The effect of Cornus mas fruit extract on vasomotor symptoms and sex hormones in postmenopausal women: a randomized, double-blind, clinical trial.

OBJECTIVES: Cornus mas fruit has various antioxidants and anti-inflammatory properties, so this study aims at assessing its effect on menopausal symptoms and sex hormones in postmenopausal women. METHODS: In the current randomized, double-blind clinical trial, 84 individuals (42 per group) were participated. C mas hydroalcoholic extract was prepared, and participants received 300 mg C mas extract or placebo three times a day (900 g in total) for 8 weeks. The demographic, dietary intake, and physical activity information were gathered. Anthropometric indices were measured by standard methods. Furthermore, menopause symptoms were assessed by Greene Climacteric Scale. Also, sex hormones were measured by enzyme-linked immunosorbent assay. RESULTS: Based on the results, there was a significant difference in total Greene score reduction between the intervention and placebo groups (-3.19 ± 0.54, -0.76 ± 0.32, and P < 0.001). In addition, vasomotor symptoms had a remarkable decrease in the C mas extract group (P < 0.001). Also, the intervention group demonstrated a decreasing trend in the number and duration of hot flushes. Moreover, follicle-stimulating hormone remarkably decreased and estradiol increased in the intervention group (P = 0.016 and P = 0.018). CONCLUSIONS: It has been found that the extract of C mas fruit has a favorable effect on vasomotor symptoms, sex hormones, and related complications in women experiencing menopausal symptoms.

Evaluation of anti-inflammatory effects of leaf and seed extracts of Plantago major on acetic acid-induced ulcerative colitis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantago major (P. major) has traditionally been used in Iranian Persian medicine to treat gastrointestinal ulcers and bleeding. RESEARCH OBJECTIVES: This study aimed to investigate the anti-inflammatory effects of the leaf and seed extracts of P. major in rats with acetic acid-induced ulcerative colitis (UC). MATERIALS AND METHODS: To this end, 49 rats were randomly divided into seven groups. UC was induced in all groups but the control (vehicle) group using a single intra-rectal administration of 2 ml of 4% acetic acid. Other groups received daily intraperitoneal (i.p.) injections of the seed extract of P. major (400 mg/kg and 700 mg/kg), the leaf extract of P. major (400 mg/kg and 700 mg/kg), and sulfasalazine (400 mg/kg) for seven consecutive days, respectively. The rats' rectum was surgically removed and evaluated for macroscopic and microscopic damage. The tissue levels of oxidative stress and inflammatory markers were measured using the ELISA method. RESULTS: The high-dose leaf extract significantly decreased ulcer index and histopathologic damage as well as the tissue levels of IL-6, TNF-α, PGE2, IL-1ß, MPO, and MDA compared to the damage group. The low-dose leaf extract also significantly reduced the levels of some markers. The seed extract in the two used doses caused a modest decrease in the histopathological damages and ulcer index. CONCLUSIONS: P. major leaf extract effectively reduces inflammation and mucosal damage in rats with UC, especially when administered in high doses. P. major seed extract has minimal protective effects on UC.

The effect of Cornus mas extract consumption on bone biomarkers and inflammation in postmenopausal women: A randomized clinical trial.

The drastic decrease in estrogen levels in menopausal women can elevate bone resorption and osteoporosis. Cornus mas extract (C. mas extract) is a potential candidate for treating menopausal-related bone complications because of its phytoestrogen and anti-inflammatory contents. It was an interventional double-blind placebo-controlled randomized study. Eighty-four women aged 45-60 years old were randomly allocated to either the extract group receiving 3 capsules of 300 mg C. mas extract or the placebo group receiving 3 capsules of 300 mg of starch powder per day for 8 weeks. Then, venous blood was used to measure bone-specific alkaline phosphatase (BAP), osteocalcin (OC), C-terminal telopeptide (TC) as well as serum levels of PTH and hsCRP. Our results indicated the decrease in alkaline phosphatase, PTH, and as an inflammation biomarker, hsCRP, between two groups at the end of the study. No statistically significant difference was observed in telopeptide C, osteocalcin, and calcium between the placebo and extract groups after 8 weeks of intervention. In conclusion, the results indicate that the C. mas extract supplement of 900 mg/day may decrease levels of BAP, PTH, and hsCRP. However, this intervention had no beneficial effect on OC and TC in healthy postmenopausal women.

