Pharmacology and phytochemistry of the Nitraria genus (Review)

  • Authors:
    • Qiaohui Du
    • Hailiang Xin
    • Cheng Peng
  • View Affiliations

  • Published online on: October 16, 2014
  • Pages: 11-20
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Plants from the Nitraria genus, members of the Zygophyllaceae family, grow naturally in Europe, Africa, Australia and the central Asian desert. Previous pharmacological research has provided evidence that members of the Nitraria genus have numerous beneficial effects. In the present review, the pharmacological and phytochemical studies of Nitraria were presented and assessed. The review was written using information published between 1968 and 2013 from a number of reliable sources, including ScienceDirect, Springer, PubMed, EMBASE and CNKI. Numerous compounds, such as alkaloids and flavonoids have been isolated from the plants of this genus in the past, and multiple members of these constituents have been demonstrated to exert antitumor or anti‑oxidative activities. The extracts of plants of the Nitraria genus possess antitumor, antiproliferative, anti‑oxidative, antifatigue, anti‑mutagenic, antimicrobial, hypotensive, hepatoprotective, lipid‑lowering and hypoglycemic effects. However, the possible active components in the fraction and the molecular mechanisms require further investigation prior to their use in clinical practice.

1. Introduction

The Nitraria genus, a member of the family Zygophyllaceae, is one of the dominant species in the Mediterranean and central Asian deserts. The English name Nitre-bush is from the Latin word saltpetre, referring to the fact that it can thrive in saline soil. It serves an key ecological role due to its superior tolerance to severe drought and high salinity. Nitraria are shrubs 25–200-cm tall, with spiny branches at the apex and simple serrated leaves. The flowers are yellowish-gray or white, 2–4 cm pubescent, with five petals and five sepals, while the fruit is a fleshy drupe. The Nitraria genus consists of 13 species across the world, which are mainly distributed in Asia, Europe, Africa and Australia (Table I).

Table I

Species of the Nitraria genus and the geographical distribution.

Table I

Species of the Nitraria genus and the geographical distribution.

No.SpeciesGeographical distribution
1N. schoberiChina, Europe
2N. sibiricaChina, Siberia
3N. senegalensisAfrica
4N. billardieriAustraria
5N. retusaMediterranean coast
6N. sphaerocarpaNorthwest China
7N. roborowskiiNorthwest China, Russia
8N. komaroviiEurope caspian coast
9N. tangutorumNorthwest China
10N. praevisaNorthwest China
11N. pamiricaChina
12N. sinensisChina
13N. tridentateAfrica

A growing body of evidence now demonstrates that Nitraria extract has numerous biomedical properties, including antifatigue, antitumor, anti-oxidative and antimutagenic activities. In addition, the fruit of Nitraria sibirica is extensively used to treat hypertension, menstrual disorders and gastroenteritis in folklore medicines of Northwest China (1,2). The leaves of Nitraria retusa also serve as supplement tea and are used as a poultice in Africa (3,4).

To provide further support and evidence for the clinical use of this genus, a systematic review of the modern phytochemical and pharmacological properties of Nitraria was performed. The available information on the pharmacology and phytochemistry of the Nitraria genus was collected via libraries and electronic searches using PubMed (, ScienceDirect (, Springer (, EMBASE ( and CNKI (

2. Phytochemical studies

Currently, the following six species of the Nitraria genus have been observed for their phytochemical properties: N. komarovii, N. schoberi, N. sibirica, N. tangutorum, N. retusa and N. billardieri. These investigations suggested that members of the Nitraria genus contain numerous components categorized as alkaloids, flavonoids and phenolic acid, of which alkaloids and flavonoids are the most abundant constituents. An overview of ingredients contained in the Nitraria genus is presented in Table II.

Table II

Compounds isolated from the Nitraria genus.

Table II

Compounds isolated from the Nitraria genus.

