Chemical Constituents of Cymbocarpum erythraeum (DC.) Boiss., and Evaluation of Its Anti-Helicobacter pylori Activity.

OBJECTIVE: Cymbocarpum erythraeum (Apiaceae) is an endemic species in Iran. Up to now, there have been no phytochemical and biological investigations on this species. Therefore, isolation of the main secondary metabolites of the plant along with its anti-H. pylori activity have been considered in this paper. MATERIALS AND METHODS: The dried parts of the plant were extracted with different solvents using solvent percolation and the antibacterial activity of the extracts evaluated by the disk diffusion method. Four compounds were isolated using different column chromatography methods. RESULTS: The compounds were identified by proton nuclear magnetic resonance and carbon-13 nuclear magnetic resonance as isoquercetin (1), rutin (2), ß-sitosterol (3) and 2-decenol (4). CONCLUSION: Anti-H. pylori evaluation of the extracts and isolated compounds against three clinical isolates of H. pylori revealed that hexane extract of the plant inhibited all H. pylori strains.

Phytochemical Analysis and Antioxidant Activity of Salvia chloroleuca Aerial Extracts.

BACKGROUND: Salvia, known as Maryam Goli in the Persian language, is an important genus that includes approximately 900 species in the Lamiaceae family. There are 58 Salvia species growing naturally in Iran, including Salvia chloroleuca Rech. f. and Allen., which grows wild in the northeastern and central parts of the country. OBJECTIVES: This study was designed to determine the chemical composition, in vitro antioxidant activity, and total phenol content of various extracts of S. chloroleuca. MATERIALS AND METHODS: Dried aerial parts of the plant were crushed, then sequentially extracted with n-hexane, ethyl acetate, and methanol. The fractions of S. chloroleuca were subjected to silica gel column chromatography and Sephedex LH-20. The antioxidant activities of these extracts were measured by ferric reducing antioxidant power (FRAP), and the total phenolic contents of the extracts were evaluated using Folin-Ciocalteu reagent. RESULTS: The separation and purification processes were carried out using different chromatographic methods. Structural elucidation was on the basis 1H-NMR and 13C-NMR spectral data, in comparison with that reported in the literature. The isolated compounds were salvigenin (1), luteolin (2), cirsiliol (3), ß-sitosterol (4), and daucosterol (5). Ethyl acetate extract displayed the highest level of total antioxidants and total polyphenols compared to the other analyzed extracts (n-hexane and methanol). In the FRAP assay, ethyl acetate extract had the highest (230.4±10.5) FRAP value, followed by methanol (211.4 ± 8.3) and n-hexane (143.4 ± 12.04). Total phenol contents were calculated to be 13.8 ± 0.3, 58.25 ± 0.05, and 43.48 ± 0.38 mg of gallic acid/100 g in the n-hexane, ethyl acetate, and methanol extracts, respectively. CONCLUSIONS: The above-mentioned compounds were isolated for the first time from S. chloroleuca. The antioxidant activity of this plant could be in part related to isolated flavonoids and sterols. The results of this study indicated that S. chloroleuca could be an important dietary source of phenolic compounds with high antioxidant capacity.

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.

A new rearranged tricyclic abietane diterpenoid from Salvia chloroleuca Rech. f. & Allen.

Phytochemical investigation of the roots of Salvia chloroleuca led to the isolation and identification of a new rearranged abietane diterpenoid (1). Its structure was elucidated by interpretation of the 1D and 2D NMR spectra and completed by the analysis of the HR-ESI-MS data. Compound 1 is the secondly reported compound on a rearranged tricyclic abietane (4,5-seco-5,10-friedo-abietane) diterpenoid with a ketal functionality between C-2 and C-11. A plausible biosynthetic pathway of 1 was also proposed.

A new bioactive monoterpene-flavonoid from Satureja khuzistanica.

