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.

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 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.

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.

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.

Evaluation of anxiolytic and sedative effect of essential oil and hydroalcoholic extract of Ocimum basilicum L. and chemical composition of its essential oil.

Ocimum basilicum belongs to Lamiaceae family and has been used for the treatment of wide range of diseases in traditional medicine in Iranian folk medicine. Due to the progressive need to anti-anxiety medications and because of the similarity between O. basilicum and Salvia officinalis, which has anti-anxiety effects, we decided to investigate the anxiolytic and sedative activity of hydroalcoholic extract and essential oil of O. basilicum in mice by utilizing an elevated plus maze and locomotor activity meter. The chemical composition of the plant essential oil was also determined. The essential oil and hydroalcoholic extract of this plant were administered intraperitoneally to male Syrian mice at various doses (100, 150 and 200 mg/kg of hydroalcoholic extract and 200 mg/kg of essential oil) 30 min before starting the experiment. The amount of hydroalcoholic extract was 18.6% w/w and the essential oil was 0.34% v/w. The major components of the essential oil were methyl chavicol (42.8%), geranial (13.0%), neral (12.2%) and ß-caryophyllene (7.2%). HE at 150 and 200 mg/kg and EO at 200 mg/kg significantly increased the time passed in open arms in comparison to control group. This finding was not significant for the dose of 100 mg/kg of the extract. None of the dosages had significant effect on the number of entrance to the open arms. Moreover, both the hydroalcoholic extract and the essential oil decreased the locomotion of mice in comparison to the control group. This study shows the anxiolytic and sedative effect of hydroalcoholic extract and essential oil of O. basilicum. The anti-anxiety and sedative effect of essential oil was higher than the hydroalcoholic extract with the same doses. These effects could be due to the phenol components of O. basilicum.

Antiviral and cytotoxic evaluation of coumarins from Prangos ferulacea.

CONTEXT: Prangos ferulacea (L.) Lindl. (Apiaceae) is a perennial plant found in the Middle-East, where it is commonly used as an antispasmodic and anti-inflammatory agent. It is a rich source of coumarins. OBJECTIVE: To purify several coumarins from P. ferulacea and to screen their cytotoxicity and anti-herpes activity. MATERIALS AND METHODS: Acetone extract of roots of P. ferulacea was subjected to several chromatographic separations to render pure coumarins (1-8). Anti-herpes virus effects of 1-7 were evaluated at concentration 2.5, 5, and 10 µgmL(-1), on a confluent monolayer of Vero cells infected with 25 PFU of HSV1. Cytotoxic effects of 1 and 2 were evaluated on an A2780S cell line using the MTT assay. The cells were exposed to a series of concentrations of coumarins (0.01-2.5 mM, 37°C, 72 h). RESULTS: Compounds 1-8 were identified as osthole, isoimperatorin, oxypeucedanin, psoralen, oxypeucedanin hydrate, gosferol, oxypeucedanin methnolate, and pranferol. This is the first report of occurrence of 4 and 7 in this plant. Compound 1 showed a viability of 9.41% ± 2.4 at 2.5 mM on A2780S cells (IC50 = 0.38 mM). The cell survival of 2 at 2.5 mM was 46.86% ± 5.5 with IC50 equal to 1.1 mM. DISCUSSION AND CONCLUSION: Compound 1 shows cytotoxic effects on the A2780S cell line. Compound 2 is a cyclooxygenase-2 inhibitor and the A2780S cell line does not express COX-2 which may interpret the non-toxic effect of the compound on this cell line. None of the tested compounds showed an anti-HSV effect at non-toxic concentrations.

Antiproliferative evaluation of terpenoids and terpenoid coumarins from Ferulago macrocarpa (Fenzl) Boiss. fruits.

BACKGROUND: Ferulago macrocarpa is a plant used as flavoring agent and protectant in the food industry and as a folk medicinal plant in Iran with no available information on its chemical identity. Ferulago spp. showed to contain biologically terpenoids and coumarins. OBJECTIVE: The objective was to isolate and characterize terpenoids and coumarins from the acetone extract of F. macrocarpa fruits and to evaluate their antiproliferative effects on several cell lines. MATERIALS AND METHODS: A series of normal and reverse phase gravity and high-performance liquid chromatography analyses were used to purify constituents. Compounds 1-5 and 7 were evaluated for their cytotoxic effects on MCF-7, HT-29 and H-1299 cell lines. RESULTS: Six compounds including bornyl acetate (1), 1,10-di-epi-cubenol (2), stigmasterol (3) and three coumarins grandivittin (4), prantschimgin (5) and 4"-hydroxygrandivittin (7) along with mixtures of feruloyl derivatives (6a-6c) have been purified. Their structures were established by spectroscopic methods including nuclear magnetic resonance and MS analyses. Compound 2 showed moderate cytotoxicity effect with IC50 values of 5.0 and 6.7 mM on MCF-7 and HT-29, respectively. CONCLUSION: 1,10-di-epi-Cubenol could be considered as a potential proliferation inhibitor of MCF-7 and HT-29 cell lines.

