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.

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.

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.

The first application of a new polysaccharide from Acanthophyllum bracteatum for the health improvement of Atlantic salmon exposed to mercury chloride.

Polysaccharides are biopolymers that play key roles as therapeutic agents. The current study examined the efficiency of a polysaccharide newly derived from a plant resource for detection of sub-acute mercury (Hg) exposure on blood characteristics of Atlantic salmon. The polysaccharide was extracted from the roots of Acanthophyllum bracteatum, and the Atlantic salmon were divided into three groups and placed in fiberglass tanks: one with no Hg as a control, one filled with 60 µg l(-1) of Hg solution, and one with 60 µg l(-1) Hg solution plus 1% weight/weight (w/w) of polysaccharide, which had been added 24 hours before the addition of Hg solution. Serum hematological and biochemical parameters were analysed. Results of the study showed that the blood factors were significantly adjusted in the group that had been exposed to the polysaccharide and Hg compared to the group that had been exposed only to Hg. The polysaccharide had an adjustment effect on lymphocytes, granulocytes, red blood cells (RBCs), Hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), protein, chlorine (Cl), sodium (Na), and glucose. It did not have a significant effect on hematocrit (Ht), mean corpuscular hemoglobin concentration (MCHC), potassium (K), and monocytes. Finally, the results confirmed that the new polysaccharide has useful effects on the host, possibly acting as a probiotic by selectively motivating the activity of some useful bacteria, which can improve the host health. This is the first report on application of this polysaccharide for the health improvement of Atlantic salmon exposed to mercury chloride.

Evaluation of the cytotoxicity of Satureja spicigera and its main compounds.

Satureja spicigera (Lamiaceae) grows wildly in Northwest of Iran. In this study, bioassay-guided isolation and identification of the main compounds has been reported using various chromatographic methods and comparison of their spectral data with those reported in the literature. Brine shrimp lethality and four cancerous cell lines HT29/219, Caco(2), NIH-3T3, and T47D were used for cytotoxicity evaluations. From the aerial parts of S. spicigera, nine known compounds including two flavanones, 5,7,3',5'-tetrahydroxy flavanone (8) and 5,4'-dihydroxy-3'-methoxyflavanone-7-(6''-O-α-L-rhamnopyranosyl)-ß-D-glucopyranoside (9), one dihydrochalcone, nubigenol (7), together with thymoquinone (1), thymol (2), carvacrol (3), ß-sitosterol (4), ursolic acid (5) and oleanolic acid (6) were identified. Among the isolated chalcone and flavanones, compound 8 was effective against Artemia salina larva (LC(50)= 2 µg/mL) and only the compound 9 demonstrated IC(50) value of 98.7 µg/mL on the T47D (human, breast, ductal carcinoma). Other compounds did not show significant inhibition of the cell growth.

Evaluation of cytotoxicity and anticonvulsant activity of some Iranian medicinal Ferula species.

Several Ferula (Umbelliferae) species have been used in Iranian traditional medicine as antiflatulent, antispasmodic, anticonvulsant, expectorant, etc. In the present study, cytotoxicity and anticonvulsant activity of the methanol extracts from several Ferula species were evaluated. Air-dried samples of different parts of these plants (Ferula diversivittata Regel & Schmalh. (roots), Ferula persica Willd. (aerial parts), Ferula ovina (Boiss.) Boiss. (roots), Ferula badrakema Kos.-Pol. (roots), Ferula diversivittata (flowers), Ferula latisecta Rech. F. & Aell. (roots), and Ferula badrakema (fruits)) were macerated with methanol for 3 days. The mixtures were then filtered, concentrated and dried. For determination of the cytotoxicity of the extracts and also the oleo-gum-resin of F. assafoetida L., the brine shrimp (Artemia salina) was employed as a model assay system since it provides a convenient in-house pre-screening method for evaluating general cytotoxicity. The methanol extracts of different Ferula species and the oleo-gum-resin of F. assafoetida exhibited cytotoxic effect with LC(50) values in the range of 6-321 microg/mL. For the anticonvulsant testing, seizure was induced by injection of pentylenetetrazole (PTZ), 90 mg/kg intraperitoneally (i.p.). This dose was given to 10 groups, each consisting of 6 mice, which were pretreated i.p. with the extracts (300 mg/kg), Diazepam (10 mL/kg) or saline (10 mL/kg). The results showed that none of the tested Ferula species can prevent PTZ-induced seizure at the used dose. In conclusion, all of the extracts and the oleo-gum resin of F. assafoetida showed dose-dependent cytotoxicity which was highest in F. badrakema fruits and lowest in F. badrakema roots. Our findings also revealed that the methanol extracts and F. assafoetida oleo-gum resin do not possess anticonvulsant activity.

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.

Bioactive compounds of the volatile oil of Dracocephalum kotschyi.

Trypanocidal activity was found in the volatile oil of dried Dracocephalum kotschyi. GC-MS analysis determined that the major constituents of the oil were geranial (35.8%), C10H14O (26.6%), limonene (15.8%) and 1,1-dimethoxy decane (14.5%). In order to isolate the unknown biologically active monoterpene, fractionation of the volatile oil was carried out by silica gel column chromatography. The structure of the oxygenated compound was confirmed to be limonene-10-al (C10H14O) by analysis of physical and spectroscopic data (1H NMR, 13C NMR, HMBC and HMQC).

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.

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.

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.

Bioactive constituents from Dracocephalum subcapitatum (O. Kuntze) Lipsky.

From an EtOAc extract of Dracocephalum subcapitatum, five flavonoids, calycopterin, xanthomicrol, isokaempferide, luteolin and apigenin, together with five terpenoids, oleanolic acid, ursolic acid, geranial, neral and limonene-10-al, were isolated. Among them, citral and limonene-10-al were the most effective components against epimastigotes of Trypanosoma cruzi, the parasitic agent of Chagas disease.

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.

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.

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.

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.

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.