Protective effect of a standardized Allium jesdianum extract in an Alzheimer's disease induced rat model.

Alzheimer's disease (AD) is a complex disorder with multiple underlying mechanisms. Existing treatment options mostly address symptom management and are associated with numerous side effects. Therefore, exploring alternative therapeutic agents derived from medicinal plants, which contain various bioactive compounds with diverse pharmacological effects, holds promise for AD treatment. This study aims to assess the protective effects of the hydroalcoholic extract of Allium jesdianum on cognitive dysfunction, mitochondrial and cellular parameters, as well as genetic parameters in an intracerebroventricular Streptozotocin (icv-STZ) induced rat model of AD. Male Wistar rats were injected with a single dose of STZ (3 mg/kg, icv) to establish a sporadic AD model. A. jesdianum extract (100, 200, and 400 mg/kg/day) and donepezil (5 mg/kg/day) were orally administered for 14 days following model induction. Cognitive function was evaluated using the radial arm water maze test. Mitochondrial toxicity parameters in various brain regions (whole brain, frontal cortex, hippocampus, and cerebellum) were assessed. Gene expression analysis of miR-330, miR-132, Bax, and Bcl-2 in isolated rat brain neurons was performed using RT-qPCR. A. jesdianum extract significantly attenuated cognitive dysfunction and mitigated mitochondrial toxicity induced by icv-STZ administration. Following STZ injection, there was upregulation of Bax gene expression and downregulation of miR-330, miR-132, and Bcl-2 gene expression. Treatment with A. jesdianum extract resulted in the reversal of the expression of these microRNAs and genes, indicating its potential for improving AD and reducing neuronal apoptosis. This study demonstrates the neuroprotective capabilities of A. jesdianum against STZ-induced oxidative stress and cognitive impairment in rats, highlighting its therapeutic potential in the management of AD.

Beneficial effects of Teucrium polium hydroalcoholic extract on letrozole-induced polycystic ovary syndrome in rat model.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that disrupts the menstrual cycle and causes infertility. Considering the increasing use of medicinal plants, the present study aimed to evaluate the effects of Teucrium polium L. on letrozole-induced PCOS in female rats. METHODS: Six groups of rats (n=7 each) were evaluated. The control group received 1% carboxy methyl cellulose as vehicle, while the five other groups received letrozole 1 mg/kg orally for 21 days. After PCOS induction, the rats were orally administered T. polium extract (50, 100, and 200 mg/kg) or metformin (200 mg/kg) for 28 days. Subsequently, body and ovarian weights and serum levels of follicle stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, and testosterone were measured. Finally, the ovarian tissues were isolated for histological examination. RESULTS: There were no significant changes in weekly body weight in any group. After 21 days of letrozole administration, PCOS induction was confirmed by estrous cycle irregularities and increased LH and testosterone levels. After treatment with the hydroalcoholic extract of T. polium, testosterone and LH levels were significantly reduced in all groups (P<0.05). Histological studies of ovaries in the metformin and T. polium groups exhibited normal follicular development with fewer and smaller cystic follicles than those in the PCOS group. CONCLUSION: The hydroalcoholic extract of T. polium improves serum levels of sex hormones, restores ovarian morphology in PCOS-induced rats, and is a good candidate for further clinical trials.

Antifatigue Effects of the Aqueous Extracts of Myrtle Berries, Apple and Clove: An Animal Study.