A new monoterpene-flavonoid, saturejin (3'-(2,5-dihydroxy-p-cymene) 5,7,4'-trihydroxy flavone) (4), together with twelve known flavonoids consist of two flavanonols (aromadendrin (8) and taxifolin (12)), two flavanones (naringenin (3) and 5,7,3',5'-tetrahydroxy flavanone (9)) and eight flavones (xanthomicrol (1), acacetin (2), cirsimaritin (5), 7-methoxy luteolin (6), apigenin (7), cirsilineol (10), diosmetin (11) and 6-hydroxyluteolin 7,3'-dimethyl ether (13)), were isolated from an ethyl acetate extract and identified for the first time in the dried aerial parts of Satureja khuzistanica Jamzad, an endemic medicinal plant traditionally used as dental anesthetic, oral antiseptic and anti-inflammatory among the nomadic inhabitants of southwestern Iran. The structures of these compounds were determined using the usual spectroscopic methods including 2D-NMR and MS analyses. Saturejin showed a significant ß-glucosidase inhibitory activity at concentration of 10 µg as well as positive antioxidant activity at the amount of 1 µg. These results could be correlated with the in vitro and in vivo anti-inflammatory, anti-oxidant and anti-diabetic properties reported from this medicinal plant. Similar activities were also described for some of the other isolated compounds.

Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.

Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin) and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1ß,5α,7αH-4ß-hydroxy-guai-9(10),11(13)-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0), (39.0, 11.8), and (55.7, 15.3) µg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies.

α-Amylase inhibitory activity of some traditionally used medicinal species of Labiatae.

BACKGROUND: Natural α-amylase inhibitors of herbal origin are an attractive therapeutic approach to control post-prandial hyperglycemia via reducing the glucose release from starch and delaying carbohydrate absorption. These compounds are able to inhibit the activity of the carbohydrate hydrolyzing enzymes in the small intestine and potentially useful in control of diabetes. The enlarged Lamiaceae (Labiatae) family contains about 6,900 to 7,200 species worldwide and many species of this family possess medicinal properties and have been used traditionally for treatment of chronic illnesses including diabetes. METHODS: In the present study particular species of Labiatae family from the genera, Phlomis, Satureja, Salvia, Scutellarua, Stachys and Hymenocrater, which are growing wildly in Iran, selected to evaluate for possible in vitro α-amylase inhibitory activity, compared to acarbose as a positive control. RESULTS: The inhibitory activities of all the herbal extracts were varied from 1.9 to 18.6 (IC50, µg/mL). Additionally, the ethyl acetate extract of P. bruguieri (IC50 = 1.9 µg/mL) and the butanol extract of P. persica (IC50 = 3.6 µg/mL) exhibited the lowest IC50 values among all the species as the most potent herbal extracts, while the inhibitory activity of S. sahendica and S. macrosiphon (ethyl acetate extracts) as well as P. caucasica (butanol extract) on α-amylase enzyme was observed as weak and did not reach at least to the 50% of the enzyme inhibition level. CONCLUSIONS: Taking together, P. bruguieri and P. persica among the Phlomis species can be the promising sources of α-amylase inhibitors. However, P. rigida, S. bizantina and H. bituminosus that exhibited moderate activity can be stand on second level of interest.

Presence of monoterpene synthase in four Labiatae species and Solid-Phase Microextraction- Gas chromatography-Mass Spectroscopy analysis of their aroma profiles.

BACKGROUND: The family Lamiaceae (Labiatae) has included some medicinal plants. some monoterpene synthases, including linalool and limonene synthases, have been cloned and functionally characterized from several plants of Labiatae family. MATERIALS AND METHODS: In this study, presence of linalool and limonene synthases, in four species of Labiatae family including Nepeta cataria, Lavandula angustifolia, Hyssopus officinalis and Salvia sclarea has been determined by molecular biological techniques together with the Head space SPME - GC-MS analysis of the aroma profile of these species. RESULTS: Indicated that none of the plant species produced distinguishable bands with primer pairs related to d-limonene synthase. Distinguishable bands around 1800 bp in cDNA samples of L. angustifolia, H. officinalis and S. sclarea were observed regarding to the presence of linalool synthase. Head space SPME-GC-MS analysis of the aroma profiles of the above-mentioned plants showed that linalool (31.0%), linalyl acetate (18.2%), were found as the major compounds of L. angustifolia, while geraniol (5.5%), nerol (34.0%) and α- citral (52.0%) were identified as the main compounds of the N. cataria. The major components of H. officinalis and S. sclarea oils were determined as cis-pinocamphone (57.3%), and linalool (19.0%), linalyl acetate (51.5%), respectively. CONCLUSION: H. officinalis was rich of cyclic monoterpenes, L. angustifolia, N. cataria and S. sclarea showed considerable amount of linear monoterpenes. The aroma profile of the above-mentioned plants contained low concentration of sesquiterpenes except N. cataria, which indicated no sesquiterpene. The profiles of the main components of these plants are in agreement with molecular assays.

