Chemical composition and bioactivities of essential oils from different plant parts of Ferula pseudalliacea Rech.f. as an endemic plant from Iran.

The essential oils of leaf, flower, immature and mature fruit from Ferula pseudalliacea (Apiaceae) which grow wildly in Iran as an endemic plant were obtained by hydro-distillation and subsequently analysed by GC-FID and GC-MS. The oils obtained in yields 0.4-4.0% (w/w) and the analysis of GC-MS/FID chromatogram was resulted in the identification of 43-47 compounds, representing 90.9 - 96.7% of the total oils. α-Pinene was the main compound in all samples. The oils exhibited mild activity against Bacillus pumilus, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus with or more than 15 mm zones of growth inhibition and MIC values of 9-15 mg/ml. Essential oil of immature and mature fruits showed potent antioxidant activity with IC50 values of 35.4 ± 0.4 and 39.1 ± 0.4 µg/mL, respectively. So, this plant as an antibacterial and antioxidant agent can be useful in food and medicine industry. [Formula: see text].

Molecular networking based dereplication of AChE inhibitory compounds from the medicinal plant Vincetoxicum funebre (Boiss. & Kotschy).

Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting 47 million people worldwide. While acetylcholinesterase (AChE) inhibitors such as donepezil and galantamine are leading drugs in the symptomatic treatment of AD, new AChE inhibitors continue to be explored for improved potency and selectivity. Herein, a molecular networking approach using high resolution (HR-MS) and tandem mass spectrometry (MS2) has been used for rapid chemical profiling of an extract of the medicinal plant Vincetoxicum funebre Boiss. & Kotschy (Apocynaceae family) that was active against AChE. A total of 44 compounds were identified by combining the MN with traditional natural product methods, including the isolation and identification of five known compounds (13, 41-44) and a novel C13-norisoprenoid (40). In addition, the potential inhibitory activity of all 44 compounds was evaluated against the AChE enzyme via molecular docking to provide further support to the proposed structures. The glycosylated flavonoid querciturone (31) exhibited the highest affinity with a docking score value of -13.43 kJ/mol. Another five compounds showed stronger docking scores against AChE than the clinically used donepezil including the most active isolated compound daucosterol (44), with a binding affinity of -10.11 kJ/mol towards AChE. These findings broaden our understanding of Vincetoxicum metabolites and highlight the potential of glycosylated flavonoids as AChE inhibitors.Communicated by Ramaswamy H. Sarma.

Exploring Gunnera tinctoria: From Nutritional and Anti-Tumoral Properties to Phytosome Development Following Structural Arrangement Based on Molecular Docking.

Gunnera tinctoria, an underexplored invasive plant found in Azores, Portugal, was studied regarding its nutritional, antioxidant, and antitumoral properties. Higher antioxidant activity was found in baby leaves, followed by adult leaves and inflorescences. A phenolic fraction of the plant was enriched using adsorbent resin column chromatography (DiaionTM HP20LX, and Relite EXA90). Antitumoral effects were observed with the enriched fractions in breast (MCF-7) and pancreatic (AsPC-1) cancer cell lines, being more pronounced in the latter. To improve protection and membrane absorption rates of phenolic compounds, nano-phytosomes and cholesterol-conjugated phytosomes coated with natural polymers were loaded with the enriched fraction. The particles were characterized, and their physiochemical properties were evaluated and compared. All samples presented anionic charge and nanometer size in relation to the inner layer and micrometer size regarding the external layers. In addition, the molecular arrangement of phenolics within both types of phytosomes were studied for the first time by molecular docking. Polarity and molecular size were key factors on the molecular arrangement of the lipid bilayer. In conclusion, G. tinctoria showed to be an interesting source of nutrients and phenolic compounds with anti-tumoral potential. Moreover, phytosome loading with these compounds can increase their stability and bioavailability having in view future applications.

Physicochemical Characterization, Antioxidant Activity, and Phenolic Compounds of Hawthorn (Crataegus spp.) Fruits Species for Potential Use in Food Applications.

Hawthorn belongs to the Crataegus genus of the Rosaceae family and is an important medicinal plant. Due to its beneficial effects on the cardiovascular system and its antioxidant and antimicrobial activity hawthorn has recently become quite a popular herbal medicine in phytotherapy and food applications. In this study, physicochemical characterization (color parameters, pH, titratable acidity, total soluble solids, soluble carbohydrate, total carotenoid, total phenols, and flavonoid contents), antioxidant activity (by ferric-reducing antioxidant power, FRAP assay), and quantification of some individual phenolic compounds of fruits of 15 samples of different hawthorn species (Crataegus spp.) collected from different regions of Iran were investigated. According to findings, the total phenols, total flavonoid content, and antioxidant activity were in the range of 21.19-69.12 mg gallic acid equivalent (GAE)/g dry weight (dw), 2.44-6.08 mg quercetin equivalent (QUE)/g dw and 0.32-1.84 mmol Fe++/g dw, respectively. Hyperoside (0.87-2.94 mg/g dw), chlorogenic acid (0.06-1.16 mg/g dw), and isoquercetin (0.24-1.59 mg/g dw) were found to be the most abundant phenolic compounds in the extracts of hawthorn fruits. The considerable variations in the antioxidant activity and phenolic compounds of hawthorn species were demonstrated by our results. Hence, the evaluation of hawthorn genetic resources could supply precious data for screening genotypes with high bioactive contents for producing natural antioxidants and other phytochemical compounds valuable for food and pharma industries.

