The old world salsola as a source of valuable secondary metabolites endowed with diverse pharmacological activities: a review

Abstract

Salsola is an important genus in the plant kingdom with diverse traditional, industrial, and environmental applications. Salsola species are widely distributed in temperate regions and represent about 45% of desert plants. They are a rich source of diverse phytochemical classes, such as alkaloids, cardenolides, triterpenoids, coumarins, flavonoids, isoflavonoids, and phenolic acids. Salsola spp. were traditionally used as antihypertensive, anti-inflammatory, and immunostimulants. They attracted great interest from researchers as several pharmacological activities were reported, including analgesic, antipyretic, antioxidant, cytotoxic, hepatoprotective, contraceptive, antidiabetic, neuroprotective, and antimicrobial activities. Genus Salsola is one of the most notorious plant genera from the taxonomical point of view. Our study represents a comprehensive review of the previous phytochemical and biological research on the old world Salsola secies. It is designed to be a guide for future research on different plant species that still belong to this genus or have been transferred to other genera.

Graphical Abstract

Keywords:

• Genus Salsola
• phytochemicals
• traditional uses
• biological activity
• enzyme inhibition

1. Introduction

Plants are considered as a latent treasure and a vital source for the discovery of medicines. They include a plethora of secondary metabolites that act as modulators for the enzymes involved in human diseases^1,2. Plant extracts and their derived natural products or analogues are extensively reported to exert promising effects on human devastating diseases including different types of cancer^3–6. They are also reported to protect humans against different types of microbes⁷ and recently evolved infectious diseases as COVID-19^8,9.

The genus Salsola (commonly known as saltwort) belongs to the family Amaranthaceae, previously Chenopodiaceae. The genus name is from the Latin words “salsus” or “sallere” meaning salty because they are halophytes capable of living in saline environments or due to their content of alkaline salts, such as potassium and sodium carbonates^10–12. The old genus Salsola comprised about 150 sp. growing in extreme climatic conditions as arid, semi-arid, and temperate regions worldwide^11,13. They represented about 45% of the desert plants¹¹ and some of them are invasive species¹⁴. Various plants of the genus Salsola are edible and some of them have been used in traditional medicine¹⁵. Some of them are also reported to be rich in fibre content¹⁶. They have important value as animal feed and they are beneficial in the reclamation and phytoremediation of soil contaminated with heavy metals^11,14. Plants belonging to this genus also represent a rich source for endophytic microbes that could be used for potential biological applications^17,18. Furthermore, different plants of the genus Salsola were reported to have industrial value as the use of S. soda and S. kali as a source of sodium carbonate, in linin, and cotton bleaching, and in glass and soap making^14,19,20.

Despite the importance of plants belonging to the genus Salsola, they do not receive great research attention. Most of the research is done on the respiratory diseases and the hypersensitivity caused by the pollen grains of some Salsola spp. and developing vaccines for it^21–23. Very limited reviews are made on the genus Salsola such as the one made by Altay and Ozturk¹¹ that discuss its fodder value. Hanif et al.¹⁴ discussed the environmental, industrial, and traditional uses of Salsola spp. and they mentioned a small fraction of the biological studies made on them. This article addresses almost all the research articles concerning the phytochemistry and the biological activity of the plants belonging to the old genus Salsola until 2021.

2. Morphological characters

Members of the genus Salsola are shrubs, sub-shrubs, annual or perennial herbs. They are characterised by small, sessile, often succulent leaves that may be opposite or alternate. Most have bisexual axillary flowers that can be solitary or clustered to form loose or dense spikes (Figure 1). Each flower is subtended by two prominent bracteoles, with a frequently hard 5-segmented perianth (often winged in fruit), and a superior ovary. Seeds are horizontal, subglobose, with a spiral embryo^11,24,25.

Figure 1. Photographs of selected Salsola spp.; a. S. kali (adapted from kali https://gobotany.nativeplanttrust.org/sp./salsola/kali/), b. S. collina, c. S. tragus, d. S. imbricata (adapted from https://www.floraofqatar.com/amaranthaceae.htm), e. S. komarovii, f. S. oppositifolia Desf. (adapted from adapted from https://powo.science.kew.org/), g. S. soda (adapted from https://eunis.eea.europa.eu/sp./168053), h. S. laricifolia (adapted from https://panama.inaturalist.org/taxa/985676-Salsola-laricifolia).

3. Taxonomic classification

Genus Salsola belongs to the flowering plant family Amaranthaceae descending from the order Caryophyllales²⁶. Salsola has a long history of being considered as one of the largest genera within the family Chenopodiaceae containing 100 to 190 sp.²⁷. While it is classified now as one of the Amaranthaceae genera after merging family Chenopodiaceae with the family Amaranthaceae according to the angiosperm phylogeny group (AGP-IV)^26,28–30. Plants belonging to the genus Salsola have the following taxonomic classification^27,30–32.

• Kingdom: Plantae - Plants

• Subkingdom: Tracheobionta - Vascular plants

• Superdivision: Spermatophyta - Seed plants

• Division: Magnoliophyta - Flowering plants

• Class: Magnoliopsida - Dicotyledons

• Subclass: Caryophyllidae

• Order: Caryophyllales

• Family: Amaranthaceae (previously, Chenopodiaceae)

• Subfamily: Salsoloideae

• Tribe: Salsoleae

• Genus: Salsola

The taxonomy of Salsola spp. is debateable and confusing due to their diversity and distribution in the Asian and the middle east deserts that lead to difficulties in their collection and investigation³¹. The close relationship between Salsola spp. and the dependence on minor morphological differences in their old classification together with the recent use of molecular techniques in plant systematics led to major changes in the classification of the genus Salsola²⁷. The classification of the genus Salsola has been revised by Akhani et al. (2007) and it was spitted into 10 different genera. The transfer of different sp. from the old world Salsola to other genera, such as Caroxylon genus resulted in decreasing the number of its sp. to 25²⁷.

The type of the genus Salsola was Salsola soda^27,31, which has been recently changed by the International Code of Nomenclature into Salsola Kali as suggested by Mosyakin et al.³³. This resulted in changing the name of many traditionally known Salsola spp. into Soda²⁸.

These taxonomical and nomenclatural changes together with the presence of different synonyms for several Salsola spp. would obscure the determination of the phytochemical constituents and the biological activities of the old world Salsola species.

Therefore, in this article, we will review the phytochemical content and the biological activities of the old world Salsola spp. and indicate their current taxonomic status as illustrated in Table 1.

Table 1. Current taxonomic status and synonyms of Salsola plants mentioned in this review article.

Plant	Genus	Basionym and synonyms according to POWO^34 and IPNI^35	Native Distribution range^34
S. arbuscula	Xylosalsola Tzvelev	Synonyms: S. arborescens S. exasperate S. transhyrcanica	European Russia to Mongolia and Pakistan
S. collina	Salsola	Basionym of Kali collinum^31 Synonyms: S. chinensis Gand. S. erubescens Schrad. S. ircutiana Gand. S. kali subsp. collina (Pall.)	South European Russia to Korea
S. cyclophylla	Transferred to Genus Caroxylon^31	Basionym of Caroxylon cyclophyllum (Baker)^31	Syria to Sudan and South Pakistan
S. grandis	Salsola	Basionym for Soda grandis^28	Turkey
S. imbricata	Transferred to Genus Caroxylon^31	Basionym of Caroxylon imbricatum^31 Synonyms: S. baryosma Schult. Caroxylon foetidum Moq. Nitrosalsola baryosma (Schult.) Theodorova S. marosteum Moq. S. moorcroftiana Wall. Chenopodium baryosmon Schult. S. foetida Del.^36	Sahara & Sahel to west India distributed throughout warm desert areas of northwest India, Pakistan, Iran, Afghanistan and tropical east Africa^36
S. inermis Forssk	Transferred to Genus Caroxylon^31	Basionym of Caroxylon inermis (Forssk.)^31	Egypt, Arabian Peninsula, and Iran
S. kali	Salsola	It has different varieties and synonyms such as S. scariosa, S. spinosa, S. turgida	Atlantic and Mediterranean coast countries
S. komarovii	Salsola	Basionym of Kali komarovii (Iljin)^31	It grows in sand dunes and beaches in Japan, China, and Korea^37
S. laricifolia Turcz	Salsola	–	Central Asia to Mongolia and North Xinjiang
S. longifolia Forssk.	Salsola	Basionym of Soda longifolia (Forssk.)^28 Synonyms as S. fruticosa Cav. S. longiflora J.F.Gmel. S. oppositifolia Sieber ex Moq.	Sahara to Arabian Peninsula
S. micranthera	Caroxylon	Basionym of Caroxylon micrantherum (Botsch.) Nitrosalsola micranthera (Botsch.)^38	Central Asia to Southern Xinjiang
S. oppositifolia Desf.	Salsola	Basionym of Soda oppositifolia (Desf.)^28 Synonyms: S. oppositifolia f. feminea Botsch. Seidlitzia oppositifolia (Desf.) Iljin	Mediterranean countries
S. richteri	Xylosalsola Tzvelev	Synonyms: Xylosalsola richteri (Moq.) Salsola arborescens var. richteri Moq.	Central Asia and Pakistan
S. rigida Pall.	Caroxylon	Synonyms: Caroxylon orientale Salsola orientalis S.G.Gmel. Salsola syriaca Botsch. Salsola heliaramiae Mouterde	Central Sinai to North Xinjiang and West Pakistan
S. soda L.	Salsola	Its name has been modified to Soda inermis^28 Synonyms: Salsola longifolia Lam.	Growing on saline soils throughout Armenia, Iran, Turkey, and Turkmenistan, is cultivated and highly prized as a leaf vegetable (agretti) in the Mediterranean region
S. somalensis	Halothamnus Jaub. & Spach	Basionym of Halothamnus somalensis	Tropical Africa
S. tetrandra	Transferred to Genus Caroxylon^31	Basionym of Caroxylon tetrandrum (Forssk.)	North Africa, Palestine, Saudi Arabia, Sinai
S. tetragona	Caroxylon	Synonyms: Caroxylon tetragonum Salsola pachoi Volkens & Asch. Salsola diplantha Botsch Halogeton tetragonus (Delile) Moq.	North Africa to Palestine
S. tragus	Salsola	Basionym of S. kali var. tragus (L.) Moq. S. kali subsp. tragus (L.) Čelak. S. ruthenica var. tragus (L.) Morariu Synonyms as S. ruthenica S. pestifer A.Nelson	Europe to Siberia and Korea
S. tuberculatiformis	Caroxylon	Basionym of Caroxylon tuberculatiforme (Botsch.)^39 Synonyms: S. tuberculate^40	Cape, South Africa
S. villosa Schult.	Caroxylon	Synonyms as Salsola palaestinica Botsch. Salsola mandavillei Botsch. Salsola libyca Botsch.vSalsola delileana Botsch. Salsola damascena Botsch. Nitrosalsola palaestinica (Botsch.) Theodorova	Egypt, India, Lebanon-Syria, Libya, Palestine, Saudi Arabia, Sinai
S. volkensii	Caroxylon/Nitrosalsola	Basionym of Caroxylon volkensii (Schweinf. & Asch.)^31 Basionym of Nitrosalsola volkensii (Schweinf. & Asch.)^38	Egypt, Iraq, and Arabian Peninsula

4. Chemistry

4.1. Volatile constituents

Hexahydro-farnesyl acetone and benzoic acid esters were reported as the major constituents of S. cyclophylla volatile oil^15,41. However, GC analysis of the volatile fractions of different parts of S. vermiculate L. plant revealed that carvone and β-caryophylline were the major components in leaves (52.2% and 5.8%, respectively), while carvone and cuminaldehyde were the major components in roots (49.9% and 4.4%, respectively). Additionally, carvone, limonene, and linalool were detected as the major constituents of the stems of S. vermiculate L. (53%, 17.4%, and 11.3%, respectively)⁴².

