New coumarin from the roots of Prangos pabularia growing wild in Tajikistan.

Dichloromethane and butanol extracts of the roots of Prangos pabularia were analyzed to determine chemical constituents and biological activity. The new coumarin 1, yuganin B ((5-(((2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-((2-oxo-2H-chromen-7-yl)oxy)tetrahydro-2H-pyran-3-yl)oxy)-3,4-dihydroxytetrahydrofuran-3-yl)methyl 4-hydroxy-3-methoxybenzoate) along with three phenolic and twenty-four known coumarins were isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by UV, HR-ESIMS, and 1 D and 2 D NMR spectroscopy. In addition, the anti-melanogenic effect of several of the isolated individual compounds and their inhibitory effect on B16 cells were evaluated. Isolating and testing compounds may proof to be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

Mechanisms of anti-ulcer actions of Prangos pabularia (L.) in ethanol-induced gastric ulcer in rats.

Peptic ulcer disease is the greatest digestive disorder that has increased incidence and recurrence rates across all nations. Prangos pabularia (L.) has been well documented as a folkloric medicinal herb utilized for multiple disease conditions including gastric ulcers. Hence, the target study was investigation the gastro-protection effects of root extracts of Prangos pabularia (REPP) on ethanol-mediated stomach injury in rats. Sprague Dawley rats were clustered in 5 cages: A and B, normal and ulcer control rats pre-ingested with 1 % carboxymethyl cellulose (CMC)); C, reference rats had 20 mg/kg omeprazole; D and E, rats pre-supplemented with 250 and 500 mg/kg of REPP, respectively. After one hour, group A was given orally 1 % CMC, and groups B-E were given 100 % ethanol. The ulcer area, gastric acidity, and gastric wall mucus of all stomachs were determined. The gastric tissue homogenates were examined for antioxidant and MDA contents. Moreover, the gastric tissues were analyzed by histopathological and immunohistochemically assays. Acute toxicity results showed lack of any toxic effects or histological changes in rats exposed to 2 and 5 g/kg of REPP ingestion. The ulcer controls had extensive gastric mucosal damage with lower gastric juice and a reduced gastric pH. REPP treatment caused a significant reduction of the ethanol-induced gastric lacerations represented by an upsurge in gastric mucus and gastric wall glycoproteins (increased PAS), a decrease in the gastric acidity, leukocyte infiltration, positively modulated Bax and HSP 70 proteins, consequently lowered ulcer areas. REPP supplementation positively modulated oxidative stress (increased SOD, CAT, PGE2, and reduced MDA) and inflammatory cytokines (decreased serum TNF-α, IL-6, and increased IL-10) levels. The outcomes could be scientific evidence to back-up the folkloric use of A. Judaica as a medicinal remedy for oxidative stress-related disorders (gastric ulcer).

Identifying phenolics by UPLC-MS/MS in some Prangos Lindl. species and α-glucosidase inhibitory activities.

Diabetes mellitus is a chronic metabolic disorder associated with biochemical, physiological, and pathological changes in the liver and characterized by some deficiencies in insulin secretion or insulin action. Prangos Lindl. species are important plants used as spice and medicine in Asian countries, including Türkiye. This study first aimed to evaluate the antidiabetic potential of the aerial parts of the 5 different Prangos species (Apiaceae) collected from various locations to discover and identify bioactive phenolic components. The results revealed that the methanolic extract of P. heyniae exhibited the highest activity against α-glucosidase inhibition compared to the other Prangos species (IC50 = 458.54 ± 5.62 µg/mL). For this reason, the active species P. heyniae (an endemic species) was subjected to UPLC-MS/MS to evaluate the possible active phenolic components. The results showed that 53 phenolic compounds were correctly screened, 21 were precisely determined by UPLC-MS/MS in P. heyniae. Therefore, it was concluded that the aerial parts of P. heyniae might have therapeutic potential for hyperglycemia due to its phenolic compounds. Moreover, quinic acid (3.66%), chlorogenic acid (2.35%), rutin (2.96%), and hesperidin (0.79%) might be potential markers of the methanolic extract of P. heyniae. In the end, this study provides comprehensive knowledge regarding the phenolic profile of P. heyniae related to antidiabetic activity for the first time in this study.

