Anticonvulsant evaluation of aminoalkanol derivatives of 2- and 4-methylxanthone

A series of 17 new aminoalkanol derivatives of 6-methoxy- or 7-chloro-2-methylxanthone as well as 6-methoxy-4-methylxanthone was synthesized and evaluated for anticonvulsant activity. All compounds were verified in mice after intraperitoneal (ip) administration in maximal electroshock (MES) and subcutaneous pentetrazole (scMet) induced seizures as well as neurotoxicity assessment. Eleven of the tested substances showed protection against electrically evoked seizures in the majority of the tested mice at the dose of 100 mg/kg. Additionally, one was effective at the dose of 30 mg/kg. Five substances were active at the dose of 300 mg/kg or at the dose of 100 mg/kg in the minority of the tested mice. The most promising compound revealed ED₅₀ value of 47.57 mg/kg in MES (mice, ip, 1 h after administration) and at the same time its TD₅₀ was evaluated as above 400 mg/kg. Those values gave PI (calculated as TD₅₀/ED₅₀) of more than 8.41. Three other synthesized xanthone derivatives also proved to act as anticonvulsants and showed ED₅₀ values in MES test (mice, ip) ranged 80–110 mg/kg. Results were quite encouraging and suggested that in the group of xanthone derivatives new potential anticonvulsants might be found.     

Anticonvulsant and Antioxidant Effects of Cyano-carvone and Its Action on Acetylcholinesterase Activity in Mice Hippocampus

The anticonvulsant effect of cyano-carvone, a monoterpene monocyclic, was investigated in epilepsy model induced by pilocarpine. Cyano-carvone at doses of 25, 50 or 75 mg/kg promoted a reduction of 16.7, 33 and 66.7%, respectively, against pilocarpine-induced seizures, and it was efficacious in increasing both the latency to first seizures and the survival percentage, resulting in 33.3, 67 and 91.7% of protection against death induced by seizures, respectively (P < 0.05). The reference drug atropine (25 mg/kg) also produced a significant protection (100%). Its monoterpene, at 25, 50 and 75 mg/kg, was also capable to increase the latency for installation of status epilepticus induced by pilocarpine, and presented a significant protection against lipid peroxidation and nitrite formation in mice hippocampus (P < 0.05). In addition, it was observed that the cyano-carvone pretreatment increased the acetylcholinesterase activity in mice hippocampus after pilocarpine-induced seizures. The present results clearly indicate the anticonvulsant ability of cyano-carvone, which can be, at least in part, explained by the increased activity of the acetylcholinesterase enzyme. Our data suggest that the action mechanism can also be due to a direct activation of the antioxidant enzymes that could be associated with a reduction observed in oxidative stress in mice hippocampus, probably involving an inhibition of free radical production.     

Anticonvulsant activity of aqueous extract of Leonotis leonurus.

Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90 mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg). However, all the doses of aqueous extract of L leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.     

Behavioral responses to intracerebroventricularly administered neurohypophyseal peptides in mice

Lysine vasopressin (LVP), arginine vasopressin, oxytocin, and arginine vasotocin administered intraventricularly (icv) to mice all provoked a dose-dependent behavioral response in the range 0.1 – 1.0 μg. This response included a pronounced hyperactivity, extensive foraging, increased grooming, and at higher doses, stereotyped scratching, squeaking, and occasional barrel rolling. The four hormones were all approximately equipotent. Desglycinamide lysine vasopressin and [desaminocys₁, D-Arg₈] vasopressin produced some of the characteristic behaviors, but were much less potent. While pretreatment of the animals with reserpine (5 mg/kg ip), haloperidol (0.5 mg/kg ip), or physostigmine (0.5 mg/kg ip) sedated the animals and attenuated the locomotion and grooming, these drugs did not substantially alter the characteristic behavioral responses to LVP. Pretreatment with α-methyl-p-tyrosine (400 mg/kg ip), p-chlorophenylalanine (320 mg/kg ip), 6-hydroxydopamine (100 μg icv), ergotamine (0.5 μg icv), ethoxolamide (52 ng icv), diphenhydramine (20 μg icv), prostaglondin F_2α (2 μg icv), or naloxone (1 mg/kg ip) did not alter the LVP-induced behaviors. None of these drugs or -amphetamine (0.5 to 20 mg/kg ip) or nicotine (0.1 or 1 μg icv) mimicked the behavioral effects of the hormones.     

