Cytotoxic Sulfoquinovosyl Glycerols from the Seaweed Sargassum Angustifolium from Persian Gulf.

Backgrounds: Seaweeds are an important source of marine organisms that produce a lot of bioactive compounds. Materials and Methods: In this research, the seaweed Sargassum angustifolium was collected from Bushehr province of Persian Gulf of Iran. The seaweed was extracted by methanol:ethyl acetate (1:1) using maceration method. The compounds were isolated with different column chromatography and HPLC(High Performance Liquid Chromatography) by silica gel and hexane:ethyl acetate as mobile phase. Results: The isolated compounds were elucidated structurally by various 1 and 2 D-NMR and MS spectra. Besides the cytotoxicity test was done against HeLa using standard MTT assay and normal cells. Conclusion: It afforded four known sulfoquinovosyl diacylglycerides and fucosterol. Compounds 1-5 showed cytotoxic effects against HeLa and HUVEC cell lines, with IC50 values of 12.2 ± 2.3, 25.8 ± 3.7, 14.9 ± 2.6, 9.8 ± 1.2 µM, and 5.6 ± 1.2, respectively.

Gas Chromatography-Mass Spectrometry Analysis of Anbarnesa Smoke and Its Antiviral Activity.

Background: Anbarnesa is the female donkey dung typically collected after the labor and in early springtime. Materials and Methods: The chemical composition of the smoke collected from Anbarnesa was evaluated by gas chromatography-mass spectrometry (GC/MS), and its antiviral activity was analyzed based on 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: As a result, twenty-two constituents representing 97.1% of the Anbarnesa smoke could be identified. Hexadecanoic acid (29.4%), cis-9-octadecenoic acid (17.7%), and octadecanoic acid (10.8%) were the smoke's main constituents, respectively. Antiviral activity was evaluated using MTT assay. The CC50 value of the compound on Hep2 and Verro cells was 2271.2 µg/mL and 5077.5 µg/mL, respectively. Furthermore, the 50% inhibitory concentration value on adenovirus and herpes simplex type-1 was 802.55 µg/mL and >5077.5, respectively. Conclusions: it was revealed that Anbarnesa was nontoxic in 1/64, 1/128, and 1/256 dilutions, while the toxicity was detected in 1/32 dilution after 72 h. In addition, in 1/8 and 1/16 dilutions, cell toxicity was identified in the first hour.

Phytochemical analysis of Daphne pontica L. stems with their pro-apoptotic properties against DU-145 and LNCaP prostate cancer cells.

BACKGROUND: Daphne pontica is an endemic plant grown wild in the North part of Iran, with anticancer activities. OBJECTIVES: This study aims to analyze the phytochemistry and screen the cytotoxic activity of new bioactive compounds against a panel of cancer cells, in addition to proapototic properties against prostate cancer cells. METHOD: Purification procedure was done using repeated column chromatographies by MPLC and HPLC systems. The structures were elucidated by the NMR and exact mass spectroscopy, stereochemistry by NOESY, and absolute configuration by electronic circular dichroism (ECD) spectra. Cytotoxicity was done against DU 145, LNCaP, HeLa, MCF-7, and MDA-MB 231 cells by standard MTT assay. An annexin V/PI assay was performed to measure the type of death following treatment with these compounds for 48 h, followed by the caspase-3 activity test. RESULTS: In this study, one new dilignan named lignopontin A (9), in addition to 13 known compounds including two phenolic acids (3, 5), one flavanone (6), one bis flavonoid (1), one cumarin glycoside (2), one mono (4) and two dicumarins (10, 11), two lignans (7, 8), and three daphnane diterpenoids (12-14) were isolated for the first time from D. pontica stems. Complete spectral data of compound 12, named as 6,7α-epoxy-5ß-hydroxy-9,13,14-ortho-(4,2E)-pentadeca-2,4-diene-1-yl)-resiniferonol, and compound 14, named as 6,7α-epoxy-5ß-hydroxy-9,3,14-ortho-(2,4E)-pentadeca-2,4-di-1-yl)-resiniferonol-12ß-yl-acetate are reported for the first time. In the MTT assay of newly described compounds against a panel of cancer cells, compounds 9, 12, and 14 possessed moderate to potent cytotoxicity against prostate, breast, and cervical cancer cells in a dose-dependent manner. Flow cytometry analysis against prostate cancer cells indicated that the cytotoxicity of compounds 12 and 14 was due to their ability to induce apoptosis. In the case of compound 9, in Du 145 cells, cell death was mainly through apoptosis. In contrast, LNCaP cells showed both apoptosis and necrotic cell death, predominated by necrosis at the higher concentrations. Caspase-3 activity confirmed apoptosis observed in these compounds through the caspase pathway in prostate cancer cells. CONCLUSION: D. pontica is a new source of dimeric phenolic compounds, including bisflavonoids, phenylpropanoid-cumarin adduct, and dilignans, as well as daphnane diterpenoids with resiniferonol core with long-chain orthoester moieties. In cytotoxicity screening, compounds 9, 12, and 14 inhibited the growth of DU-145 and LNCaP cells in a dose-dependent manner with IC50 varied from 0.9 - 27.3 and 25.2 - 87.4 µM, respectively. Among them, 9 exhibited selective growth inhibition against DU 145 treated cells. LNCaP cells demonstrated the highest sensitivity to treatment with compound 12.