4.1.1. Non-volatile constituents

Previous phytochemical investigations of plants belonging to the genus Salsola indicates the presence of diverse groups of secondary metabolites, such as alkaloids^43–49, cardenolides and steroids^50,51, coumarins and coumarolignans⁵², fatty acids^50,51,53, flavonoids and isoflavonoids^54–59, phenolics⁶⁰, and triterpene glycosides^61–64.

4.1.2. Alkaloids and nitrogenous compounds

Different classes of alkaloids and other nitrogenous compounds have been reported from plants of the genus Salsola, Figure 2. A unique group of optically active l-methyl-tetrahydro-isoquinoline alkaloids have been early detected by Proskurnina and Orekhov⁴⁵ from Salsola richteri Karel and the isolated alkaloids were identified as carnegine 1.2, salsoline 1.16, and N-norcarnegine (salsolidine) 1.19. The southern Turkmenistan salsola, S. richteri Karel yielded 0.16​% of salsoline⁴⁴. A fourth related derivative, N-methylisosalsoline 1.12, was detected by GC/MS in the aerial parts of S. oppositofolia, S. soda and S. tragus⁶⁵. In addition, 3,4-dihydro-6,7-dihydroxy-1(2H)-isoquinolinone; namely pericampylinone-A (iseluxine) 1.14, was also isolated from S. collina Pall.⁶⁶. The presence of optically active (-) pyrrolo[2,1-a]isoquinoline type alkaloids has been reported from S. collina Pall.^{43,45,47–49}. Particularly, Zhao and Ding⁴⁷ isolated and identified the first alkaloid of this group namely, salsoline A (trolline) 1.17; (S)-8,9-dihydroxy-1,2,5,6-tetrahydropyrrolo[2,1-a]isoquinolin-3(10bH)-one followed by Xiang et al.⁴³ who were able to isolate and identify another related positional isomer namely; salsoline B 1.18 from the same plant. Another group of nitrogenous derivatives, moupinamides has been reported from different Salsola spp. in both free and combined (glucoside) forms. They possess a skeleton of N-trans-feruloyltyramine or N-trans-feruloyldopamine structures. The structures of N-trans-feruloyl-3-O-methyldopamine 1.9 and N-trans-feruloyl-3′″-methoxydopamine 4′-O-β-D-glucopyranoside 1.6, were reported in S. collina⁴³ whereas, N-trans-feruloyltyramine 1.13 and 7′-hydroxy N-trans- feruloyltyramine 1.10, were found in S. collina and S. tetrandra^43,53,66. Also, trans-N-feruloyl tyramine-4′″-O-β-D-glucopyranoside 1.7, was reported from S. inermis Forssk⁵¹. The only reported moupinamide derivative with a "cis" double bond configuration of the cinnamoyl moiety was cis-N-feruloyltyramine 1.5 which was isolated from the aerial parts of S. baryosoma⁶⁷. It is worth noting that several tentatively (incompletely) defined structures were reported by UPLC/qTOF-MS analysis of the aerial parts and roots of S. vermiculata and S. tetrandra⁶⁸. They included N-caffeoyl tyramine, N-(3′,4′-dimethoxy-cinnamoyl)-norepinephrine, N-(4′-methoxy-cinnamoyl)-norepinephrine, N-feruloyl-3′″-methoxytyramine However, further spectral analysis, such as 1 D and 2 D NMR are required to confirm their structures.

Figure 2. Structures of alkaloids and nitrogenous compounds (1.1–1.23) reported in the genus Salsola.

Another miscellaneous group of nitrogenous compounds was reported from different Salsola spp., including simple nitrogenous compounds, such as methyl carbamate 1.11 from S. tetrandra, S. kali, S. longifolia and S. rigida⁶⁹. The amino acid derivative, N-acetyltryptophan 1.1 was isolated from S. collina Pall. and S. grandis Freitag, Vural & Adiguzel^66,70. Pericampylinone-A 1.14, terrestric acid 1.20, uracil 1.22, and uridine 1.23 were reported by Jin et al.⁶⁶ from S. collina Pall. While salisomide 1.15 was reported by Saleem et al.⁵⁷ from S. imbricata Forssk. The alkylamine, tridecanamine 1.21, was also reported from the aerial parts of S. terrandra Forssk⁷¹.

4.1.3. Cardenolides and steroids

Steroids are a group of natural products biosynthesized from the isoprenoid pathway via the 2,3-oxidosqualene (C₃₀) route. Cardenolides are cardioactive steroidal lactones with a 5-membered (furanones) or 6-membered (pyranone) ring at C-17. They are naturally present free or glycosylated with mono- or multi-sugar moieties. Several families are known for their high cardenolides content, such as Asclepidaceae, Apocynaceae, and others⁷². However, only one report on cardenolides from the Amaranthaceae family has been described. It addressed the isolation of five cardenolides, salsotetragonin 2.1, calactin 2.2, 12-dehydroxyghalakinoside 2.3, desglucouzarin 2.4, and uzarigenin 2.5 from the Algerian plant, Salsola tetragona Delile, Figure 3⁵⁰. Other reported steroids comprised several phytosterols with diversity in the alkyl side chains at C-17, including campesterol 2.6, cholesterol 2.7, and desmosterol 2.8 from S. collina⁷³, β-sitosterol 2.9, stigmastanol 2.10, and stigmasterol 2.11, in addition to a combined phytosterol, stigmasterol-3-O-β-D-glucopyranoside 2.12 from the aerial parts of S. inermis⁵¹.

Figure 3. Structures of cardenolides and steroids (2.1–2.12) reported in the genus Salsola.

The existence of fatty acid esters or acylated sterols was reported by Mayakova et al.⁷³ from the genus Salsola. They investigated the contents of the saponified acylsterols fraction of the pentane extract of S. collina. The neutral fraction indicated the presence of four sterols, including β-sitosterol, stigmasterol, cholesterol, and campesterol, whereas the acyl fraction of the hydrolysed esters composed of stearic, palmitic, and oleic acids⁷³.

4.1.4. Coumarins and coumarinolignans

Coumarins are bioactive secondary metabolites biosynthesized in plants from the phenylpropanoid (C₆C₃) pathway by cyclisation of cinnamic acid. They contribute to diverse biological activities, such as anticoagulant, antimicrobial, antiviral, and anticancer activities⁷⁴. Several studies reported the presence of simple coumarins in members of the genus Salsola. These reported coumarins are either free or glycosylated with mostly methoxylated C-6 and oxygenated C-7 positions. Two simple coumarins, namely umbelliferone 3.1 and scopoletin 3.2 were reported from the aerial parts of S. inermis⁵¹. Whereas S. kali showed the presence of fraxidin 3.3⁷⁵ . However, the highest record of coumarins from this genus was noted to S. laricifolia that included several simple coumarins (3.3–3.10) and two unusual coumarinolignans; cleomiscosin B 3.11, cleomiscosin D 3.12, formed by the association with another cinnamic acid moiety (C₆C₃)⁵². Calycantoside 3.10, a compound possessing the structure of 6,8-dimethoxy-coumarin-7-O-β-glucopyranoside was reported with the miss-spelled name, calicantoside from the epigeal (aerial) parts of S. laricifolia⁷⁶ Figure 4.

Figure 4. Structures of coumarins and coumarinolignans (3.1–3.12) reported in the genus Salsola.

4.1.5. Fatty acids and their derivatives

Few saturated fatty acids compared to unsaturated ones were reported from Salsola plants, Table 2 and Figure 5. Ghorab et al.⁵⁰ reported the isolation of the fatty acid ester, 2,3-dihydroxypropylpalmitate 4.1 from the aerial parts of S. tetragona. Whereas free palmitic acid 4.10, in addition to three unsaturated fatty acids, including linoleic, linolenic, and oleic acids (4.5, 4.6, and 4.9, respectively) were detected by UPLC/qTOF-MS analysis of S. vermiculata and S. tetrandra⁶⁸. Also, oleic acid 4.9 was isolated from the aerial parts of S. tetragona⁵⁰. A characteristic group of trihydroxylated mono-, di-, and tri-unsaturated fatty acids was reported from several plants of the genus Salsola, including 9,12,13-trihydroxyoctadeca-10(E),15(Z)-dienoic acid 4.13 and 9,12,13-trihydroxy-10(E)-octadecenoic acid 4.14 from the aerial parts of S. tetrandra⁵³ and 9,12,13-trihydroxydocosan-10,15,19-trienoic acid 4.15 from the aerial parts of S. inermis⁵¹. Additionally, several fatty acids, including hydroxyoctadecenoic acid, dihydroxyoctadecenoic acid, hydroxyoctadecatrienoic acid, hydroxyoctadecadienoic acid, and trihydroxyoctadecadienoic acid were also tentatively identified from the aerial parts and roots of S. vermiculata and S. tetrandra by UPLC/qTOF-MS analysis method⁶⁸.

Figure 5. Structures of fatty acids and their derivatives (4.1–4.17) reported in the genus Salsola.

Table 2. Non-volatile constituents from the genus Salsola.