Phytochemical Profile and In Vitro Antioxidant and Photobiological Properties of Different Extracts from Prangos ferulacea Lindl.

Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO2 extraction showing the highest activity (IC50 = 4.91 µg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

New coumarin glycosides from endemic Prangos heyniae H. Duman & M.F. Watson.

Two new coumarin glycosides, named 7-methoxy isoarnottinin 4'-O-ß-ᴅ-glucopyranoside and 7-methoxy isoarnottinin 4'-O-rutinoside (1 and 2) along with six known compounds (3-8) were isolated from the roots of Prangos heyniae, an endemic plant of Turkey. 1-methylethyl 6-O-D-apio-ß-ᴅ-furanosyl-ß-ᴅ-glucopyranoside (7) and cnidioside A (8) have been obtained from the genus Prangos for the first time. Structures of isolated compounds were established using spectroscopic methods (1 D and 2 D NMR, HR-MS, UV and IR). Moreover, all extracts and isolated compounds were evaluated for their cytotoxic activity against NIH/3T3, HK-2, A-549, MCF-7, PC-3 and SH-SY5Y cell lines by WST-1 method. One of the new coumarin glycosides, 7-methoxy isoarnottinin 4'-O-ß-ᴅ-glucopyranoside (1) exhibited selective cytotoxic activity against SH-SY5Y cells with IC50 value of 31.41 ± 1.04 µM.

Chemical Composition and Biological Activities of Prangos ferulacea Essential Oils.

Prangos ferulacea (L.) Lindl, which belongs to the Apiaceae family, is a species that mainly grows in the eastern Mediterranean region and in western Asia. It has been largely used in traditional medicine in several countries and it has been shown to possess several interesting biological properties. With the aim to provide new insights into the phytochemistry and pharmacology of this species, the essential oils of flowers and leaves from a local accession that grows in Sicily (Italy) and has not yet been previously studied were investigated. The chemical composition of both oils, obtained by hydrodistillation from the leaves and flowers, was evaluated by GC-MS. This analysis allowed us to identify a new chemotype, characterized by a large amount of (Z)-ß-ocimene. Furthermore, these essential oils have been tested for their possible antimicrobial and antioxidant activity. P. ferulacea essential oils exhibit moderate antimicrobial activity; in particular, the flower essential oil is harmful at low and wide spectrum concentrations. They also exhibit good antioxidant activity in vitro and in particular, it has been shown that the essential oils of the flowers and leaves of P. ferulacea caused a decrease in ROS and an increase in the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) in OZ-stimulated PMNs. Therefore, these essential oils could be considered as promising candidates for pharmaceutical and nutraceutical preparations.

Anticholinesterase Compounds from Endemic Prangos uechtritzii.

In this study, the anticholinesterase effects of the extracts and isolated compounds from the roots of endemic Prangos uechtritzii Boiss & Hausskn (Apiaceae) are reported. A novel polyacetylenic compound; (+)-8-O-methyloplopantriol A along with two known polyacetylenes; (-)-panaxynol, (+)-falcarindiol and fifteen known coumarin derivatives; umbelliferone, 6-formylumbelliferone, suberosin, 7-demethylsuberosin, (+)-ulopterol, tamarin, psoralen, imperatorin, (+)-oxypeucedanin, (+)-oxypeucedanin hydrate, (+)-oxypeucedanin methanolate, (+)-marmesin, (-)-prantschimgin, (+)-decursinol, and (-)-adicardin were isolated from the hexane (Pu-HE), chloroform (Pu-CE), and methanol (Pu-ME) extracts of P. uechtritzii roots. (-)-Panaxynol, (+)-falcarindiol, 6-formylumbelliferone, (+)-decursinol, and (-)-adicardin were obtained from the genus Prangos for the first time. (+)-8-O-Methyloplopantriol A inhibited both AChE (IC50 =194.5±5.8 µM) and BChE (IC50 =51.9±2.96 µM) enzymes. (+)-Falcarindiol, 6-formylumbelliferone, 7-demethylsuberosin, tamarin, and imperatorin also exhibited BChE-specific inhibitory activities (IC50 =27.88-93.86 µM). (+)-Falcarindiol (IC50 =27.88±0.91 µM) and imperatorin (IC50 =30.89±1.40 µM) as the most active components could be led compounds to develop new BChE inhibitors with further research against Alzheimer's disease.