Alleviation of Morphine Withdrawal Signs but Not Tolerance by the Essential Oil of Kelussia odoratissima Mozaff.

The aim of the present study was to assess the effects of chronic and acute treatment of the essential oil (EO) of Kelussia odoratissima Mozaff. on the development of morphine tolerance and dependence in mice. Mice were rendered tolerant to and dependent on morphine by subcutaneous injection of morphine over a period of 5 days. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2 h after the final morphine injection. Repeated injection of the EO of K. odoratissima (5 and 10 mg/kg) for 4 days significantly suppressed morphine-withdrawal jumps, a sign of the development of dependence to opiate as assessed by naloxone precipitation withdrawal on day 5 of testing. A single injection (25, 50, 100 mg/kg) of the EO on day 5, 1 h prior to morphine failed to produce any significant change in morphine withdrawal signs. Neither the acute nor the chronic administration of EO of the K. odoratissima did significantly influence the development of tolerance to the analgesic effect of morphine. Alleviation in morphine signs of withdrawal after chronic injection with K. odoratissima is indicative of reversal of neuronal adaptation that takes place during morphine presence in the brain.

Isolation and Identification of Ferulic Acid From Aerial Parts of Kelussia odoratissima Mozaff.

BACKGROUND: Kelussia odoratissima Mozaff. is one of the newest genera of Umbelliferae which is represented by only one species. This sweet-smelling, self-growing monotypic medicinal plant is endemic to a restricted area in west of Iran and is locally called Karafse-koohi. The aerial parts of the plant are commonly used as a popular garnish and a sedative medicinal plant. There are several reports concerning antioxidant, anti-inflammatory, anxiolytic and hypolipidemic activities of aerial parts of K. odoratissima. OBJECTIVES: The current research aimed to evaluate some phenolic contents of the plant for the first time .It is confirmed that secondary metabolites and especially phenolic compounds have important role in the biological activities of the plant. Available information indicates that phenolic contents of K. odoratissima have not been the subject of any investigation. MATERIAL AND METHODS: Aerial parts of K. odoratissima were extracted with acetone by maceration method. Normal and reversed phase vacuum liquid chromatography used to fractionate the extract. (1)H-NMR, (13)CNMR, EI-Mass and IR spectra were used to elucidate isolated compound. RESULTS: The phenolic acid isolated compound was identified as 4-hydroxy-3-methoxycinnamic acid (ferulic acid). CONCLUSIONS: Compared with previous reported antioxidant and anti-inflammatory properties of ferulic acid, a chemical-biological relation can be postulated.

Chemical composition of the essential oil from kelussia odoratissima Mozaff. and the evaluation of its sedative and anxiolytic effects in mice.

OBJECTIVE: The present study aimed to evaluate the sedative and anxiolytic effects of the essential oils and hydroalcoholic extract of Kelussia odoratissima Mozaff. (K. odoratissima) in mice by utilizing an elevated plus maze. The chemical composition of its essential oil was also determined. METHODS: The hydroalcoholic extract or essential oil fraction from this plant were administered intraperitoneally to male mice at various doses 30 min before testing. The anxiolytic and sedative effects were determined by an elevated plus maze and locomotor activity tests, respectively. RESULTS: According to the results, none of the administered doses of hydroalcoholic extract or essential oil fraction of K. odoratissima changed the percentage of the time spent or number of entries into the open arms of the elevated plus maze. In contrast, the cumulative spontaneous locomotor activity of mice treated with the essential oil or hydroalcoholic extract was significantly decreased. Chemical analysis of the essential oil by Gas chromatography-mass spectromentry (GC-MS) showed that 3-butylidene-4,5-dihydrophthalide (85.9%) was the major component. CONCLUSION: These data confirm the sedative properties of K. odoratissima, yet there were no profound anxiolytic effects observed.

Antinociceptive and anti-inflammatory activities of Bunium persicum essential oil, hydroalcoholic and polyphenolic extracts in animal models.

OBJECTIVE: Fruits of Bunium persicum (Boiss.) B. Fedtsh. (Apiaceae) are widely used in Iranian folkloric medicine for controlling colic pain and dysmenorrhea. This study was aimed to evaluate the anti-inflammatory and analgesic effects of the plant fruits and analyzing its essential oil. MATERIALS AND METHODS: Hydroalcoholic extract, polyphenolic extract and essential oil were prepared using standard methods. The acetic acid and formalin tests were used in male mice (25-35 g) to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema and croton oil-induced ear edema were used. RESULTS: Hydrodistillation of the fruits of B. persicum afforded a pale yellowish oil in a yield of 2%. GC/MS analysis identified 10 compounds, and gamma-terpinene (46.1%), cuminal (23.9%) and p-cymene (15.9%) were the main components. Hydroalcoholic and polyphenolic extracts (400 and 800 mg/kg, i.p.) and essential oil (100-400 µl/kg, p.o.) significantly (p < 0.01) reduced acetic acid-induced writhings. They also significantly reduced the pain response of both early and late phases of the formalin test. In the carrageenan test and croton oil-induced ear edema both extracts and essential oil showed considerable anti-inflammatory response. DISCUSSION AND CONCLUSIONS: These results clearly show the analgesic and anti-inflammatory effects of the plant fruits, and since extracts and essential oil relieved the pain of the first phase of the formalin test, it seems that at least a part of analgesic activity is mediated centrally. Meanwhile, the effects observed in this study provide evidence for folkloric uses of the plant fruits in painful and inflammatory conditions.