Antioxidant and genoprotective effects of osthole against cadmium-induced DNA damage: an in vitro study using comet assay.

Background and purpose: Osthole, a plant-derived coumarin, has shown numerous pharmacological effects. However, its genoprotective effects against cadmium-induced DNA damage have not been determined yet. Therefore, this project aimed to assess the effectiveness of osthole against genotoxicity caused by cadmium. Experimental approach: For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of osthole (40, 60, 80, and 120 µM) 24 h before cadmium chloride (CdCl2) treatment (40 µM), and then DNA damage was evaluated by comet assay. Furthermore, DPPH and free thiol group assays were applied to evaluate reactive oxygen species scavenger and antioxidant capacities of osthole. Findings / Results: In the present study, all concentrations of osthole significantly decreased CdCl2-induced DNA damage. Furthermore, the antioxidant properties of the osthole were confirmed by DPPH and free thiol assays. Conclusion and implications: Overall, the findings of this project revealed that osthole could ameliorate cadmium-induced genotoxicity probably by its antioxidant activity.

Analgesic and Anti-Inflammatory Effects of Hydroalcoholic and Hexane Extracts of Smyrniopsis aucheri in Animal Models.

BACKGROUND: The fruits of Apiaceae family have been widely used in traditional medicine for the treatment of pain and inflammation. In this study, we evaluated the analgesic and anti-inflammatory effects of wild celery (Smyrniopsis aucheri) seeds, as a member of the Apiaceae family. METHODS: Hydroalcoholic and hexane extracts of seeds were prepared and for the evaluation of analgesic activity, acetic acid, formalin, and hotplate tests in male mice (20-30 g) and for anti-inflammatory assessment carrageenan-induced paw edema in rats and croton oil-induced ear edema in mice were used. RESULTS: Hydroalcoholic and hexane extracts (100-400 mg/kg) significantly reduced abdominal spasms in the acetic acid test. In the formalin test, the hydroalcoholic extract at doses of 200 and 400 mg/kg reduced the pain of the chronic phase while hexane extract was effective in both acute and chronic phases. In the hot plate test, both extracts were ineffective. In the carrageenan and croton tests, both extracts at a dose of 400 mg/kg significantly reduced edema. CONCLUSIONS: The results revealed the analgesic and anti-inflammatory effects of plant seed extracts. Due to the lack of response of the extracts in the hot plate test, it seems that the plant mainly has a peripheral analgesic effect.

Citral Protects Human Endothelial Cells Against Hydrogen Peroxide-induced Oxidative Stress.

OBJECTIVES: Oxidative stress plays a major role in endothelial dysfunction. Citral is a monoterpene aldehyde with antioxidant properties. This study aimed to investigate the effect of citral on human umbilical vein endothelial cells (HUVECs) under hydrogen peroxide (H2O2)-induced oxidative stress. MATERIALS AND METHODS: The cells were treated with citral (0.625-10 µg/mL) for 24 h before exposure to H2O2 (0.5 mM, 2 h). Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The hydroperoxide concentrations and ferric reducing ability of plasma (FRAP) were measured in intra- and extracellular fluids. RESULTS: Pretreatment of HUVECs with citral at concentrations of 5 and 10 µg/mL significantly enhanced the cell viability in H2O2-induced cytotoxicity. It reduced intracellular hydroperoxide levels at the concentrations of 5 and 10 µg/mL and extracellular hydroperoxide levels at the concentrations of 2.5-10 µg/mL. Pretreatment with citral significantly increased the FRAP value in intra- and extracellular fluids at the concentration range of 1.25-10 µg/mL. CONCLUSION: Antioxidant and cytoprotective effects were found for citral against oxidative damage induced by H2O2 in human endothelial cells. However, more studies in this area are needed to assess its clinical value for prevention and treatment of cardiovascular diseases.