No.	Class/Name	Plant/ part	Reference
I- Alkaloids and nitrogenous compounds
1.1	N-Acetyltryptophan	The whole plant of S. collina Pall.; S. grandis Freitag, Vural & Adiguzel	^66^,^70^,^77
1.2	Carnegine	S. richteri; GC/MS of the aerial parts of S. oppositifolia Desf.	^45^,^48
1.3	N-[2-(3,4-Dihydroxyphenyl)-2-hydroxyethyl]-3-(4-methoxyphenyl)prop-2-enamide	The whole plant of S. foetida	^78
1.4	N-[2-(3,4-Dihydroxyphenyl)-2-hydroxyethyl]-3-(3,4-dimethoxyphenyl)prop-2-enamide	The whole plant of S. foetida	^78
1.5	Cis-N-Feruloyltyramine	The aerial parts of S. baryosoma	^67
1.6	N-Trans-feruloyl-3′″-methoxydopamine 4′-O-β-D-glucopyranoside	The aerial parts of S. collina	^43
1.7	Trans-N-Feruloyl tyramine-4′″-O-β-D-glucopyranoside	The aerial parts of S. inermis Forssk	^51
1.8	N-[2-(3-Hydroxy-4-methoxyphenyl)-2-hydroxyethyl]3-(4-methoxyphenyl)-prop-2-enamide	The whole plant of S. foetida	^78
1.9	7′-Hydroxy-3′-methylmoupinamide; N-trans-feruloyl-3-O-methyldopamine	The whole plant of S. collina Pall.; HPLC of the aerial parts of S. komarovii	^43^,^66^,^79
1.10	7′-Hydroxymoupinamide (7′-Hydroxy N-trans- feruloyltyramine); trans-N-Feruloyloctopamine	The whole plant of S. collina Pall. and aerial parts of S. tetrandra; aerial parts of S. baryosoma	^53^,^66^,^67
1.11	Methyl carbamate	S. tetrandra, S. kali, S. longifolia and S. rigida	^69
1.12	N-Methylisosalsoline	By GC/MS of the aerial parts of S. tragus L., S. oppositifolia Desf., and S. soda L.	^48
1.13	Moupinamide (N-trans-Feruloyltyramine)	The whole plant of S. collina Pall. and aerial parts of S. tetrandra; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. Tetrandra; Forssk; aerial parts of S. baryosoma; HPLC of the aerial parts of S. komarovii	^43^,^53^,^66–68^,^80^,^79
1.14	Pericampylinone-A (iseluxine)	The whole plant of S. collina Pall.	^66
1.15	Salisomide	The arial parts S. imbricata Forssk	^57
1.16	Salsoline	Aerial parts and root of Salsola kali L. and S. longifolia Forssk; GC/MS of the aerial parts of S. tragus L., S. oppositifolia Desf., and S. soda L.	^44^,^45^,^48^,^75^,^81
1.17	Salsoline A (Trolline)	S. collina Pall.; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^47^,^49^,^66^,^68
1.18	Salsoline B	S. collina Pall.	^43
1.19	Salsolidine (N-Norcarnegine)	The aerial parts of S. kali L. and S. longifolia Forssk; GC/MS of the aerial parts of S. tragus L., S. oppositifolia Desf., and S. soda L.	^45^,^48^,^81
1.20	Terrestric acid; 4-Amino-1,2,5,6-tetrahydro-6-oxo-1,3,5-triazine-2-carboxylic acid	The whole plant of S. collina Pall.	^66
1.21	Tridecanamine	By GC-MS analysis of the aerial parts of S. tetrandra	^71
1.22	Uracil	The whole plant of S. collina Pall.	^66
1.23	Uridine	The whole plant of S. collina Pall.	^66
II- Cardenolides and steroids
A. Cardenolides
2.1	3-O-β-D-Allopyranosylcoroglaucigenin (salsotetragonin)	The aerial parts of S. tetragona	^50
2.2	Calactin	The aerial parts of S. tetragona	^50
2.3	12-Dehydroxyghalakinoside	The aerial parts of S. tetragona	^50
2.4	Desglucouzarin	The aerial parts of S. tetragona	^50
2.5	Uzarigenin	The aerial parts of S. tetragona	^50
B. Steroids
2.6	Campesterol	S. collina	^73
2.7	Cholesterol	S. collina	^73
2.8	Desmosterol	S. collina	^73
2.9	β-Sitosterol	The aerial parts of S. inermis; S. collina	^51^,^73
2.10	Stigmastanol	The aerial parts of S. inermis	^51
2.11	Stigmasterol	The aerial parts of S. inermis; S. collina	^51^,^73
2.12	Stigmasterol-3-O-β-D-glucopyranoside	The aerial parts of S. inermis	^51
III- Coumarins and coumarinolignans
3.1	Umbelliferone	The aerial parts of S. inermis	^51
3.2	Scopoletin	The aerial parts of S. inermis	^51
3.3	Fraxidin	The epigeal part of S. laricifolia; Herb and root of S. kali L.	^75^,^82
3.4	Fraxidin-8-O-β-D-glucopyranoside	The epigeal part of S. laricifolia	^82
3.5	Isofraxidin	The epigeal part of S. laricifolia	^82
3.6	Fraxetin	The epigeal part of S. laricifolia	^82
3.7	Fraxin	The epigeal part of S. laricifolia	^82
3.8	Scopolin	The epigeal part of S. laricifolia	^82
3.9	7-[O-β-D-Apiofuranosyl-(l→ 2)-6-D-glucopyranosyloxy]- 6-methoxy-2H-l-benzopyran-2-one (lariside)	The epigeal part of S. laricifolia	^82^,^83
3.10	Calycantoside; Calicantoside	The epigeal part of S. laricifolia	^76^,^82
3.11	Cleomiscosin B	S. laricifolia	^52
3.12	Cleomiscosin D	S. laricifolia	^52
IV- Fatty acids and their derivatives
4.1	2,3-Dihydroxypropylpalmitate	The aerial parts of S. tetragona	^50
4.2	2,7-Dimethyl-1-octanol	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.3	3,9-Diethyl-6-tridecanol	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.4	2,3-Dihydroxypropyl octadecanoate	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.5	Linoleic acid	UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^68
4.6	Linolenic acid	UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^68
4.7	9-Octadecynoic acid	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.8	9,12-Octadecadienoic (Z,Z) methyl ester	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.9	Oleic acid	The aerial parts of S. tetragona; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^50^,^68
4.10	Palmitic acid; Hexadecenoic acid	UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^68
4.11	Palmitic acid methyl ester; methyl palmitate	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.12	Palmitic acid ethyl ester; Hexadecenoic acid ethyl ester	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.13	9,12,13-Trihydroxyoctadeca-10(E),15(Z)-dienoic acid	The aerial parts of S. tetrandra	^53
4.14	9,12,13-Trihydroxy-10(E)-octadecenoic acid
4.15	9,12,13-Trihydroxydocosan-10,15,19-trienoic acid	The aerial parts of S. inermis	^51
4.16	Tetradecanoic acid methyl ester	By GC-MS analysis of the aerial parts of S. tetrandra	^71
4.17	9,​12,​13-​Trihydroxy-​7-​octadecenoic acid	UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^68
V- Flavonoids and flavonolignans:
A. Flavones and their derivatives
5.1	Apigenin	HPLC analysis of whole plant of S. imbricata Forssk	^84
5.2	Chrysin	HPLC analysis of whole plant of S. imbricata Forssk	^84
5.3	Flavonol (Flavon-3-ol; 3-Hydroxyflavone)	S. grandis Freitag, Vural & Adiguzel	^70
5.4	Isorhamnetin	The whole plant of S. collina Pall.; leaves of S. Imbricata; HPLC of the aerial parts of S. komarovii	^66^,^79^,^80
5.5	Isorhamnetin-3-O-rutinoside (Narcissoside)	S. kali; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra; S. grandis Freitag, Vural & Adiguzel; aerial parts of wild S. soda; aerial parts of S. Oppositifolia; HPLC of the aerial parts of S. komarovii	^10^,^54^,^68^,^70^,^77^,^79^,^85
5.6	Isorhamnetin-3-O-α-L-arabinopyranosyl (1→6)-β-D-glucopyranoside	The whole plant of S. collina	^60
5.7	Isorhamnetin-3-O-β-D-galactopyranoside	S. grandis Freitag, Vural & Adiguzel Leaves of S. Imbricata	^70^,^77^,^80
5.8	Isorhamnetin-3-O-β-D-glucopyranoside	The whole plant of S. collina; aerial parts of S. inermis, and S. kali; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra; S. grandis Freitag, Vural & Adiguzel; leaves of S. imbricata Forssk; aerial parts of S. oppositifolia; HPLC of the aerial parts of S. komarovii	^Citation51,Citation54,Citation60,Citation68,Citation70,Citation77,79,80,85
5.9	Isorhamnetin-7-O-β-D-glucopyranoside	The whole plant of S. collina	^60
5.10	Isorhamnetin-3-O-β-D-glucuronate methyl ester (1′″→4′`)-β-glucuronate methyl ester	Leaves of S. imbricata Forssk	^80
5.11	Isorhamnetin-3-O-β-D-glucuronide	S. grandis Freitag, Vural & Adiguzel; aerial parts of wild S. soda	^10^,^70^,^77
5.12	Isorhamnetin-3-O-β-D-glucuronyl-(1′``→4′`)-β-D-glucuronic acid	Leaves of S. imbricata Forssk	^80
5.13	Kaempferol-3-O-methylether	The aerial parts of S. inermis	^51
5.14	Kaempferol-3-O-β-D-(6′`-O-(E)-p-coumaroyl)glucopyranoside); trans-Tiliroside	S. grandis Freitag, Vural & Adiguzel	^70^,^77
5.15	Kaempferol-3-O-β-D-glucopyranoside; Astragalin	The aerial parts of S. tetragona, and S. inermis; HPLC of the aerial parts of S. komarovii	^50^,^51^,^79
5.16	Kaempferol-3-O-rutinoside	HPLC of the aerial parts of S. komarovii	^79
5.17	Luteolin-7-O-β-D-glucoside	HPLC analysis of aerial parts and root of S. kali L.	^75
5.18	Quercetin	S. collina Pall., S. kali; HPLC analysis of S. imbricata Forssk; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra; S. grandis Freitag, Vural & Adiguzel; LC-MS of S. cyclophylla	^15^,^66^,^68^,^70^,^77^,^84
5.19	Quercetin-3-O-β-D-galactoside; Hyperin; Hyperoside	HPLC analysis of aerial parts and root of S. kali L.; S. grandis Freitag, Vural & Adiguzel; LC-MS analysis of S. cyclophylla	^15^,^70^,^77^,^75
5.20	Quercetin-3-​O-​glucopyranoside; Isoquercitrin	HPLC of the aerial parts of S. komarovii	^79
5.21	Quercetin-3-O-β-D-glucopyranosyl-(1→6)-glucopyranoside	The aerial parts of S. tetragona	^50
5.22	Quercetin-3-​O-​glucuronopyranoside	The aerial parts of wild S. soda	^10^,^79
5.23	Quercetin-3-O-methylether	S. grandis Freitag, Vural & Adiguzel	^77
5.24	Quercetin 3-α-L-rhamnoside; Quercetrin	HPLC analysis of whole plant of S. imbricata Forssk; S. grandis Freitag, Vural & Adiguzel	^70^,^77^,^84
5.25	Quercetin-3-O-rutinoside; Rutin	S. collina Pall.; HPLC analysis of S. imbricata Forssk; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra; S. grandis Freitag, Vural & Adiguzel; aerial parts of wild S. soda; HPLC of the aerial parts of S. komarovii	^10^,^66^,^68^,^70^,^77^,^79^,^84
5.26	Quercetin 3-O-rutinoside-(1:2)-O-rhamnoside; Quercetin 3-O-(2′`,6′`-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside (Manghaslin)	S. grandis Freitag, Vural & Adiguzel	^70^,^77
5.27	Selagin; 3′-O-Methyltricetin	The whole plant of S. collina Pall.	^60
5.28	Tricin	The whole plant of S. collina Pall.	^60^,^66
5.29	Tricin-4′-O-[erythro-β-guaiacylglyceryl] ether; Erythro-4′-O-(β-guaiacylglyceryl)tricin (salcolin B)	The epigeal part of S. collina	^56^,^86
5.30	Tricin-4′-O-[threo-β-guaiacylglyceryl] ether; Threo-4′-O-(β-guaiacylglyceryl)tricin (salcolin A)	The epigeal part of S. collina