Neurobehavioral effect of essential oil of Cymbopogon citratus in mice

Tea obtained from leaves of Cymbopogon citratus (DC) Stapf is used for its anxiolytic, hypnotic and anticonvulsant properties in Brazilian folk medicine. Essential oil (EO) from fresh leaves was obtained by hydrodistillation and orally administered to Swiss male mice 30 min before experimental procedures. EO at 0.5 or 1.0 g/kg was evaluated for sedative/hypnotic activity through pentobarbital sleeping time, anxiolytic activity by elevated plus maze and light/dark box procedures and anticonvulsant activity through seizures induced by pentylenetetrazole and maximal electroshock. EO was effective in increasing the sleeping time, the percentage of entries and time spent in the open arms of the elevated plus maze as well as the time spent in the light compartment of light/dark box. In addition, EO delayed clonic seizures induced by pentylenetetrazole and blocked tonic extensions induced by maximal electroshock, indicating the elevation of the seizure threshold and/or blockage of seizures spread. These effects were observed in the absence of motor impairment evaluated on the rotarod and open field test. Our results are in accord with the ethnopharmacological use of Cymbopogon citratus, and after complementary toxicological studies it can support investigations assessing their use as anxiolytic, sedative or anticonvulsive agent.     

Assessment of the genotoxicity of imidacloprid and metalaxyl in cultured human lymphocytes and rat bone-marrow

Imidacloprid and metalaxyl are two pesticides that are widely used in agriculture, either separately, or in combination. These agents were studied for their possible genotoxic effects with respect to the following cytogenetic end-points: (1) in vitro micronucleus (MN) formation and sister-chromatid exchange (SCE) induction in human lymphocytes and (2) in vivo micronucleus induction in polychromatic erythrocytes (PCEs) of the rat bone-marrow. The results of the MN analysis indicate that MN frequencies after treatment with both pesticides, separately or as a mixture, do not significantly differ from those in the controls except after treatment with metalaxyl alone at 50 μg/ml (p < 0.05). The results of the SCE analysis show that SCE frequencies after treatment with imidacloprid do not differ significantly from those in the controls. A statistically significant increase (p < 0.05) in SCE frequency resulted from treatments with metalaxyl at 5, 10 and 100 μg/ml and with the combination of imidacloprid and metalaxyl at 100 and 200 μg/ml. Finally, the in vivo micronucleus assay with rat bone-marrow polychromatic erythrocytes showed a statistically significant effect upon separate treatments with imidacloprid and metalaxyl at doses of 300 mg/kg body weight (b.w.) (p < 0.01) or upon combined treatment with 200 mg/Kg b.w. (p < 0.001) and 400 mg/kg b.w. (p < 0.05).     

Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats

The aim of this study was to investigate the synergistic hepatoprotective effect of lignans from Fructus Schisandrae chinensis (LFS) with Astragalus polysaccharides (APS) on chronic liver injury in male Sprague-Dawley rats. Subcutaneous injection of 10% CCl₄ twice a week for 3 months resulted in significantly (p<0.001) elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the liver, significantly elevated levels (p<0.001) of malondialdehyde (MDA), lowered levels of reduced glutathione (GSH) (p<0.05) and catalase (CAT) (p<0.001), superoxide dismutase (SOD) (p<0.01)were observed following CCl₄ administration. ‘LFS+ASP’ treatment of rats at doses of ‘LFS (45 mg/kg)+APS (150 mg/kg)’ and ‘LFS (135 mg/kg)+APS (450 mg/kg)’ displayed hepatoprotective and antioxidative effects than the administration of either LFS or APS, as evident by lower (p<0.005 or 0.001) levels of serum ALT, AST, ALP and hepatic MDA (p<0.001) concentration, as well as higher SOD (p<0.05 or 0.005), CAT activities(p<0.01 or 0.005), GSH concentration (p<0.05 or 0.005) compared to the toxin treated group. Histopathological examinations revealed severe fatty degeneration in the toxin group, and mild damage in groups treated with ‘LFS+APS’ were observed. The coefficients drug interaction (CDI) between each individual drug and their combination (at the same dose of their single treatment) of these foregoing parameters were all less than 1, indicating that LFS and APS display hepatoprotective and antioxidant properties and act in a synergistic manner in CCl₄ induced liver injury in rats.     

Search for anticonvulsant and analgesic active derivatives of dihydrofuran-2(3H)-one

A series of derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone, GBL) was synthesized and tested for anticonvulsant, neurotoxic and analgesic activity. In the anticonvulsant screening 10 lactones were effective in the maximal electroshock test (MES) at the highest doses (300 and 100 mg/kg, 0.5 h, ip, mice). Statistical analysis showed correlation between the anticonvulsant activity and relative lipophilicity parameters determined by experimental and computational methods (R_M0, C log P and M log P). Preliminary antinociceptive evaluation of selected derivatives revealed strong analgesic activity. The majority of the tested compounds showed high efficacy in animal models of acute pain (hot plate and writhing tests) and strong local anesthetic activity (modified tail immersion test). The obtained ED₅₀ values were comparable with such analgesics as acetylsalicylic acid and morphine.     