Protective Effect of Vitis vinifera (Black Grape) Seed Extract and Oil on Acetic Acid-Induced Colitis in Rats.

BACKGROUND: Vitis vinifera (black grape) is cultivated worldwide and has numerous oral and therapeutic applications. It has proven anti-inflammatory, antioxidant, antimicrobial, and wound healing properties. The aim of this study was to investigate the effect of black grape seed (hydroalcoholic) extract (BGSE) and black grape seed oil (BGSO) on experimental colitis. METHODS: BGSE (50, 100, and 200 mg/kg) and BGSO (2, 4, and 8 mL/kg) were administered orally (p.o.) in groups of six male Wistar rats, 2 h before induction of colitis and continued further for 4 days. Prednisolone (4 mg/kg) and mesalamine (100 mg/kg) were used as reference drugs. Weight/length of colons, macroscopic and histopathologic indices, and biochemical parameters including myeloperoxidase (MPO) and malondialdehyde (MDA) were evaluated. RESULTS: All doses of BGSE and BGSO significantly decreased the colon weight, ulcer index, and total colitis index in comparison with the control group, although greater doses of both fractions had more significant protection. Data of MPO activity revealed that all treated groups with the exception of BGSE (50 mg/kg) and BGSO (2 mL/kg) showed a meaningful decline in comparison with the control group. Concerning the MDA values in colonic tissue, it was demonstrated that BGSE (100, 200 mg/kg) and BGSO (8 mL/kg) caused a significant dip in this oxidative stress parameter. CONCLUSIONS: Oral administration of BGSE and BGSO had an appropriate anti-inflammatory effect and so could be considered as a suitable candidate for treating or preventing ulcerative colitis. Furthermore, detailed studies are warranted to explore the exact mechanism of action and clinical preference of these compounds.

Anti-inflammatory effect of Adiantum capillus-veneris hydroalcoholic and aqueous extracts on acetic acid-induced colitis in rats.

OBJECTIVE: Colitis is an inflammatory bowel disease with unknown etiology where many factors might play a role. Adiantum capillus-veneris may have beneficial effects in colitis because of its anti-inflammatory, antioxidant, wound healing and antimicrobial effects. The aim of this study was to explore the anti-inflammatory and anti-ulcerative effects of A. capillus-veneris on acetic acid-induced colitis in a rat model. MATERIALS AND METHODS: A. capillus-veneris aqueous (ACAE; 150, 300, and 600 mg/kg) and hydroalcoholic extract (ACHE; 150, 300, and 600 mg/kg) were given orally (p.o.) to male Wistar rats 2 hr before induction of colitis by intra-rectal administration of acetic acid 3%, and continued for 4 days. Prednisolone (4 mg/kg) and mesalazine (100 mg/kg) were applied p.o., as reference drugs for comparison. On day five, colitis indices of tissue specimens were evaluated and levels of biochemical markers including myeloperoxidase (MPO) and malondialdehyde (MDA) were determined. RESULTS: In all groups treated with ACAE and ACHE with the exception of ACAE (150 mg/kg), ulcer index and wet weight of colon as parameters of macroscopic injuries, total colitis index as marker of microscopic features and MPO activity were significantly reduced in comparison to the control group; however, MDA value was only diminished in ACAE (300 and 600 mg/kg) and ACHE (300 mg/kg) groups significantly. CONCLUSION: This research showed that ACAE and ACHE had dose-related beneficial effects on acetic acid-induced colitis and these effects could be attributed to anti-inflammatory, ulcer healing and antioxidant activities of these extracts.

A new sesquiterpenoid from the shoots of Iranian Daphne mucronata Royle with selective inhibition of STAT3 and Smad3/4 cancer-related signaling pathways.