5.31	Tricin-7-O-β-D-glucopyranoside	The whole plant of S. collina Pall	^60^,^66
5.32	Tricin-4′-O-β-D-apioside	The whole plant of S. collina	^60
B. Flavanols and flavanones
5.33	Catechin	HPLC analysis of whole plant of S. imbricata Forssk	^84
5.34	Hesperidin	HPLC analysis of whole plant of S. imbricata Forssk	^84
5.35	Hesperitin	HPLC analysis of whole plant of S. imbricata Forssk	^84
5.36	Naringenin	HPLC analysis of whole plant of S. imbricata Forssk	^84
C. Isoflavonoids
5.37	5,2′-Dihydroxy-5′-methoxy-6,7-methylenedioxy-isoflavone (Tetranin B)	S. tetrandra Folsk roots	^59
5.38	5,2′-Dihydroxy-6,7-methylenedioxyisoflavone (Irisone B)	The whole plant of S. collina Pall.	^66^,^87
5.39	5,3′-Dihydroxy-2′-methoxy-6,7-methylenedioxyisoflavone	The roots of S. somalensis	^55^,^88
5.40	5,3′-Dihydroxy-6,7,2′-trimethoxyisoflavone	The roots of S. somalensis	^55
5.41	5,3′-Dihydroxy-6,7,8,2′-tetramethoxyisoflavone	The roots of S. somalensis	^55^,^88
5.42	5,3′-Dihydroxy-7,8,2′-trimethoxyisoflavone	The roots of S. somalensis	^55^,^88
5.43	6,3′-Dihydroxy-5,7,2′-trimethoxyisoflavone	The roots of S. somalensis	^55
5.44	7,3′-Dihydroxy-5,6,2′-trimethoxyisoflavone	The roots of S. somalensis	^55
5.45	8,3′-Dihydroxy-5,7,2′-trimethoxyisoflavone	The roots of S. somalensis	^55
5.46	3′-Hydroxy-5,6,7,2′-tetramethoxyisoflavone	The roots of S. somalensis	^55
5.47	5,6,3′-Trihydroxy-7,2′-dimethoxyisoflavone	The roots of S. somalensis	^55
5.48	5,8,3′-Trihydroxy-7,2′-dimethoxyisoflavone	The roots of S. somalensis	^55
5.49	6,7,3′-Trihydroxy-5,2′-dimethoxyisoflavone	The roots of S. somalensis	^55
5.50	5,2′,3′-Trimethoxy-6,7- methylenedioxyisoflavone	The roots of S. somalensis	^88
5.51	5,6,7,2′,3′-Pentamethoxyisoflavone	The roots of S. somalensis	^55
5.52	5,7,8,2′,3′-Pentamethoxyisoflavone	The roots of S. somalensis	^88
D. Isoflavan
5.53	Salisoflavan	The arial parts S. imbricata Forssk	^57
VI-Lignans
6.1	Acanthoside D	The whole plant of S. collina	^60
6.2	Alangilignoside C	The aerial parts of S. komarovii	^89
6.3	Conicaoside	The aerial parts of S. komarovii	^89
6.4	(8S,8′R,7′R)-9′-[(β-Glucopyranosyl)oxy]lyoniresinol	The aerial parts of S. komarovii	^89
6.5	Lariciresinol-9-O-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
6.6	(+)-Lyoniresinol 9′-O-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
VII- Triterpenoids and their derivatives
A. Triterpenoids
7.1	3-O-β-D-Glucopyranosyl-6β,11β,23,24- tetrahydroxyolean-12-en-28-oic acid	The whole plant of S. baryosma	^64
7.2	Guavenoic acid; 2α,3β,6β,23-Tetrahydroxyursa-12,20(30)-dien-28-oic acid	S. baryosma	^90
7.3	Momordin IIb; Silphioside G; Oleanolic acid 3-glucuronide 28-glucoside	S. imbricata Forssk root; S. grandis Freitag, Vural & Adiguzel	^61^,^70^,^77
7.4	Momordin IId; 3β-(([O-β-D-Xylopyranosyl-(1→2)-O-β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranuronosyl)oxy)-olean-12-ene-28-glucopyranoside	By HPLC-ESI-MS from aerial parts of wild S. soda	^10
7.5	Olean-12-en-3,28-diol	The aerial parts of S. inermis	^51
7.6	Oleanolic acid; Olean-12-en-28-oic acid	The aerial parts of S. inermis; aerial parts of wild S. soda	^10^,^51
7.7	Oleanolic acid-3-O-β-D-glucopyranosyl	The aerial parts of S. inermis	^51
7.8	1α,2α,3β,19α,23-Pentahydroxyursa-12,20(30)-dien-28-oic acid	S. baryosma	^90
7.9	Pseudoginsenoside RT1	S. imbricata Forssk root	^61
7.10	Salsolin A; 3β,11β,24,30-Tetrahydroxyolean-12-en-28-oic acid	The whole plant of S. baryosma	^64
7.11	Salsolin B; 2α,3β,23,24-Tetrahydroxyurs-12-en-28-oic acid	The whole plant of S. baryosma	^64
7.12	Salsolic acid; 3β,6α,24-Trihydroxyolean-12-en-28-oic acid	S. baryosma	^90
7.13	Salsoloside C; Momordin IIc; Oleanolic acid 28-O-β-D-glucopyranoside 3-O-[O-β-D-xylopyranosyl-(l→4)-β-D-glucuropyranoside]	The epigeal part of S. micranthera Botsch; S. grandis Freitag, Vural & Adiguzel; By HPLC-ESI-MS aerial parts of wild S. soda	^10^,^62^,^70^,^77
7.14	Salsoloside D; Hederagenin 28-O-β-D-glucopyranoside 3-O-[O-β-D-xylopyranosyl-(l→4)-β-D-glucuropyranoside]	The epigeal part of S. micranthera Botsch	^62
7.15	Salsoloside E; Oleanolic acid 28-O-β-D-glucopyranoside 3-O-[O-β-D-glucopyranosyl-(1→2)-[O-β-D-xylopyranosyl-(l→4)-β-D-glucuropyranoside]	The epigeal part of S. micranthera Botsch	^63
7.16	3-O-β-D-Xylopyranosyl-(1→2)- O-β-D-glucuronopyranosyl-29-hydroxyoleanolic acid 28-O-β-D-glucopyranoside	S. imbricata Forssk root	^61
B. Nortriterpenoids
7.17	3-O-β-D-Glucuronopyranosyl-30-norolean-12,20(dien-28-O-[β-D-glucopyranosyl] ester (boussingoside A2)	S. imbricata Forssk root	^61
7.18	3-O-β-D-Xylopyranosyl-(1→2)-O-β-D-glucuronopyranosyl-akebonic acid 28-O-β-D-glucopyranoside	S. imbricata Forssk root	^61
VIII- Phenolic acids and simple phenols
8.1	Acetyl ferulic acid	S. collina Pall.	^66
8.2	Anisic acid	S. collina Pall.	^66
8.3	Benzoic acid	HPLC analysis of whole plant of S. imbricata Forssk	^84
8.4	Caffeic acid	HPLC analysis of whole plants of S. kali and S. imbricata Forssk; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. tetrandra	^12^,^68^,^84
8.5	Caffeic acid phenethyl ester; β-​Phenylethyl caffeate	LC-MS analysis of S. cyclophylla	^15
8.6	Catechol	HPLC analysis of herb and root of S. kali	^12
8.7	Chlorogenic acid	HPLC analysis of whole plant of S. imbricata Forssk; LC-MS analysis of S. cyclophylla	^15^,^84
8.8	Cinnamic acid	HPLC analysis of whole plant of S. imbricata Forssk; LC-MS analysis of S. cyclophylla	^15^,^84
8.9	p-Coumaric acid	HPLC analysis of whole plants of S. kali and S. imbricata Forssk; S. collina Pall.; LC-MS analysis of S. cyclophylla	^12^,^15^,^60^,^66^,^84
8.10	Ferulic acid	Whole plant of S. collina; HPLC analysis of whole plants of S. kali and S. imbricata Forssk; UPLC/qTOF-MS analysis of whole plants of S. vermiculata and S. Tetrandra; LC-MS analysis of S. cyclophylla	^12^,^15^,^60^,^68^,^80^,^84
8.11	Gallic acid	HPLC analysis of whole plant of S. imbricata Forssk; LC-MS of S. cyclophylla	^15^,^84
8.12	Gentisic acid	HPLC analysis of herb and root of S. kali	^12
8.13	4-Hydroxy-acetophenone; 1-(4-hydroxy-phenyl)-ethanone	S. tuberculatiformis Botsch.	^40
8.14	4-Hydroxy-3-methoxy-acetophenone; 1-(4-hydroxy-3-methoxy-phenyl)-ethanone	S. tuberculatiformis Botsch.	^40
8.15	4-Hydroxybenzaldehyde	S. tuberculatiformis Botsch.	^40
8.16	p-Hydroxybenzoic acid	S. collina Pall.; HPLC analysis of herb and root of S. kali; leaves of and S. imbricata Forssk	^12^,^66^,^80
8.17	p-Hydroxyphenylacetic acid	HPLC analysis of herb and root of S. kali	^12
8.18	Isovanillic acid	Leaves of S. imbricata Forssk	^80
8.19	Protocatechuic aldehyde	S. collina Pall.	^66
8.20	Protocatechuic acid	HPLC analysis of whole plants of S. kali and S. imbricata Forssk	^12^,^84
8.21	Resorcinol	HPLC analysis of aerial parts and root of S. kali L.	^75
8.22	α-Resorcylic acid	HPLC analysis of herb and root of S. kali	^12
8.23	β-Resorcylic acid	HPLC analysis of herb and root of S. kali	^12
8.24	Rosmarinic acid	HPLC analysis of S. imbricata Forssk	^84
8.25	Salicylic acid	S. collina Pall.; HPLC analysis of whole plants of S. imbricata Forssk	^60^,^66^,^84
8.26	Syringic acid	HPLC analysis of herb and root of S. kali	^12
8.27	Tetranin A	S. tetrandra Folsk roots	^59
8.28	Vanillic acid	HPLC analysis of whole plants of S. kali and S. imbricata Forssk; from the aerial parts of S. tetragona	^12^,^50^,^84
8.29	Vanillin	S. collina Pall.	^66
IX- Miscellaneous glycosides
9.1	Benzyl 6-O-β-D-apiofuranosyl-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
9.2	Biophenol 2	The aerial parts of S. komarovii	^89
9.3	Blumenol B 9-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
9.4	Blumenyl A β-D-glucopyranoside; Roseoside A	The aerial parts of S. komarovii	^89
9.5	Blumenyl B β-D-glucopyranoside	The aerial parts of S. komarovii	^89
9.6	Canthoside C	The aerial parts of S. tetragona and S. komarovii	^50^,^89
9.7	Canthoside D	The aerial parts of S. tetragona	^50
9.8	Corchoionoside C	The whole plant of S. collina Pall.	^66
9.9	Cuneataside C	The aerial parts of S. komarovii	^89
9.10	2-(3,4-Dihydroxy)-phenyl-ethyl-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
9.11	9-​Hydroxylinaloyl glucoside	The aerial parts of S. tetrandra	^53
9.12	Icariside B2	The aerial parts of S. komarovii	^89
9.13	Isotachioside	The aerial parts of S. komarovii	^89
9.14	Lyohebecarpin A (3β-Hydroxy-5R,6R-epoxy-β -ionone-2R-O-β-D-glucopyranoside)	The aerial parts of S. tetrandra	^53
9.15	Staphylionoside D	The aerial parts of S. komarovii	^89
9.16	Tachioside	The aerial parts of S. komarovii	^89
9.17	Taxiphyllin	The aerial parts of S. tetrandra	^53
9.18	3,4,5-Trimethoxyphenyl-β-D-glucopyranoside	The aerial parts of S. tetrandra	^53
9.19	(6R,9S)-3-Oxo-α-ionol β-D-glucopyranoside	The aerial parts of S. komarovii	^89
9.20	3-Oxo-α-ionol 9-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside	The aerial parts of S. komarovii	^89
X- Phenylpropanoids
10.1	Biphenylsalsinol; 4′-[3-(hydroxymethyl)oxiran-2-yl]-3- [(E)-3-hydroxyprop-1-en-1-yl]-6, 2′-dimethoxy [1, 1′-biphenyl]-2-ol	The aerial parts of S. villosa Delile. ex Schul.	^91
10.2	Biphenylsalsonoid A; 4′-(9′- (Hydroxymethyl) oxiran-7′-yl)-4-((E)-3-hydroxyprop-7-en-7-yl)-3,3′-dimethoxy-[1,1′-biphenyl]-2,5′-diol	Roots of S. imbricata	^92
10.3	Biphenylsalsonoid B; 4,4′-bis-(9-hydroxymethyl) oxiran-7-yl)-5,3′,5′-trimethoxy [1,1′biphenyl]-3-ol	Roots of S. imbricata	^92
XI- Polyhydric alcohols and carbohydrates
11.1	Ethyl β-D-fructopyranoside	S. collina Pall.	^93
11.2	Ethyl β-D-glucopyranoside	S. collina Pall.	^93
11.3	D-Fructose	S. collina Pall.	^93
11.4	D-Glucose	S. collina Pall.	^93
11.5	D-Mannitol	S. collina Pall.	^93
11.6	Myoinositol	S. collina Pall.	^93
XII- Miscellaneous group
12.1	Salsolanol; 4-(4′-hydroxy-2′-methylcyclopent-2′-enyloxy)- 4-methylcyclopent-2-enol	The aerial parts of S. villosa Delile. ex Schul.	^91
12.2	Sulphurous acid, isohexyl 2- pentyl ester	By GC-MS analysis of the aerial parts of S. tetrandra	^71