New hybrid molecules with anticonvulsant and antinociceptive activity derived from 3-methyl- or 3,3-dimethyl-1-[1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]pyrrolidine-2,5-diones

The purpose of this study was to synthetize the focused library of 34 new piperazinamides of 3-methyl- and 3,3-dimethyl-(2,5-dioxopyrrolidin-1-yl)propanoic or butanoic acids as potential new hybrid anticonvulsants. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5–38 were prepared in a coupling reaction of the 3-methyl- or 3,3-dimethyl-2-(2,5-dioxopyrrolidin-1-yl)propanoic (1, 2) or butanoic acids (3, 4) with the appropriately substituted secondary amines in the presence of the N,N-carbonyldiimidazole reagent. The initial anticonvulsant screening was performed in mice (ip) using the ‘classical’ maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6 Hz) model of pharmacoresistant limbic seizures. The acute neurological toxicity was determined applying the chimney test. The broad spectra of activity across the preclinical seizure models in mice ip displayed compounds 7, 15, and 36. The most favorable anticonvulsant properties demonstrated 15 (ED₅₀ MES = 74.8 mg/kg, ED₅₀ scPTZ = 51.6 mg/kg, ED₅₀ 6 Hz = 16.8 mg/kg) which showed TD₅₀ = 213.3 mg/kg in the chimney test that yielded satisfying protective indexes (PI MES = 2.85, PI scPTZ = 4.13, PI 6 Hz = 12.70) at time point of 0.5 h. As a result, compound 15 displayed comparable or better safety profile than clinically relevant AEDs: ethosuximide, lacosamide or valproic acid. In the in vitro assays compound 15 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and L-type calcium channels. Beyond the anticonvulsant properties, 6 compounds diminished the pain responses in the formalin model of tonic pain in mice.     

Comparative study on methyl orange removal by growing cells and washed cell suspensions of <Emphasis Type="Italic">Lactobacillus casei</Emphasis> TISTR 1500

Lactobacillus casei TISTR 1500 possesses cytoplasmic azoreductase, and converts methyl orange to N,N-dimethyl-p-phenylenediamine and 4-aminobenzenesulfonic acid. In culture growth, the strain completely degraded methyl orange at 200 mg/l, even though the pH value was lower than 4. The decolorization was inhibited in the growing culture with 800 mg of the dye/l after incubation for 12 h. The percentage of decolorization and specific decolorization rate with 400 and 800 mg/l were 66 and 15%, and 14.2, and 8.7 mg/gCell/h, respectively. Additionally, a growing culture is more tolerant to a high initial dye concentration than when using washed cell suspensions supplied with only sucrose. Moreover, incubation of a low cell density in 600 μM of Na⁺ and 20 mM of sucrose increased the specific decolorization rate from 2.34 mg/gCell/h (without Na⁺) to 4.32 mg/gCell/h. However, Na⁺ had no effect on the enhancement of azoreductase activity in the reaction mixture.     

Effect of bis(acetato)tetrakis(imidazole) copper(II) in delaying the onset and reducing the mortality rate of strychnine- and thiosemicarbazide—Induced convulsions

The anticonvulsant activity of bis(acetato)tetrakis(imidazole) copper(II), Cu(OAc)₂(Im)₄, was studied in normal mice using chemical convulsions induced by strychnine, thiosemicarbazide, picrotoxin, and pentelenetetrazol. Intraperitoneal administration of Cu(OAc) ₂(Im)₄, 50 mg/kg body mass, has delayed the onset of strychnine (3 mg/kg)-induced convulsion by 204% (p≤0.005) and thiosemicarbazide (20 mg/kg)-induced convulsant by 61% (p≤0.005). The changes in the onset of picrotoxin-(6 mg/kg) and pentelenetetrazol (50 mg/kg)-induced convulsions were not significant. The same dosage of the copper compound was effective in delaying the lethal time and reducing the mortality rate of treated animals. The anticonvulsant activity of Cu(OAc) ₂(Im)₄ complex against strychnine was not related to its constituents because the inorganic form of copper such as copper chloride, copper acetate, and the parent imidazole has no anticonvulsant activity. Other copper(II) complexes like copper(II)aspirinate and bis(acetato)bis(2-methyl imidazole) copper(II) were less effective.     