Phytochemistry and pharmacology of berberis species.

The genus Berberis (Berberidaceae) includes about 500 species worldwide, some of which are widely cultivated in the north-eastern regions of Iran. This genus consists of spiny deciduous evergreen shrubs, characterized by yellow wood and flowers. The cultivation of seedless barberry in South Khorasan goes back to two hundred years ago. Medicinal properties for all parts of these plants have been reported, including: Antimicrobial, antiemetic, antipyretic, antioxidant, anti-inflammatory, anti-arrhythmic, sedative, anti-cholinergic, cholagogic, anti-leishmaniasis, and anti-malaria. The main compounds found in various species of Berberis, are berberine and berbamine. Phytochemical analysis of various species of this genus revealed the presence of alkaloids, tannins, phenolic compounds, sterols and triterpenes. Although there are some review articles on Berberis vulgaris (as the most applied species), there is no review on the phytochemical and pharmacological activities of other well-known species of the genus Berberis. For this reason, the present review mainly focused on the diverse secondary metabolites of various species of this genus and the considerable pharmacological and biological activities together with a concise story of the botany and cultivation.

Anticancer properties of Teucrium persicum in PC-3 prostate cancer cells.

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ß-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.

Methods for the discovery of new anti-aging products--targeted approaches.

INTRODUCTION: Aging is considered to be one of the most complicated and heterogeneous phenomena and is the main risk factor for most chronic diseases, disabilities and declining health. Aging cells cease to divide and drive the progression of illness through various pathways. Over the years, a number of anti-aging medicines of natural and synthetic origin have been introduced. Indeed, some studies have identified senescent cells as potential therapeutic targets in the treatment of aging and age-related diseases. AREAS COVERED: In this review, the authors highlight and critically review the possible mechanisms of the aging process and related illnesses. The authors give particular attention to illnesses, including Alzheimer's disease, Parkinson's disease, skin aging and cardiovascular diseases. EXPERT OPINION: Several reports have highlighted that mitochondria are a key factor in the progression of aging and neurodegenerative illnesses. This is due to their production of extra amounts of reactive oxygen species, which leads into progressive caspase-dependent apoptosis and cell death. Therefore, strategies to prevent/reduce oxidative stress-mediated aging, whether environmental, nutritional and pharmacological, need to be taken into account. Presently, Drosophila melanogaster and Caenorhabditis elegans, which focus on the evolutionary and genetic foundations of aging, have helped to establish the screening of several synthetic and natural compounds with large cohorts in a quick manner. However, there is yet to be any efficient experimental evidence to prove the exact role of senescent cells in age-related dysfunction and further studies are required to better understand these processes.

Bioactive Terpenoids and Flavonoids from Daucus littoralis Smith subsp. hyrcanicus Rech.f, an Endemic Species of Iran.