4.1.6. Flavonoids and isoflavonoids

Flavonoids and isoflavonoids are predominant plant polyphenols having a C₆-C₃-C₆ skeleton and are considered as one of the frequently studied plant phytochemicals⁹⁴. Flavonoids are yellow-colored compounds possessing a highly distinctive biosynthetic pathway as they are synthesised from the mixed phenylpropanoid (4-coumaroyl-CoA) and polyketide (3 malonyl-CoA) pathway⁹⁵. The isoflavonoids subclass is characterised by the presence of a 2-phenyl instead of 3-phenyl substitution at the benzo-γ-pyrone moiety⁹⁴. Concerning the biological activities, flavonoids are the main dietary antioxidants due to their action as scavengers of harmful free radicals. In addition, they act as signalling molecules by their modulatory effect on several protein kinases, such as MAP kinase (mitogen-activated protein kinase). The latter mechanism can explain their neuroprotection, cardioprotection, and anticancer activities⁹⁶. Isoflavonoids are much limited in their distribution in plant families (e.g. Leguminosae) compared to flavonoids and are characterised by their phytoestrogenic activity as in the case of genistein⁹⁷. In the genus Slasola, the reported flavonoids (Figure 6) can be classified into flavones (such as apigenin 5.1, chrysin 5.2, luteolin-7-O-β-D-glucoside 5.17, and tricin 5.28, from S. imbricata Forssk, S. kali L., and S. collina Pall., respectively^60,66,75,84, flavonols (such as isorhamnetin 5.4, quercetin 5.18, and kaempferol derivatives 5.13–5.16), flavanols (such as catechin 5.33), and flavanones (such as hesperidin 5.34, hesperitin 5.35, and naringenin 5.36). The free flavonol aglycone, kaempferol was incompletely identified by UPLC/qTOF-MS analysis of the aerial parts and roots of S. vermiculata and S. Tetrandra plants⁶⁸. The presence of OCH₃ groups (i.e. methoxylated flavonoids) was mainly observed at C-3`and C-4′ in the B-ring of flavones (in tricin and its derivatives 5.28–5.32), and at C-3′ of flavonols (in the isorhamnetin derivatives 5.4–5.13). However, diversity in methoxylation positions was recorded for the isoflavonoids group (5.37–5.52), as both the A-ring (positions C-5, 6, 7, and 8) and the B-ring (positions C-2′, 3′, and 5′) acquired OCH₃ groups. For detailed references and the plant source, see Table 2. Finally, a unique 8,2′-dimethoxylated isoflavan derivative, salisoflavan 5.53, was reported from the arial parts S. imbricata Forssk⁵⁷.

Figure 6. Structures of flavonoids and isoflavonoids derivatives (5.1–5.53) reported in the genus Salsola.

4.1.7. Lignans

Lignans are natural secondary metabolites biosynthesized from the oxidative coupling of two p-hydroxyphenylpropane moieties (C₆-C₃) linked by a bond connecting the middle (β-β`) carbons of their side chains<sup>98</sup>. Regarding the genus Salsola, six derivatives from two major subclasses, lignans and cylolignans, were identified. For the lignans subclass, three tetrahydrofuran derivatives, alangilignoside C 6.2, conicaoside 6.3, and lariciresinol-9-O-β-D-glucopyranoside 6.5 were isolated from the aerial parts of S. komarovii<sup>89</sup>. Regarding the cylolignans subclass, two tetrahydronaphthalene derivatives, namely (8S,8`R,7`R)-9′-[(β-glucopyranosyl)oxy]lyoniresinol 6.4 and (+)-lyoniresinol 9′-O-β-D-glucopyranoside 6.6, were isolated from the same plant⁸⁹, Table 2 and Figure 7. In addition, another bicyclolignan derivative having a 3,7-dioxabicyclo[3.3.0]octane ring system, namely acanthoside D 6.1 was isolated from S. collina plant⁶⁰.

Figure 7. Structures of lignans (6.1–6.6) reported in the genus Salsola.

4.1.8. Triterpenoids and their derivatives

Triterpenoids are structurally diverse widely distributed natural phytochemicals possessing a C₃₀-skeleton and are biosynthesized from the isoprenoid precursor, squalene⁹⁹. Pentacyclic triterpenoids of the C–C–C–C(–C) 6–6-6–6-6 rings were reported in some Salsola spp. categorised as triterpenoids and nortriterpenoids (Table 2 and Figure 8). The triterpenoids group included mainly ursane, and oleanane skeletons, both free and combined. However, oleanane derivatives are the predominant group. Free hydroxylated oleanolic acid/derivatives are represented by guavenoic acid 7.2, 1α,2α,3β,19α,23-pentahydroxyursa-12,20(30)-dien-28-oic acid 7.8, salsolin A 7.10, and salsolic acid 7.12 were isolated from S. baryosma⁹⁰ and oleanolic acid 7.6 from S. inermis and S. soda^10,51. Whereas, only olean-12-en-3,28-diol 7.5 found in S. inermis showed the presence of a primary alcoholic group (28-CH₂OH) instead of a COOH at C-17 ⁵¹. One ursane derivative, namely salsolin B 7.11 was identified from S. baryosma⁹⁰. Concerning the reported combined triterpenoids, two positions of the triterpenoid's skeleton were noticed to possess sugar moieties; the first position is C-3 that showed the presence of a sugar chain of variable length ranging from 1–3 sugars (e.g. glucose, xylose, and glucuronic acid). The second one is C-28 which showed the presence of glucosyl esters. Of these saponins, three characteristic salsolosides were reported, including salsoloside C 7.13 from S. micranthera Botsch, S. grandis Freitag, Vural, and S. soda^10,62,70,77, salsolosides D 7.14, and E 7.15 from S. micranthera Botsch⁶³. Two 3-β-hydroxy 30-noroleana-12,20(29)-dien-28-oic acid (syn. akebonic acid) derivatives were isolated from the roots of S. imbricata Forssk and identified as 3-O-β-D-glucuronopyranosyl-30-norolean-12,20(dien-28-O-[β-D-glucopyranosyl] ester 7.17 and 3-O-β-D-xylopyranosyl-(1 → 2)-O-β-D-glucuronopyranosyl-akebonic acid 28-O-β-D-glucopyranoside 7.18⁶¹.

Figure 8. Structures of triterpenoids and nortriterpenoids (7.1–7.18) reported in the genus Salsola.

Figure 9. Structures of phenolic acids derivatives and simple phenols (8.1–8.29) reported in the genus Salsola.

4.1.9. Phenolic acids and simple phenols

Simple phenols are a minor class of natural products defined as aromatic compounds with at least one hydroxyl group attached to a benzene ring, such as catechol, resorcinol, and phloroglucinol. However, phenolic acids/derivatives represent a major class of plant-derived natural products, categorised into benzoic acids, such as protocatechuic and gallic acids (C₆-C₁) and cinnamic acids, such as caffeic and coumaric acids (C₆-C₃)¹⁰⁰. HPLC analysis of the aerial parts and root of S. kali revealed the presence of two simple phenols viz, catechol 8.6 and resorcinol 8.21^12,75. The presence of simple aromatic aldehydes was reported from S. tuberculatiformis Botsch. (4-hydroxybenzaldehyde 8.15) and S. collina Pall. (protocatechuic aldehyde 8.19 and vanillin 8.29)⁶⁶. However, diverse benzoic acids were found in several plants of the genus Salsola, the most characteristic of which are gentisic acid 8.12, α-resorcylic acid 8.22, and β-resorcylic acid 8.23 from the herb and root of S. kali¹², and the dihydrostilbene, tetranin A 8.27 from the roots of S. tetrandra Folsk⁵⁹. In addition, various free cinnamic acids and their esters were reported from the plants of this genus. Regarding free cinnamic acids, previous phytochemical studies on S. kali, S. imbricata Forssk, S. vermiculata, S. tetrandra, S. cyclophylla, and S. collina Pall. showed the presence of caffeic 8.4, cinnamic 8.8, p-coumaric 8.9, and ferulic acids 8.10^{12,15,66,68,80,84}. Whereas cinnamic acid esters were described in two Salsola spp. viz., S. cyclophylla and S. imbricata Forssk., including β-​phenylethyl caffeate 8.5, chlorogenic acid 8.7, and rosmarinic acid 8.24^15,84, Table 2 and Figure 9.

4.1.10. Miscellaneous glycosides

Several miscellaneous glycosides with both phenolic and isoprenoid aglycones were reported from several plants of the genus Salsola. The glycone part in most cases is either glucose or β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranose. The phenolic glycosides, benzyl 6-O-β-D-apiofuranosyl-β-D-glucopyranoside 9.1, biophenol 2 9.2, cuneataside C 9.9, and 2–(3,4-dihydroxy)-phenyl-ethyl-β-D-glucopyranoside 9.10 were isolated from the aerial parts of S. komarovii⁸⁹. The cyanogenic glycosides, taxiphyllin 9.17 and 3,4,5-trimethoxyphenyl-β-D-glucopyranoside 9.18 were reported in the aerial parts of S. tetrandra⁵³. Whereas the isoprenoid glycosides comprised the acyclic monoterpene, 9-​hydroxylinaloyl glucoside 9.11 from S. tetrandra⁵³, in addition to several ionone derivatives with different unsaturation and oxidation status, such as roseoside A 9.4 and blumenyl B β-D-glucopyranoside 9.5 from S. komarovii⁸⁹ and the epoxy derivatives icariside B2 9.12 and lyohebecarpin A 9.14 from S. komarovii and S. tetrandra, respectively^53,89 were reported, Table 2 and Figure 10.

Figure 10. Structures of miscellaneous glycosides (9.1–9.20) reported in the genus Salsola.

Figure 11. Structures of biphenylpropanoids (10.1–10.3) reported in the genus Salsola.

4.1.11. Biphenylpropanoids

Biphenylpropanoids (Table 2 and Figure 11) were isolated from the aerial parts of S. villosa Delile. ex Schul. and the roots of S. imbricata. They are formed of dimeric C₆C₃ residues (linked head to head) with a characteristic oxirane ring formed by epoxidation of either one of the side chains' double bond as in biphenylsalsinol 10.1⁹¹ and biphenylsalsonoid A 10.2⁹² or both as in case of biphenylsalsonoid B 10.3⁹².

4.1.12. Polyhydric alcohols and carbohydrates

Syrchina et al.⁹³ described the presence of a few monosaccharide derivatives, including two simple ethyl glucosides namely, ethyl β-D-fructopyranoside 11.1 and ethyl β-D-glucopyranoside 11.2 from S. collina Pall. In addition, they reported the presence of two polyhydric alcohols (D-mannitol 11.5 and myoinositol 11.6) from the same plant⁹³, Table 2 and Figure 12.