Background: Fatigue is one of the most prevalent symptoms, increasing worldwide with no specific medication for fatigue. Iranian traditional medicine (ITM), or Persian medicine, is a reliable source for discovering natural medicine for diseases and their symptoms. Myrtus communis L. (Myrtle), Malus domestica Borkh. (Apple), and Syzygium aromaticum (L.) Merr. & L. M. Perry (Clove) have been utilized as brain and heart tonics in ITM. Based on ITM, cardiac tonics decrease fatigue by enhancing heart function and increasing blood flow to tissues. These plants, particularly myrtle berries, have been utilized as potent enlivening agents that reduce mental fatigue. Objectives: This study aims to investigate the effects of aqueous extracts of these plants on weight-loaded forced swimming (WLFS) tests and three doses of aqueous myrtle extract in an animal model of chronic sleep deprivation-induced fatigue. Methods: Five groups of rats (n = 6) were evaluated: Sham, control, apple-treated, clove-treated, and myrtle-treated groups. After 28 days of treatment, the WLFS test was performed, and swimming time was recorded. Subsequently, central fatigue was induced in rats by chronic sleep deprivation for 21 days. Five groups of rats (n = 6) were evaluated: Sham, control (sleep-deprived, which received water), and three sleep-deprived + treatment groups, which received aqueous myrtle extract (350, 700, and 1000 mg/kg). An open field test on the 20th day and a WLFS test on the 21st day were performed. Results: The myrtle berries significantly increased glucose, reduced lactate dehydrogenase (LDH) levels, and enhanced swimming time. Fatigue caused by chronic sleep deprivation increased malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and LDH while decreased superoxide dismutase (SOD), glucose, and swimming time. In all treatment groups, SOD levels and swimming time were increased, whereas MDA, IL-1ß, and TNF-α levels were decreased significantly. Only the 1000 mg/kg dose significantly reduced LDH levels (P < 0.001). The treatment significantly improved the velocity and the total distance moved in the open-field test. Conclusions: According to the results, the myrtle berries reduced fatigue in two animal models, probably due to its phenolic compounds, flavonoids, and polysaccharides.

Cuscuta epithymum Murr. crude extract pre-conditioning protects C6 cells from L-glutamate-induced neurotoxicity.

BACKGROUND: Cuscuta epithymum Murr. (C. epithymum), as an herbal medicine, has played an anti-cancerous role in various studies; however, its possible neuroprotective effects have been neglected. Here, we aimed to investigate the protective effects of C. epithymum seeds crude extract and different fractions on rat glioblastoma cells (C6) in L-glutamate oxidative condition. METHODS: Initially, the total phenolic content of C. epithymum crude extract and the fractions (all produced by maceration method) was determined. Subsequently, C6 cells were pre-treated with the various concentrations of crude extract and fractions 24 h before L-glutamate exposure. Likewise, C6 cells were treated with the same concentrations of crude extract and fractions 24 h after exposure to L-glutamate. The cell viability and morphology were compared in crude extract and fractions groups, then superoxide dismutase (SODs) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were measured. The flow cytometry test was used to study C. epithymum crude extract's effects on the cell cycle and also to quantify the apoptosis, necrosis, and live cells population in different groups. RESULTS: C. epithymum crude extract and fractions (hexanoic, dichloromethanolic, and methanolic) had concentration-dependent cytotoxicity (IC50:126.47, 2101.96, 140.97, and 218.96 µg/ml, respectively). The crude extract and methanolic fraction contained phenolic compounds (55.99 ± 2.795 and 50.80 ± 2.969 mg gallic acid/g extract), while in hexanoic and dichloromethanolic fractions, the phenolic content was undetectable. In the cell viability assay, in comparison to fractions, the crude extract showed a more protective effect against glutamate-induced oxidative condition (P < 0.0001). The crude extract increased the SODs activity (P < 0.001) and decreased MDA and ROS levels (P < 0.0001) in comparison to the glutamate group. The crude extract significantly increased the population of cells in G1 (from 63.04 to 76.29) and decreased the percentage of cells in G2 (from 11.56 to 6.7) and S phase (from 25.4 to 17.01). In addition, it decreased the apoptotic and necrotic cell populations (from 34 to 17.1) and also increased the percentage of live cells (from 66.8 to 83.4 percent) in the flow cytometry test. CONCLUSION: C. epithymum crude extract plays a neuroprotective role by activating the defense mechanisms in cell against the oxidative condition.

