Metabolomic Profiling and DNA-Fingerprinting of Newly Recorded White-Flowered Populations of Salvia lanigera Poir. in Egypt.

Salvia lanigera Poir. is a small herbaceous perennial species with violet flowers that grows in low-altitude deserts, and sandy loam. During the collection of S. lanigera, unusual populations with white flowers were found. Therefore, the two populations (violet- and white-flowered) were subjected to comparative investigations, including DNA fingerprinting, chemical composition, and biological evaluation. The two populations showed DNA variations, with 6.66 % polymorphism in ISSR and 25 % in SCoT markers. GC/MS and UHPLC/HRMS of aqueous methanol extracts, led to the tentative identification of 43 and 50 compounds in both populations. In addition, the structures of nine compounds, including four first-time reported compounds in the species, were confirmed by NMR. Furthermore, the total extracts exhibited weak radical scavenging activity against DPPH and a lower inhibitory effect towards acetylcholinesterase. In conclusion, the obtained data suggested that the white-colored flower could be an additional important character record for the Egyptian S. lanigera.

Retraction notice to "Dobera glabra (Forssk.) Poir. (Salvadoraceae); Phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities" [Heliyon 7 (2021) e06205].

[This retracts the article DOI: 10.1016/j.heliyon.2021.e06205.].

Discriminative Metabolomics Analysis and Cytotoxic Evaluation of Flowers, Leaves, and Roots Extracts of Matthiola longipetala subsp. livida.

Matthiola longipetala subsp. livida is an annual herb in Brassicaceae that has received little attention despite the family's high reputation for health benefits, particularly cancer prevention. In this study, UPLC-HRMS-MS analysis was used for mapping the chemical constituents of different plant parts (i.e., flowers, leaves, and roots). Also, spectral similarity networks via the Global Natural Products Social Molecular Networking (GNPS) were employed to visualize their chemical differences and similarities. Additionally, the cytotoxic activity on HCT-116, HeLa, and HepG2 cell lines was evaluated. Throughout the current analysis, 154 compounds were annotated, with the prevalence of phenolic acids, glucosinolates, flavonol glucosides, lipids, peptides, and others. Predictably, secondary metabolites (phenolic acids, flavonoids, and glucosinolates) were predominant in flowers and leaves, while the roots were characterized by primary metabolites (peptides and fatty acids). Four diacetyl derivatives tentatively assigned as O-acetyl O-malonyl glucoside of quercetin (103), kaempferol (108 and 112), and isorhamnetin (114) were detected for the first time in nature. The flowers and leaves extracts showed significant inhibition of HeLa cell line propagation with LC50 values of 18.1 ± 0.42 and 29.6 ± 0.35 µg/mL, respectively, whereas the flowers extract inhibited HCT-116 with LC50 24.8 ± 0.45 µg/mL, compared to those of Doxorubicin (26.1 ± 0.27 and 37.6 ± 0.21 µg/mL), respectively. In conclusion, the flowers of M. longipetala are responsible for the abundance of bioactive compounds with cytotoxic properties.

Feature-Based Molecular Networking for the Exploration of the Metabolome Diversity of Common Egyptian Centaurea Species in Relation to Their Cytotoxic Activity.

Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 µM against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2.

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

Molecular Networking Leveraging the Secondary Metabolomes Space of Halophila stipulaceae (Forsk.) Aschers. and Thalassia hemprichii (Ehrenb. ex Solms) Asch. in Tandem with Their Chemosystematics and Antidiabetic Potentials.

The Red Sea is one of the most biodiverse aquatic ecosystems. Notably, seagrasses possess a crucial ecological significance. Among them are the two taxa Halophila stipulacea (Forsk.) Aschers., and Thalassia hemprichii (Ehrenb. ex Solms) Asch., which were formally ranked together with the genus Enhalus in three separate families. Nevertheless, they have been recently classified as three subfamilies within Hydrocharitaceae. The interest of this study is to explore their metabolic profiles through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS/MS) analysis in synergism with molecular networking and to assess their chemosystematics relationship. A total of 144 metabolites were annotated, encompassing phenolic acids, flavonoids, terpenoids, and lipids. Furthermore, three new phenolic acids; methoxy benzoic acid-O-sulphate (16), O-caffeoyl-O-hydroxyl dimethoxy benzoyl tartaric acid (26), dimethoxy benzoic acid-O-sulphate (30), a new flavanone glycoside; hexahydroxy-monomethoxy flavanone-O-glucoside (28), and a new steviol glycoside; rebaudioside-O-acetate (96) were tentatively described. Additionally, the evaluation of the antidiabetic potential of both taxa displayed an inherited higher activity of H. stipulaceae in alleviating the oxidative stress and dyslipidemia associated with diabetes. Hence, the current research significantly suggested Halophila, Thalassia, and Enhalus categorization in three different taxonomic ranks based on their intergeneric and interspecific relationship among them and supported the consideration of seagrasses in natural antidiabetic studies.

Dobera glabra (Forssk.) Poir. (Salvadoraceae); phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities.