Antiprotozoal Germacranolide Sesquiterpene Lactones from Tanacetum sonbolii.

A phytochemical investigation of extracts from flowers and aerial parts of Tanacetum sonbolii afforded 7 new germacranolide sesquiterpene lactones. The structures were established by a combination of 1- and 2-dimensional nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and electronic circular dichroism. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and cytotoxicity against rat myoblast (L6) cells were determined. Compounds 4: and 5: showed IC50 values of 5.1 and 10.2 µM and selectivity indices of 3.9 and 4.0, respectively.

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.

Antiprotozoal Diterpenes from Perovskia abrotanoides.

As part of a screening for new antiparasitic natural products from Iranian plants, n-hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani. The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids (1: -17: ), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5R,10S)-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene (2: ), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan (6: ), and 12-methoxybarbatusol (9: ) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani, and Plasmodium falciparum. Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7α-ethoxyrosmanol (4: ) with an IC50 of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC50 of 1.8 µM (SI 6.9) against L. donovani, ferruginol (8: ) with an IC50 of 2.9 µM (SI 19.2) against P. falciparum, and miltiodiol (10: ) with an IC50 of 0.5 µM (SI 10.5) against T. b. rhodesiense. None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6).

Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-ß-Rhamnoside Isolated from Parrotia persica.

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-ß-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-ß-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-ß-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-ß-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-ß-rhamnoside and chlorogenic acid.

A nor-diterpene from Salvia sahendica leaves.

Phytochemical investigation of n-hexane extract of Salvia sahendica by normal phase column chromatography resulted in the isolation of six compounds. Structures were established by 1D and 2D NMR spectroscopy, and HRMS, as a new norditerpene 1, and known terpenoids, sclareol (2), oleanolic acid (3), ß-sitosterol (4), salvigenin (5) and 3α-hydroxy-11α,12α-epoxyoleanan-28,13ß-olide (6). The absolute configuration of 1 was confirmed by a combination of X-ray single crystal analysis and electronic circular dichroism spectroscopy. In vitro cytotoxic activity on breast cancer cell line (MDA-MB-231) and also the antimicrobial activity of the pure compounds were tested against Staphylococcus aureus, Bacilus cereus and Escherichia coli.

Non-polyphenolic compounds of a specific kind of dried grape (Maviz) inhibit memory impairments induced by beta-amyloid peptide.

OBJECTIVES: Although grape has been recently the topic of many investigations, Maviz (a kind of dried one) has remained neglected. The aim of this study was to assess anti-Alzheimer activity of Maviz. METHODS: To reach this goal, total phenolic content (TPC) of ethanolic (Eth) and aqueous (Aq) extracts were determined and radical scavenging activity was assayed by 2,2-diphenyl-1-picrylhydrazyl. Chemical compositions of each extract were also determined via GC-Mass. Behavioral changes were studied via passive avoidance and Morris water maze in Aß-induced model of Alzheimer's disease. Catalase (CAT) and superoxide dismutase (SOD) determination were also done on rats' hippocampus. RESULTS: The results showed that seed Eth extract has a high level of TPC and radical scavenging activity. However, this extract had surprisingly no effect on memory and CAT and SOD activities. In contrast, fruit Aq and Eth extracts (containing furfurals as major compounds) inhibited memory impairment (P < 0.001) and elevated brain levels of CAT and SOD(P < 0.05). CONCLUSION: It seems that Maviz non-phenolic compounds-most probably 5-hydroxymethylfurfural and other similar derivatives-are responsible for these actions.

Chemical Composition, Antioxidant, and Antimicrobial Activities on Laserpitium carduchorum Hedge & Lamond Essential Oil and Extracts During Various Growing Stages.