Phytochemical Screening, Antioxidant, and Enzyme Inhibitory Properties of Three Prangos Species (P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) Depicted by Comprehensive LC-MS and Multivariate Data Analysis.

The aim of the present study was to identify/quantify bioactive compounds and determine the antioxidant activity and enzyme inhibitory effects of various solvent extracts (n-hexane, ethyl acetate, methanol, and water) of Prangos heyniae H. Duman and M.F. Watson, Prangos meliocarpoides var. meliocarpoides, and Prangos uechtritzii Boiss. and Hausskn. This is the first time such a report has been designed to validate the phytochemical composition and bioactivity (especially enzyme inhibitory properties) of these plants. A combined approach of liquid chromatography (LC) with mass spectrometry (HR-MS and MSn) allowed to identify that P. heyniae contains condensed tannins; P. meliocarpoides is rich in hydrolysable tannins; and P. uechtritzii possesses coumarins, flavonoids, and hydroxycinnamic acids. Different extracts were tested for antioxidant activities using a battery of assays, such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum), and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase as target enzymes. The obtained results depended on the extraction solvents used for each Prangos species. The methanol extract of P. meliocarpoides var. meliocarpoides exhibited significant radical scavenging activity (DPPH: 52.27 mg Trolox equivalent (TE)/g; ABTS: 92.84 mg TE/g), the most potent-reducing potential (CUPRAC: 154.04 mg TE/g; FRAP: 104.34 mg TE/g), and high TAC (2.52 mmol TE/g). Moreover, the strongest BChE (7.97 mg galantamine equivalent/g), α-amylase (0.46 mmol acarbose equivalent/g), and tyrosinase (81.15 mg kojic acid equivalent/g) inhibitory effects were observed for the hexane extract of P. meliocarpoides var. meliocarpoides. Correlation analysis showed a significant positive correlation between hydrolysable tannins and antioxidant activities. The same trend was also observed between the same class of compounds and the inhibitory effects on enzymatic activities. These results suggest a principal role of hydrolysable tannins in the observed bioactivities of Prangos. Our results suggested that the tested Prangos species could be valuable as sources of natural agents in the development of health-promoting applications.

Relaxation mechanisms of chloroform root extracts of Prangos heyniae and Prangos uechtritzii on mouse corpus cavernosum.

Erectile dysfunction (ED) is the inability to achieve/maintain an erection. Because of the side effects, interactions, or ineffectiveness of currently used drugs, novel drug discovery studies are ongoing. The roots of Turkish endemic plants Prangos uechtritzii and Prangos heyniae are traditionally used as aphrodisiacs in Anatolia and contain coumarin-like relaxant compounds. This study aims to reveal the relaxant effect mechanisms of chloroform root extracts of P. heyniae (Ph-CE) and P. uechtritzii (Pu-CE). Isolated organ bath experiments were performed on Swiss albino mouse corpus cavernosum by DMT strip myograph. Relaxant responses to extract (10-7 -10-4  g/ml) were obtained in the presence/absence of NO and H2 S synthesis inhibitors nitro-l-arginine methyl ester (l-NAME, 100 µM) and aminooxyacetic acid (AOAA, 10 mM) respectively. Sodium nitroprusside (SNP, 10-9 to 10-4  M) and Na2 S (10-6 to 3 × 10-3  M)-induced relaxations and CaCl2 (10-6 to 10-4  M), KCl (10-2.1 to 10-0.9  M) and phenylephrine (3 × 10-8 to 3 × 10-5  M)-induced contractions were taken in the presence/absence of the extracts (10-4  g/ml). Relaxations induced by Ph-CE but not by Pu-CE were inhibited in the presence of l-NAME and AOAA. Ph-CE increased Na2 S- and SNP-induced relaxations. Ph-CE and Pu-CE decreased the contractions of KCl, phenylephrine, and CaCl2 . It was concluded that NO and H2 S synthesis/downstream mechanisms play roles in relaxations of Ph-CE but not in Pu-CE-induced relaxations. Inhibition of calcium influx appears to be involved in the relaxant effect of Ph-CE and Pu-CE. Since the extracts act directly by relaxing smooth muscle or through H2 S as well as NO, they may be a potential therapeutic agent in diseases such as ED where the bioavailability of NO is impaired.

