil of Pistacia atlantica harvested from the ouled Brahim region, Saida; Algeria, South Asian Journal of Experimental Biology, 8 (2018) 202-206.

48.    J. Tavakoli, K.H. Soq, A. Yousefi, P. Estakhr, M. Dalvi, A.M. Khaneghah, Antioxidant activity of Pistacia atlantica var mutica kernel oil and it’s unsaponifiable matters, Journal of food science and technology, 56 (2019) 5336-5345.

49.    M. Fathollahi, M. Aminzare, M. Mohseni, H. Hassanzadazar, Antioxidant capacity, antimicrobial activities and chemical composition of Pistacia atlantica subsp. kurdica essential oil, in: Veterinary Research Forum, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran, 2019, pp. 299.

50.    C. Bakka, M. Hadjadj, O. Smara, H. Dendougui, S. Mahdjar, In vitro antioxidant activities and total phenolic content of extracts from Pistacia atlantica desf, Journal of Pharmaceutical Sciences and Research, 11 (2019) 3634-3637.

51.    Z. Khiya, Y. Oualcadi, A. Gamar, S. Amalich, F. Berrekhis, T. Zair, F.E. Hilali, In vitro Evaluation of Antioxidant Activity of the Methanol and Ethanol Extracts of Pistacia atlantica Desf from Morocco, Phytothérapie, 17 (2019) 321-333.

52.    F. Hefied, Z. Ben Ahmed, M. Yousfi, In vitro antioxidant and α‐amylase inhibitory potential of methanolic and lipid fractions from Pistacia atlantica Desf. galls, Journal of Food Processing and Preservation, (2020) e14956.

53.    A. Karimi, M.T. Moradi, A. Gafourian, In vitro anti-adenovirus activity and antioxidant potential of Pistacia atlantica Desf. leaves, Research Journal of Pharmacognosy (RJP), 7 (2020).

54.    M.A. Roozegar, F.A. Jalilian, M.R. Havasian, J. Panahi, I. Pakzad, Antimicrobial effect of Pistacia atlantica leaf extract, Bioinformation, 12 (2016) 19.

55.    G. Rigane, H. Ghazghazi, C. Aouadhi, R. Ben Salem, Z. Nasr, Phenolic content, antioxidant capacity and antimicrobial activity of leaf extracts from Pistacia atlantica, Natural product research, 31 (2017) 696-699.

56.    B. Doosti, The comparison of antibacterial and antifungal effects of Pistacia atlantica gum with some inuse antibiotics, Journal of Cellular and Molecular Research (Iranian Journal of Biology), 32 (2019) 115-124.

57.    M. Ranjbar, M.H. Azizi, A. Mirmajidi Hashtjin, Evaluation of physico-mechanical and antimicrobial properties of gelatin-carboxymethyl cellulose film containing essential oil of bane (Pistacia atlantica), Nutrition and Food Sciences Research, 4 (2017) 11-17.

58.    A.H. Barzinji, K. Dzaye, Antimicrobial Effect of Pistacia Atlantica Kurdica as an Intra Canal Medicament in Root Canal Treatment on Enterococcus Fecalis, Annals of the Romanian Society for Cell Biology, (2021) 8485-8492.

59.    F. Benabdallah, M. El Bentchikou, A. Zellagui, N. Gherraf, Ethnobotanical and phytochemical studies and assessment of antimicrobial activity of the leaves of pistachio oleoresin of the atlas (Pistacia atlantica Desf.), Phytothé rapie, (2017).

60.    F. AAla, S. Khodaveisi, E. Baghdadi, S. Rezaei, The antifungal effect of Pistacia Atlantica subsp. Kurdica on the growth of Aspergillus parasiticus, Journal of School of Public Health and Institute of Public Health Research, 13 (2016) 79-84.

61.    M. Mohammadzadeh, F. Babaeifar, F. Babaei, Combination thrapy of hydroalcoholic extract of Pistacia atlantica kurdica and fluvoxamine on spatial memory of immobilization rat, Journal of Gorgan University of Medical Sciences, 19 (2017) 24-31.

62.    A. Aleebrahim, I. Nabipour, Ethnopharmacology of Medicinal Plants in the Kangan-Asaluyeh Area, ISMJ, 21 (2018) 409-428.

63.    Z.B. Ahmed, M. Yousfi, J. Viaene, B. Dejaegher, K. Demeyer, D. Mangelings, Y. Vander Heyden, Potentially antidiabetic and antihypertensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting, Journal of pharmaceutical and biomedical analysis, 149 (2018) 547-556.

64.    M.A. Behmanesh, S.M. Poormoosavi, Pistacia atlantica's effect on ovary damage and oxidative stress in streptozotocin-induced diabetic rats, JBRA assisted reproduction, 25 (2021) 28.

65.    S. Hosseini, A. Nili-Ahmadabadi, S.M. Nachvak, D. Dastan, S. Moradi, H. Abdollahzad, R. Mostafai, Antihyperlipidemic and antioxidative properties of pistacia atlantica subsp. Kurdica in streptozotocin-induced diabetic mice, Diabetes, metabolic syndrome and obesity: targets and therapy, 13 (2020) 1231.

66.    K. Solati, M. Karimi, M. Rafieian-Kopaei, N. Abbasi, S. Abbaszadeh, M. Bahmani, Phytotherapy for wound healing: The most important herbal plants in wound healing based on iranian ethnobotanical documents, Mini reviews in medicinal chemistry, 21 (2021) 500-519.

