Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety

Aim:

The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT₃) receptor antagonist in experimental mouse models of anxiety.

Materials and Methods:

The anxiolytic activity of “6g” (1 and 2 mg/kg, intraperitoneally [i.p.]) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus maze (EPM), light-dark (L&D) box, hole board (HB), and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. None of the tested dose of “6g” affects the base line locomotion.

Results:

The new chemical entity “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the percentage of time spent and number of entries in open arm in the EPM test. In the L&D test compound “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the total time spent in light compartment as well as number of transitions from one compartment to other. Compound “6g” (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly (P < 0.05) increased number of head dips, whereas significantly (P < 0.05) decreased the head dipping latency in HB test as compared to vehicle control group. In addition, 6g (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores (square crossed) in OFT and there was no significant effect of 6g (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) on rearing scores.

Conclusion:

In conclusion, these findings indicated that compound “6g” exhibited an anxiolytic-like effect in animal models of anxiety.KEY WORDS: Anxiety, elevated plus maze, hole-board, 5-HT₃ receptor antagonist, open field test     

Anticolitis activity of chinese herbal formula Yupingfeng powder via regulating colonic enterochromaffin cells and serotonin

Objective:

To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved.

Materials and Methods:

YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability.

Results:

The results showed that the body weight of colitis mice was markedly decreased by 10, 12, 14, and 17% at 1, 3, 5, and 7 days (P < 0.05), whereas stool consistency score (3.6 vs. 0.4, P < 0.05), histopathological score (3.6 vs. 0.3, P < 0.05), and MPO activity (2.7 vs. 0.1, P < 0.05) in colitis mice were significantly increased compared to that of the normal mice; YPF powder treatment dose-dependently increased the body weight (7–13% increase) and decreased the stool consistency score (0.4–1.4 decrease), histopathological score (0.2–0.7 decrease), and MPO activity (0.1–0.9 decrease) in colitis mice. Colonic EC cell density (70% increase) and 5-HT content (40% increase) were markedly increased in colitis mice (P < 0.05), YPF powder treatment dose-dependently reduced EC cell density (20–50% decrease), and 5-HT content (5–27% decrease) in colitis mice.

Conclusion:

The findings demonstrate that the anti-inflammatory effect of YPF powder on TNBS - induced colitis may be mediated via reducing EC cell hyperplasia and 5-HT content. The important role of YPF powder in regulating colonic EC cell number and 5-HT content may provide an alternative therapy for colonic inflammation.KEY WORDS: Colonic inflammation, enterochromaffin cell, serotonin, ulcerative colitis     

Anti-anxiety effect of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide (6k) using battery tests for anxiety in mice

Objective:

To investigate the anti-anxiety activity of “6k”, a novel 5-hydroxytryptamine type 3 (5-HT₃) receptor antagonist in in mice.

Materials and Methods:

Anti-anxiety activity of “6k” (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). Diazepam (2 mg/kg, i.p.) served as reference standard.

Results:

“6k” significantly (P < 0.05) increased the time and entries in open arm in EPM as compared to vehicle control group. Further, “6k” significantly (P < 0.05) increased the central and peripheral ambulation along with rearings and time in central area; whereas, reduced the fecal pellets in OFT as compared to vehicle control group. There was significant (P < 0.05) reduction in the latency to enter dark chamber; whereas, increased number of crossings and time in light chamber in L&D aversion test by treatment with “6k” as compared to vehicle control group. In HBT, “6k” significantly (P < 0.05) increased the number of head dipping and squares crossed; whereas, reduced the latency for first head dip and number of fecal pellets as compared to vehicle control group.

Conclusion:

A novel 5-HT₃ receptor antagonist has anti-anxiety action.KEY WORDS: 5-HT₃ antagonist, anxiety, elevated plus maze, open field test, hole board test     

Calotropis procera: A potential cognition enhancer in scopolamine and electroconvulsive shock-induced amnesia in rats

Objectives:

Present study evaluates the effect of Calotropis procera (Apocynaceae) dry latex on cognitive function in rats using scopolamine and electroconvulsive shock (ECS) induced amnesia model.