PURPOSE: Daphne mucronata Royle grown in Iran has shown anticancer activities against different cancer cell lines. Therefore, within this study, we investigate the phytochemical pattern of this plant. METHOD: Phytochemical investigation was done using standard column chromatography system: The structures were recognized by the interpretation of one and two-dimensional nuclear magnetic resonance (NMR) spectra and the help of High-Resolution Electrospray Ionization Mass spectroscopy (HR-ESIMS) and Infrared spectroscopy (IR) data. Stereochemistry was determined using 2D and 3D NOESY, and comparison of coupling constant values with literature. The absolute configuration was determined and confirmed using specific rotation and electronic circular dichroism experiments. Cytotoxicity was done against HeLa cells by standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Luciferase assay was used to check if the compounds can inhibit the activation of cancer-related signaling pathways. Molecular docking simulation was done for biological activity evaluation and to examine the interaction of the ligand with each of the proteins. RESULTS: A new sesquiterpenoid, 4,11(12)-guiadiene-1-ol-3-one (4), together with eight specialized metabolites, betulinic acid (1), coniferyl aldehyde (2), oleanolic acid (3), daphnetoxin (5), apigenin (7), syringin (8), and genkwanol A (9) were isolated and reported for the first time from the shoots of the plant. Compound 4 as an undescribed compound was submitted for cytotoxicity assay and showed moderate activity with the IC50 value of 51.3 ± 4.2 µM against HeLa cancer cells. It showed selective inhibition of Interleukin-6 mediated signal transducer and activator of transcription 3 pathway (STAT-3/ IL-6), and Smad protein / transforming growth factor beta (TGF-ß) transcription factors when screened through an array of cancer signaling pathways. Molecular docking confirmed biological tests and showed the interaction with STAT3 and Smad proteins. CONCLUSION: An undescribed sesquiterpenoid: 4,11(12)-guiadiene-1-ol-3-one in addition to eight known compounds were isolated. The new sesquiterpene was evaluated for the luciferase assay on 14 main cancer-related signaling pathways and showed selective inhibition of STAT3/IL6, and Smad/ TGF-ß transcription factors. Molecular docking simulation showed more interactions with STAT3 than Smad, which confirms better interaction of compound 4 with STAT3 than Smad proteins. Graphical abstract.

Two new dammarane triterpenes isolated from Cleome khorassanica Bunge & Bien with cytotoxicity against DU-145 and LNCaP prostate cancer cell lines.

From the aerial parts of Cleome khorassanica Bunge & Bien, a new 3-oxo-4-oxa-A-homo-25,26,27-trinordammarano-24,20-lactone triterpene (1), a new natural product 20,25-dihydroxy-3-oxodammarane triterpene (2), together with known 5-hydroxy-3,6,7,8,3',4',5'-heptamethoxyflavone (3), have been isolated and characterized. The chemical structure of the new compounds was determined by 1D and 2D NMR and HR tandem MS measurements. All three compounds were subjected to biological tests for evaluation of their cytotoxicity against prostate (DU-145 and LNCaP) cancer cells. Compounds 1, 2, and 3 showed cell growth inhibition in a dose dependent manner against DU-145 and LNCaP cells.

Flavone constituents of Phlomis bruguieri Desf. with cytotoxic activity against MCF-7 breast cancer cells.

Phlomis bruguieri (P. bruguieri) is a large genus in the Lamiaceae family, with a wide variety distributed in Euro-Asia, Central Asia, Iran, and China. Phlomis flowers have been used as herbal tea for gastrointestinal disturbances, protection of liver and cardiovascular systems. The aim of this study was to analyse phytochemical of flavonoid constituents in semi polar fraction of P. bruguieri. Methanol extract of plant material (4 kg) yielded 361 g dark green concentrated extract gum. After preliminary fractionation by normal column chromatography on silica gel, Fr. 2 eluted with chloroform: methanol (90:10) selected as semi polar fraction and was more purified using different chromatography columns on silica gel, polyamide SC6 and Sephadex LH-20 adsorbents. Finally one new and three known flavonoids (1-4) were characterized in semi polar fraction. Isolated structures were identified using 1H-NMR, 13C-NMR, 31P-NMR, HSQC, HMBC, negative ESI mass, and UV spectra using different shift reagents. Using standard MTT assay, cytotoxicity of isolated new compound was done against michigan cancer foundation-7 (MCF-7) breast cancer cells. Phytochemical analysis of P. bruguieri resulted in identification of one new 4'-methoxy-luteolin-7-phosphate and three known flavones including luteolin, apigenin, and tricin for the first time in this plant. In MTT cytotoxicity test, 4'-methoxy-luteolin-7-phosphate showed cytotoxicity with IC50 value of 43.65 ± 8.56 µM agasint MCF-7 breast cancer cells.