67.    S.A. Hamidi, A.T. Naeini, A. Oryan, M.R. Tabandeh, N. Tanideh, S. Nazifi, Cutaneous wound healing after topical application of pistacia atlantica gel formulation in rats, Turkish Journal of Pharmaceutical Sciences, 14 (2017) 65.

68.    S. Fakour, S. Heydari, L. Akradi, A. Rahimi, Effect of Pistacia atlantica mastic extract on experimental wound healing and various biochemical parameters of blood serum in rabbit models, فصلنامه علمی پژوهشی گیاهان دارویی, 16 (2017) 78-91.

69.    M. Mehrabani, S.M. Seyyedkazemi, M.H. Nematollahi, E. Jafari, M. Mehrabani, M. Mehdipour, Z. Sheikhshoaee, A. Mandegary, Accelerated burn wound closure in mice with a new formula based on traditional medicine, Iranian Red Crescent Medical Journal, 18 (2016).

70.    F.S. Bonab, M.R. Farahpour, Topical co-administration of Pistacia atlantica hull and Quercus infectoria gall hydroethanolic extract improves wound-healing process, Comparative Clinical Pathology, 26 (2017) 885-892.

71.    N. Tanideh, M. Davarmanesh, A. Andisheh‐Tadbir, Z. Ranjbar, P. Mehriar, O. Koohi‐Hosseinabadi, Healing acceleration of oral mucositis induced by 5‐fluorouracil with Pistacia atlantica (bene) essential oil in hamsters, Journal of Oral Pathology & Medicine, 46 (2017) 725-730.

72.    E. Heidarian, E. Jafari-Dehkordi, P. Valipour, K. Ghatreh-Samani, L. Ashrafi-Eshkaftaki, Nephroprotective and anti-inflammatory effects of Pistacia atlantica leaf hydroethanolic extract against gentamicin-induced nephrotoxicity in rats, Journal of dietary supplements, 14 (2017) 489-502.

73.    C. Bakka, O. Smara, M. Hadjadj, H. Dendougui, S. Mahdjar, A. Benzid, In vitro Anti-inflammatory activity of Pistacia atlantica Desf. extracts, Asian Journal of Research in Chemistry, 12 (2019) 322-325.

74.    Z. Shakarami, H.E.G. Ghaleh, B.M. Motlagh, A. Sheikhian, B.J. Kondori, Evaluation of the protective and therapeutic effects of Pistacia atlantica gum aqueous extract on cellular and pathological aspects of experimental asthma in Balb/c mice, Avicenna journal of phytomedicine, 9 (2019) 248.

75.    N. Tanideh, A.A. Zareh, M.M. Fani, Evaluation of the Effect of a Topical Gel Form of Pistacia Atlantica and Trachyspermum Ammi on Induced Oral Mucositis in Male Golden Hamsters by Bio-Marker Indices and Stereological Assessment, Journal of Dentistry, 20 (2019) 240.

76.    M. Minaiyan, F. Karimi, A. Ghannadi, Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat, Research Journal of Pharmacognosy, 2 (2015) 1-12.

77.    G. Hajjaj, A. Bahlouli, M. Tajani, Y. Cherrah, A. Zellou, In vivo analgesic and anti-inflammatory properties of the aqueous extract of Pistacia atlantica Desf. from Morocco, Journal of Ayurvedic and Herbal Medicine, 3 (2017) 196-199.

78.    D. Pranitha, M.R. Ch, Inflammation lowering property of pistacia atlantica in cotton pellet granuloma, International Journal of Review in Life Sciences, 9 (2019) 14-17.

79.    L. Hashemi, M. Asadi-Samani, M.-T. Moradi, S. Alidadi, Anticancer activity and phenolic compounds of Pistacia atlantica extract, International Journal of Pharmaceutical and Phytopharmacological Research, 7 (2017) 26-31.

80.    Y. Rahbar Saadat, A. Barzegari, S. Zununi Vahed, N. Saeedi, M. Eskandani, Y. Omidi, J. Barar, Cyto/genotoxic effects of Pistacia atlantica resin, a traditional gum, DNA and cell biology, 35 (2016) 261-266.

81.    Z. Jaafari-Ashkvandi, S.Y. Shirazi, S. Rezaeifard, A. Hamedi, N. Erfani, Cytotoxic effects of Pistacia atlantica (Baneh) fruit extract on human KB cancer cell line, ACTA MEDICA, 62 (2019) 30-34.

82.    H. Pasban-Aliabadi, Effects of Baneh (Pistacia atlantica) Gum on Human Breast Cancer Cell Line (MCF-7) and Its Interaction with Anticancer Drug Doxorubicin, Iranian journal of pharmaceutical research: IJPR, 18 (2019) 1959.

83.    M. Zibaei, R. Rostamipour, H. Nayebzadeh, Effect of Pistacia atlantica fruit and leaf extracts on hydatid cyst protoscolices, Recent patents on anti-infective drug discovery, 11 (2016) 53-58.

84.    S. Nadri, H. Mahmoudvand, H. Mahmoudvand, M. Rashnoo, M. Khaksarian, Chemical composition, antinociceptive and acute toxicity of Pistacia atlantica fruit extract, Entomol Appl Sci Letters, 5 (2018) 8-12.

85.    H.O. Dyary, H.S. Rahman, H.H. Othman, S.M.A. Hassan, R. Abdullah, Acute toxicity of Pistacia atlantica green seeds on Sprague-Dawley rat model, J Zankoy Sulaimani, 19 (2017) 9-16.

 

 

 

Received on 19.07.2022                    Modified on 12.08.2022

Accepted on 10.09.2022                   ©AJRC All right reserved