Materials and Methods:

Male Wistar rats were pretreated with 200, 400 and 800 mg/kg of C. procera dry latex in scopolamine-induced amnesia model. Dose showing maximum effect in cognitive performance was selected and further evaluated using scopolamine and ECS-induced amnesia model for its effect on neurochemical enzymes and cognitive performance. Acetylcholinesterase (AChE) activity, β amyloid_1-42, and dopamine level were analyzed, while the cognitive performance was assessed by elevated plus maze, step-through passive avoidance test, and Morris water maze. Simultaneously, C. procera dry latex (25, 50, 100, 250, 500, and 1000 μg/mL) was screened for in vitro AChE inhibition assay.

Results:

Pretreatment with (200, 400 and 800 mg/kg) C. procera dry latex shows dose dependent increase in cognitive performance in scopolamine-induced amnesia. Further, pretreatment with the selected dose (800 mg/kg) showed significant improvement in transfer latency (P < 0.001, P < 0.01), escape latency (P < 0.05), time spent in target quadrant (P < 0.001) also significant decrease in AChE activity (P < 0.05), β amyloid_1-42 level (P < 0.001), and increase in dopamine level (P < 0.01) in rat brain homogenate when compared with scopolamine and ECS disease control groups. IC₅₀ for C. procera dry latex was found to be <1000 μg/mL.

Conclusions:

Pretreatment with C. procera dry latex (800 mg/kg) produced significant cognition enhancement by improving cognitive performance and decreasing the marker neurochemical enzyme activity in scopolamine and ECS-induced amnesia model.KEY WORDS: Acetylcholinesterase, Alzheimer''s disease, Dopamine, β amyloid1-42     

The protective effect of Rubia cordifolia against lead nitrate-induced immune response impairment and kidney oxidative damage

Objectives:

To evaluate the in vivo antioxidant activity of the ethanolic extract of the roots of Rubia cordifolia (RC) and to study its influence on lead nitrate-induced impairment of immune responses.

Materials and Methods:

Seventy-two adult male Swiss albino mice were used for biochemical and immunological studies and were divided into six groups of six mice each. Mice were treated with lead nitrate (40 mg/kg, orally) either alone and or in combination with RC (50 and 100 mg/kg body weight) daily for 40 days. For immunological studies, all mice were challenged twice with sheep RBC with on days 14 and 20 of the experiment. The immune function was assessed using macrophage yield, viability of macrophage, phagocytic index, serum immunoglobulin level, and plaque forming cell count (PFC), whereas the oxidative stress was assessed by estimating lipid peroxidation (LPO), reduced glutathione (GSH) content, and the activities of superoxide dismutase (SOD) and catalase (CAT).

Results:

Lead nitrate administration induced a significant (P<0.001) increase in LPO, whereas a significant (P<0.001) depletion of CAT and GSH in renal tissues. In addition, it also showed a significant (P<0.001) reduction in macrophage yield, viability of macrophage, phagocyte index, serum immunoglobulin level, and PFC in kidney. However, combination treatment with RC observed a significant (P<0.001) reversal of lead nitrate-induced toxicity on oxidative stress and immunological parameters.

Conclusion:

The lead nitrate-induced immunosuppression is due to oxidative stress and RC can prevent the same by virtue of its in vivo antioxidant property.     

Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney

Objectives:

The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine.

Materials and Methods:

Rats were divided into four groups: Renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG).

Results:

The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) μmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 μmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively.

Conclusions:

It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect.KEY WORDS: DNA mutation, ischemia-reperfusion, oxidative damage, rat, thiamine pyrophosphate     

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway

Objectives:

The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action.

Materials and Methods:

Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2’,7’-dichlorodihydrofluorescein diacetate.

Results:

PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01.

Conclusions:

The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.KEY WORDS: Analgesic, arachidonic acid, pain, reactive oxygen species, writhing     

Antioxidant potential of the methanol-methylene chloride extract of Terminalia glaucescens leaves on mice liver in streptozotocin-induced stress

Aim:

The antioxidant effect of the methanol–methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress.