BACKGROUND: Daucus littoralis Smith subsp. hyrcanicus Rech.f. (Apiaceae) is an endemic species in northern parts of Iran where it is commonly named Caspian carrot. The fruits have been used as condiment. METHODS: In a series of in vitro assays, antioxidant (DPPH and FRAP assays), cytotoxic and antimicrobial activities of different extracts of roots and fruits were evaluated for the first time. The separation and purification of the compounds were carried out on the most potent extracts using various chromatographic methods and identified by spectroscopic data (1H and 13C NMR). RESULTS: The results showed that among the extracts only fruit methanol extract (FME) has significant antioxidant activity (IC50 = 145.93 µg.ml-1 in DPPH assay and 358 ± 0.02 mmol FeII/g dry extract in FRAP assay). The radical scavenging activity of FME at 400 µg.ml-1 was comparable with α-tocopherol (40 µg.ml-1) and with BHA (100 µg.ml-1) (p > 0.05). FME did not show any toxicity against cancerous and normal cell lines. Fruit ethyl acetate extract (FEE) had cytotoxic activity against breast carcinoma and hepatocellular carcinoma cells (IC50 168.4 and 185 µg.ml-1, respectively), while it did not possess antioxidant activity in comparison with α-tocopherol and BHA as standard compounds. Ethyl acetate and methanol extract of fruits showed antimicrobial activity against Staphylococcus aureus (MIC: 3.75 mg.ml-1) and Candida albicans (MIC: 15.6 and 7.8 mg.ml-1, respectively). Four terpenoids were isolated form FEE including: ß-sitosterol (1), stigmasterol (2), caryophyllene oxide (3), ß-amyrin (4). Also, three flavonoids namely quercetin 3-O-ß-glucoside (5), quercetin 3-O-ß-galactoside (6) and luteolin (7) were isolated from FME. CONCLUSION: This study showed that FEE and FME of D. littoralis Smith subsp. hyrcanicus Rech.f. had the highest biological activities which may be correlated with in vitro cytotoxic, antimicrobial and antioxidant activities of terpenoids and flavonoids components of the extracts.

Alpha-amylase inhibitory activity and phytochemical study of Zhumeria majdae Rech. f. and Wendelbo.

BACKGROUND: Zhumeria majdae (Lamiaceae) is an endemic species growing in the South parts of Iran especially Hormozgan province. The plant is so-called Mohrekhosh locally and widely used for medicinal purposes including stomachache and dysmenorrhea. OBJECTIVE: In order to separation and identification of the main flavonoid glycosides of the plant (aerial parts including leaves, stems, flowers, and fruits were used) and evaluation of its alpha-amylase inhibitory (AAI) activity, methanolic extract was prepared and fractionated to botanolic portion. MATERIALS AND METHODS: Isolation of the main compounds of the butanol extract of the plant have been performed using different column chromatography methods such as high-performance liquid chromatography (C18 column) and Sephadex LH-20 as well. The isolated compounds were identified by Hydrogen-1 nuclear magnetic resonance and Carbon-13 nuclear magnetic resonance spectra and comparison with those reported in previous literature. Moreover, inhibitory activity of the butanolic extract of the plant against alpha-amylase enzyme was examined in different concentrations (15-30 mg/mL), where acarbose used as a positive control. RESULTS: Three flavonoid glycosides: Linarin (1), hispidulin-7-O-(4-O-acetyl-rutinoside) (2), hispidulin-7-O-rutinoside (3) were successfully identified in the extract. The activity of alpha amylase enzyme was dose-dependently suppressed by the butanol extract. The extract exhibited the highest inhibition at 30 mg/mL toward enzyme (77.9 ± 2.1%), while acarbose inhibited the enzyme at 20 mg/mL by 73.9 ± 1.9%. The inhibitory concentrations of 50% for the extract and acarbose were calculated at 24.5 ± 2.1 and 6.6 ± 3.1 mg/mL, respectively. CONCLUSION: Z. majdae contains glycosylated flavones and could be a good candidate for anti-diabetic evaluations in animal and clinical trials due to possessing AAI activity.

Alpha-amylase inhibitory activity and sterol composition of the marine algae, Sargassum glaucescens.

BACKGROUND: Sargassum species (phaeophyceae) are economically important brown algae in southern parts of Iran. Sargassum is mainly harvested as a row material in alginate production industries and is a source of plant foods or plant bio-stimulants even a component of animal foods. OBJECTIVE: In this study, Sargassum glaucescens, collected from the seashore of Chabahar, was employed for phytochemical and biological evaluations. MATERIALS AND METHODS: For that purpose, the dried algae was extracted by methanol and subjected to different chromatographic separation methods. RESULTS: Six sterols, fucosterol (1), 24(S)-hydroxy-24-vinylcholesterol (2), 24(R)-hydroxy-24-vinylcholesterol (3), stigmasterol (4), ß-sitosterol (5) and cholesterol (6) were identified by spectroscopic methods including (1)H-NMR, (13)C-NMR and mass spectroscopy. In vitro alpha-amylase inhibitory test was performed on the methanolic extract and the results revealed a potent inhibition (IC50 = 8.9 ± 2.4 mg/mL) of the enzyme compared to acarbose as a positive control. CONCLUSION: Various biological activities and distribution of sterols in Sargassum genus have been critically reviewed here. The results concluded that these algae are a good candidate for further anti-diabetic investigations in animals and human.