A, Alkaloid compounds

No.CompoundSpeciesPart of plantReference
1NitraricineN. komaroviiEpigeal5
2NitrarizineN. komaroviiEpigeal5
3IsokomarovineN. komaroviiEpigeal6
4KomarovidinineN. komaroviiEpigeal6
5KomarovinineN. komaroviiEpigeal7
6Peganine N-oxideN. komaroviiEpigeal8
7 NallylschoberineN. komaroviiEpigeal8
8 DehydronitramidineN. komaroviiEpigeal8
9KomavicineN. komaroviiiEpigeal9
10DeoxypeganineN. komaroviiEpigeal10
11NitraramineN. schoberi/N. komaroviiEpigeal11
12KomarovineN. komaroviiEpigeal12
13KomarovidineN. komaroviiEpigeal12
14KomaroineN. komaroviiEpigeal13
15NitraraineN. schoberiEpigeal14
16NitrabirineN. sibiricaEpigeal14
17NitramineN. sibiricaEpigeal15
18IsonitramineN. sibiricaEpigeal16
19SibirineN. sibiricaEpigeal17
20Vasicinone N-oxideN. komaroviiEpigeal18
21Deoxyvasicinone N-oxideN. komaroviiEpigeal18
22 DihydronitraraineN. komaroviiEpigeal19
23 DeoxyvasicinoneN. komaroviiEpigeal20
24VasicinoneN. komaroviiEpigeal20
25PeganineN. komaroviiEpigeal20
26DeoxypeganineN. komaroviiEpigeal20
27 DehydroschoberineN. komaroviiEpigeal20
28NitraroxineN. komaroviiEpigeal20
29TryptamineN. komaroviiEpigeal20
30SchoberineN. komaroviiEpigeal20
31SchoberidineN. komaroviiEpigeal21
32NitrarineN. schoberiEpigeal22
33 Tetramethylenetetrahydro-β-carboline N-oxideN. komaroviiEpigeal23
34SibirinineN. sibiricaEpigeal24
35 DihydroschoberineN. sibiricaAerial25
36Nitrabirine N-oxideN. sibiricaAerial25
37 O-acetylnitraraineN. schoberiAerial26
38 N-methylnitrarineN. schoberiAerial27
39KomavineN. komaroviiAerial28
40AcetylkomavineN. komaroviiAerial28
41 N-allylnitrarineN. komaroviiAerial29
42Komarovidinine N-oxideN. komaroviiAerial29
43SibiridineN. sibirica/N. schoberiAerial30
44NitraramidineN. sibiricaAerial31
45NitraraidineN. sibiricaAerial31
46KomarinN. komaroviiAerial32
47Peganol N-oxideN. komaroviiAerial32
48 N-allylisonitrarineN. schoberiAerial33
49NitraridineN. komaroviiAerial34
50 DihydronitraridineN. komaroviiAerial34
51 TetrahydronitraridineN. KomaroviiAerial34
52SchobericineN. SchoberiAerial35
53KomaroidineN. Komarovii/N. SchoberiAerial35
54 AcetylkomaroidineN. Komarovii/N. SchoberiAerial35
55 TetrahydronitramarineN. Komarovii.Epigeal36
56 TetrahydrokomarovinineN. KomaroviiEpigeal36
57 DihydroisokomarovineN. KomaroviiEpigeal36
58 TetrahydroisokomarovineN. KomaroviiEpigeal36
59NazlininN. SchoberiEpigeal39
60TangutorineN. TangutorumLeaves40
61NitrarineN. BillardieriAerial41
62 1-EpinitraramineN. BillardieriAerial41
633-EpinitrarineN. BillardieriAerial41
64 5,7-Dihydroxy-3-deoxy-vasicineN. RetusaAerial42
65 7-Hydroxy-3-deoxy-1-vasicieneN. RetusaAerial42
66AllantoinN. TangutorumSeed48

B, Flavanoid compounds

No.CompoundSpeciesPart of plantReference

67NarcissinN. KomaroviiLeaves28
68RutinN. RetusaLeaves and stems43
69KaempferolN. RetusaLeaves and stems43
70Isorhamnetin 3-O-4rham-galactosylrobinobiosideN. RetusaLeaves and stems44
71Isorhamnetin 3-robinobiosideN. RetusaLeaves and stems44
72Isorhamnetin 3-rutinosideN. RetusaLeaves and stems44
73Isorhamnetin 3-galactosideN. RetusaLeaves and stems44
74Isorhamnetin 3-glucosideN. RetusaLeaves and stems44
75IsorhamnetinN. RetusaLeaves and stems44
76Isorhamnetin 3-xylosylrobinobiosideN. RetusaLeaves and stems44
77 Isorhamnetin-7-O-α-L-rhamnosideN. TangutorumSeeds45
78 Isorhamnetin-7-O-β-D-glucosideN. TangutorumSeeds45
79 Kaempferol-7-O-α-L-rhamnosideN. TangutorumSeeds45
80 Quercetin-7-O-α-L-rhamnosideN. TangutorumSeeds45
81QuercetinN. TangutorumSeeds45
82 3,5-Dimethylether-kaempfrol-7-O-β-D-glucosideN. TangutorumLeaf46
83 3-Methylether-kaempferol-7-O-β-D-glucosideN. TangutorumLeaf46
84 Isorhamnetin-3-O-β-D-glucopyranosyl-(1–2)-α-L-rhamnopyranosideN. TangutorumFruit47
85 5,7,2′-TrihydroxyflavonolN. TangutorumFruit47
86Cyaniding 3-[6′-(6-trans-p-coumaroyl-β-D-glucopyranosyl)-β-D-galactopyranoside]N. TangutorumFruit47
87Apigenin 5-O-(2′-O-E-P-coumaroyl)-β-D-glucopyranosideN. TangutorumFruit47