Methods:

Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded.

Results:

In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase.

Conclusion:

These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.     

Short-term differences in drug prices after implementation of the national essential medicines system: A case study in rural Jiangxi Province,China

Objectives:

China''s 2009 national essential medicine system (NEMS) was designed to reduce prices through a zero-markup policy and a centralized bidding system. To analyze NEMS''s short-term impact on drug prices, we estimated the retail and wholesale prices before and after the reform at health institutions in rural Jiangxi Province.

Materials and Methods:

We undertook two cross-sectional surveys of prices of 39 medicines in November 2008 and May 2010, calculated inflation adjusted prices, and used the Wilcoxon signed-rank and rank-sum tests to examine price changes at different health institutions.

Results:

Retail prices at pilot (P < 0.01) and nonpilot (P < 0.01) township health centers decreased significantly, whereas the declines at retail pharmacies (P = 0.57) and village clinics (P = 0.29) were insignificant. The decline at pilot township health centers was the largest, compared with other kinds of health institutions (P < 0.01). Retail prices of essential and non-essential medicines declined significantly at pilot facilities (P < 0.05); price drops for non-essential medicines occurred only at pilot facilities (P < 0.05). No significant decline of wholesale prices were found at pilot (P = 0.86) and nonpilot units (P = 0.18), retail pharmacies (P = 0.18), and village clinics (P = 0.20). The wholesale prices changes at pilot units before and after the reform were higher than at nonpilot public units (P < 0.05), retail pharmacies (P < 0.05), and village clinics (P < 0.05).

Conclusion:

While the NEMS zero-markup policy significantly reduced retail prices at pilot health institutions, the centralized bidding system was insufficient to lower wholesale prices. A drug price management system should be constructed to control medicine prices and a long-term price information system is needed to monitor price changes.KEY WORDS: China, drug prices, healthcare reform, national essential medicine system, rural healthcare     

An evaluation of the protective role of α-tocopherol on free radical induced hepatotoxicity and nephrotoxicity due to chromium in rats

Aim:

To avert the health problems induced by many environmental pollutants, available antioxidants have been evaluated. The present study was aimed to investigate whether α-tocopherol could protect the hexavalent chromium (Cr VI)-induced peroxidation in the liver and kidney and to explore the underlying mechanism of the same.

Materials and Methods:

A total of 24 Wistar adult female rats were equally divided into four groups. Group 1 served as control while Groups 2 and 3 were administered K₂Cr₂O₇(10 mg/kg b.wt. s.c. single dose). In addition to (Cr VI), Group 3 also received α-tocopherol (125 mg/kg, daily) by oral gavage for 14 days. Group 4 was maintained as α-tocopherol control (dose as above). At the end of 14 days, blood samples were drawn for hematology. Subsequently, all the rats were sacrificed to collect liver and kidney samples for assay of tissue peroxidation markers, antioxidant markers and functional markers and histopathology.

Results:

Administration of chromium (Cr VI) in Group 2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide dismutase and reduced glutathione along with significant (P < 0.05) increase in peroxidation markers such as malondialdehyde and protein carbonyls in the liver and kidney as compared with other groups. The functional markers in serum such as total protein was decreased significantly (P < 0.05), whereas other functional markers viz. alanine transaminase, blood urea nitrogen and creatinine were increased significantly (P < 0.05) in Group 2 as compared with the other groups. Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total leukocyte count were observed in Cr VI treated Group 2 rats. Prominent pathological changes were observed in the liver and kidney of Group 2. Co-treatment with α-tocopherol in Group 3 rats significantly (P < 0.05) reversed the Cr VI induced changes. The parameters in the study in Group 4 did not differ as compared with Group 1.

Conclusions:

α–tocopherol exhibited protective effect against Cr VI-induced damage to the liver and kidney by inhibition of lipid peroxidation owing its antioxidant activity.KEY WORDS: α-tocopherol, chromium (Cr VI), kidney, lipid peroxidation, liver     

Hepatoprotective activity of Tephrosia purpurea against arsenic induced toxicity in rats

Aim:

The present study was conducted to evaluate the hepatoprotective activity of Tephrosia purpurea (TP) against sodium arsenite (NaAsO2) induced sub-acute toxicity in rats.

