Gastroprotective Effect of Zingerone on Ethanol-Induced Gastric Ulcers in Rats.

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.

Long-term treatment with royal jelly improves bleomycin-induced pulmonary fibrosis in rats.

This study investigated the anti-fibrotic potential of royal jelly (RJ) powder against bleomycin-induced pulmonary fibrosis in rats. The rats were given RJ orally (25, 50, and 100 mg/kg per day) for 7 consecutive days before the administration of single intratracheal instillation of bleomycin (BLM) at 7.5 IU/kg. RJ doses were continued for 21 days after BLM exposure. Fibrotic changes in the lungs were studied by cell count and analysis of cytokine levels in the bronchoalveolar lavage fluid (BALF), histopathological examination, and assaying oxidative stress biomarkers in lung tissue. The results showed that BLM administration significantly increased the fibrotic changes, collagen content, and levels of malondialdehyde and decreased total thiol and glutathione peroxidase antioxidant contents in the rats' lung tissue. An increase in the level of cell counts and pro-inflammatory and pro-fibrotic cytokines such as TNF-α and TGF-ß in BALF was observed. Also, it significantly decreased IFN-γ, an anti-fibrotic cytokine, in BALF. However, RJ (50 and 100 mg/kg) reversed all of these biochemical indices as well as histopathological alterations induced by BLM. The present study demonstrates that RJ, by its antioxidant and anti-inflammatory properties, attenuates oxidative damage and fibrosis induced by BLM.

Red Lentil Extract: Neuroprotective Effects on Perphenazine Induced Catatonia in Rats.

INTRODUCTION: Parkinsonism is a neurodegenerative disease that is defined by certain symptoms such as muscle rigidity, impaired movement, catatonia, tremor and disorientation of body. AIM: The aim was to investigate the effect of red lentil extract on perphenazine-induced Catatonia in model of rat. MATERIALS AND METHODS: This experimental study was done on 48 male albino rats (weight 180-200g) of the Sprague-Dawley strain. Animals were randomly divided into six groups and were pre-treated with a single dose of red lentil extract (200, 400, 800 and 1000 mg/kg), most effective dose of bromocriptine (30mg/kg) and normal saline (5ml/kg) via intraperitoneal (IP) route. perphenazine (5 mg/kg) was after 30 minutes, administered (IP) to induce catatonia. The scoring method of Morpurgo was used to determine the muscular rigidity of animals. RESULTS: The results showed that the 200mg/kg red lentil extract treated group had no significant reduction in catatonic responses after perphenazine administration in comparison with control group while the groups that received 800 and 1000mg/kg of red lentil extract showed significant difference (p<0.05) at all the time points. CONCLUSION: The results revealed that hydroalcoholic extract of red lentil has protective effect on Catatonia induced by perphenazine in rats. So this extract may be probably beneficial for catatonia in Parkinsonism.

Effect of royal jelly on formalin induced-inflammation in rat hind paw.

BACKGROUND: Royal Jelly (RJ), a food item secreted by worker honeybees, is a mixture that contains protein, glucose, lipid, vitamins, and minerals; it is widely used as a commercial medical product. Previous studies have shown that RJ has a number of physiological effects, such as anti-inflammatory, antitumor, antiallergic and antioxidant activities. OBJECTIVES: In the present study, the anti-inflammatory properties of RJ were investigated in formalin-induced rat paw edema. MATERIALS AND METHODS: In this study, 30 male Wistar albino rats were divided into five equal groups (n = 6) as follows: test groups received different doses (25, 50 and 100 mg/kg, ip) of RJ and a negative control group received normal saline (5 mL/kg) and a positive control group received aspirin (300 mg/kg, i.p). Edema was induced on the right hind paw of the rat by a subplantar injection of 100 µL of formalin (2.5%) after 30 minutes. Paw edema was measured in the rats received the drugs, saline and aspirin before and after the formalin injection during 5 hours, using a plethysmometer. RESULTS: The results showed that RJ has a dose-dependent anti-inflammatory effect and the highest anti-inflammatory effect was observed in the doses of 50 and 100 mg/kg. CONCLUSIONS: Royal jelly has potent anti-inflammatory effects compared to aspirin and it could be used in the treatment of inflammation. However, further studies are required to determine the active components in RJ responsible for this effect and its mechanism of action.

Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats.