Heavy metal and arsenic accumulating fern species as potential ecological indicators in As-contaminated abandoned mines

Ferns are good ecological indicators of arsenic accumulation in contaminated abandoned mines. The rhizomes of ferns were analyzed for arsenic and other heavy metals using inductively coupled plasma-mass spectrometry. In addition, we examined the ribulose-bisphosphate carboxylase (rbcL) gene isolated from the indigenous species of ferns at the pithead, tailings and soil sites in the vicinity of the Myoungbong abandoned mine, Republic of Korea. A search of the GenBank database revealed that the predicted amino acid sequence of this gene was homologous with 99% of Pteridium aquilinum As-2 (EU476184), 99% of Deparia petersenii As-6 (EU476188), 97% of Deparia lobatocrenata As-8 (EU476190), and 98% of Deparia conilii As-7 (EU476189). High concentrations of heavy metals (arsenic, 17.6 mg/kg in rhizomes and 2690 mg/kg in soil; copper, 17.1 mg/kg in rhizomes and 40.7 mg/kg in soil; cadmium, 2.9 mg/kg in rhizomes and 12.2 mg/kg in soil; lead, 41.9 mg/kg in rhizomes and 135 mg/kg in soil; zinc, 27.0 mg/kg in rhizomes and 172 mg/kg in soil) were found in P. aquilinum As-2 (EU476184) from the Myoungbong mine area, which may play an important role as ecological indicators of the contaminated areas.     

The Effects of Alpha-Tocopherol on Hippocampal Oxidative Stress Prior to in Pilocarpine-Induced Seizures

Reactive oxygen species have been implicated in seizure-induced neurodegeneration, and there is a correlation between free radical level and scavenger enzymatic activity in the epilepsy. It has been suggested that pilocarpine-induced seizures is mediated by an increase in oxidative stress. Current research has found that antioxidant may provide, in a certain degree, neuroprotection against the neurotoxicity of seizures at the cellular level. Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol (TP) in rats, against oxidative stress caused by pilocarpine-induced seizures. 30 min prior to behavioral observation, Wistar rats were treated with, 0.9% saline (i.p., control group), TP (200 mg/kg, i.p., TP group), pilocarpine (400 mg/kg, i.p., P400 group), or the combination of TP (200 mg/kg, i.p.) and pilocarpine (400 mg/kg, i.p.). After the treatments all groups were observed for 6 h. The enzymatic activities, lipid peroxidation and nitrite concentrations were measured using speccitrophotometric methods and these data were assayed. In P400 group mice there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase (SOD) and catalase activities. In the TP and pilocarpine co-administered mice, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content, as well as increased the SOD and catalase activities in rat hippocampus after seizures. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus during pilocarpine-induced seizures, indicate that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and imply that strong protective effect could be achieved using alpha-tocopherol.     

Phytase can reduce theneedfor monocalcium phosphate supplementation in soybean and rapeseed meal‐based diets of black sea bream,Acanthopagrus schlegelii (Bleeker, 1854)

A feeding trial was conducted to study the effect of partial replacement of dietary monocalcium phosphate (MCP) with phytase on growth performance, feed utilization and phosphorus discharge in black sea bream, Acanthopagrus schlegelii. In the feeding trial, the control diet (designated as P1.5) was prepared with 1.5% MCP but without phytase, and the three other diets (designated as PP1.0, PP0.5 and PP0, respectively) were supplemented with 1.0%, 0.5% and 0% MCP, respectively, along with 200 mg (400 U) phytase/kg diet in each. Each diet was tested in triplicate tanks and fish were fed twice daily to satiation. After an 8‐week feeding trial in indoor flow‐through cylindrical fibreglass tanks (25 fish per tank, initial body weight: 11.5 ± 0.12 g), fish fed with PP1.0 and PP0.5 had no significant change in weight gain (WG), specific growth rate (SGR), protein efficiency rate (PER) or feed conversion ratio (FCR) compared to the control (p > .05), whereas fish fed with PP0 showed a significantly lower growth performance in the above parameters (p < .05). The addition of phytase did not affect the body composition or muscle composition. The apparent digestibility coefficients (ADCs) of crude protein and phosphorus increased when fish were fed diets in which MCP was replaced by phytase. Phosphorus discharge was also significantly reduced in fish fed diets in which MCP was replaced by phytase (10.2 ± 0.50 to 8.01 ± 0.47 g/kg weight gain). The present study suggests that dietary MCP can be reduced when phytase is added to the black sea bream diet, with a maximum MCP reduction level of up to 1% when phytase is supplemented at 200 mg (400 U)/kg diet. Thus, phytase in the diet of black sea bream is economically and ecologically beneficial.     