Figure 12. Structures of polyhydric alcohols and carbohydrates (11.1–11.6) reported from the genus Salsola.

Figure 13. Miscellaneous compounds (12.1–12.2) reported in the genus Salsola.

4.1.13. Miscellaneous group

Only two compounds are included in this group; the first one is a dimeric methylcyclopentenyl alcohol namely, salsolanol 12.1 isolated from the aerial parts of S. villosa Delile. ex Schul. ⁹¹. While, the second compound is an isohexyl 2- pentyl ester of sulphurous acid 12.2 detected by GC-MS analysis of the aerial parts of S. tetrandra⁷¹, Table 2 and Figure 13.

5. Pharmacological activities

Plants of the genus Salsola are widely used in the folk medicine of different countries for the treatment of several diseases, such as hypertension, broken bones as well as for boosting the immunity (Table 3).

Table 3. Traditional medical uses of Salsola species.

Country	S. sp.	Traditional use	Reference
China	S. collina Pall.	Treatment of hypertension, headache, and vertigo	^43^,^66
Saharo-arabic and Soudano-deccanian	S. baryosma	Vascular hypertension	^101
Middle East	S. baryosoma	Against inflammation and as a diuretic agent	^14^,^102
Chhindwara, India	The whole plant of S. kali L.	Treatment of cough	^14^,^103
Ethiopia	S. somalensis	Anthelmintic	^55^,^88
Mongolia	Aerial parts of S. laricifolia	Used by the nomads of the Gobi Desert as winter tonic tea, for wound healing, and treatment of broken bones and swollen joints	^76
Saudi Arabia	Leaves of S. cyclophylla	Used by local Bedouin as diuretic, laxative, anthelmintic, and anti-inflammatory	^15^,^41
Turkmenistan, Tajikistan, and Kyrgyzstan	S. richteri	Used to treat skin conditions and hypertension in Tajik folk medicine	^76
Southern Africa	Aqueous extract of S. tuberculatiformis	Used by Bushmen women as oral contraceptive	^40^,^104

Research studies showed that extracts of different Salsola spp. and compounds isolated from them exert a wide range of variable pharmacological activities. These activities will be discussed in detail in this section. They are also summarised in Table 4 and Figure 14.

Figure 14. Reported pharmacological activities of plants belonging to the old genus Salsola.

Table 4. Reported pharmacological activities of Salsola species.

Pharmacological action/medicinal use	Salsola spp./part used	Extract /or product used	Collection place	Reference
Effect on the cardiac system and blood pressure
Antihypertensive	S. kali, S. longifolia, and S. ruthenic	–	–	^81^,^105
Angiotensin-converting enzyme inhibiting activity	Aerial parts of S. oppositifolia, and S. soda	Ethyl acetate extracts	Italy	^106
Cardioprotective effect	Whole shrub of S. kali	Aqueous extract	New Damietta City, Egypt	^107
Anti-inflammatory, analgesic, and antipyretic activities
Anti-inflammatory and antinociceptive activities	Aerial parts of S. grandis	Ethanolic extract	Nallıhan bird sanctuary, Ankara, Turkey	^77
Anti-inflammatory and analgesic activity	Aerial parts of S. Cyclophylla	Aqueous-ethanolic extract	Al-Fuwayliq City in the Qassim region, Saudi Arabia	^15
Anti-inflammatory	S. komarovii	Ethanol extract	Yongin, Korea	^37
Anti-inflammatory	Leaves of S. imbricata Forssk	Aqueous methanolic extract	Baharia Oasis, Egypt	^80
Anti-inflammatory, analgesic, and antipyretic	Aerial parts of S. imbricata	Aqueous ethanol (30:70 v/v) extract	Cholistan desert, Punjab, Pakistan	^108
Antioxidant and Iron chelation activity
Antioxidant and Iron chelation activity	S. cyclophylla	Aqueous ethanolic Extract	Al-Fuwayliq City in the Qassim region, Saudi Arabia	^15
Antioxidant	S. Cyclophylla	Essential oil	Qassim region, Saudi Arabia	^41
Antioxidant	Leaves and stems of S. kali L.	Methanol extract	Borj-Cédria coastal Region, Tunis	^75
Antioxidant activity	Aerial parts of S. oppositofolia, S. soda, and S. tragus	Alkaloid extract	Central and Southern Italy	^48
Antioxidant activity	Aerial parts of S. komarovii	Ethyl acetate extract	Gangneung, Korea	^79
Antioxidant	S. baryosma	Ethyl acetate fraction	Cholistan desert, Pakistan	^109
Antioxidant	S. baryosma	80% (v/v) Aqueous methanol extract	Algeria	^22
Cytotoxic activity
Cytotoxic activity	Aerial parts of S. oppositifolia Desf.	Different extracts were tested	Sicily, Italy	^85
Cytotoxic activity	S. collina	Ethanol extract	–	^110
Phytotoxic activity	S. baryosma	Ethyl acetate fraction	Cholistan desert, Pakistan	^109
Effect on the liver and the gallbladder
Hepatoprotective effect	Aerial parts of S. collina Pall	25% Ethanol extract	Russia	^111
Anti-cholelithiasis	S. collina Pall	Aqueous extract	Russia	^112
Hepatoprotective effect	Aerial parts of S. tetrandra	70% Hydroalcoholic extract	Saudi Arabia	^113
Hepatoprotective and antioxidant effect	Whole plants of S. imbricata Forssk	Ethanolic and methanolic extracts	Muhaisnah desert, Dubai, UAE	^84
Hepatoprotective effect	Aerial parts of S. tetrandra and S. baryosma	70% Ethanol-water	Saudi Arabia	^113
Hepatoprotective effect	S. villosa and S. volkensii	Aqueous-alcoholic extract	Egypt	^114
Effects on the gastrointestinal system
Gastroprotective	S. komarovii	50% Alcohol extract	Korea	^115
Gastroprotective	S. tetrandra	70% Alcoholic extract	El Doubia at ElRiyadh- El Dallamroad, Saudi Arabia	^71
Anthelmintic Activity	Bark of S. imbricata	Chloroform extract	Bahawalpur District, Pakistan	^116
Antispasmodic	S. baryosma	Ethyl acetate fraction	Cholistan desert, Pakistan	^109
Antispasmodic and bronchorelaxant activities	Aerial parts of S. imbricata	Aqueous-ethanol extract	Cholistan desert, district Bahawalpur, Pakistan	^117
Improving gastric emptying	S. collina	Ethyl acetate extract	–	^118
Antidiabetic activity
α-amylase inhibitory activity	S. kali	Ethyl acetate fraction	Calabria, Italy	^65
Moderate α-amylase inhibitory activity	Whole plant of S. collina Pall	N-Acetyltryptophan isolated from 80% EtOH extract	Shandong province, China	^66
α-Glucosidase and α-Amylase enzyme inhibitory	S. vermiculata and S. baryosma	Phenolic extract	Algeria	^22
Aldose reductase inhibition	Aerial parts and cultivated buds of wild S. soda	The n-BuOH extracts	Pisa, Italy	^10
Effect on neurodegenerative diseases
Nerve growth factor induction	Aerial parts of S. komarovii	80% Methanol extract	Jejudo, Korea	^89
Anti-Alzheimer's, and antioxidant activity	Aerial parts of S. oppositofolia, S. soda, and S. tragus	Alkaloid extract	Central and Southern Italy	^48
Acetylcholinesterase inhibitory activity	Root of S. vermiculata	Methanol extract	Marsa Matrouh, Egypt	^68
Acetylcholinesterase inhibitory activity	Aerial parts of S. grandis	96% EtOH extract	Ankara, Turkey	^70
Butyrylcholinesterase inhibitory activity	S. baryosma	Chloroform extract	Pakistan	^90
Contraceptive activity
Contraceptive effect on Female sheep and rats	S. tuberculatiformis	96 % Ethanol extract	South West Africa	^119
Contraceptive effect on male rats	S. imbricata Forssk	Ethanol extract	Muhaisnah Desert, Dubai, UAE	^104
Effect on melanin biosynthesis
Tyrosinase enzyme inhibitory activity	S. foetida	Trans-N-feruloyltyramine derivatives	Lal Sohanra National Forest Park of Bahawalpur, Pakistan	^78
Antimicrobial activity
Antibacterial	Aerial parts of S. villosa	Chloroform extract and isolated compounds	Arar, Saudi Arabia	^91
Antibacterial	Roots of S. imbricata	Biphenylsalsonoids A and B	Arar, Saudi Arabia	^92
Antibacterial	S. kali L. stem	Methanol extract	Borj-Cédria coastal Region, Tunis	^75
Antibacterial and antifungal activities	S. cyclophylla	Essential oil	Qassim region, Saudi Arabia	^41
Antibacterial	Roots of S. vermiculate	Ethanolic extract	Monastir, Tunisia	^42
Antifungal activity	Aerial parts of S. vermiculate	Aqueous extract	kanadssa Bechar, Algeria	^120
Antifungal activity	S. collina Pall	Terrestric acid	Shandong province, China	^66
Insecticidal activity
against Trogoderma granarium	Leaves of S. baryosma (schultes)	Ethanol extract	Pakistan	^121

5.1. Effect on the cardiac system and blood pressure

One of the early reported pharmacological activities of Salsola spp. is their antihypertensive action. Different Salsola spp. are used as ingredients in different Chinese patents obtained from Faming Zhuanli Shenqing for treating hypertension. Of these, S. collina was the most extensively used sp. as indicated by the number of patents addressed this particular plant. Also, S. ruthenica and S. arbuscula were used in some Chinese patents. Likewise, S. ruthenic, a synonym for S. tragus, was reported as a potential treatment for essential hypertension¹⁰⁵. Ammon et al.⁸¹ attributed the antihypertensive activity of S. kali and S. longifolia Forsk to salsoline 1.16 and salsolidine 1.19 alkaloids due to their ability to stimulate respiration and to decrease blood pressure⁸¹.

Loizzo et al.¹⁰⁶ investigated the inhibitory activity of different extracts of the aerial parts of S. oppositifolia Desf., S. soda L., and S. tragus against the angiotensin-converting enzyme (ACE). The ethyl acetate extracts of S. oppositifolia and S. soda showed interesting activities with IC₅₀ values of 181.04 and 284.27 µg/mL, respectively which further support the traditional antihypertensive use of these species.

The aqueous extract of the whole shrub of S. kali was reported to display a cardioprotective effect against adriamycin-induced cardiotoxicity in male Swiss albino mice¹⁰⁷. This effect was attributed to lowering the oxidative stress in the heart and inhibiting lipid peroxidation¹⁰⁷.

5.2. Anti-inflammatory, analgesic, and antipyretic activities

Janbaz et al.¹⁰⁸ tested the aqueous-ethanol extract of the aerial parts of S. imbricata to assess its traditional use in inflammatory conditions. They confirmed the anti-inflammatory activity of S. imbricata as it significantly inhibited carrageenan-induced paw edoema in rats. The same research group also tested the analgesic activity of S. imbricata extract using NaCl-induced writhing and formalin-induced paw licking models in rats. Their obtained results indicated that S. imbricata exhibited a dose-dependant analgesic activity by reducing the number of abdominal writhing mediated by 4% NaCl intraperitoneal injection at all tested doses (100, 300, and 500 mg/kg)¹⁰⁸. Nevertheless, it decreased the time of paw licking by rats only at the dose of 500 mg/kg. Also, S. imbricata showed significant antipyretic activity in the brewer’s yeast-induced pyrexia model in rats¹⁰⁸. The aqueous methanolic extract of S. imbricata leaves and the phenolic compounds isolated from it decreased the NO production levels in in-vitro LPS-induced inflammation in RAW 264.7 macrophage cells and were found to be non-toxic at the concentration of 100 µg/mL⁸⁰. Regarding the tested phenolic compounds, isorhamnetin-3-O-glucopyranoside 5.8 displayed higher activity than its corresponding galactopyranoside glycoside 5.7 and aglycone 5.4⁸⁰.