Chemical composition, antitumor and antioxidant effects of four lebanese plants extracts on human pulmonary adenocarcinoma.

Lung cancer leading cause of humans' cancer-related death remains incurable with current drug therapies having many side-effects. Finding new natural cancer remedies would help design better therapies. This study aims to investigate the anticancer and antioxidant effects of the Levant endemic plants Prango sasperula, Stachys ehrenbergii, Hirtellina lobelia, and Salvia multicaulis on human pulmonary adenocarcinoma. GC/MS and NMR analyzed the bioactive compounds of methanolic extracts of these plants. Their antioxidant effect was measured by ABTS assay. The effect of these extracts on the viability of A549 (Human lung adenocarcinoma cell line) and NHBE (Normal Human Bronchial Epithelial Cells) was examined using MTT and Anchorage-Independent Colony Formation assays. Our findings show an interesting, specific cytotoxic effect of these plant extracts on A549 cells. Additionally, S. ehrenbergii and H. lobelii present a specific high alkylation potential. Data reveal an interesting antitumor potential attributed to their antiproliferative and alkylation actions towards human pulmonary adenocarcinoma.

Composition and biological activities of the essential oil from a Sicilian accession of Prangos ferulacea (L.) Lindl.

Prangos ferulacea (L.) Lindl. (Fam. Apiaceae), is an orophilous species of eastern Mediterranean and western Asia which possesses several biological properties, which are worthy of exploitation in different fields. With the aim to provide new insights into the phytochemistry and pharmacology of this species, a local accession growing in Sicily (South Italy) was investigated as well. Notably, the P. ferulacea essential oil chemical composition and the antioxidant, anti-acetylcholinesterase (AChE) and cytotoxic activities have been studied. This analysis allowed to identify a new chemotype and to report good biological results for this oil.

Acetylcholinesterase-inhibitory activity of Iranian plants: Combined HPLC/bioassay-guided fractionation, molecular networking and docking strategies for the dereplication of active compounds.

In order to search for discovery of acetylcholinesterase (AChE) inhibitors, as a therapeutic strategy for treatment of the Alzheimer's disease, twenty-five Iranian plants have been evaluated by an in vitro enzymatic Ellman method and molecular docking study. Each plant was successively extracted by n-hexane, ethyl acetate and methanol to obtain a total of 75 extracts. The inhibiting effect of extracts was measured by a colorimetric assay in 96-well microplates. The n-hexane extract of Prangos ferulacea showed the highest AChE inhibitory activity with 75.6% inhibition at a concentration of 50 µg/mL. The chemical composition of this extract was investigated in detail based on a combination of HPLC/bioassay-guided fractionation and molecular networking techniques. The results led to the identification of seventeen compounds, one of them was a fatty acid derivative, two compounds had flavonoid structure and others were furanocoumarin type compounds. In vitro analysis showed that the subfraction F10f was the most potent inhibitor against the activity of AChE with an IC50 value of 25.2 µg/mL and good docking scores of its constituents confirming its high activity.

New coumarin from the roots of Prangos pabularia.

The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3-methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O-ß-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-ß-D-glucopyranoside (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7), heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose (11), have been isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by spectroscopic means, especially, UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic effect of yuganin A and its inhibitory effect on B16 cells were evaluated. Yuganin A may be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

Antibacterial Activities of Pyrenylated Coumarins from the Roots of Prangos hulusii.

The dichloromethane extract of the roots of Prangos hulusii, a recently described endemic species from Turkey, has yielded nine known and one new prenylated coumarins. The structures were elucidated by spectroscopic methods and direct comparison with the reference compounds where available. The root extract and its prenylated coumarins exhibit antimicrobial activity against nine standard and six clinically isolated strains at a concentration between 5 and 125 µg/mL. In particular, the new coumarin, 4'-senecioiloxyosthol (1), displayed 5 µg/mL MIC (Minimum Inhibitory Concentration) value against Bacillus subtilis ATCC 9372, murraol (4) and auraptenol (5) showed 63 µg/mL MIC value against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 9372, and isoimperatorin (9) exhibited 16 µg/mL MIC value.