Numerous studies (536) have been conducted to explore the alkaloids contained in the members of the Nitraria genus. Nearly all known alkaloids (Table II, nos. 1–36) identified in plants of the Nitraria genus were initially isolated in these studies. These studies also observed that the content of alkaloids in the leaves is higher than the content in the roots, stems and seeds of Nitraria komarovii and Nitraria sibirica (3738). There are also various types of alkaloids that have been isolated and purified in other studies. In the crude MeOH extracts of N. rhoberi, nazlinin was purified by Üstunes et al (39). In a proceeding study, tangutorine was isolated from the leaves of N. tangutorum (40). Three novel alkaloids, 3-epinitrarine, 1-epinitraramine and nitrarine (41) were identified in N. billardieri, which is a species that is mainly distributed in Australia. Phytochemical studies of the aerial sections of N. retusa reported the novel alkaloids 5,7-dihydroxy-3-deoxy vasicine and 7-hydroxy-3-deoxy-1-vasiciene (42) (Fig. 1). Nitraria was also reported by Saleh et al (43) to contain the flavonoids rutin, kaempferol and isorhamnetin. The flavonoids isolated in other studies are listed in Table II, nos. 67–87 (4448) (Fig. 2).

Wang et al (49) determined fatty acids in N. tangutorum seed by supercritical carbon dioxide extraction and high-performance liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry. Using gas chromatograph-mass spectrometry, numerous volatile substances were detected in the extract of the stem, leaves and fruits of N. tangutorum and N. sibirica (5052). Additionally, Wu et al (53) isolated phenolic acid from the water extraction of N. tangutorum.

3. Pharmacological effects

Antifatigue activity

The antifatigue activity of polysaccharides from the fruits of N. tangutorum was assessed in mice using the forced swim test (FST). The results demonstrated that the FST-induced reductions in glucose, superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the increases in creatine phosphokinase, lactic dehydrogenase, blood urea nitrogen, triglyceride (TG) and malondialdehyde (MDA) levels, were inhibited by the polysaccharides from N. tangutorum. Additionally, at the same dosage, the extract of N. tangutorum is more potent than Hippophae rhamnoides and Lycium ruthenicum, which are traditionally used as medicinal foods with antifatigue and antioxidant potential in Tibet (54). Fruit extracts of N. tangutorum markedly prolonged the swimming time, climbing time and survival time in low temperature of mice compared with the control group in a study by Suo et al (55). The seed oil of N. tangutorum, when extracted by supercritical CO2, displayed similar effects as the fruit, and upregulated the contents of serum urea-nitrogen and hepatic glycogen, but downregulated the serum lactic acid contents, consequently improving the swimming and climbing time. This result has been repeated in other studies (56,57).

Antitumor activity

Boubaker et al investigated the apoptotic potential of N. retusa ethyl acetate (EA) extract and isorhamnetin 3-O-rutinoside (I3-O-R) isolated from the ethyl acetate extract, in K562 human chronic myelogenous erythroleukemia cells. After 48 h incubation with N. retusa extract and I3-O-R, K562 cell viability was significantly suppressed by inducing apoptosis, and the caspase 3 and caspase 8 activity was increased (58). The extract and the component inhibited the genotoxicity induced by hydroxyl radicals in K562 cells (59). Another similar study indicated that EA extract of N. retusa and I3-O-R have a strong antiproliferative effect on TK6 human lymphoblastoid cells, possibly due to their involvement in the apoptotic pathway (60).

The hexane (Hex), chloroform (Chl) and methanol (MeOH) extracts of N. retusa were utilized to test their antiproliferative effects on K562 cells. The Hex and Chl extracts were demonstrated to induce stronger antiproliferative effects than the MeOH extracts, by ameliorating the DNA fragmentation, poly ADPribose polymerase cleavage, and caspase 3 and caspase 8 activity (61). In another study, 3H-thymidine incorporation-induced proliferation of the HT29 human colon cancer cells was reduced in a dose-dependent manner following treatment with tangutorine, a β-carboline alkaloid from the leaves of N. tangutorum. Tangutorine may induce p21 suppression of all cyclins and their associated kinases, such as the topoisomerase II, and thus inhibit normal DNA replication and mitosis (62). The activities of fractions/extracts of N. retusa were compared with their flavanoid contents, which consisted of the following four major flavonoids: Isorhamnetin; isorhamnetin-3-O-glucoside (I3-O-G); I3-O-R; and isorhamnetin-3-O-robinobioside (I3-O-Rb). They inhibited the proliferation of Caco-2 cells in vitro (63).

