Ameliorative Effect of Ethanolic Extract of Moringa oleifera Leaves in Combination with Curcumin against PTZ-Induced Kindled Epilepsy in Rats: In Vivo and In Silico.

The ameliorative effect of ethanolic extract of M. oleifera (MOEE) leaves in combination with curcumin against seizures, cognitive impairment, and oxidative stress in the molecular docking of PTZ-induced kindled rats was performed to predict the potential phytochemical effects of MOEE and curcumin against epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250 mg/kg and 500 mg/kg, orally), curcumin (200 mg/kg and 300 mg/kg, orally), valproic acid used as a standard (100 mg/kg), and the combined effect of MOEE (250 mg/kg) and curcumin (200 mg/kg) at a low dose on Pentylenetetrazole was used for (PTZ)-induced kindling For the development of kindling, individual Wistar rats (male) were injected with pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular docking was performed by the Auto Dock 4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of human glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and M. oleifera ethanolic extracts (MOEE) showed dose-dependent effects. The combined effects of MOEE and curcumin leaves significantly improved the seizure score and decreased the number of myoclonic jerks compared with a standard dose of valproic acid. PTZ kindling induced significant oxidative stress and cognitive impairment, which was reversed by pretreatment with MOEE and curcumin. Glutathione reductase (GR) is an enzyme that plays a key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift antioxidant properties, which leads to the inhibition of ROS-induced cell death in the brain. The combination of the ethanolic extract of M. oleifera (MOEE) leaves and curcumin has shown better results than any other combination for antiepileptic effects by virtue of antioxidant effects. As per the docking study, chlorogenic acid and quercetin treated with acombination of curcumin have much more potential.

Formulation of Isopropyl Isothiocyanate Loaded Nano Vesicles Delivery Systems: In Vitro Characterization and In Vivo Assessment.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

Evaluation of Ficus retusa L. Leaves with Special Reference to Antidiarrheal and Anti-spasmodic Activity.

AIMS: The aim of present investigation was to evaluate the traditional claim of Ficus retusa as an anti-diarrheal and anti-spasmodic agent using different pharmacological models. BACKGROUND: Diarrhea is considered as major cause of mortality, especially in children and aged persons. Because of diarrhoea, 17% of admitted children get die. In order to treat the diarrhea, natural drugs may be useful. OBJECTIVE: In order to prove the traditional claim of Ficus retusa, present work was undertaken with objective to prove antidiarrheal and antispasmodic activity. METHODS: The anti-diarrhoeal activity was evaluated by magnesium sulphate induced diarrhea and 5-hydroxy tryptamine(5HT) induced diarrhea. Further, the exact were subjected to gastrointestinal motility test using standard procedure. RESULT: Finding of the present study suggested that significant response was exhibited by ethanolic extract (400mg/kg bw.) of Ficus retusa. CONCLUSION: The response towards bioactivity was dose dependent. It was concluded that 400mg/kg bw of ethanolic extract is most potent in antidiarrhoeal and antispasmodic activity.

Evaluation of Toxicity and Antihyperlipidemic Activity of Spondias Mombin l. Leaves Methanolic Extract in Laboratory Rats.

AIMS: To study the toxicological profile and anti-hyperlipidemic effects of Spondias mombin leaves methanolic extract in experimental rats. BACKGROUND: Preventing high levels of lipids or its recurrence is currently one of the key aims of clinical and experimental studies. OBJECTIVE: This study was carried out to investigate the toxicological profile and anti-hyperlipidemic effects of methanolic extract of leaves of Spondias mombin. METHODS: The acute toxicity study was carried out where the limited dose of 2000 mg/kg body weight was administered to five rats at 48 h intervals. The interpretation was prepared and recorded for 24 h. In the sub-acute toxicity study, rats were treated with 250, 500, and 1000 mg/kg doses of the extract every 24 h for 28 days. The hematological, biochemical, and histopathological tests of treated animals were carried out at the end of the test. The anti-hyperlipidemic activity of plant extract (100, 200 mg/kg) was studied on Triton-X-100 induced hyperlipidemia in rats. Histopathological changes in the liver of rats were examined. RESULTS: For acute and subacute treatment, the extract did not reveal any signs of toxicity or mortality, or any significant effects on hematological, biochemical parameters, and histopathology of organs. The extract demonstrated an important anti-hyperlipidemic result by decreasing the serum levels of cholesterol, TGs, LDL, VLDL, and enhancing HDL. CONCLUSION: Taking up the evidence of the experimental study, we can conclude that the methanolic extract of Spondias mombin leaves helps in declining hyperlipidemia in rats and it can be safely used for a period of 28 days to treat hyperlipidemia.

Extraction, GC-MS Evaluation and Anti-epileptic Potential of Seeds Ethanolic Extract of Putranjiva roxburghii Wall.