Laserpitium carduchorum is frequently used as a spice, and in Bane folk medicine, the aerial parts of this are used to treat urinary infections. Variation in the quantity and quality of the essential oil of Iranian L. carduchorum at different developmental growth stages including vegetative, flowering, and seed ripening is reported. In total, 33 compounds were identified and quantified in the oils of vegetative, flowering, and seed ripening stages, representing 97.8%, 98.8%, and 98.7% of the oils, respectively. α-Pinene (45.1, 61.4, and 46.4%), sabinene (16.5, 10.3, and 17.5%), and limonene (6.4, 8.5, and 20.4%) were the main compounds in all samples. The antioxidant activities of different extracts of L. carduchorum at different developmental growth stages were examined by employing various established in vitro experiments including DPPH, FRAP, and TEAC assays. The amounts of total phenolics were also determined spectrophotometerically. Antimicrobial activities of different extracts and essential oils of L. carduchorum at different developmental growth stages were examined against five Gram-positive and four Gram-negative bacteria, as well as two fungi. The results showed that maximum antioxidant and antimicrobial activity of extracts were at the flowering stage of the plant. Maximum antimicrobial activity of essential oils was at seed ripening stage.

New coumarin derivatives from Ferula pseudalliacea with antibacterial activity.

In this study, the antibacterial activity of disesquiterpene coumarin and sesquiterpene coumarins obtained from Ferula pseudalliacea roots was evaluated by determination of minimum inhibitory concentration using the broth micro-dilution method against seven pathogenic bacterial strains (Staphylococcus aureus ATCC 25,923, vancomycin resistant clinical strain of Enterococcus faecium, Bacillus cereus PTCC 1015, Escherichia coli ATCC 25,922, Pseudomonas aeruginosa PTCC 1430, clinical strain of Klebsiella pneumoniae and a clinical strain of Helicobacter pylori). The overall inhibitory activities of the compounds were higher against Gram positive tested bacteria. Sanandajin and ethyl galbanate demonstrated significant activity against H. pylori strain, as well as S. aureus strain in concentration of 64 µg/ml. Methyl galbanate inhibited vancomycin resistant strain of E. faecium in concentration of 64 µg/ml. The results of the present investigation indicated that disesquiterpene and sesquiterpene coumarins isolated from F. pseudalliacea root extract can be considered as potent antibacterial agents for pharmaceutical and food industries.

Antioxidant and antidiabetic activities of 11 herbal plants from Hyrcania region, Iran.

In the present study, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, α-amylase and α-glucosidase inhibition activities, and total phenolic contents of n-hexane, ethyl acetate, and methanol extracts of various parts of Allium paradoxum, Buxus hyrcana, Convolvulus persicus, Eryngium caucasicum, Heracleum persicum, Pimpinella affinis, Parrotia persica, Primula heterochroma, Pyrus boissieriana, Ruscus hyrcanus, and Smilax excelsa were investigated. These plants, which mostly serve as food flavoring, were collected from Hyrcania region, Sari, Iran. Some extracts of H. persicum, S. excels, P. boissieriana, P. persica, and P. heterochroma exhibited significant antidiabetic activities in α-amylase and α-glucosidase assays, more effective than acarbose (concentrations that cause 50% inhibition = 75.7 µg/mL and 6.1 µg/mL against α-amylase and α-glucosidase, respectively). Also, C. persicus, P. boissieriana, and P. heterochroma showed strong antioxidant activities, compared with butylated hydroxytoluene (concentration that causes 50% inhibition = 16.7 µg/mL). In conclusion, this study can recommend these plants as good candidates for further investigations to find potent antidiabetic natural products or probable lead compounds. Statistical analysis showed significant correlation between the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and total phenolic contents (r = 0.711, p < 0.001).

New ursane triterpenoids from Salvia urmiensis Bunge: Absolute configuration and anti-proliferative activity.

Two new triterpenoids, urmiensolide B (1) and urmiensic acid (2), with rare carbon skeletons together with three known compounds were isolated from the aerial parts of Salvia urmiensis Bunge, an endemic species of Iran. The structures were established by a combination of 1D and 2D NMR, and HRESIMS, and in the case of 2 and 3, their structures were confirmed by single-crystal X-ray analysis. The absolute configuration of 2 was established by electronic circular dichroism (ECD) spectra. The new compounds were evaluated for their anti-proliferative activities against A549 and MCF-7 human cancer cell lines. Compounds 1 and 2 showed IC50 values of 2.8 and 1.6 µM against MCF-7 cells, respectively.

Seco-ursane-type Triterpenoids from Salvia urmiensis with Apoptosis-inducing Activity.

Fractionation of an acetone extract of the aerial parts of Salvia urmiensis led to the isolation of a new (1) and a known (2) E-seco-ursane-type triterpenoid, together with four other known compounds. Their structures were established by 1D and 2D nuclear magnetic resonance as well as high-resolution electrospray ionization mass spectrometry. The effect of compounds 1 and 2 on cell viability of HeLa and HepG2 cells was investigated with the MTT assay. We also report the mechanism of action of compound 2 as a potential anticancer agent in HeLa cells. Bcl-2, Bax, and caspases signaling pathway expression in HeLa cells was analyzed. HeLa cells treated with compound 2 were assayed for the cleavage of poly-(ADP-ribose)-polymerase and DNA fragmentation resulting in nuclear shrinkage. Taken together, these results suggest that treatment of HeLa cells with compound 2 can induce apoptosis by regulating Bcl-2 family members and by suppressing caspase cascade activation.