BACKGROUND: The plant kingdom is considered one of the most common sources for structural and biological diversity. In particular, the wild category acquires our attention to investigate the phytochemical and the biological evaluations. METHODS: Dobera glabra was exposed to phytochemical examination using HPLC-ESI-MS analysis. Furthermore, the anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema model, whereas both the central and peripheral analgesic activities were tested via hot plate test in rats and acetic acid-induced writhing in mice, respectively. RESULTS: Twenty phenolic compounds of D. glabra aqueous leaves extract were emphasized by liquid chromatography coupled with mass spectrometry. Moreover, D. glabra exhibited both anti-inflammatory and peripheral analgesic activities. Furthermore, D. glabra significantly decreased the immune expression of MMP-9, TNF-α and TGF-ß1 in the hind paw of rats. CONCLUSION: D. glabra possess peripheral anti-nociceptive and anti-inflammatory effects in rats mediated through its anti-oxidant and anti-inflammatory activities. The activity of D. glabra leaves extract might be attributed to the presence of hydroxy and keto structures.

Morphological, phytochemical and anti-hyperglycemic evaluation of Brachychiton populneus

Abstract Brachychiton populneus (Schott & Endl.) R.Br., Malvaceae, is one of five Brachychiton species cultivated in Egypt. Little information was found concerning the morphological, phytochemical and biological investigations of B. populneus. Morphological investigations of B. populneus were performed on fresh and dried leaves. Air-dried, ground leafy branches were extracted with 70% methanol/water yielding B. populneus extract. Seventeen flavonoids were isolated and identified using different chromatographic and spectroscopic techniques; eleven of them were reported for the first time from this plant. Potential activity of B. populneus extract against alloxan inducing oxidative stress and diabetes in male rats was preliminary investigated (four groups of ten rats /group). B. populneus extract (500 mg/kg bw i.p.) exhibited significant acute anti-hyperglycemic activity with blood glucose levels of 227.3 and 157.6 mg/dl after 4 and 24 h, respectively, compared to alloxan and standard Diamicron (5 mg/kg bw p.o.) groups, as well as to a normoglycemic control group at p < 0.05. The extract reverted the body weight values of the alloxan-induced diabetic rats to that of control animals after 24 h. In addition, B. populneus extract counteracted the effect of the oxidative stress induced by alloxan causing significantly increase in the glutathione content level (2.35 mmol/l) and relative decrease in the malondialdehyde level (21.31 nmol/l) and nitric oxide content (1.98 µmol/l) in serum after 24 h of treatment compared to alloxan-induced diabetic rats (1.01 mmol/l, 118.9 nmol/l, 4.69 µmol/l, respectively) and to normoglycemic control at p < 0.05. These effects appear to be related to the flavonoid principles. The intergeneric relationship of the genus Brachychiton and other related genera assessed well-supported differentiation between them. Furthermore, a significant dissimilarity was observed at interspecific level.

Phenolic constituents of Pulicaria undulata (L.) C.A. Mey. sub sp. undulata (Asteraceae): Antioxidant protective effects and chemosystematic significances.

One new naturally isoflavone compound, 5,7,2',3',4' penta hydroxyl isoflavone-4'-O-ß-glucopyranoside (1) was isolated from the aqueous methanol extract (AME) of Pulicaria undulata subsp. undulata, together with seven known compounds: kaempferol (2), kaempferol 3-O-ß-glucoside (3), quercetin (4), quercetin 3-O-ß-glucoside (5), quercetin 3-O-ß-galactoside (6), quercetin 3,7-di OCH3 (7), and caffeic acid (8). Their structures were established through chemical (acid hydrolysis) and spectral analysis (UV, NMR, and ESIM). The AME and some isolated compounds were evaluated as protective agents. Free radical scavenging using a microscaled 2,2-diphenyl-1-picrylhydrazyl assay was used to assess the direct antioxidant properties that were evaluated by the ability to protect murine Hepa1c1c7 liver cells against damage induced by the organic peroxide tert-butyl hydroperoxide. The neutral red uptake assay (NRU) was used to record the activity. Results of the 2,2-diphenyl-1-picrylhydrazyl assay recorded differential scavenging properties in ascending order: 5,7,2',3',4' penta hydroxyl isoflavone-4'-O-ß-glucopyranoside>quercetin>quercetin 3-O-galactoside>caffeic acid>quercetin 3,7-di-OCH3>kaempferol with 50% inhibitory concentrations of 3.9 µM, 7.5 µM, 11.4 µM, 12.2 µM, 78.1 µM, and 252.3 µM, respectively. The antioxidative potential reveals the potency of AME, quercetin, and quercetin 3,7-di-OCH3. The latter compound showed full protection at 100 µM (33 µg/mL) against the induced toxicant effect where the 50% effective concentration was calculated as 33.6±1.7 µM (11.1 µg/mL). In addition to quercetin, which was extensively shown previously as a cytoprotective agent, AME was less potent; it was capable of protecting 75% at 100 µg/mL with 50% effective concentration of 92.3±4 µg/mL. Moreover, the isolated flavonoids were found to be significantly chemosystematic markers.