The anti-inflammatory and antinociceptive activities of S. grandis were tested using the carrageenan-induced paw edoema model in rats and p-benzoquinone-induced nociception tests in mice, respectively⁷⁷. The ethanolic extract obtained from the aerial parts of S. grandis was fractionated and the most bioactive fraction (n-BuOH) was further subjected to a bioassay-guided fractionation to isolate the compounds responsible for S. grandis’s activity. The flavonoidal compounds, tiliroside 5.14 and quercetin-3-O-β-D-galactoside 5.19 displayed the highest activities in the used models⁷⁷.

The anti-inflammatory activity of different extracts of the aerial parts of S. cyclophylla was evaluated by Mohammed et al.¹⁵ using the carrageenan-induced paw edoema method. The aqueous-ethanolic extract showed the highest anti-inflammatory activity among the tested extracts and its activity was close to the well-known anti-inflammatory drug, diclofenac. Mohammed et al. attributed this anti-inflammatory activity to the antioxidant potential of the phenolic and flavonoid components present in the aqueous-ethanolic extract. The same research group also investigated the analgesic activity of S. cyclophylla using the hot-plate and acetic-acid writhing models in mice. The aqueous ethanolic extract showed the highest activity with 87.50– 99.66% pain reduction rates after different time intervals, which was comparable to the diclofenac activity¹⁵.

Seo et al.³⁷ reported that the ethanol extract of S. komarovii showed effective anti-inflammatory activity as hydrocortisone by reducing the production of LPS-induced IL-6. It also exerted glucocorticoid receptor binding activity and interfered with NF-κB nuclear translocation³⁷.

The synthetic analogue of the active principle of S. tuberculata, 2–(4-acetoxyphenyl)2-chloro-N-methylethylammonium-chloride, was reported to inhibit UVB induced intracellular interleukin-1 alpha (icIL-1α) in the UVB in-vitro model for inflammation¹²². Contrarily, the methanol extract of S. tuberculata exerted a pro-inflammatory activity by boosting the UVB induced-icIL-1α production and enhanced cytotoxicity. While the dichloromethane extract showed no significant effect on skin cells inflammation¹²². The investigated synthetic analouge was also suggested to exert its anti-inflammatory and contraceptive activities by competitive inhibition of glucocorticoid binding to corticosteroid-binding globulin (CBG) leading to increased levels of the in-vivo free corticosterone^123,124.

5.3. Antioxidant and iron chelation activities

The antioxidant potential is one of the most extensively studied activities of Salsola species. It could be concluded from the reported results that the used plant parts and the extraction solvent could greatly affect the antioxidant activity. Flavonoids and their glucosidal derivatives are mostly the responsible compounds for antioxidant activities. While other compounds, such as essential oil components, alkaloids, and biphenylpropanoids showed only moderate activities.

The antioxidant activity of S. cyclophylla extracts was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay method¹⁵. The best DPPH-free radicals scavenging potential was observed for the aqueous-ethanolic extract that showed comparable activity to the used standard, quercetin. While, the ethyl acetate extract showed the highest ferrous ions (Fe²⁺) chelating activity using ferrozine-based assay¹⁵. The same group reported the antioxidant activity of the essential oil obtained by water distillation of S. cyclophylla that showed only one-half of the quercetin activity. They attributed this activity to the benzoic acid esters and the hexahydrofarnesyl acetone components that occur in the essential oil in high concentrations⁴¹.

Antioxidant and iron chelation activities of the methanolic extract of different plant parts of S. kali were also investigated by Boulaaba et al.⁷⁵ using the same methods used for S. cyclophylla extracts. Leaf and stem extracts showed the highest antioxidant activity while leaf and root extracts showed the highest iron chelation activity⁷⁵.

The alkaloidal extracts of S. oppositofolia, S. soda, and S. tragus were prepared by extraction of their aerial parts with methanol, alkalinization with NH₄OH then extraction with ethyl acetate. The three alkaloidal extracts showed significant antioxidant activity when tested using the DPPH method. Remarkably, S. oppositifolia showed the highest activity with an IC₅₀ value of 16.30 µg/mL⁴⁸.

Oueslati et al.⁹² investigated the antioxidant activity of biphenylsalsonoids A (10.2) and B (10.3) isolated from the ethyl acetate fraction of the roots of S. imbricata using DPPH and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS⁺) assay methods. The two compounds showed moderate antioxidant activity⁹². Trans-N-feruloyltyramine derivatives isolated from S. foetida (1.3, 1.4, and 1.8) exhibited moderate antioxidant activity with IC₅₀ ranging from 378 to 427 µM using DPPH radical scavenging assay⁷⁸.

The ethyl acetate extract of S. komarovii aerial parts was subjected to HPLC separation and the obtained elutes were tested for antioxidant activity using ABTS⁺ radical scavenging method. The components responsible for the antioxidant activity were identified by HPLC-MS as the flavonoids, isorhamnetin 5.4, astragalin 5.15, isoquercitrin 5.20, and rutin 5.25⁷⁹.

The ethyl acetate fraction of S. baryosma showed 77% DPPH radicals scavenging activity while other tested fractions showed lower activities below 57%¹⁰⁹. This result is contradictory with that obtained by Khacheba et al.¹²⁵ who reported weak antioxidant activity of S. baryosma ethyl acetate extract using DPPH assay.

The antioxidant activity of 80% (v/v) aqueous-methanol extracts of S. vermiculata and S. baryosma in addition to other Algerian herbs was tested using the hydroxyl (OH^•), nitroxide (NO^•) and (ABTS⁺) radicals scavenging assays, and Fe³⁺–TPTZ complex reductive power assay. The results showed that S. baryosma exhibited the highest antioxidant activity in OH^• radical assay with an EC₅₀ of 0.26 ppm despite its low phenolic content²².

Beyaoui et al.⁵⁹ investigated the antioxidant activity of two compounds, tetranins A and B, isolated from the ethyl acetate extract of S. tetrandra roots using DPPH and ABTS assays. The dihydrostilbene, tetranin A 8.27 exerted higher antioxidant activity than the isoflavonoid, tetranin B 5.37. However, both compounds showed lower activity than the standard antioxidant, Trolox⁵⁹.

The ethanol extract of S. collina Pall demonstrated anti-oxidative activity through DPPH radical scavenging capacity (Oh et al., 2014).

5.4. Cytotoxic activity

Only a few studies were made for investigating the cytotoxic activity of a small number of Salsola spp., including S. cyclophylla, S. oppositifolia, S. collina Pall, and S. baryosma. The cytotoxic activity of 95% aqueous-ethanolic extract of the aerial parts of S. cyclophylla was investigated using MTT assay against M14 melanoma derived epithelial breast cancer (MDA cells), human pancreatic cancer (PANC-1), Michigan Cancer Foundation-7 (MCF-7) breast cancer cells, and the normal human fibroblast cells. The aqueous-ethanolic extract of S. cyclophylla showed low to moderate cytotoxic activity only at high concentrations (50–400 µg/mL) against the tested cell lines and no significant cytotoxic effect was observed at low concentration (< 50 µg/mL)¹⁵.

Different fractions obtained from the extract of the aerial parts of S. oppositifolia were screened for cytotoxic activity against a panel of cancer cell lines⁸⁵. The n-hexane fraction showed the highest cytotoxic activity on lung carcinoma (COR-L23) and amelanotic melanoma (C32) cell lines with IC₅₀ values of 19.1 μg/mL and 24.4 μg/mL, respectively. The dichloromethane fraction also demonstrated cytotoxic activity against these two cell lines with IC₅₀ values of 30.4 μg/mL and 33.2 μg/mL for COR-L23 and C32 cell lines, respectively. The ethyl acetate fraction exhibited a selective moderate cytotoxic activity against breast cancer, MCF-7 cells (IC₅₀ 67.9 μg/mL). The major constituents isolated from the ethyl acetate fraction, isorhamnetin-3-O-glucopyranoside 5.8 and isorhamnetin-3-O-rutinoside 5.5 also demonstrated a potential activity against MCF-7 with IC₅₀ values of 18.2 and 25.2 μg/mL, respectively. Additionally, isorhamnetin-3-O-rutinoside 5.5 showed high activity against the hormone-dependent prostate carcinoma cell line (LNCaP) with an IC₅₀ value of 20.5 μg/mL⁸⁵.

The ethanol extract of S. collina Pall showed cytotoxic activity against human colon carcinoma cells (HT29). It resulted in a reduction in the number and size of the cells through cell cycle regulation and caused cell arrest in the G2/M phase¹¹⁰.

The ethanol extract of S. baryosma whole plant showed no significant cytotoxic activity when tested with other plant extracts using the brine shrimp method¹²⁶. The same result was reported by Ahmed et al.¹⁰⁹, while 80% ethanol extract of S. baryosma did not exhibit cytotoxic activity against brine shrimp larvae and only the ethyl acetate fraction showed 50% cytotoxic activity. However, all tested fractions of S. baryosma showed phytotoxicity against Lemna minor plant growth¹⁰⁹.

5.5. Effect on the immune system

Interestingly, S. laricifolia Turcz is reported to be one of the immune system-boosting drugs, and a pharmaceutical product derived from it “Salimon” represents one of the best-selling immunostimulant drugs in the Mongolian drug market⁷⁶.

5.6. Effect on the liver and the gallbladder

Lochein, a liquid extract of the Russian thistle S. collina Pall., was reported to show a significant hepatoprotective effect on patients with chronic hepatitis¹²⁷. It also has been approved as an active food supplement by the Ministry of Health of the Russian Federation¹¹¹. Ethanol extract (25%) of the aerial parts of S. collina Pall. was reported to decrease the signs of paracetamol-induced liver damage in rats and to exert a better hepatoprotective activity than the reference drug, silymarin¹¹¹. It was also reported to decrease the levels of the liver enzymes and lipid peroxidation products and to enhance the detoxification of bilirubin, and ammonia¹¹¹. Moreover, S. collina aqueous extract was reported to protect against cholelithiasis in rabbits through enhancing cholesterol and water absorption and decreasing inflammation and formation of biliary slough¹¹².

Oral administration of S. imbricata methanol extract was reported to prevent liver toxicity in CCl₄-induced hepatotoxicity in mice. This hepatoprotective activity was attributed to the ability of the phenolic content of S. imbricata to enhance the antioxidant capacity of the liver⁸⁴.

Ethanol extracts (70%) of S. tetrandra and S. baryosma showed a prophylactic and therapeutic hepatoprotective activity against paracetamol-induced hepatorenal toxicity in rats¹¹³. The results showed that S. tetrandra was more active and showed a higher ability to decrease the levels of inflammatory markers, such as interleukin-1β (IL-1β) and tumour necrosis factor alpha (TNF-α)¹¹³.

The alcoholic extracts of S. volkensii and S. villosa showed hepatoprotective effects with a broad safety margin against CCl₄-induced hepatotoxicity in Sprague Dewaly rats indicating their potential use for the treatment of liver damage¹¹⁴,.

5.7. Effects on the gastrointestinal system

Different plants of the Salsola genus were reported to exert several effects on the gastrointestinal tract, including gastroprotective activity against ulcer, anthelmintic, and antispasmodic activities.