Sedative-hypnotic, anxiolytic and possible side effects of Salvia limbata C. A. Mey. Extracts and the effects of phenological stage and altitude on the rosmarinic acid content.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia limbata C. A. Mey. (Persian name: Maryam Goli-e-labeh dar) has been used for treating central nervous disorders such as insomnia, anxiety and depression in Persian traditional medicine. S. limbata is known for its pharmacological activities which could be at least in a part, upon the presence of rosmarinic acid (RA). However, the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extract has not yet been examined. AIM OF THE STUDY: In the current study the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extracts were evaluated. Besides, the effects of altitude and phenological stage on the RA content of S. limbata were investigated. MATERIALS AND METHODS: Sedative-hypnotic and anxiolytic effects were evaluated through the pentobarbital induced loss of righting reflex test and open field test, respectively. Flumazenil was used to reveal the mechanism of action. Possible side effects were investigated in the passive avoidance and grip strength tests. Besides, the effects of altitude and phenological stage (vegetative, flowering, and seed setting) on the RA content of S. limbata were evaluated using reversed-phase high-performance liquid chromatography (RP-HPLC). RESULTS: Following behavioral tests, sedative-hypnotic and anxiolytic effects were observed. Since the observed effects were reversed by flumazenil and no side effect on the memory and muscle strength was reported, modulation of the α1-containing GABA-A receptors could be proposed as one of the involved mechanisms. According to the RP-HPLC analysis, harvesting S. limbata in the vegetative stage at the altitude of 2500 m led to the highest content of RA (8.67 ± 0.13 mg/g dry matter). Among different extract of the plant samples collected in the vegetative stage at the altitude of 2500 m, the hydroalcoholic extract showed the highest rosmarinic acid content. CONCLUSION: The obtained results help to find the optimum situation to gain the highest content of RA as well as the pharmacological activity that could be economically important for the pharmaceutical industries.

Effects of Ziziphus Jujuba Extract Alone and Combined with Boswellia Serrata Extract on Monosodium Iodoacetate Model of Osteoarthritis in Mice.

Background: As a chronic joint condition, osteoarthritis (OA) is a common problem among older people. Pain, aching, stiffness, swelling, decreased flexibility, reduced function, and disability are the symptoms of arthritis. Objectives: In this study, we tested the extracts of Ziziphus jujuba (ZJE) and Boswellia serrata (BSE) to reduce OA symptoms as an alternative treatment. Methods: NMRI mice were administered an intra-articular injection of monosodium iodoacetate (MIA; 1 mg/10 mL) in the left knee joint cavity for the induction of OA. Hydroalcoholic extracts of ZJE (250 and 500 mg/kg), BSE (100 and 200 mg/kg), and combined ZJE and BSE were orally administered daily for 21 days. Following behavioral tests, plasma samples were collected to detect inflammatory factors. To screen for general toxicity, acute oral toxicity was evaluated. Results: Oral administration of all the hydroalcoholic extracts significantly increased the locomotor activity, pixel values of the foot-print area, paw withdrawal threshold, the latency of the withdrawal response to heat stimulation, and decreased the difference between pixel values of hind limbs compared to the vehicle group. Also, the elevated levels of IL-1ß, IL-6, and TNF-α were reduced. As tested in this study, ZJE and BSE were practically nontoxic and had a high degree of safety. Conclusions: This study demonstrated that the oral administration of ZJE and BSE slows the progression of OA through anti-nociceptive and anti-inflammatory properties. Oral co-administration of ZJE and BSE extracts can be used as herbal medicine to inhibit OA progression.

LC-ESI-QTOF-MS/MS characterization of phenolic compounds from Prosopis farcta (Banks & Sol.) J.F.Macbr. and their potential antioxidant activities.

Prosopis farcta (Banks & Sol.) J.F.Macbr. is an emerging medicinal plant containing a diverse array of phytochemicals, including protein, fat, carbohydrate, fibre, alkaloids, fatty acids, glycosides, and polyphenols, with strong antioxidant potential. However, the screening and characterization of phenolic compounds in P. farcta is limited. This study is conducted to determine the polyphenol contents and their antioxidant activity in P. farcta leaves samples via liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography-photodiode array (HPLC-PDA). Total phenolic content (TPC), total flavonoid content (TFC), and total tannins content (TTC) were determined for polyphenol estimation. The antioxidant properties were measured by total antioxidant capacity (TAC), 2,2'-Diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and 2,2"²-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). LC-ESI-QTOF-MS/MS was used to identify and characterize 47 phenolic compounds, which mainly included phenolic acids (13), flavonoids (28), other polyphenols (4), lignans (1), and stilbenes (1). According to HPLC-PDA quantification, chlorogenic acid (9.78 ± 2.15 mg/g dw) was the most abundant phenolic acid, while the main flavonoids included catechin (12.73 ± 1.29 mg/g dw) and kaempferol (7.93 ± 1.47 mg/g dw). The study demonstrated the significance of P. farcta as a rich source of phenolic compounds with antioxidant capacity that can be widely used in food, beverage, feed, and pharmaceutical applications.