BACKGROUND: Bleomycin (BLM), a chemotherapeutic agent is indicated in the management of some types of cancers. This drug produces a dose-dependent pulmonary fibrosis (PF) in most patients as well as experimental animals through oxidative injury. This study aimed to investigate the effect of gallic acid (GA), a polyphenolic compound, against PF-induce by BLM in rats. MATERIALS AND METHODS: The rats were given GA orally at doses (50, 100, and 200 mg/kg/day) for 7 consecutive days before the administration of single intratracheal (it) instillation of BLM at 7.5 IU/kg. GA doses were continued for 21 days after BLM exposure. The regulatory effects of GA on BLM-induced pulmonary toxicity were determined by assaying oxidative stress biomarkers, lung and serum cytokine levels, and by histopathological examination of lung tissue. RESULTS: The results showed that intratracheal BLM administration significantly increased the inflammatory or fibrotic changes, collagen content, levels of malondialdehyde (MDA), and pro-inflammatory cytokines such as TNF-α and IL1ß in lung. Also, it significantly decreased non-enzymatic (total thiol) and enzymatic (glutathione peroxidase (GPx)) antioxidant contents in the rats' lung tissue. However, oral administration of GA reversed all of these biochemical indices as well as histopathological alterations induced by BLM. CONCLUSION: Results of the present study demonstrate that GA, by its antioxidant properties, attenuates oxidative damage and fibrosis induced by BLM. Thus, an effective supplement with GA as an adjuvant therapy may be a very promising compound in reducing the side effects of BLM.

Quercetin preventive effects on theophylline-induced anomalies in rat embryo.

BACKGROUND: Theophylline has been shown to cause heart anomaly in animal and human fetus. OBJECTIVES: The present study aimed to investigate the protective effect of quercetin on theophylline-induced heart disorders in rat embryo. MATERIALS AND METHODS: Theophylline-induced teratogenicity in rats was used as the animal model. Pregnant rats were administered theophylline (259 mg/kg, po) or theophylline plus quercetin (259 mg/kg, po and 100 mg/kg, ip, respectively) on 9th and 10th days of pregnancy. On day 19, cardiac changes were assessed, measuring malondialdehyde (MDA) and glutathione peroxidase (GPx) activity levels in blood samples and also the fetus heart weight. Histopathological examination was also performed on all specimens. RESULTS: Theophylline-treated rats showed MDA level elevation and GPx activity reduction. Quercetin treatment improved heart conditions and resulted in a significant reduction in MDA levels and elevation in GPx activity. Moreover, co-administration of quercetin and theophylline increased the heart weight significantly. Furthermore, histophatological study showed no changes in the treated groups. CONCLUSIONS: This study demonstrated that quercetin have beneficial effects on theophylline-induced-anomalies in rat embryo.

Antinociceptive Effect of Hydroalcoholic Extract of Iranian Green tea in the Formalin Test in Rats.

BACKGROUND: Tea (Camellia sinensis) has been utilised, since time immemorial, as a beverage possessing encouraging health benefits. Little scientific evidence exists in literature on the effect of this plant on pain. OBJECTIVES: To investigate the antinociceptive activity of Iranian green tea extract. MATERIALS AND METHODS: The hydroalcoholic extract was administered to male Wistar rats. Formalin paw test was used to evaluate the antinociceptive activity. Plant extract (25, 50, 100 and 200 mg/kg, i.p.) (n = 6 for each group) or vehicle (n = 6) was administered 30 min before the subplantar formalin injection. RESULTS: The extract caused a significant dose-related (50, 100, 200 mg /kg, i.p.) inhibition of the first phase and onset of chronic phase (200 mg /kg, i.p.) of formalin induced nociception. The results showed that the pre-treatment of rats with naloxone (1 mg/kg, i.p.) significantly (P < 0.001) reversed antinociception by Green tea extract (GTE) (200 mg/kg, i.p.) in the inflammatory phase and had no effect on phase 1. CONCLUSIONS: These results indicate that GTE produces dose-related antinociception in chemical pain model and one of its possible mechanisms involves opioid pathways.

Evaluation of the Effects of Caffeic Acid Phenethyl Ester on Prostaglandin E2 and Two Key Cytokines Involved in Bleomycin-induced Pulmonary Fibrosis.

OBJECTIVE(S): Pulmonary fibrosis (PF) is the most common outcome of a collection of diverse lung disorders known as interstitial lung diseases. It is proposed that alterations in the levels of fibrogenic mediators and the profibrotic/antifibrotic imbalance play a substantial role in the progression of PF in animal models and possibly in humans. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has numerous biological effects. In the present study, the main objective was to investigate the effects of CAPE on some key mediators including TGF-ß1, TNF-α and prostaglandin E2 (PGE2) involved in profibrotic/antifibrotic balance and pathogenesis of idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: In this study, forty male Sprague-Dawley rats were divided into 5 groups (n=8). (1) "Bleomycin (BLM)-treated (Model) group": BLM (5 mg/kg, single intratracheal dose), (2) "Saline-treated group": the rats were given only saline, (3) "Treatment-1 group": BLM + CAPE (5 µmol/kg/day, 28 days, IP), (4) "Treatment-2 group": BLM + CAPE (10 µmol/kg/day, 28 days, IP) and (5) "Vehicle + CAPE group": CAPE (10 µmol/kg/day, 28 days, IP). RESULTS: BLM could significantly increase the levels of TNF-α and TGF-ß1 and decrease the PGE2 concentration compared to the saline control group. CAPE could considerably improve these values almost close to normal levels. CONCLUSION: Briefly, CAPE can be suggested as a novel, attractive and effective agent for prevention and treatment of pulmonary fibrosis.