Crocin Acting as a Neuroprotective Agent against Methamphetamine-induced Neurodegeneration via CREB-BDNF Signaling Pathway.

Methamphetamine (METH) abuse causes neurodegeneration. Medicinal herb such as crocin has neuroprotective properties. The current study evaluates the role of CREB-BDNF signaling pathway in mediating the neuroprotective effects of crocin against METH-induced neurodegeneration in rats. Sixty adult male rats were divided randomly into group 1 and group 2 which received 0.7 mL/rat of normal saline and 10 mg/kg of METH intraperitoneally (i.p) respectively, and groups 3, 4, 5 and 6 which treated concurrently with METH (10 mg/kg) and crocin (10, 20, 40 and 80 mg/kg I.P respectively) for 21 days. Morris water maze (MWM) was used to evaluate cognitive activity. According to the critical role of hippocampus in cognitive behavior, the molecular and biochemical parts of our study were done in hippocampus and according to this, hippocampal neurodegenerative parameters and also CREB and BDNF levels were evaluated in isolated hippocampus. METH disturbed the learning, memory, and simultaneous treatment with various doses of crocin reduced the METH-induced cognition disturbances. In addition, METH treatment increased lipid peroxidation and the levels of oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and Bax, while reducing reduced form of glutathione (GSH), Bcl-2, P-CREB, and BDNF levels in the hippocampus. METH also reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in the hippocampus. In contrast, crocin (40 and 80 mg/kg) attenuated METH-induced apoptosis, oxidative stress, and inflammation, while elevating P-CREB and BDNF levels. Thus, crocin confers neuroprotection against METH-induced neurodegeneration in hippocampus and this is probably through activation of P-CREB/BDNF signaling pathway.

Evaluation of Anticancer Activity of Camellia Sinensis in the Caco-2 Colorectal Cancer Cell Line

Background: Colorectal cancer (CRC) is widespread across the world. While conventional anticancer treatments can help the affected patients, cells of vital organs such as the kidney, lungs, bladder and nervous system may suffer from side effects of chemotherapeutic drugs, so that it is necessary to search for alternatives. From ancient times, attention has focused on medicinal plants and natural products. In the current work, Camellia sinensis, whose leaves are used to produce green tea was evaluated for anticancer effects in cell culture. Materials and Methods: A hydroalcoholic extract of Camellia sinensis young leaves was prepared by percolation and compared with Cisplatin as a known anticancer drug for effects on two cell lines: Caco-2, colon carcinoma cells, and mouse normal fibroblasts (L929). Cytotoxicity of 50, 100, 200, 400 and 800 µg/ml of Camellia sinensis extract was evaluated by MTT assay and aquaporin 5 (AQP5), detected as a biomarker for surviving cells using immunofluorescence microscopy. Results: MTT assays with hydroalcoholic extract of Camellia sinensis showed considerable inhibition of growth of Caco-2 cells, significant at 800 µg/ml (P<0.05), with little effect on L929 cells. Levels of aquaporin 5 protein decreased in Caco-2 cell culture following green tea extract treatment. Conclusion: According to the results of the current study, Camellia sinensis is a medicinal plant with potent anticancer influence which might be specific.

Anticonvulsant Effects of the Hydroalcoholic Extract of Alpinia officinarum Rhizomesin Mice: Involvement of Benzodiazepine and Opioid Receptors.