Pimpinelol, a novel atypical Sesquiterpene lactone from Pimpinella haussknechtii fruits with evaluation of endoplasmic reticulum stress in breast cancer cells.

Pimpinella haussknechtii is an annual native plant grows in west of Iran. Phytochemical study of the fruits of P. haussknechtii led to the isolation of a novel irregular sesquiterpene lactone with a new skeletone and oxidation pattern named: pimpinelol. The structure of the isolated compound was elucidated by extensive spectroscopic methods. Cytotoxic activity of Pimpinelol was evaluated using standard MTT assay against breast cancer cells. Induced endoplasmic reticulum stress and related gene expressions were evaluated with fluorescence microscopy analysis and real time PCR, respectively. These findings confirmed that Pimpinelol concentrations dependently increased protein aggregation and the mRNA expression of ATF-4, CHOP, GADD34 and TRIB3 in MCF-7 breast cancer cell line. According to the obtain results, we demonstrated for the first time that Pimpinelol decreased breast cancer cell viability by inducing ER stress.

Anxiolytic effects of Lippia citriodora in a mouce model of anxiety.

Lippia citriodora is commonly used in Iranian folk medicine for treatment of many disorders. Since there scientific data to prove the anxiolytic properties of this plant in Iran are scarce, we aimed to evaluate the sedative and anxiolytic activity of the leaf extract and essence of L. citriodora in an animal model of anxiety. The extract and the essence used were obtained after maceration and hydro-distillation of the leaves of L. citriodora, respectively. We evaluated the anti-anxiety profile and sedative activity of diazepam (1 mg/kg i.p. as the standard), hydroethanolic extract (200 and 400 mg/kg i.p.) and the essence (10, 15, and 50 mg/kg i.p.) of leaves of L. citriodora using elevated plus-maze and locomotor activity. We also used flumazenil, to find out if the possible effects are mediated through gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. The results showed that the essence of L. citriodora at a dose of 15 mg/kg is the most effective anxiolytic dose. Interestingly, flumazenil reversed this action of the essence as well as that of diazepam. The extract even at a dose of 400 mg/kg did not show significant anxiolytic effect. In locomotor activity studies, the essence caused sedation to a lesser extent than diazepam. The results suggest that the essence of this plant could be a better candidate for further analysis and fractionation. As the anxiolytic effect of the essence is reversed by flumazenil, it is possible that the GABA receptor could be involved in mediating these effects.

Isolation and Identification of Two Phenolic Compounds from a Moderately Cytotoxic Fraction of Cousinia verbascifolia Bunge.

BACKGROUND: Little information is available about chemical components of the Cousinia genus. A primary cytotoxicity screening on Cousinia verbascifolia showed moderate cytotoxic activity against OVCAR-3 ovarian and HT-29 colon cancer cells. Therefore, the aim of this study is a phytochemical investigation to identify the compounds responsible for this bioactivity. MATERIALS AND METHODS: Extraction was done through percolation and fractionations by reverse phase column chromatography and normal column chromatography. Using standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay Fr.b8 with moderate cytotoxicity was selected for identification of major components. Fr.b8 was subjected to polyamide column chromatography. More purification was done using a new modified recycle high-performance liquid chromatography (HPLC) with flow splitter. RESULTS: Two known compounds: Apigenin (flavone) and caffeic acid (phenolic acid) were obtained from phenolic bioactive fraction for the first time from this plant. CONCLUSIONS: Apigenin and caffeic acid with known antitumor and matrix metalloproteinase inhibitory effects seem to be the bioactive components responsible for moderate cytotoxicity of phenolic fraction. Recycle HPLC following with flow splitting is a new method useful for isolation of closely eluted compounds in HPLC chromatogram.

Isolation and Identification of Secondary Metabolites from the Aerial Parts of Stachys lavandulifolia Vahl.