Phenolic Bioactives as Antiplatelet Aggregation Factors: The Pivotal Ingredients in Maintaining Cardiovascular Health.

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor-alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.

High-performance thin-layer chromatography fingerprinting, total phenolic and total flavonoid contents and anti-platelet-aggregation activities of Prosopis farcta extracts.

Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.

An In-Vivo Study on Anticonvulsant, Anxiolytic, and Sedative-Hypnotic Effects of the Polyphenol-Rich Thymus Kotschyanus Extract; Evidence for the Involvement of GABAA Receptors.

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has been so far devoted to T. kotschyanus, and there is a lack of information on the other neurobehavioral effects and side effects of this species. In the current study, the anticonvulsant, anxiolytic, and sedative-hypnotic, effects of Thymus kotschyanus extract on male NMRI mice were evaluated using pentylenetetrazole, maximal electroshock, elevated plus maze, and pentobarbital-induced sleeping tests. Since phenolic compounds and flavonoids have main roles in pharmacological effects of most plant extracts, the phenolic and flavonoid contents of the extract were measured with Folin-Ciocalteu and AlCl3 reagents. Acute toxicity, passive avoidance, and open field tests were carried out to assess the toxicity of the extract. To find out the possible mechanism of action, flumazenil as the specific GABAA receptor antagonist was used. Anticonvulsant and hypnotic effects of the extract were observed at 400 and 600 mg/kg. The extract at the dose of 200 mg/kg revealed significant anxiolytic effects, but it did not show any adverse effects on learning and memory at all the tested doses. Results of this study indicate that Thymus kotschyanus extract has anticonvulsant , anxiolytic, and hypnotic effects, which are likely related to the ability of some phenolic compounds to activate α1-containing GABAA receptors but more experiments still need to be carried out in order to find the exact mechanism, active component, and the toxicity of the Thymus kotschyanus extract.

Evaluation of Anticonvulsant Effect of Aqueous and Methanolic Extracts of Seven Inula Species.

In Iranian traditional medicine, Inula species have been used for the treatment of seizure. In this study we decided to investigate the anticonvulsant activity of seven species from this genus to find an effective remedy for seizure with less adverse effects compared to the available medicines. Aqueous and methanolic extracts of Inula britannica, Inula helenium, Inula viscidula, Inula oculus-christi, Inula aucheriana, Inula thapsoides, and Inula salicina were prepared and their antiepileptic activity was investigated by maximal electroshock (MES) and pentylentetrazole (PTZ) tests on Male NMRI Albino mice. Diazepam was used as positive control in both tests. In addition, two extracts with the best anticonvulsant activities were selected and their sedative and hypnotic effects were evaluated using open field and righting reflex tests, respectively. The effects of the both extracts on memory and motor coordination were also assessed by step-through passive avoidance and rotarod tests, respectively. Aqueous extract of Inula britannica and Inula viscidula showed the best activity in MES model and their ED50 (with 95% confidence interval) was 19.5 (7.9~48.5) mg/kg and 12.7(10.0~16.3) mg/kg, respectively. None of the extracts showed noticeable anticonvulsant effects in the PTZ model. The active extracts also showed sedative-hypnotic effects in righting reflex and open field tests. Furthermore, both extracts did not affect the memory and motor coordination in the experimental models. The anticonvulsant and sedative activities of the extracts were antagonized by flumazenil, indicating that benzodiazepine receptors are probably involved in the effects. This study indicates that Inula britannica and Inula viscidula are good candidates for further phytochemical and mechanistic studies in order to find anticonvulsant and sedative-hypnotic compounds with less adverse effect on memory and motor coordination.

Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin.

OBJECTIVES: Coenzyme Q10 (CoQ10, ubiquinone) stands among the safest supplements in the elderly to protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury. METHODS: Adult rats underwent transient middle cerebral artery occlusion after atorvastatin pretreatment (5 or 10 mg/ kg/day; po; 30 days) with or without CoQ10 (200 mg/kg/day). After 24 hours ischemic/reperfusion injury, animals were subjected to functional assessments followed by cerebral molecular and histological to detect inflammation, apoptosis and oxidative stress. RESULTS: Animals dosed with 10 mg/kg presented the worst neurological function and brain damage in the acute phase of stroke injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Such benefits were associated with remarkable anti-inflammatory and anti-apoptotic effects, based on the analyzed tumor necrosis factor-α, interleukin-6, Bax/Bcl2 and cleaved caspase 3/9 immunoblots. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. No parallel alteration was detected in stroke-induced oxidative stress as determined by malondialdehyde and 8-oxo-2'-deoxyguanosine levels. DISCUSSION: These data suggest that all stroke animals may benefit from CoQ10 administration through modulating inflammatory and degenerative pathways. This study provides empirical evidence for potential advantages of CoQ10 supplementation in atorvastatin-receiving patients which may not shadow its antioxidant properties.

Preliminary investigation of the effects of topical mixture of Lawsonia inermis L. and Ricinus communis L. leaves extract in treatment of osteoarthritis using MIA model in rats.

BACKGROUND: Many plants have been introduced in Iranian traditional medicine for treatment of different joint problems including knee pain. Topical application of the mixture of Lawsonia inermis L. leaves (Henna) with aqueous extract of Ricinus communis L. leaves have been mentioned to have significant effects on reducing knee pain. The present study was designed to evaluate the analgesic and anti-inflammatory effects of the mixture of these two herbs in male rats. METHODS: We induced knee osteoarthritis as a model of chronic pain by intra-articular injection of mono sodium iodoacetate (MIA). Mechanical allodynia, hotplate latency test, spontaneous movements and gait analysis were used for the evaluation of analgesic activity. Anti-inflammatory activity was evaluated by measuring the diameter and the volume of the injected paw compared to contralateral paw. These tests were monitored at days 1, 3, 7, 14 and 21 of MIA administration. Histopathological evaluations were also used to assess the efficacy of the treatment on inflammation and lesions in knee tissue. In all tests, diclofenac topical gel was used as a positive control. The herbal extracts, their mixture, and vehicle or diclofenac gel were administered daily for 14 days by topical route. RESULTS: The mixture of these two extracts significantly reduced the knee joint width and volume of the injected paws and also improved foot prints in gait analysis after 3 days of MIA injection. Analysis of mechanical allodynia (after 21 days), hotplate latency test (after 10 days), spontaneous movements (after 7 days) and in positive control group (after 3 days in all tests and in mechanical allodynia after 14 days) compared to the vehicle group, showed significant effects. Topical usage of the selected formulation made significant histopathological changes on the knee of the rats. Compared to the vehicle group, the tests and diclofenac groups showed less reactions characterized by negligible edema and a few scattered inflammatory lymphoid cells. CONCLUSION: The present findings showed that the present formulation not only was able to mitigate pain and inflammation in the paws but also made significant histopathological changes on the knee of the rats. Further studies are necessary to confirm the effect of the formulation.

Hydroalcoholic extract of Myrtus communis can alter anxiety and sleep parameters: a behavioural and EEG sleep pattern study in mice and rats.