BACKGROUND AND PURPOSE: Epilepsy is one of the most common serious neurological conditions. The current therapeutic treatment of epilepsy with modern antiepileptic drugs is associated with side effects, dose-related and chronic toxicity, and teratogenic effects and in approximately 30% of the patients is ineffective. Alpinia officinarum is used in Iranian traditional medicine for treatment of different diseases like back pain and seizure. METHODS: In this study, anticonvulsant effects of hydroalcoholic extract of Alpinia officinarum rhizomes were examined by using pentylentetrazole (PTZ) model in mice. Alpinia officinarum rhizomes extract (200, 400 and 600 mg/kg), diazepam (1 mg/kg) and normal saline (10 mL/kg) were injected (ip) 30 minutes before PTZ (90 mg/kg, ip). The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For further clarification of the mechanism of action for Alpinia officinarum, flumazenil (2 mg/kg, ip) and naloxone (5 mg/kg, ip) were also injected 5 minutes before Alpinia officinarum extract. RESULTS: Alpinia officinarum extract at the doses of 200 and 400 mg/kg prolonged the time of onset of seizure and decreased the duration of seizures compared to control (saline) group (p < 0.05). At the dose of 600 mg/kg, percentage of seizure protection was 16.66%. Naloxone and flumazenil could suppress anticonvulsant effects of Alpinia officinarum. CONCLUSIONS: It seems that Alpinia officinarum could be a good candidate and be useful for seizure control and treatment, and in these effects, opioid and benzodiazepine receptors might probably be involved.

Anti-inflammatory activity of Elaeagnus angustifolia fruit extract on rat paw edema.

BACKGROUND: The Elaeagnus angustifolia fruit has been traditionally used in Iranian herbal medicine to treat diarrhea and rheumatoid arthritis. In the present study, the effects of E. angustifolia fruit extract on the acute and chronic phases of formalin-induced rat paw edema were examined. METHODS: The acute and chronic anti-inflammatory effects of E. angustifolia fruit extract were investigated through the subcutaneous injection of 100 µL of formalin (2.5%) into a rat's hind paw. Thirty minutes before the procedure, the experimental groups were treated intraperitoneally with hydroalcoholic fruit extracts of E. angustifolia (concentrations of 100, 300, 700, and 1000 mg/kg); sodium salicylate (SS, 400 mg/kg) and distilled water were used as positive and negative control groups, respectively. Treatment with SS and the fruit extracts were performed daily for 8 days, and the degree of edema was measured by using mercury plethysmometer and digital caliper. RESULTS: In the acute anti-inflammatory study, the extract showed a significant anti-inflammatory effect in a dose-dependent manner. The results of 1000 mg/kg of the extract was significantly different compared with the negative control group (p<0.05) and was comparable to sodium salicylate (p<0.05). Results from the chronic study suggested that E. angustifolia extract significantly reduced paw edema and inflammation in a dose-dependent manner. The results also showed that the measurement by digital caliper and mercury plethysmometer were both reliable and might be applied interchangeably (p<0.01). Phytochemical tests indicated that the hydroalcoholic fruit extract of E. angustifolia was positive for cardiac glycosides, flavonoids, terpenoids, and saponins. CONCLUSIONS: Based on our findings, the E. angustifolia fruit extract probably has acute and chronic anti-inflammatory activities to support its applications in folk medicine.

The neuroprotective effect of lithium against high dose methylphenidate: Possible role of BDNF.