Flavonoid constituents of Dobera glabra leaves: amelioration impact against CCl4-induced changes in the genetic materials in male rats.

CONTEXT: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations. OBJECTIVE: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials. MATERIALS AND METHODS: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats. RESULTS: Isorhamnetin-3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-ß-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-ß-glucopyranoside, kaempferol-3-O-ß-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min). DISCUSSION AND CONCLUSION: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.

Chemosystematic significance of flavonoids isolated from Diplotaxis acris (Brassicaceae) and related taxa.

The chemosystematic relationship of four Diplotaxis species; Diplotaxis acris, Diplotaxis erucoides, Diplotaxis harra and Diplotaxis muralis were surveyed from the flavonoids point of view. These species were found to produce 33 flavonoids (7 flavones and 26 flavonols), including 11 compounds were isolated in the present study from D. acris. Among them, seven flavonoids were identified for the first time; luteolin (4), kaempferol (8), kaempferol 3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside (13), quercetin 3-O-ß-glucopyranoside (16), quercetin 7-O-ß-glucopyranoside (20), isorhamnetin (22) and isorhamnetin 3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside (32). Their structures were recognized on the basis of chemical and spectroscopic techniques (1D & 2D NMR, UV, EI & ESI/MS). The isolated flavonoids may provide useful taxonomic characters at the infraspecific levels of classification where the flavonoid profile of D. acris and D. harra is similar and different from the other species.

Phytochemical constituents and chemosystematic significance of Chrozophora tinctoria (L.) Raf.

Twelve compounds were isolated from Chrozophora tinctoria (L.) Raf. They were identified as kaempferol, kaempferol 3-O-ß-glucopyranoside, kaempferol 3-O-(6″-α-rhamnopyranosyl)-ß-glucopyranoside, quercetin, quercetin 3-O-ß-glucopyranoside, quercetin 3-O-(6″-α-rhamnopyranosyl)-ß-glucopyranoside, apigenin, apigenin 7-O-ß-glucopyranoside, acacetin, gallic acid, methyl gallate and ß-sitosterol-3-O-ß-glucopyranoside. Their structures were elucidated by chemical and spectral methods. Furthermore, chemosystematics of the isolated compounds is briefly discussed. It was indicated that C. tinctoria is the only species of Chrozophora that has the capability to synthesis kaempferol aglycone and their glycosides, and the finding is supported by its distinct morphological and anatomical aspects.

Two new flavonol glycosides and biological activities of Diplotaxis harra (Forssk.) Boiss.

Two new flavonol glycosides, isorhamnetin 3-O-ß-glucopyranoside-4'-O-ß-xylopyranoside (1) and kaempferol 3-O-ß-glucopyranoside -4'-O-ß-xylopyranoside (2), were isolated from the defatted aqueous methanol extract of the whole plant Diplotaxis harra along with 12 known flavonols (3-14). They were characterised by chemical and spectral methods. The 70% aqueous methanol, chloroform and defatted aqueous methanol plant extracts exhibited significant antioxidant effects (nitroblue tetrazolium reduction method). Their cytotoxic activity was carried out against 11 tumour cell lines (sulphorhodamine B assay). The three extracts expressed the greatest antiproliferative activity against colon 38, P388 and MKN-28 with GI50 (0.45, 0.4, 0.07 µg/mL) and against P388 [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay] with IC50 (0.26, 0.24, 0.25 µg/mL), respectively. The chloroform extract showed the highest activity as eukaryotic DNA topoisomerase II inhibitors of P388 with IC50 0.24 µg/mL. Antiviral screening of the extracts and the pure compounds against foot-and-mouth disease virus types A and O revealed a prominent inhibition of its cytopathic effect.

Flavonoid constituents and biological screening of Astragalus bombycinus Boiss.

Two new flavonoid compounds were isolated from Astragalus bombycinus Boiss. and identified as quercetin-3,7-di-O-ß-glucopyranoside 4'-O-α-rhamnopyranoside and 5,2',4'-trihydroxy-flavone-8-C-α-arabinopyranoside-7-O-ß-glucopyranoside. In addition, apigenin, apigenin-7-O-ß-glucopyranoside, apigenin 7-O-gentobioside, luteolin, luteolin-7-O-ß-glucopyranoside, quercetin-3,7-di-O-ß-glucopyranoside, quercetin-3-O-ß-glucopyranoside-7-O-α-rhamnopyranoside and daidzein were also isolated and identified. The structure elucidation of the isolated compounds was performed by chromatographic, chemical and spectroscopic methods. Antioxidant and cytotoxic activities were also determined for the four consecutive extracts of the plant.

A sulphated flavone glycoside from Livistona australis and its antioxidant and cytotoxic activity.

A new flavone glycoside tricin 7-O-ß-glucopyranoside-2″-sulphate sodium salt along with 14 known flavonoid compounds were isolated and identified from the aqueous methanol extract of Livistona australis leaves. Their structures were established on the basis of extensive NMR (¹H, ¹³C, HSQC and H-H COSY) and ESIMS data. Antioxidant and cytotoxicity properties of the methanol extract of the leaves as well as the new compound were investigated.