A comparison of the genotoxicity of ethylnitrosourea and ethyl methanesulfonate in lacZ transgenic mice (Muta™Mouse)

We compared the induction of gene mutations and chromosomal aberrations by ethylating agents in lacZ transgenic mice (Muta™Mouse). Chromosomal aberrations were detected by the peripheral blood micronucleus assay. Gene mutations were detected in the lacZ transgene. A small amount of blood was sampled from a tail vessel during the expression time for fixation of gene mutations in vivo; this enabled us to detect and compare clastogenicity and gene mutations in the identical mouse. Single intraperitoneal injections of ENU (50–200 mg/kg) and EMS (100–400 mg/kg) strongly induced micronucleated reticulocytes (MN) detectable in peripheral blood 48 h after treatment. The maximum MN frequencies induced were 6.6% and 3.3% for ENU (100 mg/kg) and EMS (400 mg/kg), respectively (the control value was 0.3%). lacZ mutant frequency (MF) was analyzed in bone marrow and liver 7 days after treatment. Spontaneous MFs were 2.0–4.6x10⁻⁶. MF in bone marrow was increased by ENU to 3.4x10⁻⁵ at 200 mg/kg and induced by EMS to 1.8x10⁻⁵ at 400 mg/kg. In liver, however, both chemicals at their highest doses induced only slight increases in MF. The induction of both micronuclei and lacZ mutations in bone marrow by both ENU and EMS correlated better with O⁶-ethylguanine adducts than with N7-ethylguanine adducts. The mutants (19 for ENU and 12 for EMS) were subjected to DNA sequence analysis. Among EMS-induced mutations, 75% were GC to AT transitions, which were probably caused by O⁶-ethylguanine. Among ENU-induced mutations, in contrast, 40% occurred as AT base pair substitutions (6 AT to TA transversions and 2 AT to GC transitions) (no such mutations were induced by EMS). These results, together with the known reactivity of ENU to thymine suggest that thymine adducts play a significant role in the ENU mutagenesis.     

Effect of the Leaf Essential Oil from Cinnamosma madagascariensis Danguy on Pentylenetetrazol‐induced Seizure in Rats

In the Malagasy traditional practices, the smoke from burning leaves of Cinnamosma madagascariensis Danguy is inhaled to treat brain disorders such as dementia, epilepsy, and headache. In the present work, we have evaluated the in vivo anticonvulsant effects of the essential oil from leaves of C. madagascariensis (CMEO). CMEO was isolated by steam distillation. The anticonvulsant activity of CMEO (0.4 and 0.8 ml/kg bw) administered subcutaneously was evaluated on pentylenetetrazol (PTZ)‐induced seizures in Wistar rats; diazepam was used as positive control. Linalool, limonene, and myrcene were the major CMEO constituents. At the dose of 0.8 ml/kg, CMEO completely arrested the PTZ‐induced convulsions with moderate sedative effects. The traditional anticonvulsant use of C. madagascariensis was confirmed allowing us to candidate molecules from CMEO as potential drugs to treat convulsions associated with strong agitation.     

In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N-(4-nitrophenyl)-N-propylglycinamide

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmania infantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5 mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease activity assay. Both compounds showed nuclease activity in the presence of copper salt. The results suggest that compounds 4Aa, 4Ba and 5 represent possible candidates for drug development in the therapeutic control of leishmaniasis.     

The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats

In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320 mg/kg body wt.), crocin (100, 200 and 400 mg/kg body wt.), safranal (0.1, 0.2 and 0.4 ml/kg), sildenafil (60 mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320 mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.     

Evaluation of the neuroprotective activity of stansin 6, a resin glycoside from Ipomoea stans

Stansin 6 a tetrasaccharide resin glycoside isolated from the root of Ipomoea stans was evaluated as anticonvulsant and neuroprotective in kainic acid-induced seizures of rats. Intraperitoneal injection of kainic acid (10 mg/kg) induced typical behavioral seizures such as wet dog shakes and limbic seizures, and histopathological changes in the hippocampus (degeneration and loss of pyramidal cells in CA1 to CA4 areas). Stansin 6 (10–80 mg/kg) had no effect on the behavior of rats and did not induce hippocampal damage. Pretreatment with stansin 6 inhibited convulsions in rats from kainic acid-induced seizures, reduced the degeneration pattern in the CA3 region, decreased astrocytic reactivity, and reduced the expression of IL-1β and TNF-α induced by kainic acid. These results suggest that stansin 6 possesses neuroprotective and anticonvulsant activities.