The total flavones from the N. tangutorum fruits repress proliferation of the SGC-7901 human gastric adenocarcinoma cell line and A-704 human kidney adenocarcinoma cell line by regulating the levels of Ca2+, K+ and P3+ in the cell (6465). The in vivo experiment demonstrated that flavones, in addition to the aqueous extract of N. tangutorum, combined with 5-fluorouracil, induced a significantly increased inhibitory rate in the Hep human throat cancer cell line and U14 human cervical cancer cell line by regulating the weight of immune organs, the formation value of serolysin and phagocytic index (6667). Additionally, the lipids of N. tangutorum were cytotoxic against the MGC-803 human gastric carcinoma cell line (68).

Antioxidant activity

EA extract of N. retusa and I3-O-R indicated a protective effect against lipid peroxidation induced by H2O2. It demonstrated significant antioxidant effects on oxidation induced by 2,2′-azobis (2-amidinopropane) dihydrochloride in K562 cells with 50% inhibitory concentration values (IC50) of 0.225 mg/ml and 0.31 mg/ml (59). Sterols, the main constituents of Hex extract, and sterol and polyphenolic compounds, the main constituents of Chl extract, may participate in the protective effect against lipid peroxidation induced by H2O2 in K562 cells (61). Chl extract exhibited the highest ability to protect plasmid DNA against hydroxyl radical-induced DNA damage, and the highest antioxidant capacity, with 0.95 mM trolox equivalent capacity when tested using the ferric reducing/antioxidant method (69). Furthermore, the extract of fruits from N. tangutorum displayed a significantly different antioxidant activity when assessed with the 1,1-diphenyl-2-picrylhydrazy (DPPH), 2,2′-Azinobis (3-ethylbenzothiaz-oline-6-sulfonate) (ABTS) and ferric-reducing antioxidant power assays (70).

The DPPH scavenging activity, xanthine oxidase inhibition and superoxide scavenging activity of various N. retusa extracts and compounds, including isorhamnetin, I3-O-G, I3-O-R and I3-O-Rb, were evaluated to confirm the association between the activities of the fractions and their flavonoid contents. The EA extracts were identified to be most effective at scavenging the DPPH stable free radical, and the CHCl3 extracts exhibited the highest xanthine oxidase inhibition activity; however, only BuOH extract exhibited a scavenging activity toward superoxide radicals. Overall, all the compounds exhibited some level of DPPH and superoxide scavenging and xanthine oxidase inhibition activity, and the aglycone compounds were more active than their glycosylated derivatives (63). Antiradical activities against DPPH, and β-carotene and Fe-reducing power were more efficient in leaf non-polar fractions compared with polar fractions of N. retusa (61). Similar studies investigating anti-oxidant properties were also performed by Bouaziz et al (71) and demonstrated that the EA fraction and MeOH fraction of N. retusa indicated DPPH scavenging activity and reduction of the ABTS radical cation.

Anthocyanins have also been demonstrated to elicit scavenging effects against O2, OH and DPPH in a dose-dependent manner. Notably, these scavenging capacities were greater than those of vitamin C according to results of in vitro anti-oxidative tests (72). Nazlinin isolated from Nitraria and its derivative 1-(4-butylamino)-3,4-dihydro-β-carboline have been indicated to be inhibitors of pig kidney diamine oxidase, while 1-(4-butylamino)-β-carbolin was demonstrated as a substrate (73).

Antimicrobial activity

The EA, ethanol and Chl extracts from the fruits of N. tangutorum had antibacterial effects against Escherichia coli, Bacillus subtilis and Staphyloccocus aureus. The EA fraction presented the highest level of antibacterial activity (74,75). In addition, Chl extract from N. retusa leaves was more efficient against all human pathogen strains, particularly Escherichia coli and Staphylococcus aureus (76). The EA and MeOH extracts of N. retusa revealed antimicrobial effects against Pseudomonas aeruginosa and Aspergillus niger in vitro (71). The ethanol extracts of N. retusa also exhibited cytotoxicity in brine shrimp with LC50 values of 6.2 μg/ml (77).