Materials and Methods:

Twenty four wistar albino rats of either sex were randomly divided into three groups. Group II and III were orally administered with sodium arsenite (10 mg/kg) daily in drinking water for 28 days. Additionally Group III was orally treated with hydro-alcoholic extract of Tephrosia purpurea (TP) @ 500 mg/kg daily for the same time period, whereas only deionized water was given to Group I (control). Serum biomarker levels, oxidative stress parameters and arsenic concentration were assessed in liver. Histopathology was also conducted.

Results:

It has been seen that TPE (500 mg/kg) significantly (P < 0.01) reduced serum ALT, AST, ALP activity and increased total protein and reduced necrosis and inflammation in liver of group III compared to group II. A significantly (P < 0.01) higher LPO and lower GSH levels without change in SOD activity in liver was also observed in group II compared to group III, though there was no significant difference in arsenic accumulation between them. The plant extract also protects the animals of group III from significant (P < 0.01) reduction in body weight.

Conclusion:

Our study shows that supplementation of Tephrosia purpurea extract (500 mg/kg) could ameliorate the hepatotoxic action of arsenic.KEY WORDS: Arsenic, hepatotoxicity, rats, sub-acute toxicity, Tephrosia purpurea     

Efficacy and safety of add on therapy of bromocriptine with metformin in Indian patients with type 2 diabetes mellitus: A randomized open labeled phase IV clinical trial

Objective:

To compare the effectiveness and safety of add on therapy of bromocriptine with metformin in type 2 diabetes mellitus (DM) patients.

Material and Methods:

Adult type 2 DM patients fulfilling the inclusion criteria were randomized in three groups. Group A received metformin (1000 mg/ day), while group B patients were treated with metformin (1000 mg/day) plus bromocriptine (0.8 mg/day) and group C received metformin (1000 mg/day) plus bromocriptine (1.6 mg/day) for 12 weeks. Fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), and body weight were measured at week 4, 8, and 12 visits and glycosylated hemoglobin (HbA_1C) at week 12 visit.

Results:

Metformin alone and in combination with bromocriptine in escalating dose (0.8 mg/day and 1.6 mg/day) significantly (P < 0.05) decreased FPG and PPPG levels at weeks 4, 8, and 12 compared with pretreatment values. HbA_1C level in all three treatment groups significantly (P < 0.05) decreased at week 12 as compared with pretreatment baseline value. HbA_1C level in groups B and C significantly (P < 0.05) decreased as compared with group A at week 12. Addition of bromocriptine to metformin also significantly (P < 0.05) decreased FPG and PPPG levels in a dose-dependent manner as compared with metformin alone. Intergroup analysis did not show any statistically significant change in weight of study subjects at different intervals.

Conclusion:

The combination of bromocriptine with metformin significantly decreased FPG, PPPG, and HbA_1C compared with metformin alone in type 2 DM patients in a dose-dependent manner.KEY WORDS: Bromocriptine, diabetes mellitus, metformin     

Does tramadol affect coagulation status of patients with malignancy?

Aim:

The study investigated the direct effects of tramadol on the coagulation status of women with gynecologic malignancies in vitro.

Materials and Methods:

Citrated whole-blood samples from 21 patients with gynecologic tumors were spiked ex vivo with 2 or 6 μl/ml tramadol. Thrombelastography (TEG) analysis was performed using ROTEM^® to assess clotting time (CT), clot formation time (CFT) and maximum clot formation (MCF).

Results:

In the INTEM assay, CT (P < 0.05) and CFT (P < 0.01) were significantly prolonged with tramadol at a 6 μl/ml concentration compared with baseline. There were no significant differences in MCF values between the baseline and the tramadol-treated samples (P > 0.05). Blood medicated with tramadol (6 μl/ml) clotted slowly (increased CT and CFT).