Methylphenidate (MPH) is a neural stimulant with unclear neurochemical and behavioral effects. Lithium is a neuroprotective agent in use clinically for the management of manic-depressive and other neurodegenerative disorders. This study investigated the protective effect of lithium on MPH-induced oxidative stress, anxiety, depression and cognition impairment. Forty-eight adult male rats were divided randomly and equally into 6 groups. Treatment groups were received MPH (10mg/kg) and various doses of lithium (75, 150 and 300mg/kg) simultaneously and also lithium (150mg/kg) alone for 21 days. Elevated Plus Maze and Forced Swim Test were used to determine the level of anxiety and depression in animals. Morris Water Maze was used to evaluate spatial learning and memory. The hippocampi of rats were isolated and the level and activity of oxidative, anti-oxidant and inflammatory factors were measured. Also brain derived neurotropic factor expression level was measured by RT-PCR and western blotting. MPH (10mg/kg) caused behaviors indicative of anxiety and depression-like phenotypes in EPM and FST and cognition impairment in MWM. While lithium in all mentioned doses inhibited these effects. Treatment with MPH significantly increased lipid peroxidation, mitochondrial GSH content and IL-1ß and TNF-α levels in isolated hippocampal cells. Moreover superoxide dismutase and glutathione peroxidase activities and BDNF expression remarkably decreased. Various doses of lithium attenuated these effects and significantly mitigated MPH-induced oxidative damage, inflammation and increased BDNF expression level. Lithium has the potential to act as a neuroprotective agent against MPH induced toxicity in rat brain and this might be mediated by BDNF expression in hippocampus of rats.

Increase in mRNA Level of Orexin1 and 2 Receptors Following Induction of Experimental Autoimmune Encephalomyelitis in Mice.

Orexin A and B are hypothalamic peptides with a wide variety of effects such as anti-inflammation and neuroprotection. Impaired function of orexin system has been reported in some neurodegenerative diseases like Parkinson, Huntington and Alzheimer. In this study, the mRNA expression levels of some hypothalamic peptides were investigated in C57BL/6 female mice with experimental autoimmune encephalomyelitis (EAE). Animals were randomly divided into two control and EAE groups. EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG) with complete Ferund's adjuvant and pertussis toxin. Twenty-first days following immunization, mice were decapitated to remove the brains. Then, the expression profiles of prepro-orexin, orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) in hypothalamic region were assessed using real-time PCR method. In this study, we found a considerable increase in the mRNA expression of OX1R and OX2R following EAE induction in C57BL/6 mice. Elevation levels of OX1R and OX2R following EAE induction suggest that alteration in orexinergic system may involve in pathogenesis of multiple sclerosis.

Anticonvulsant Activity of Hydroalcoholic Extract of Citrullus colocynthis Fruit: Involvement of Benzodiazepine and Opioid Receptors.

This study investigated the anticonvulsant activity of Citrullus colocynthis fruit extract used traditionally in the treatment of convulsion. Albino mice were pretreated with extract in different doses (10, 25, 50, and 100 mg/kg), prior to injection of pentylenetetrazole. Animals received pretreatments with naloxone and flumazenil to further clarify the mechanisms of anticonvulsant action. The total flavonoid content of Citrullus colocynthis extract was also determined. Citrullus colocynthis hydroalcoholic extract with doses 25 and 50 mg/kg prolonged the onset of seizures and decreased the duration compared with control group. Pretreatment by flumazenil could inhibit the effect of Citrullus colocynthis on latency of seizure to some extent and administration of naloxone significantly inhibited changes in latency and duration of seizure produced by Citrullus colocynthis This study showed that Citrullus colocynthis has significant anticonvulsant effect in pentylenetetrazole-induced seizures in mice, and these effects may be related to its effect on γ-aminobutyric acid-ergic and opioid systems. These results confirmed the traditional use of Citrullus colocynthis in Iranian traditional medicine.

Evaluation of Anti-inflammatory and Analgesic Activity of the Extract and Fractions of Astragalus hamosus in Animal Models.