BACKGROUND: Putranjiva roxburghii Wall is traditionally known to cure many pathological conditions including epilepsy. OBJECTIVE: The present study is aimed at determining bioactive compounds in ethanolic extract of Putranjiva roxburghii test extract (PRTE) seeds by GCMS analysis and to assess its antiepileptic potential using various experimental models of epilepsy. METHODS: The ethanolic extract of seeds of Putranjiva roxburghii was subjected to GC-MS analysis to detect the bioactive phytoconstituents. Acute oral toxicity of the extract was performed using OCED guideline 420. Pentylenetetrazol (PTZ) kindling model of epilepsy and Maximal electroshock epilepsy (MES) model of epilepsy were used to determine anti-epileptic potential. RESULTS: The GC-MS analysis of the extract revealed the presence of 20 phytoconstituents. The major phytoconstituents included n-Propyl heptyl ether (25.25%), 5-Ethyl hydantoin (8%), octadec- 9-enoic acid (16.25%) and 1, 2-Benzene dicarboxylic acid (11.86%). The PRTE (50 mg/kg and 100 mg/kg) afforded a significant and dose-dependent protection against PTZ-induced kindling epilepsy and MES induced epilepsy (p<0.001 and p<0.01). CONCLUSION: Based on the above findings, it is evident that Putranjiva roxburghii seeds contain biologically active compounds. It can also be concluded that the extract possesses anti-epileptic potential.

Cardioprotective Effect of Coenzyme Q10 on Apoptotic Myocardial Cell Death by Regulation of Bcl-2 Gene Expression.

OBJECTIVES: To investigate the effect of coenzyme Q10 (CoQ10) on apoptotic myocardial cell death in rat model of heart ischemia and reperfusion I/R injury. MATERIALS AND METHODS: Eighteen rats (200-250 g) were divided into three groups of 6 rats in each. Group I (sham-operated control group): this is the control group. The animals received the surgical procedure without IR injury or any drug treatment. Group II (I/R group): ischemia was accomplished by the occlusion of coronary artery for 30 min followed by reperfusion for 45 min and Group-III (Coenzyme Q10 treated group): Treated with CoQ10 at a dose of 1 mg/kg, postoperative for 7 days before induction of IR injury. RESULTS: The study revealed that pretreatment with CoQ10 has shown protective effect on apoptotic rat heart and agreed with earlier reports that CoQ10 significantly protects from oxidative stress and cytopathological changes caused by cardiac ischemia followed by reperfusion and attenuated decrease of antioxidant enzymes. Nitric oxide production in the heart of ischemic rats was significantly increased by the pretreatment with CoQ10 in comparison with IR group. CONCLUSIONS: CoQ10 protects against cardiac apoptosis induced by IR injury by significantly decreasing the apoptotic DNA and regulating the expression of Bcl-2 gene.

Evaluation of Acute and Subacute Oral Toxicity Induced by Ethanolic Extract of Marsdenia tenacissima Leaves in Experimental Rats.

The objective of this study is to evaluate the acute and subacute toxicity of the ethanolic extract of Marsdenia tenacissima (MTE) leaves (family: Asclepiadaceae) in albino rats. The acute toxicity was performed where the limit dose of 5000 mg/kg body weight used. Observations were made and recorded for 24 h, and once daily further for a period of 14 days. The rats were weighed and various observations, like mortality, behavior, injury, or any signs of illness were conducted once daily during the period. For subacute study, four groups of 10 animals (female rats) received 10% Tween 20 in distilled water (control), and 250, 500, and 1000 mg/kg of freshly-prepared extracts, respectively, every 24 h orally for 28 days. At the end of each study, hematological analysis and biochemical parameters were evaluated. Histopathological examination of vital organs of the animals were taken for gross findings, compared to controls. There was no significant difference (p > 0.05) observed in the relative organs, body weights, hematological, biochemical parameters, and gross abnormalities, compared to the control. No mortality was recorded. Therefore, analysis of results may lead to the conclusion that the medium-term oral administration of the MTE leaves for 28 days does not cause toxicity.

In Vivo Psychopharmacological Investigation of Delphinium Denudatum and Amaranthus Spinosus Extracts on Wistar Rats.

INTRODUCTION: In our modern era, life style of human being changes and updates every day that may affect their health status. There is an incredible expectation that natural origin drugs lack undesirable effects not like synthetic drugs, though have the same potency and efficacy. No scientific data is available about the antianxiety properties of Delphinium denudatum root and Amaranthus spinosus leaves. In this regard, the present study was designed to carry out comparative and combined study on antianxiety properties of Delphinium denudatum root and Amaranthus spinosus leaves. METHODS: Delphinium denudatum root and Amaranthus spinosus leaves were defatted with petroleum ether, and then extracted with hydroalcoholic solvent by soxhlation process. The hydroalcoholic extract of both drugs singly and in combination were evaluated for their anxiolytic effects on Wistar albino rats in doses of 200 and 400 mg/kg using different anti-anxiety tests like Elevated Plus Maze, Staircase, Actophotometer, and Light and Dark tests. RESULTS: Both hydroalcoholic extracts possessed flavonoids, alkaloids, saponins, tannins, carbohydrates, proteins, amino acids, carbohydrates, steroids, sterols, etc. In the dose dependent manner, both the hydroalcoholic extracts produced good anxiolytic activity. The best result was obtained by a combination of them in higher dose. CONCLUSION: Hydroalcoholic extracts of Delphinium denudatum root and Amaranthus spinosus leaves and their combination may act as a potent anxiolytic agents in rats. Amaranthus spinosus was found to be more effective than Delphinium denudatum.