Conclusion:

The changes observed by TEG demonstrated that tramadol impairs hemostasis in a concentration-dependent manner in the whole blood of women with gynecologic malignancies in vitro.KEY WORDS: Coagulation, malignancy, thromboelastography, tramadol     

Trends in self-medication for dental conditions among patients attending oral health outreach programs in coastal Karnataka,India

Objectives:

To determine the prevalence, pattern, and awareness of self-medication practices among patients presenting at oral health outreach programs in coastal Karnataka, India.

Materials and Methods:

The cross-sectional study, based on an interview conducted in randomly selected 400 study subjects from the patients presenting at these oral health outreach programs. Data were collected regarding demographic information and the interview schedule consisting of 14 questions was administered.

Results:

Prevalence of self-medication was 30%. Respondents’ gender (χ² = 5.095, P < 0.05), occupation (χ² = 10.215, P < 0.05), the time from the last dental visit (χ² = 8.108, P < 0.05), recommendation of drug(s) to family members or friends (χ² = 75.565, P < 0.001), and the likelihood of self-medication in the next 6 months (χ² = 80.999, P < 0.001) were significantly associated with self-medication. Male respondents were less likely to have undertaken self-medication (odds ratio = 0.581 [0.361, 0.933]). The frequently self-medicated drug was analgesics (42.5%) for toothache (69.2%). The regression model explained 39.4% (Nagelkerke R²) of the variance in self-medication practices.

Conclusions:

Prevalence of self-medication was 30% with demographic influence. Hence, this study highlights the policy implications for drug control by government agencies and stresses on the need for dental health education to discourage irrational drug use.KEY WORDS: Dentists, drug resistance, oral health, self-medication     

Effect of trapidil in myocardial ischemia-reperfusion injury in rabbit

Objectives:

To evaluate the cardioprotective effects of trapidil on myocardial ischemia-reperfusion injury (MIRI) in rabbits.

Materials and Methods:

Rabbits were subjected to 40 min of myocardial ischemia followed by 120 min of reperfusion. Blood for superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. At the end of reperfusion, the rabbits were sacrificed and the hearts were isolated for histological examination. An apoptotic index (AI) was determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) method. The expression of apoptosis-related proteins Bax and Bcl-2 was analyzed using immunohistochemistry. Statistical analyses were performed by one-way analysis of variance (ANOVA), P < 0.05 considered statistically significant

Results:

Trapidil caused a significant (P < 0.05) increase in SOD activity, as decreased MDA levels and significantly (P < 0.05) reduced the expression of Bax as compared with the ischemia-reperfusion (IR) control group.

Conclusion:

Trapidil may attenuate the myocardial damage produced by IR injury and offer potential cardioprotective action.KEY WORDS: Apoptosis index, ischemia-reperfusion, myocardial ischemia-reperfusion injury, trapidil     

Evalution of anti-ulcer activity of Polyalthia longifolia (Sonn.) Thwaites in experimental animals

Objective:

To evaluate the anti-ulcer activity of ethanol extract of leaves of Polyalthia longifolia (Sonn.) Thwaites.

Materials and Methods:

The ethanol extract of Polyalthia longifolia was investigated for its anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer in rats, HCl -Ethanol induced ulcer in mice and water immersion stress induced ulcer in rats at 300 mg/kg body weight.p.o.

Results:

A significant (P < 0.01, P < 0.001) anti ulcer activity was observed in all the models. Pylorous ligation showed significant (P< 0.01) reduction in gastric volume, free acidity and ulcer index as compared to control. It also showed 89.71% ulcer inhibition in HCl- Ethanol induced ulcer and 95.3% ulcer protection index in stress induced ulcer.

Conclusion:

This present study indicates that P. longifolia leaves extract have potential anti ulcer activity in the three models tested.     

Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

Aims:

The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R) injury in rats and the mechanisms of action of LGB.

Materials and Methods:

The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF) and neurotrophin-3 (NT-3) were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry.

Statistical analysis:

All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant.

Results:

Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05, P < 0.01). LGB significantly increased NGF and NT-3 mRNA (messenger RNA) and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01).