The objective of this study was to evaluate the anti-inflammatory and analgesic activities of the hydro-alcoholic extract of the pods of Astragalus hamosus (HAAH), a plant used in Iranian traditional medicine, and antinociceptive effects of different fractions in animal models. The anti-inflammatory effect was evaluated by the rat paw edema induced by formalin. Also the analgesic effect was examined by the acetic-acid-induced writhing response and hot plate test. The analgesic effects of chloroform, hexane, ethyl acetate and aqueous fractions were evaluated by the hot-plate method. The hydroalcoholic extract of Astragalus hamosus could reduce the edema in a dose-dependent manner (P<0.05). In the acute phase, the result of 1000 mg/Kg and in the chronic phase, the result of 100 and 300 mg/Kg of the extract were more significant and comparable with the effect of sodium salicylate. Also application of different doses of HAAH had significant anti-nociceptive effects on both animal models. The findings showed that HAAH at doses of 700 and 1000 mg/Kg produced analgesic effects comparable to sodium salicylate. The hexane and ethyl acetate (but not the other fractions) showed significant analgesic activity in hot plate test, when compared to morphine. The results of this study demonstrated the anti-inflammatory and analgesic effects of HAAH extract and hexane and ethyl acetate fractions of the extract in animal models and justify traditional use of this plant in the treatment of pain and inflammatory conditions. More studies to clarify the active components are necessary.

Evaluation of anti-inflammatory and analgesic activities and the phytochemical study of Astragalus arbusculinus gum in animal models.

BACKGROUND: The importance of inflammatory diseases and side effects of conventional drugs necessitate the finding of new anti-inflammatory agents from natural sources. In this study, for the first time, the anti-inflammatory and analgesic effects of the aqueous extract of Astragalus arbusculinus gum were evaluated in animal models. METHODS: Thirty-five male Wistar rats were divided into five groups and pretreated with different doses of A. arbusculinus gum extract before the injection of formalin. Paw edema was measured by a plethysmometer at time 0 and after 8 days and compared to controls. The analgesic effect of the extract was evaluated using the hot-plate test in 42 male albino mice. RESULTS: The extract of A. arbusculinus gum decreased the rat paw edema in a dose-dependent manner. The effect on inflammation of the highest dose of extract was comparable to sodium salicylate. Astragalus arbusculinus gum extract at doses of 300 and 1000 mg/kg showed analgesic effects comparable to sodium salicylate and morphine, respectively. A preliminary phytochemical study and the determination of the total phenolic content of the gum extract were performed for the first time. CONCLUSIONS: The aqueous extract of A. arbusculinus gum reduced the inflammation and pain in a dose-dependent manner and is a good candidate for further studies of safety and efficacy. The clarification of active components of the plant is necessary.

Comparison of the efficacy of nifedipine and hydralazine in hypertensive crisis in pregnancy.

Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancy. Oral nifedipine is an alternative in management of these patients. In this study the efficacy of nifedipine and hydralazine in pregnancy was compared in a group of Iranian patients. Fifty hypertensive pregnant women were enrolled in the study. A randomized clinical trial was performed, in which patients in two groups received intravenus hydralazine or oral nifedipine to achieve target blood pressure reduction. The primary outcomes measured were the time and doses required for desired blood pressure achievement. Secondary measures included urinary output and maternal and neonatal side effects. The time required for reduction in systolic and diastolic blood pressure was shorter for oral nifedipine group (24.0 ± 10.0 min) than intravenus Hydralazine group (34.8 ± 18.8 min) (P ≤ 0.016). Less frequent doses were required with oral nifedipine (1.2 ± 0.5) compared to intravenus hydralazine (2.1 ± 1.0) (P ≤ 0.0005). There were no episodes of hypotension after hydralazine and one after nifedipine. Nifedipine and hydralazine are safe and effective antihypertensive drugs, showing a controlled and comparable blood pressure reduction in women with hypertensive emergencies in pregnancy. Both drugs reduce episodes of persistent severe hypertension. Considering pharmacokinetic properties of nifedipine such as rapid onset and long duration of action, the good oral bioavailability and less frequent side effects, it looks more preferable in hypertension emergencies of pregnancy than hydralazine.