Antinociceptive activity and effect of methanol extracts of three salvia spp. On withdrawal syndrome in mice.

PURPOSE: There are several reports about effects of Salvia spp. on CNS. The present experiment is undertaken to study effect of S. limbata, S. hypoleuca and S. macrosiphon on withdrawal syndrome in mice. METHODS: Antinociceptive activities of aerial parts of Salvia spp. is investigated using hot plate method. In addition, the effect of its aerial parts on morphine dependence is investigated in mice. After induction of morphine dependency, different concentrations of plant extract are injected. To assess morphine withdrawal, naloxone (5 mg kg-1, i.p.) are injected into mice on the 5th day. Withdrawal syndrome is assessed by placing each mouse in a glass box 30 cm in height and recording the incidence of escape jumps for 60 minutes. RESULTS: A decrease in incidence of escape jumps is observed in morphine dependence mice. S. limbata and S. hypoleuca extracts produced a statistically significant inhibition of pain induced by hot plate latency at (500, 1000 and 1500 mg kg-1) i.p. A significant increase in pain threshold is observed after 30 and 60 minutes (p < 0.001). The activity was comparable to that of morphine (30 mg kg-1, i.p., p > 0.05). The antinociceptive activity increased up to 60 minutes. CONCLUSION: S. limbataand S. hypolecuca extracts produced statistically significant inhibition of pain and development of morphine dependence in mice.

An overview on saffron, phytochemicals, and medicinal properties.

Saffron is the most valuable medicinal food product because of its importance in Iran's agricultural economy. The dried stigmas of the plant Crocus sativus (Iridaceae) are processing to produce saffron as a well-known spice which has some other importance in pharmaceutics, cosmetics, perfumery, and textile dye-producing industries. Recently, reports about the pharmacological activity of this plant increase its importance in the world. The world's annual saffron production is estimated around 300 tons per year (Iran produces 76% of total) and also saffron is considered to be the most expensive spice in the world; hence, there are efforts for its artificial production or defraud. Therefore, the quality conservation of saffron needs to certify in the international trade market following international ISO or the Food and Drug Administration (FDA) criteria and standards. In this paper, the recent (or sometimes less documented) reports on phytochemistry, pharmacology, and standard methods for quality evaluation of saffron, as a medicinal food spice, from field cultivation to market are reviewed.

Biogenic trypanocidal sesquiterpenes: lead compounds to design future trypanocidal drugs - a mini review.

Human trypanosomiasis is a parasitic disease among poor people in Africa and Latin America. Therapy against African and American trypanosomiasis is based on a few drugs that often cause severe side-effects. Therefore, it is essential to develop drug discovery especially from natural origins. Sesquiterpenes, a diverse group of natural terpenoids, are found in essential oils of many plants and show a broad range of bioactivities. They act through multiple mechanisms in the chemotherapy of trypanosomiasis. Some of these active compounds contain hydroperoxides, aldehydes, alcohols, α,ß-unsaturated γ-lactone and even halogenated moieties. Among the compounds reported, sesquiterpene lactones showed a potent anti-trypanosoma effect comparable with commercial trypanocidal drugs. Trypanocidal activity of sesquiterpene lactones mostly depends on the reaction between γ-lactone moieties and nucleophile groups of trypanithione, which is essential for Trypanosoma defense against the oxidative stresses. Elatol is a sesquiterpenoid from marine algae, with a different structure and considerable trypanocidal activity which could be an interesting candidate for further antiprotozoal investigations. To develop novel drugs with higher efficacy and lower toxicity from natural products, this review summarizes the more recent information on trypanocidal activities of various sesquiterpenes.

Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives.

BACKGROUND AND THE PURPOSE OF THE STUDY: There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines. METHODS: The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay. RESULTS: Although the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC50 values = 7.56-25.04 µg/ml). CONCLUSION: The results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.