An in vitro ethnopharmacological study on Prangos ferulacea: a wound healing agent.

Introduction: Traditionally Prangos ferulacea root is being used as an effective wound healing agent especially for pus-filled wounds both in human and stocks in the western north of Iran. Regarding the subject we decided to study P. ferulacea roots essential oil (PFE) for its antimicrobial and wound healing activities. Methods: The in vitro wound healing activity of PFE was evaluated in the mouse fibroblast cell line L929 using MTT assay of cell viability and cytotoxicity indices. Scratch assay as an in vitro model of wound healing assay was also conducted in this study. Moreover, the type I collagen content was used as an indicator of progress in wound healing process using Sircol collagen assay. Besides, PFE was subjected to GC/MS to identify the chemical constituents, and antimicrobical property was also evaluated against S. aureus, S. epidermidis, E. coli, P. aeruginosa,S. paratyphi and C. albicans using agar dilution method. Results: GC/MS analysis showed that the monoterpene hydrocarbones dominated in PFE, amounting to a total percentage of 95.1% with the major constituents: ß-Phellandrene (32.1%), m-Tolualdehyde (26.2%), and δ-3-carene (25.8%). PFE inhibited the growth of S. aureus and P. aeruginusa with the MIC value of 20 µg/mL. In addition, at the second day of treatment, PFE at concentrations of 4 and 16 µg/mL significantly (P<0.001) enhanced the migration rate of L929 cells by 87.05±2.4 and 63.5±0.08 %, respectively. Moreover, the collagen production by L929 cells was increased greatly (P<0.001). Conclusion: It is proposed that the excellent antimicrobial activity along with the significant increase of migration rate and collagen production by fibroblast cells might be associated with the high content and synergistic effect of the monoterpens, corroborating the traditional usage of this plant as a wound healing agent.

Isolation of Phenolic Derivatives and Essential Oil Analysis of Prangos ferulacea (L.) Lindl. Aerial Parts.

Prangos ferulacea (L.) Lindl. (Apiaceae) is a medicinal plant distributed in Mediterranean regions, Caucasia and southwest of Asia. In the present study phytochemical constituents of the extract obtained from the aerial parts of P. ferulacea were investigated using various chromatographic and spectroscopic methods. Essential oil of the plant aerial parts was also analyzed using GC-MS. Five phenolic derivatives, isoimperatorin (1), ferudenol (2), caffeic acid glucosyl ester (3), isorhamnetin-3-O-ß-D-glucopyranoside (4) and quercetin-3-O-ß-D-glucopyranoside (5) were isolated from the aerial parts of P. ferulacea and their structures were elucidated using 1H-NMR, 13C-NMR, EI-MS and UV spectral analyses. Twenty-seven compounds were also identified in the essential oil of plant aerial parts, of which ß-pinene (43.1%), α-pinene (22.1%) and -δ3-carene (16.9%) were characterized as main compounds. The results of this study introduce P. ferulacea as a source of potentially bioactive phenolic compounds and suggest it as an appropriate candidate for further studies.

Induction of programmed cell death by Prangos uloptera, a medicinal plant

Inhibition of the cell growth or induction of cell death is the most promising area in cancer therapy. The induction of apoptosis by dichloromethane extract of Prangos uloptera was evaluated on the McCoy cell line. This plant's roots, aerial parts and fruit have medicinal value. Cell growth inhibitory and cell cytotoxicity effects of the extract were assayed by MTT and Trypan-blue tests, respectively. Morphological changes and DNA fragmentation were also evaluated. The viability tests showed 0.49 and 0.3 mg/ml as 50 percent inhibition concentration and 50 percent cytotoxicity concentration after 24 hours of treatment, respectively. Fluorescent microscopy analysis revealed chromatin fragmentation and scanning electron microscopy showed cell shrinkage and cytoplasmic blebbing. These findings were confirmed by DNA fragmentation analysis. The results demonstrated efficient induction of apoptosis by the plant extract in moderate concentrations, but administration of higher concentrations showed that the primary manner of cell death was necrosis.