Protective effects of amlodipine on mitochondrial injury in ischemic reperfused rat heart.

The most significant finding of the present study was the release of nitric oxide (NO). The effect of amlodipine on NO production associated with ischemic reperfused (IR) injury was investigated in rat heart model. Cardiac tissues from animal groups were processed for biochemical, histopathological and electron microscopic studies. There was a significant increase in myocardial catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzymes in amlodipine treated group (1.37, 10.27, 6.39) when compared to IR injured group (0.81, 6.87, 4.53). Histopathology studies showed amlodipine reduce cardiocyte damage in cardiac injury during the cardiac IR. Transmission electron microscopic (TEM) study confirmed the cardioprotective role of amlodipine against IR induced cardiac injury. On the basis of findings, it is hypothesized that a portion of the beneficial actions of amlodipine may involve the release or action of NO and probably by its antioxidant properties.

Outcome of tissue sparing surgical intervention in mine blast limb injuries.

OBJECTIVE: To describe the pattern of mine blast limb injuries in civilian population of Kashmir, to evaluate the outcome of tissue sparing surgical intervention in these injuries and to determine the sensitivity of hand-held percutaneous Doppler for tissue viability. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Muzaffarabad and Islamic International Medical College Hospitals at Rawalpindi/Islamabad from November 1997 to May 2005. PATIENTS AND METHODS: One hundred and three patients who sustained mine blast injuries to upper or lower limbs, along side the line of control between the Indian-held Kashmir and Azad Kashmir, regardless of age and gender, were included in this study. Patients who already had amputation after injury at some other place were excluded. All patients were initially managed in emergency and had more than one surgical intervention. Transcutaneous Doppler was used to evaluate the vascularity of the remaining tissue. All patients were operated under spinal or general anaesthesia and had repeated debridements followed by skin cover by split skin graft, full thickness skin graft or rotational flaps. Every patient received at least 5 days course of antibiotics and tetanus prophylaxis. Postoperative rehabilitation and follow-up was conducted for at least 6 months after discharge from the hospital. RESULTS: Mean age of victims in this study was 22 years. Out of 103 patients, 72 (69.9%) received initial wound care in the peripheral primary health care centre but were not amputated while 31 patients (30%) were just dressed and referred for further treatment at tertiary care hospitals. Eighty-five patients (82.5%), out of the total, had some sort of traumatic amputation at presentation due to the original injury. That included loss of limb below knee in 19 (18.45%) patients, at distal tibiofibular region in 13 (12.6%), mid tarsal amputations in 39(37.9%), and hemi foot amputation in 15 (14.6%) patients. Nine (8.7%) patients had losses of two or less than two toes, 1 (0.97%) patient had injury at mid palmer region, and 5 (4.9%) patients had 2 fingers traumatic amputation. Eighteen (17.5%) patients had soft tissue ( with or without bony injury) injury only without any actual traumatic amputation. Infection rate was 27% in patients who did not have wound care in the periphery. Those who had wound toilet in-the peripheral hospital had infection rate of 16%. Two patients developed fulminating multi-resistant progressive infection requiring below knee amputation. CONCLUSION: Conservative wound debridement and early skin coverage by different means and preserving maximum soft tissues and bone results in functionally and cosmetically better limb in victims of land mine.

Evaluation of emergency revascularisation in vascular trauma.

BACKGROUND: Vascular trauma is a common life threatening injury leading to serious consequences if not timely and efficiently managed. We evaluated early surgical interventions aimed at revascularization and thus salvaging limb/organ in life threatening vascular injuries. Aims of our study were to evaluate the outcome of available diagnostic modalities, earliest possible surgical intervention and rate of related complications with particular reference to our existing situation. METHODS: Emergency diagnostic workup based mainly on clinical evaluations and required laboratory and imaging parameters leading to revascularisation was performed in 48 patients in Combined Military Hospital (CMH) Muzaffarabad and Islamic Medical College Hospitals between June 1997 and December 2001. Data was collected on pre-designed computerized proforma's which were completed by the treating surgeon and data was entered and analyzed accordingly. RESULTS: Out of the total 48 patients who sustained major vascular injuries during this period, 14 (29.2%) were having injury to upper limb vessels, 26 (54.2%) patients had injury to the lower limb vessels, 6 (12.5%) patients reported with injury to abdominal vessels. One (2%) patient had injury to common carotid artery, while an other patient to thoracic aorta respectively (2%). Penetrating trauma caused 38 (79%) and blunt trauma caused 10 (21%) major vascular injuries. Out of 48 patients, 41 (85.4%) patients were successful managed by vascular reconstruction without any residual disability. CONCLUSION: Speedy diagnostic work up and early revascularization yields favourable outcome in vast majority of patients requiring vascular repair. Selections of surgical technique including use of autologous vein graft or artificial vascular graft can save many limbs. In order to achieve good results the time lapse between injury and revascularisation should be less than 6 hours.