CONTEXT: Myrtus communis L. (Myrtaceae), myrtle, is an evergreen shrub with strong antibacterial, anti-inflammatory, antihyperglycemic and antioxidant activities. Also, it is used as a sedative-hypnotic plant in Iranian traditional medicine. OBJECTIVE: This study evaluates the effect of 80% ethanolic extract of M. communis leaves on sleep and anxiety in mice and rats. MATERIALS AND METHODS: Male NMRI mice were subjected to open field, righting reflex, grip strength and pentylentetrazole-induced seizure tests. Male Wistar rats were used to evaluate the alterations in rapid eye movement (REM) and non-REM (NREM) sleep. They were treated with 25-400 mg/kg doses of the extract intraperitoneally. RESULTS: The applied doses (50-200 mg/kg) of M. communis extract increased vertical (ED50 = 40.2 ± 6.6 mg/kg) and vertical and horizontal activity (ED50 = 251 ± 55 mg/kg), while treatment with 200 and 400 mg/kg attenuated muscle tone significantly compared to vehicle treated animals (p < 0.001 for all) in a dose-independent manner. Also, a significant hypnotic and not anticonvulsant effect was observed when animals were treated with 200 mg/kg of the extract (p < 0.01). In this regard, electroencephalography results showed that REM sleep time was decreased (2.4 ± 0.5%), while total and NREM sleep times were increased significantly compared to the control group of mice (82.5 ± 7.6%). DISCUSSION AND CONCLUSION: The data show the anxiolytic and muscle relaxant effect of the extract without anticonvulsant activities. The anxiolytic, myorelaxant and hypnotic effects without effect on seizure threshold are in line with the effect of a alpha 2 GABA receptor agonist.

Investigation of sedative and hypnotic effects of Amygdalus communis L. extract: behavioral assessments and EEG studies on rat.

Amygdalus communis L. (almond) has been traditionally used as a natural medicine in the treatment of various diseases. The present research studied the sedative and hypnotic effects of the aqueous fraction of seeds of almond in rats. In order to investigate these effects, a combination of behavioral methods (open field test and loss of righting reflex test) as well as quantitative and analytic methods (EEG and EMG) were applied. The results of the open field test showed that a dose of 400 mg/kg of the almond extract significantly inhibited the locomotion activity of rats compared to normal. The results also illustrated that the almond extract affected pentobarbital-induced sleep through increasing the number of fallings asleep and prolongation of sleeping time. Analysis of EEG recordings of the animals which had received the same dose of the almond extract as the open field test demonstrated marked changes in the animals' sleep architecture. Significant prolongation of total sleeping time as well as significant increase in NREM sleep were the main observed changes compared to the normal condition. These results suggest that the aqueous extract of almond has significant sedative and hypnotic effects, which may support its therapeutic use for insomnia.

Reversal effects of crocin on amyloid ß-induced memory deficit: Modification of autophagy or apoptosis markers.

Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer's disease. We also compared the effect of crocin administration on spatial memory with nicotine as positive control. Morris water maze results show that intra-peritoneal and intra-hippocampal administration of crocin significantly improve spatial memory indicators such as escape latency, traveled distance and time spent in target quadrant when compared to beta amyloid injection. Furthermore, we measured certain biomarkers of cell autophagy and apoptosis using Western blot analysis. Our results reveal that crocin administration does not cause any significant alteration in Beclin-1 and ratio of LC3-II/LC3-I compared to the group received beta amyloid by hippocampal injection. However, in contrast to autophagy, crocin administration significantly decreases Bax/Bcl-2 ratio and cleaved Caspase-3 level. This demonstrates that crocin inhibits beta amyloid induced apoptosis, which is possibly associated with its antioxidant properties. Our results further confirm the neuroprotective properties of crocin as a potential pharmaceutical agent for management of Alzheimer's disease.

Total phenolic and flavonoid content and antibacterial activity of Punica granatum L. var. pleniflora flowers (Golnar) against bacterial strains causing foodborne diseases.