Stachys lavandulifolia Vahl is an herbaceous wild plant native to Iran which is traditionally used in Iranian folk medicine as a mild sedative tea for reducing anxiety and for treatment of gastrointestinal disorders. Our previous study on ethyl acetate extract of S. lavandulifolia proved anti-anxiolytic activity and so the present study was designed to determine chemical components of this biologically active fraction. The extract was prepared using maceration method. Column chromatography and medium pressure liquid chromatography (MPLC) was used respectively to separate the fractions. Finally, some evaluated fractions were used for high pressure liquid (HPLC) and peak shaving recycle technique to achieve more purification. Separated compounds were determined using NMR analysis and mass spectroscopy. Six compounds have been isolated from ethylacetate extract of aerial parts of S. lavandulifolia including four flavonoids (apigenin, kumatakenin, penduletin and 4', 7-dihyroxy- 3, 5, 6-trimethoxy flavon), a labdan diterpenoid (labda-13-en-8, 15-diol), and an iridoid.

Evaluation of the Antimalarial Effect of Ferulago angulata (Schlecht.) Boiss. Extract and Suberosin Epoxide Against Plasmodium berghei in Comparison with Chloroquine Using in-vivo Test.

Resistance to most antimalarial drugs has encouraged the development of novel drugs. An alternative source for discovering such drugs is natural products. Some Ferulago species are used in folk medicine for their sedative, tonic and anti-parasitic effects. Besides, coumarins isolated from this genus found to have in vitro anti-leishmanicidal effect. The present study is aimed to evaluate the in-vivo antimalarial activity of Ferulago angulata (Schlecht.) Boiss. extract and suberosin epoxide, using suarian mice. A rodent malaria parasite, Plasmodium berghei was used to inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 23-27 g. Hydro-alcoholic extract of F. angulata (20, 100, 300, 600 mg/Kg) and suberosin epoxide suspension (10, 30, 50, 100 mg/Kg) were administered subcutaneously. Parameters including percentage of parasitemia, suppression of parasitemia and mean survival time were determined using standard test such as peterÙ¬s. Chemo-protective effects were exerted by the crude extract and suberosin epoxide. Maximum effect was observed with the larger doses of the crude extract and suberosin epoxide. Suberosin epoxide increased the survival time compared to chloroquine. However, the results of this study indicate that the plant has a promising anti-plasmodial activity against plasmodium berghei. Thus, it could be considered as a potential source of new antimalarial agents. Suberosin epoxide at the dose of 100 mg/Kg possesses relatively significant antimalarial effect. Chemical derivatization of the parent compound or preparation of the modified formulation is required to improve its systemic bioavailability.

Antileishmanial activity of prenylated coumarins isolated from Ferulago angulata and Prangos asperula.

Leishmaniasis has a wide spectrum of signs and symptoms due to infection to numbers of Leishmania species and makes enormous mortality and morbidity. There are clues of antileishmanial effects of prenylated coumarins. Apiaceae family is one of the most important sources of coumarins. Air-dried aerial parts of Ferulago angulata and fruits of Prangos asperula were extracted with n-hexane, using a soxhlet apparatus. The solvents were evaporated under reduced pressure. Column chromatography and crystallization process resulted to isolation of three prenylated coumarins. (1)H-nuclear magnetic resonance, electron ionization Mass and Infrared spectra were used for elucidation of isolated compounds. Leishmanicidal activity of isolated coumarins was assessed on Leishmania major strain (MRHO/IR/75/ER) for the first time. Suberosin epoxide and suberosin were isolated from aerial parts of F. angulata and osthol was extracted from grounded fruits of P. asperula. Osthol showed a significant antileishmanial effect on promastigotes in early hours of exposure with IC50 of 14.40 µg/mL but suberosin epoxide showed only a weak antileishmanial activity. IC50 of osthol and suberosin epoxide after 48 h were 10.79 and 54.0 µg/mL, respectively. Suberosin showed no remarkable effect in these concentrations. This is the first report on the pharmacological activity of suberosin epoxide. Substantial difference between efficacies of two isomers, osthol and suberosin remarks the importance of prenyl substituent location on C-8.

Effect of Coriandrum sativum hydroalcoholic extract and its essential oil on acetic acid- induced acute colitis in rats.