Alcoholic extract (50%) of S. komarovi in 500 mg/kg concentration was found to significantly protect against gastric ulcer and to be more potent than Ranitidine (300 mg/kg) in 60% HCl-ethanol induced gastritis model¹¹⁵. While 70% alcoholic extract of S. tetrandra showed a similar gastroprotective effect to that of Ranitidine against aspirin-induced gastric ulceration in rats⁷¹.

Chloroform extract of S. imbricata bark demonstrated anthelmintic activity against Haemonchus contortus worms¹¹⁶. Ethanol extract (80%) of S. baryosma (synonym for S. imbricata) demonstrated antispasmodic activity as it inhibited the rabbit jejunum contraction at a concentration of 0.3–3 mg/mL¹⁰⁹. It was suggested to act as a calcium channel blocker because it resulted in 70% inhibition of K⁺-induced contractions in rabbit jejunum at the concentration of 1–5 mg/mL¹⁰⁹. The ethyl acetate fraction of the aerial parts extract of the same sp. showed the highest spasmolytic and bronchorelaxant activities on isolated rabbit jejunum and tracheal preparations which were suggested to be due to its agonist action on β-adrenergic receptors and Ca⁺² antagonising activity¹¹⁷.

On the other hand, the ethyl acetate extract of S. collina was reported to increase the gastric motility and gastric emptying rate through activating M-cholinergic receptor, increasing ghrelin and gastrin plasma levels and increasing the expression of the vasoactive intestinal peptide receptors in rats^118,128.

5.8. Antidiabetic activity

Decreasing post-prandial hyperglycaemia by inhibiting digestive enzymes involved in carbohydrate hydrolysis, such as α-amylase and α-glucosidase enzymes is a commonly used therapeutic approach for the management of diabetes. Therefore extensive studies were made on the α-amylase and α-glucosidase inhibitory activity of different Salsola spp.^22,65.

The α-amylase inhibitory activity of different fractions of the aerial parts of S. kali, S. soda, and S. oppositifolia was investigated by Tundis et al.⁶⁵. The ethyl acetate fraction of S. kali showed the highest α-amylase inhibitory activity with an IC₅₀ value of 0.022 mg/mL. The bioassay-guided chromatographic separation of this most active fraction resulted in the isolation of two flavonol glycosides, of which isorhamnetin-3-O-rutinoside 5.5 displayed significant α-amylase inhibitory activity with an IC₅₀ value of 0.129 mM⁶⁵.

Djeridane et al.²² investigated the antidiabetic potential of the aqueous-methanol extracts of S. vermiculata and S. baryosma by testing their ability to inhibit α-amylase and α-glucosidase enzymes activities. The results indicated that S. baryosma exhibited the highest competitive inhibitory activity with inhibition constant (K_i) values of 7 and 16 µM against α-amylase and α-glucosidase, respectively suggesting its potential for type 2 diabetes management²². Similarly, N-acetyltryptophan 1.1 isolated from S. collina Pall by Jin et al.⁶⁶ showed 44% inhibition of α-amylase enzyme activity.

Iannuzzi et al.¹⁰ studied the chemical profile of the cultivated buds of S. soda and compared it to that of the wild plant. They also screened the inhibitory activity of the compounds isolated from their n-BuOH fraction against three enzymes of the aldo/keto reductase superfamily, namely aldose reductase (hAKR1B1), aldose-reductase-like protein (hAKR1B10), and carbonyl reductase 1 (hCBR1). They found that quercetin-3-​O-​glucuronopyranoside 5.22, the only flavonoid identified in both plant types was the most effective inhibitor for the tested enzymes and suggested its use as a functional nutraceutical to counteract diabetic complications¹⁰.

5.9. Effect on neurodegenerative diseases

The effect of the isolated compounds from the methanol extract of S. komarovii aerial parts on the production of the endogenous Nerve Growth Factor (NGF) in C6 glioma cells was investigated by Cho et al.⁸⁹. The lignan derivative, conicaoside 6.3 showed the highest NGF-production stimulating activity and the lowest toxicity among the tested compounds indicating its potential for the regulation of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases⁸⁹. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases that is combined with acetylcholine deficiency. Therefore, it can be improved by inhibiting the enzymes affecting the cleavage of acetylcholine, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

The ethanolic extract of the aerial parts of S. grandis and the different compounds isolated from its n-BuOH sub-extract were investigated for AChE inhibitory activity by Orhan et al.⁷⁰. Only N-acetyltryptophan 1.1 showed AChE inhibitory activity suggesting its neuroprotective potential against Alzheimer’s disease⁷⁰.

The methanolic extract of S. vermiculata root demonstrated strong anti-acetylcholinesterase inhibitory activity which was higher than that of S. vermiculata aerial parts and S. tetrandra roots and aerial parts. It showed an IC₅₀ of 0.45 ± 0.17 mg/mL. While the standard drug, eserine showed IC₅₀ of 0.27 ± 0.1 mg/mL⁶⁸. This activity could be attributed to the rich catecholamines content in S. vermiculata root⁶⁸.

The alkaloidal extracts of S. tragus, S. soda, and S. oppositifolia Desf. were screened for AChE and BChE inhibitory activities⁴⁸. S. tragus showed the highest inhibitory activity with IC₅₀ of 30.2 and 26.5 µg/mL against AChE and BChE, respectively. While S. soda and S. oppositifolia Desf. showed selective inhibition of BChE with IC₅₀ values of 34.3 and 32.7 µg/mL, respectively⁴⁸. Salsolic acid 7.12 and other two triterpenes 7.2 & 7.8 isolated by Ahmad et al.⁹⁰ from the chloroform extract of S. baryosma were reported to inhibit the BChE enzyme⁹⁰.

5.10. Effect on fertility

The contraceptive activity of Salsola plants was firstly described by Ploss in 1960. He reported the use of the aqueous extract of an undefined Salsola sp. as an oral contraceptive in Algeria⁴⁰. The aqueous extract of S. tuberculatiformis (previously known as S. tuberculate and commonly known as Gannabos) was reported to be used by Bushmen women as an oral contraceptive and to cause prolonged gestation and foetal post-maturity in Karakul sheep in Namibia region, South Africa^40,119,129. Swart et al.⁴⁰ investigated the phytochemicals responsible for this activity in S. tuberculatiformis. The compound responsible for this activity was reported to be a labile synephrine analogue with a reactive aziridine group. Therefore, they synthesised the compound, 2–(4-acetoxyphenyl)2-chloro-N-methylethylammonium-chloride, as a stable analogue for the active principle of S. tuberculatiformis. This compound was found to disturb the mammalian steroid hormones homeostasis and to inhibit adrenal steroidogenesis⁴⁰.

The ethanolic extract of S. imbricata was reported to cause a slight decrease in the testis weight and to cause a significant decline in the sperm count when administered orally to male albino rats suggesting its potential use as a reversible male contraceptive, with a high safety margin¹⁰⁴. They attributed this contraceptive activity to the phenolic content of the plant, especially quercitrin¹⁰⁴.

5.11. Effect on melanin biosynthesis

Trans-N-feruloyltyramine derivatives (1.3, 1.4, and 1.8) isolated from S. foetida were reported to exhibit significant tyrosinase enzyme inhibitory activity with IC₅₀ ranging from 0.40–2.61 µM which was lower than that of the standard tyrosinase inhibitors, kojic acid and L-mimosine, with IC₅₀ of 16.67 and 3.68 µM, respectively. Therefore, these derivatives could have promising activities on melanocytes and skin pigmentation abnormalities⁷⁸.

5.12. Antimicrobial activity

The chloroform extract of the aerial parts of S. villosa and the compounds isolated from it were tested against different bacterial strains using the paper disc diffusion method⁹¹. The isolated compound biphenylsalsinol 10.1 showed the highest antimicrobial activity against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacterial strains with an inhibitory zone diameter (IZD) ranging from 12.33 to 28.66 mm. While salsolanol 12.1 showed slight activity against S. aureus, E. coli, S. epidermidis with IZD ranging from 9.33 to 12.66 mm⁹¹. Oueslati et al.⁹² also investigated the antibacterial activity of the roots of S. imbricata and the bioactive compounds, biphenylsalsonoid A 10.2 and B 10.3, isolated from its ethyl acetate fraction. The two isolated compounds showed similar antibacterial activity against S. aureus, S. epidermidis and E. coli with MIC values ranging from 16–32 µg/mL⁹². While biphenylsalsonoid A 10.2 was two times more active than biphenylsalsonoid B 10.3 against Micrococcus luteus. It is worth noting that both compounds showed lower activity than the standard drug, Kanamycin which showed MIC values ranging from 2–8 µg/mL⁹²

The antimicrobial activities of the methanol extract of S. kali leaves and stems were investigated by Boulaaba et al.⁷⁵. The stem extract showed higher activity than the leaf extract. It showed antibacterial activity against P. aeruginosa and M. luteus with an inhibition zone diameter (IZD) of 10 mm. It showed weak or slight activity against other bacterial pathogens and Candida sp.⁷⁵.

Mohammed et al.⁴¹ investigated the antimicrobial activity of S. cyclophylla essential oil against different microorganisms using the agar well-diffusion method. It showed good antibacterial activity against the Gram + ve, S. aureus and Streptococcus pyogenes, and the Gram -ve, P. aeruginosa, and E. coli. However, it had no activity against S. epidermidis. It also demonstrated powerful antifungal activity against C. albicans⁴¹.

Gannoun et al.⁴² investigated the antimicrobial activities of S. vermiculate leaf, root, and stem extracts and their volatile fractions towards different pathogens. They reported that the ethanolic roots extract showed the highest activity against S. aureus with a MIC value of 0.28 mg/mL⁴². The used extracts showed low antifungal activity against the tested fungal sp. with IZD ranging from 6–9.5 mm⁴². On the other hand, S. vermiculata aqueous extract was reported to be an effective antifungal agent that can be used as a preservative during grain storage. This activity was examined by the decrease of fungal growth on wheat samples that were coated with S. vermiculata aqueous extract, dried, and stored for one year¹²⁰.

Terrestric acid 1.20 isolated from S. collina Pall by Jin et al.⁶⁶ showed antifungal activity against Candida albicans with a minimum 80% inhibitory concentration (MIC₈₀) of 8 µg/mL⁶⁶. The alkaloid salsoline A (trolline) 1.17, present in S. collina Pall. and the flowers of Trollius chinensis, was reported to exhibit significant antibacterial activity against S. aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae. It also exhibited moderate antiviral activity against influenza viruses A and B⁴⁶.

5.13. Insecticidal activity

The ethanol extract of S. baryosma was reported to cause moderate insecticidal activity (22.08% mortality) against Trogoderma granarium insects (Everts) which was lower than the standard insecticidal compound, cypermethrin (37.64% mortality)¹²¹.

6. Conclusion

The impressive diversity of the pool of phytochemicals of Salsola spp. is comprehensively studied in this review. Furthermore, up-to-date taxonomic classification and description of the important morphological characteristics of the plants of this genus were discussed herein. The phytochemical profile of Salsola spp. is composed of alkaloids, nitrogenous compounds, flavonoids and isoflavonoids, triterpenoids, cardenolides and steroids, coumarins, coumarolignans, lignans and diphenylpropanoids, and simple phenolic acids. These secondary metabolites represent a great interest for the chemotaxonomy of the genus. Furthermore, they would support the diverse traditional medicinal uses and pharmacological activities of Salsola species demonstrated by many reports as antihypertensive, immunostimulant, anti-inflammatory, hepatoprotective, anthelmintic, antispasmodic, and antidiabetic. The current study represents a guiding light for researchers studying such widely distributed wild medicinal plants.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code (22UQU4290565DSR42), [email protected].