BACKGROUND: Flowers of Punica granatum L. (Punicaceae) var. pleniflora, known as "Golnar" in Iranian traditional medicine have been used for the prevention and treatment of foodborne diseases. In this study, antibacterial activities of ethanol extract of Golnar and its fractions were scientifically evaluated against bacteria causing foodborne diseases including Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli, Shigella dysantriae, and Salmonella typhi. The total phenolic and flavonoid contents of the extract and its fractions were also determined. METHODS: The antibacterial effect of the ethanol extract and its fractions were primarily evaluated by agar well diffusion and their MIC and MBC were determined by broth macro dilution method. The total phenolic and flavonoid contents of the extract and its fractions were measured based on gallic acid and rutin equivalents (GAE and RE), respectively. RESULTS: After evaluation of total phenolic and flavonoid content the chloroform fraction showed the lowest phenolic and flavonoid contents (3.8 mg GAE/g and 1.1 mg RE/g respectively) and the methanol fraction showed the highest phenolic and flavonoid contents (18.1 mg GEA/g and 3.3 mg RE/g respectively). The total phenolic and flavonoid content was positively associated with the antibacterial activities of the fractions with chloroform extract exhibiting lowest antibacterial activity against E. coli (MIC 25 mg/ml) and the methanol fraction exhibiting the highest antibacterial effect against S. aureus (MIC 0.19 mg/ml). CONCLUSION: Golnar extract showed antibacterial activity against both Gram positive and Gram negative bacteria causing food poisoning. Therefore, the extract can be used for prevention or treatment of foodborne diseases or as preservative in the food industry. The methanol fraction with the highest phenolic and flavonoid content showed the highest antibacterial effect. This indicates that the phenolic and flavonoid compounds in the extract can be responsible for the effect.

Evaluation of Anti-Inflammatory and Anti-Nociceptive Effects of Defatted Fruit Extract of Olea europaea.

Fruits of Olea europaea L. have been used for centuries in folk medicine to treat many inflammatory diseases. In order to evaluate the anti-nociceptive activities of the methanolic and aqueous extracts of defatted fruits of O. europaea, formalin test was used and for evaluation of anti-inflammatory effects of the extract, the volume of paw edema was measured. The results revealed that both extracts did not exhibit significant analgesic activity in the first phase of formalin test, whereas methanolic extract at the 600 mg/Kg dose and aqueous extract at the 450 and 600 mg/Kg doses could inhibit induced pain in the second phase of formalin test. Furthermore, the results of paw edema volume measurement indicated that the aqueous extract has anti-inflammatory effects at dose of 600 mg/Kg. Induced anti-nociception by aqueous olive extract was not reversed by naloxone, which indicates that the opioid receptors are not involved in the analgesic effects of the extracts. The present data pointed out that the extracts of olive defatted fruit have anti-nociceptive and anti-inflammatory effects in rats but further studies are needed to elucidate the mechanism(s) of action and active components which are involved in analgesic and anti-inflammatory effects.

Synthesis of a quaternary bis derivative of imipramine as a novel compound with potential anti-enuretic effect.

OBJECTIVES: Imipramine has been used for over four decades (early reports in 1960s) for the treatment of nocturnal enuresis, although the reason for its effect is not clear. Imipramine is a tertiary amine, which may act both in the periphery and/or pass through the blood-brain barrier (BBB) in unionized form and exhibit a central effect. Since imipramine has anti-cholinergic properties, some believe it may exert its anti-enuretic effect by affecting peripheral cholinergic receptors, i.e. its anti-enuretic effect may be due to peripheral anti-cholinergic properties, whereas others think it can pass through the BBB and interact with central nervous system (CNS) receptors. If the anti-enuretic effect of imipramine is due to its peripheral anti-cholinergic effects, its entrance into the CNS is unnecessary. Therefore, the synthesis of a form of imipramine that can exhibit peripheral anti-cholinergic effects but does not have CNS adverse effects would have a safer drug profile in this case. On the other hand, if the anti-enuretic effect of imipramine is primarily due to its action on the CNS, a form of imipramine that cannot pass through the BBB has no effect on nocturnal enuresis treatment and thus may help to clarify the mechanism of action of imipramine in nocturnal enuresis treatment. METHODS: This article describes the synthesis and evaluation of the anti-cholinergic effect of a new bis derivative of imipramine, which contains two imipramine units in its structure. KEY FINDINGS: The compound exhibited anti-cholinergic activity comparable with that of imipramine on isolated guinea pig ileum. CONCLUSIONS: Being a quaternary ammonium, this compound is not expected to be able to cross the BBB and thus would cause fewer CNS side effects.

Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles.

A series of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles has been synthesized and screened for their anticonvulsant activities. Compound 3 shows considerable anticonvulsant activity both in PTZ and MES models. It seems that this effect is mediated by benzodiazepine receptors and other unknown mechanism, respectively.