Protective Effect of Caffeic Acid Phenethyl Ester (CAPE) on Amiodarone-Induced Pulmonary Fibrosisin Rat.

Treatment with amiodarone, a commonly prescribed antidysrhythmic agent, is associated with pulmonary fibrosis (PF) which is a commonly progressive and untreatable disease. Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and an active anti-inflammatory , anticancer, antimicrobial and antioxidant component of propolis (bee glue; a resinous hive product collected by honey bees). In the current study, the effects of CAPE on amiodarone-induced pulmonary fibrosis in rat were investigated. Male rats were divided in to 4 groups. The first group only received amiodarone (6.25 mg/Kg) on first and third day. The second group received only vehicle (distilled water) with the same volume and in the same time as the first group. The third and fourth groups received amiodarone and were treated with CAPE , 5 and 10 µmol /day respectively, from 2 days before the first dose of amiodarone and until 21 days after the second dose of amiodarone. At the end of treatment course, lung tissue was removed for histopathology and biochemical evaluations. Malondialdehyde (MDA) concentration, myeloperoxidase MPO) and super oxide dismutase (SOD) activities were determined in lung tissue. Histopathological evaluation was performed using light microscopy. MDA level and the activity of myeloperoxidase and superoxide dismutase enzymes significantly decreased in the group which was treated with CAPE (5 µmol/Kg). However, 10 µmol/Kg CAPE had not such an effect. Both doses of CAPE could histopathologically reduce the fibrogenic effects of amiodarone . CAPE was shown to be effective in reducing amiodarone-induced pulmonary fibrosis with the dose of 5 µmol/Kg.

Ginger (Zingiber officinale Roscoe) elicits antinociceptive properties and potentiates morphine-induced analgesia in the rat radiant heat tail-flick test.

Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used traditionally in the treatment of a wide variety of ailments. It has been shown that ginger is a calcium channel blocker; however, its influence on morphine analgesic effects has not been elucidated. We examined the effect of ginger root extract on nociceptive threshold and morphine-induced analgesia in male Wistar rats. To determine the effect of ginger on morphine analgesia, ginger extract (200, 400, and 600 mg/kg i.p.) was injected before a subeffective dose of morphine (2.5 mg/kg i.p.). The radiant heat tail-flick test was used to assess the nociceptive threshold before and at different times after drug administration. Our results showed that ginger extract elicited a significant antinociceptive effect. In addition, in groups that received both morphine and ginger, the observed analgesia was higher than that in groups treated with either morphine or ginger extract alone. Thus, the data indicate that ginger extract has a beneficial influence on morphine analgesia and can be an efficacious adjunct for pain management.

Cannabinoid CB1 receptors of the rat central amygdala mediate anxiety-like behavior: interaction with the opioid system.

Cannabinoids, which are the active compounds of marijuana, produce some pharmacological effects similar to the opioids. In addition, there are functional interactions between the cannabinoid and opioid systems. In this study, we investigated the effects of intraperitoneal (i.p.) injection of opioid drugs on responses induced by intracentral amygdala (intra-CeA) microinjection of cannabinoid CB1 receptor agents in rats, using the elevated plus maze test of anxiety. I.p. injection of morphine (6 and 9 mg/kg) 30 min before testing, increased the percentage open arm time (%OAT) and the percentage open arm entries (%OAE), but not locomotor activity, showing an anxiolytic-like response. I.p. administration of the opioid receptor antagonist, naloxone (1 mg/kg) 15 min before testing, significantly reduced %OAT, but not %OAE and locomotor activity. The drug, however, tended to decrease locomotor activity. Intra-CeA administration of arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB1 receptors; 1.25 and 5 ng/rat) increased %OAT and %OAE but not locomotor activity, indicating an anxiolytic-like response. Coadministration of morphine (6 mg/kg, i.p.) plus ACPA (0.125 ng/rat, intra-CeA) increased the anxiolytic-like response. Administration of naloxone reversed the effects of intra-CeA injection of ACPA. Intra-CeA administration of the cannabinoid CB1 receptor antagonist, AM251 (2.5, 25, and 100 ng/rat) did not alter %OAT and %OAE, but the higher doses of the drug (25 and 100 ng/rat) reduced locomotor activity. Coadministration of morphine (6 mg/kg) or naloxone (0.1 mg/kg) with AM251 showed an anxiolytic-like response. In conclusion, the results may indicate an anxiolytic-like effect for cannabinoid CB1 receptors of the CeA and the existence of an interaction between the cannabinoid and the opioid systems in the modulation of anxiety.