OBJECTIVE: The aim of this study was to determine the protective effects of Coriandrum sativum on acetic acid-inducedcolitis in rats. C. sativum (Coriander) has long been used in Iranian traditional medicine and its use as an anti-inflammatory agent is still common in some herbal formulations. MATERIALS AND METHODS: Colitis was induced by intra-rectal administration of 2ml acetic acid 4% in fasted male Wistar rats. Treatment was carried out using three increasing doses of extract (250, 500, 1000 mg/kg) and essential oil (0.25, 0.5, 1 ml/kg) of coriander started 2 h before colitis induction and continued for a five-day period. Colon biopsies were taken for weighting, macroscopic scoring of injured tissue, histopathological examination and measuring myeloperoxidase (MPO) activity. RESULTS: Colon weight was decreased in the groups treated with extract (500 and 1000 mg/kg) and essential oil (0.5 ml/kg) compared to the control group. Regarding MPO levels, ulcer severity and area as well as the total colitis index, same results indicating meaningful alleviation of colitis was achieved after treatment with oral extract and essential oil. CONCLUSION: Since the present experiment was made by oral fractions of coriander thus the resulting effects could be due to both the absorption of the active ingredients and/or the effect of non-absorbable materials on colitis after reaching the colon. In this regard, we propose more toxicological and clinical experiments to warranty its beneficial application in human inflammatory bowel diseases.

Anti-Leishmania Activity of Osthole.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) is occasionally highly resistant to pentavalent antimonials, the gold standard in pharmacotherapy of CL. Since there is no effective vaccine, the discovery of natural antileishmanial products as complementary therapeutic agents could be used to improve the current regimens. OBJECTIVE: In this study in vitro and in vivo antileishmanial activities of osthole, a natural coumarin known to possess antibacterial and parasiticidal activities are evaluated. MATERIALS AND METHODS: Leishmania major infected J774.A1 macrophages were treated with increasing concentrations of osthole. CL lesions of BALB/c mice were treated topically with 0.2% osthole. RESULTS: Osthole exhibited dose-dependent leishmanicidal activity against intracellular amastigotes with IC50 value of 14.95 µg/ml. Treatment of CL lesions in BALB/c mice with osthole significantly declined lesion progression compared to untreated mice (P < 0.05), however did not result in recovery. CONCLUSION: Osthole demonstrated remarkable leishmanicidal activity in vitro. Higher concentrations of osthole may demonstrate the therapeutic property in vivo. SUMMARY: In vitro and in vivo antileishmanial activities of osthole, a pernylated coumarin extracted from Prangos asperula Boiss., are studied against Leishmania major.

Antihypertensive and antioxidant effects of hydroalcoholic extract from the aerial parts of Kelussia odoratissima Mozaff. in dexamethasone-induced hypertensive rats.

BACKGROUND: Kelussia odoratissima Mozaff. is a monotypic endemic plant of Apiaceae growing wild in Iran. The aerial parts of this plant are used for treatment of hypertension, ulcer, and inflammatory conditions in folk medicine. In this study, the effects of hydroalcoholic extract of the aerial parts of K. odoratissima were evaluated in dexamethasone (Dex)-induced hypertension in male Wistar rats. MATERIALS AND METHODS: For induction of hypertension, Dex (30 µg/kg/day) was administered subcutaneously for 14 days. In a prevention study, rats received oral K. odoratissima extract (100, 200, and 400 mg/kg) from 4 days before Dex administration and during the test period (days 1-18). In a reversal study, K. odoratissima extract was administered orally from day 8 to 14. Systolic blood pressure (SBP) was evaluated using tail-cuff method. The hydrogen peroxide (H2O2) concentration and ferric-reducing antioxidant power (FRAP) were measured in plasma samples. RESULTS: Administrations of Dex significantly induced an increase in SBP and in plasma H2O2 and a decrease in body and thymus weights, and in FRAP value (P < 0.001). K. odoratissima extract dose-dependently prevented and reversed hypertension (P < 0.001). It also prevented and reduced the plasma H2O2 concentration and prevented the body weight loss upon Dex administration at all doses (100-400 mg/kg, P < 0.001) but failed to improve FRAP value. CONCLUSIONS: These results suggest antihypertensive and antioxidant effects of K. odoratissima extract in Dex-induced hypertension. Further studies are needed to elucidate the exact mechanism of the antihypertensive effect of this herbal medicine.