Macrocyclic diterpenoids from the Iranian plant Euphorbia bungei Boiss.

An acetone extract from the aerial parts of Euphorbia bungei afforded three new (2, 3 and 5) and one known (4) macrocyclic diterpenoids. Several cycloartane triterpenoids were also obtained, two of which (6a and 6b) were assayed for antiviral effects. The structures of all new compounds were elucidated using modern spectroscopic methods including 2D NMR and HRMS.

Chemical composition of the essential oil from kelussia odoratissima mozaff. and the evaluation of its sedative and anxiolytic effects in mice

OBJECTIVE: The present study aimed to evaluate the sedative and anxiolytic effects of the essential oils and hydroalcoholic extract of Kelussia odoratissima Mozaff. (K. odoratissima) in mice by utilizing an elevated plus maze. The chemical composition of its essential oil was also determined. METHODS: The hydroalcoholic extract or essential oil fraction from this plant were administered intraperitoneally to male mice at various doses 30 min before testing. The anxiolytic and sedative effects were determined by an elevated plus maze and locomotor activity tests, respectively. RESULTS: According to the results, none of the administered doses of hydroalcoholic extract or essential oil fraction of K. odoratissima changed the percentage of the time spent or number of entries into the open arms of the elevated plus maze. In contrast, the cumulative spontaneous locomotor activity of mice treated with the essential oil or hydroalcoholic extract was significantly decreased. Chemical analysis of the essential oil by Gas chromatography-mass spectromentry (GC-MS) showed that 3-butylidene-4,5-dihydrophthalide (85.9 percent) was the major component. CONCLUSION: These data confirm the sedative properties of K. odoratissima, yet there were no profound anxiolytic effects observed.

Diterpenoid (poly)esters and a ring A-seco-phorboid from the aerial parts of Euphorbia macroclada Boiss.

Euphorbia macroclada Boiss., a spurge endemic to the Iranian plateau, afforded four pre-myrsinane polyesters, three α-phorboids and one A-seco-phorboid, a type of compound so far unreported within natural products. All new compounds were structurally elucidated by spectroscopic methods, and especially 2D NMR measurements.

Anti-inflammatory and analgesic properties of Heracleum persicum essential oil and hydroalcoholic extract in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Heracleum persicum (Apiaceae) are used as pain killer in Iranian folkloric medicine. AIMS OF STUDY: To evaluate the anti-inflammatory and analgesic effects of the hydroalcoholic extract and essential oil of the plant fruits and analyzing the essential oil. MATERIALS AND METHODS: Essential oil and hydroalcoholic extracts of the fruits were prepared according to standard methods and the components of essential oil were identified using GC-MS method. The acetic acid-induced writhing response and formalin test were used in male mice to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema was used. RESULTS: Hexyl butyrate (56.5%), octyl acetate (16.5%), hexyl 2-methylbutanoate (5.2%) and hexyl isobutyrate (3.4%) were identified as the major constituents of the oil. Oral or intraperitoneal administration of Heracleum persicum essential oil (HPEO) at doses of 50-200 mg/kg and Heracleum persicum hydroalcoholic extract (HPHE) at doses of 250 and 500 mg/kg significantly reduced acetic acid-induced abdominal constrictions. HPEO and HPHE also significantly attenuated the pain response of the second phase of formalin test. In carrageenan test HPEO at doses of 100 and 200 mg/kg and HPHE at a dose of 400 mg/kg induced a significant reduction of paw edema. CONCLUSIONS: These results clearly show the analgesic and anti-inflammatory effects of the plant essential oil and hydroalcoholic extract. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

Essential oil of the Persian sage, Salvia rhytidea Benth.

Chemical composition of volatile compounds from Salvia rhytidea Benth. was analyzed, for the first time, by gas chromatography/mass spectrometry. The volatiles were isolated from dried aerial parts of the plant by hydrodistillation. A total yield of 2.0 mg of essential oil per g of plant dry mass was obtained and sixty compounds were identified, representing 98.2% of total volatiles. The essential oil was characterized by a high content of hydrocarbon and oxygenated monoterpenes. The main constituents were p-cymene-8-ol (11.9%), spathulenol (7.3%), pulegone (6.4%), sabinene (5.8%), terpinen-4-ol (5.5%) and alpha-copaene (5.3%).