Antimutagenic activity

The protection of N. retusa against mutagenicity induced by methyl methanesulfonate and 2-aminoanthracene in Salmonella typhimurium TA102 and TA104 strains was observed. The highest protection was elicited by Chl and MeOH extracts of N. retusa, with inhibition percentages of 44.93% at 50 μg/plate in the presence of TA102 strain and 38% at 10 μg/plate in the presence of TA104 strain. Hex and Chl extracts have been demonstrated to reduce the mutagenicity induced by 2-aminoanthracene with 83.4% in TA104 and 65.3% in the TA102 strain (69).

Hypotensive effects

Senejouxa et al conducted a study on the vasorelaxant activity and underlying mechanisms of hydroalcoholic extract from the fruits of N. sibirica on thoracic aortic rings isolated from Wistar rats. The study revealed that the hydroalcoholic extract was more effective in the induction of vasodilation of phenylephrine- than high KCl-pre-contracted aortic rings with respective Emax values of 82.9±2.2 and 34.8±3.6%. The acute intravenous injection of hydroalcoholic extract induced an immediate and transient hypotensive effect in anesthetized spontaneously hypertensive and control rats through an endothelium-dependent pathway involving nitric oxide synthase (NOS) activation, endothelium-derived hyperpolarizing factor production and muscarinic receptor stimulation (78). Flavonoids of different concentrations increased the repair of impaired human umbilical vein endothelial cells induced by high glucose or H2O2 by increasing the ratio of NOS, SOD and GPx activity, and NO level (79,80). Notably, the inhibition activity of ethanol extracts from 10 halophytes on angiotensin converting enzyme (ACE) has been investigated extensively. The Nitraria sibirica fraction has been demonstrated to significantly inhibit ACE with an IC50 value of 69.36 g/l (81).

Hypoglycemic effects

The fruit of N. tangutorum at a dosage of 1.8 g/kg and 3.6 g/kg not only had a therapeutic action in a mouse diabetes model induced by alloxan, but also led to an increase in the glucose-toleration in similar models in rats. It has also been demonstrated to reduce glucose levels in hyperglycemic animal models induced by epinephrine and glucose (82). Shabana et al (83) investigated the hypoglycemic activity of 31 desert plants from different Egyptian localities in normal fasting and alloxanised rats, and Nitraria retusa had hypoglycemic effects in normal fasting rats.

Lipid lowering effects

An in vivo study on the effects of the fruit extracts of N. tangutorum on rat and mouse models of hyperlipermia induced by high lipid levels was conducted by Suo et al. N. tangutorum significantly reduced the serum level of total cholesterol (TC) and TG in a rat hyperlipermia model, and the level of low-density lipoprotein (LDL) in Kunming strain rats. It also increased the ratio of high-density lipoprotein cholesterol (HDL)/TC, HDL/LDL and SOD activity, and reduced the MDA content in vivo and in vitro (84,85).

Hepatoprotective effects

A study by Zhang et al (86) indicated that seed oil of N. tangutorum alleviated the increased levels of aspartate aminotransferase, alanine aminotransferase and MDA induced by CCl4, and it also enhanced the level of GPx in liver.

4. Conclusion

The studies summarized above strongly support the theory that the Nitraria genus has favorable therapeutic properties, indicating its potential for clinical use. The present review presents and assesses the previous pharmacological and phytochemical studies published on the Nitraria genus, and may aid the easy identification and further research into properties of members of the Nitraria genus.

Nitraria as a halophyte, is ecologically central in stabilizing wind-blown sand and loess soils and thus reduces erosion. Hence, combined with the pharmacological effects, the rational development and utilization of Nitraria may be beneficial for the local environment and public health.

Numerous alkaloids have been isolated from the Nitraria genus. However, there is currently no research on the pharmacological properties of the alkaloid components, which are the most abundant constituents in nature. Further studies on the antitumor and anti-oxidative activities of these components are required. Furthermore, few molecular mechanisms are known, which may hamper the further clinical application of Nitraria. The possible synergistic action among the bioactive compounds of the plants must be evaluated prior to their use in clinical practice.


The current study was supported by grants from the National Natural Science Foundation of China (grant no. U1203104).



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Du Q, Xin H and Peng C: Pharmacology and phytochemistry of the Nitraria genus (Review). Mol Med Rep 11: 11-20, 2015
Du, Q., Xin, H., & Peng, C. (2015). Pharmacology and phytochemistry of the Nitraria genus (Review). Molecular Medicine Reports, 11, 11-20.
Du, Q., Xin, H., Peng, C."Pharmacology and phytochemistry of the Nitraria genus (Review)". Molecular Medicine Reports 11.1 (2015): 11-20.
Du, Q., Xin, H., Peng, C."Pharmacology and phytochemistry of the Nitraria genus (Review)". Molecular Medicine Reports 11, no. 1 (2015): 11-20.