Flavonoids from Salvia chloroleuca with α-Amylsae and α-Glucosidase Inhibitory Effect.

It is believed that the inhibition of carbohydrate hydrolyzing enzymes including α-amylase and α-glucosidase is one of the therapeutic approaches to decrease the postprandial glucose level after a meal, especially in the people with type 2 diabetes. Medicinal plants and their extracts are one of the main sources to find new inhibitors to the enzymes. In our study four flavonoids, namely luteolin 7-O-glucoside (1), luteolin 7-O-glucuronide (2), diosmetin 7-O-glucuronide (3) and salvigenin (4) were isolated from aerial parts of Salvia chloroleuca. The inhibitory activity of these compounds against α-amylase and α-glucosidase were evaluated. Compounds 1, 2 and 3 showed potent α-glucosidase inhibitory effect with IC50 values of 18.3, 14.7, and 17.1 µM, respectively. Also these compounds exhibited moderate α-amylase activity with IC50 values 81.7, 61.5, and 76.3 µM, respectively.

Effects of Hydro-alcoholic Extract of Anethum Graveolens Seed on Pentylenetetrazol-induced Seizure in Adult Male Mice.

INTRODUCTION: Regarding chronic nature of epilepsy and its side effects and to access the effective treatment procedures, herbal medicine has received remarkable interest. The aim of this study was to determine the anticonvulsant effects of hydro-alcoholic extract of Anethum graveolens seed on pentylenetetrazol (PTZ) -induced seizure in male mice. METHODS: Fifty-six albino male mice were divided randomly into seven groups including the negative control (saline), positive control (Phenobarbital) and treatment groups using different doses of hydro-alcoholic extract of Anethum graveolens seed (50, 100, 300, 500 and 1000 mg/ kg). To provoke convulsion, PTZ was injected to all groups and initiation time of myoclonic and tonic-clonic seizures as well as surveillance after 24 h were measured. RESULTS: The results indicated that hydro-alcoholic extract of Anethum graveolens seed (AGS) delayed the initiation time of myoclonic and tonic-clonic seizures in comparison with saline group. The latency was considerable for myoclonic and tonic-clonic seizures at all above mentioned doses of AGS extract except for the lowest one. Moreover, the protective effect of AGS extract against mortality was statistically significant at all doses except for 50 mg/kg. DISCUSSION: As the hydro-alcoholic extract of AGS showed an appropriate response in experimental model of convulsion, it might be considered as an adjuvant therapy with other traditional antiepileptic medications.

Bioactive sesquiterpene coumarins from Ferula pseudalliacea.

One new and five known sesquiterpene coumarins were isolated from the roots of Ferula pseudalliacea. The structures were elucidated by 1D and 2D NMR, and HR-ESIMS data as 4'-hydroxy kamolonol acetate (1), kamolonol (2), szowitsiacoumarin A (3), farnesiferon B (4), farnesiferol C (5), and flabellilobin A (6). The absolute configuration of compounds 1, 2, and 4 was established by comparison of experimental and simulated electronic circular dichroism spectra using time dependence density function theory. 4'-Hydroxy kamolonol acetate and kamolonol showed antibacterial activity against Heliobacter pylori and Staphylococcus aureus at a concentration of 64 µg/mL. Kamolonol, 4'-hydroxy kamolonol acetate, and farnesiferon B displayed a cytotoxic activity in HeLa cells, with an IC50 of 3.8, 4.5, and 7.7 µM, respectively.

Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina.

O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95% reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.

Disesquiterpene and sesquiterpene coumarins from Ferula pseudalliacea, and determination of their absolute configurations.

The first disesquiterpene coumarin, sanandajin, five sesquiterpene coumarins, kamolonol acetate, fekrynol acetate, ethyl galbanate, methyl galbanate, farnesiferol B, and a sesquiterpene, aristolone, were isolated from a n-hexane extract of Ferula pseudalliacea roots. The structures were elucidated by 1D and 2D NMR, HR-ESIMS data, and kamolonol acetate was confirmed by single-crystal X-ray analysis. The absolute configuration of compounds was established by comparison of experimental and simulated ECD spectra using time dependence density function theory (TDDFT). In vitro antiplasmodial activity against Plasmodium falciparum K1 strain was determined. sanandajin, kamolonol acetate and methyl galbanate showed moderate antiplasmodial activity, with IC(50) values of 2.6, 16.1 and 7.1 µM, respectively.