Conclusions:

LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.KEY WORDS: Cerebral I/R injury, gene, lettuce glycoside B, LGB, neuroprotective effect, P. laciniata, protein     

Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced analgesia in mice

Objective:

To study analgesic activity and to evaluate the involvement of opioid and monoamines in the antinociceptive activity of methanol extract of leaves of Aegle marmelos.

Materials and Methods:

Analgesic activity of methanol extract (ME) of A. marmelos alone (75,150 and 300mg/kg orally) and in combination with morphine or venlafaxine (subanalgesic) were studied using tail flick test and acetic acid-induced writhing in mice. The effect of pre-treatment with opioid antagonist naltrexone 1mg/kg was also studied on antinociception induced due to ME.

Result:

ME produced a dose-dependent significant antinociceptive activity in the tail flick test and acetic acid-induced writhing in mice. (P<0.05) Administration of subanalgesic dose of ME with morphine or venlafaxine also resulted in significant (P<0.05) antinociceptive activity in both the pain models. Pre-treatment with naltrexone inhibited analgesic activity induced by ME alone and combination with morphine or venlafaxine.

Conclusion:

A.marmelos in induced antinociception is mediated through both opioid and monoaminergic pain pathways, suggest its possible use in chronic pain.KEY WORDS: Aegle marmelos, analgesia, monoamines, opioid, tail flick latency     

Mechanism of testicular protection of carvedilol in streptozotocin-induced diabetic rats

Aims:

Male sub-fertility and infertility are major complications of diabetes mellitus. The non-selective β-blocker carvedilol has been reported to have favorable effects on some of the diabetic complications based on its antioxidant and anti-apoptotic effects. This study aims to evaluate the possible testicular protective effect of carvedilol in streptozotocin (STZ)-induced diabetic rat model and its possible mechanisms.

Materials and Methods:

Diabetes was induced by a single i.p. dose of 65 mg/kg of STZ. In parallel groups of diabetic rats, carvedilol in low and high doses (1 and 10 mg/kg/day orally) were administered for 4 weeks. Oxidative stress markers as reduced glutathione (GSH) and the product of lipid peroxidation; malondialdehyde (MDA) were evaluated in testicular homogenate. The level of expression of the apoptotic marker; caspase 3, was assessed using western blot, followed by densitometric analysis.

Results:

Induction of diabetes caused distortion of histological normal testicular structure, with decrease (P < 0.05) in GSH and increase (P < 0.05) in MDA, as well as induction of caspase 3 expression. Carvedilol in low or high doses reverted diabetes-induced histological damage, restored antioxidant activity and ameliorated caspase 3 expression.

Conclusion:

Carvedilol confers testicular protection against diabetes-induced damage through antioxidant and anti-apoptotic mechanisms.KEY WORDS: Apoptosis, carvedilol, diabetes, oxidative stress, testes     

Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice

Background:

Limited data is available about the toxicity of herbal remedies used for self-medication. Since a popular medicinal plant Ecliptaalba contains various bioactive molecules, the present study aimed to observe the biochemical and histological changes in liver associated with acute oral toxicity (LD₅₀) of aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice.

Materials and Methods:

For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group– I was normal control and the treatment groups were administered aqueous leaf extract of E. alba orally at different doses of 500 mg (group – I),1750 mg (group–III), 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on the eighth day and blood was collected for the analysis of ALP (alkaline phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and albumin. The liver was dissected, weighed, and processed for histopathological analysis.

Results:

The LD₅₀ was found to be 2316.626 mg/kg /body weight in female mice. Serum SGPT, total protein and albumin increased in treated group- IV (P < 0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01) and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg (group- VI).

Conclusion:

It was concluded that oral administration of aqueous leaf extract of E. alba had detrimental effects on biochemical parameters and induced histopathological alterations in liver of female Swiss albino mice at doses higher than 2000 mg/kg/day indicating that its indiscriminate use should be avoided.KEY WORDS: Biochemical, Ecliptaalba, hepatotoxicity, histopathological