Episodes In Mice Research Articles

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as β-sitosterol (1), β-amyrin (2), β-amyrin acetate (3), β-amyrin palmitate (4), β-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

Calcium Channel Inhibitory Effect of Marjoram (Origanum majorana L.): Its Medicinal Use in Diarrhea and Gut Hyperactivity.

The leaves of Origanum majorana (O. majorana) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract. Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s). The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency (p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected. Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders.

Deciphering In Vitro and In Vivo Pharmacological Properties of Seed and Fruit Extracts of Flacourtia jangomas (Lour.) Raeusch.

The objective of the study was to evaluate the pharmacological properties of the methanolic extract of Flacourtia jangomas (Lour.) Raeusch fruits (PFJM) and seeds (SFJM), along with their soluble fractions in ethyl acetate (fruit: PFJE; seed: SFJE) and chloroform (fruit: PFJC; seed: SFJC). Our phytochemical analysis of the examined extracts confirmed the presence of various therapeutically active phytoconstituents, including flavonoids, tannins, glycosides, and alkaloids. Employing the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical quenching method, SFJC exhibited the highest antioxidative potential, with an IC50 of 48.84, compared to ascorbic acid (IC50 21.77). The thrombolytic activity was assessed through rapid clot analysis of human blood samples, revealing that SFJC demonstrated the highest thrombolytic activity (60.99 ± 2.28%) compared to streptokinase (72.89 ± 2.19%). In the protein denaturation antiarthritic test, the PFJE and SFJC extracts exhibited significant potency, achieving results of 74.28 ± 1.16% and 79.25 ± 0.83%, respectively, at a dose of 500 μg/mL. All samples displayed notable anthelmintic activity by reducing Pheretima posthuma paralysis and death time in a dose-dependent manner compared to albendazole. In both in vivo analgesic tests, SFJC demonstrated substantial (p < 0.01) pain inhibition percentages (tail immersion: 49.46%; acetic acid writhing: 66.43%) at a dose of 600 mg/kg. During neuropharmacological screening, all extracts significantly (p < 0.01; p < 0.05) and dose-dependently decreased the mice's locomotion activity and motor balance. In the thiopental-induced sedation assay, SFJC significantly decreased the sleep latency time (4.18 ± 0.24 min) and increased the duration of sleep time (85.20 ± 2.39 min) at a higher dose. All samples notably reduced blood glucose levels in the oral glucose tolerance test in a dose-responsive manner, and SFJC exhibited a considerable hypoglycemic impact (7.38 ± 0.44 mmoles/L at 600 mg/kg). The frequency of diarrheal episodes in mice during the antidiarrhea assessment was significantly decreased by the tested plant samples. These findings can serve as a reference for future endeavors to isolate pure bioactive compounds from this plant for the development of novel phytomedicines.

GC-MS Analysis and In Vivo and Ex Vivo Antidiarrheal and Antispasmodic Effects of the Methanolic Extract of Acacia nilotica.

This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography–mass spectrometry (GC–MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC–MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.

A probabilistic model for the ultradian timing of REM sleep in mice.

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease.

Sentinel Acute Pancreatitis Event Increases Severity of Subsequent Episodes in Mice

Pancreatitis is the inflammatory disorder of the pancreas, which often forms a disease continuum starting with an acute pancreatitis (AP) attack followed by recurrent acute pancreatitis (RAP) episodes and eventual progression to chronic pancreatitis (CP). 1 Yadav D. et al. Gastroenterology. 2013; 144: 1252-1261 Google Scholar Progression to RAP and ultimately to CP is associated with environmental and/or genetic risk factors. The Sentinel Acute Pancreatitis Event (SAPE) hypothesis has been proposed to explain how a single episode of AP could lead to CP. 2 Whitcomb D.C. Gut. 1999; 45: 317-322 Google Scholar , 3 Schneider A. et al. Best Pract Res Clin Gastroenterol. 2002; 16: 347-363 Google Scholar , 4 Whitcomb D.C. Gastroenterology. 2013; 144: 1292-1302 Google Scholar , 5 Whitcomb D.C. et al. Pancreatology. 2016; 16: 218-224 Google Scholar This model posits that in the setting of susceptibility factors, an initial “sentinel” episode of AP sensitizes the pancreas to recurring/continual inflammation and fibrosis through activation of the immune system. The initial AP attack is called the sentinel event because it signals the beginning of CP and alerts the physician to initiate therapy for the prevention of progression. To test the SAPE concept experimentally, we set out to investigate whether an episode of experimental AP in mice would change the severity of later attacks. We also examined whether sensitization of the pancreas by the sentinel AP event is mediated by retention of inflammatory cells or by altered protease activation.

In vitro and in vivo evaluation of pharmacological potential of Begonia barbata Wall

BackgroundBegonia barbata Wall is an important medicinal plant in Bangladesh used to treat several human diseases. The intention of the existing work was to determine in vitro and in vivo pharmacological properties of petroleum-ether, dichloromethane, and ethyl acetate soluble fractions of methanol extract of B. barbata whole plant (MEBB). The total phenolic content (TPC) was determined by Folin-Ciocalteu test while antioxidant activity assay was performed by DPPH radical quenching process. Tail immersion and acetic acid-induced writhing methods were utilized to evaluate analgesic effect in albino mice. To evaluate the hypoglycemic potential, glucose tolerance test is used. Castor oil-induced diarrhea method is utilized to figure out the anti-diarrheal action in mice. Thiopental-sodium-induced sleeping time test was exploited for the appraisal of CNS antidepressant action.ResultsAntioxidant activities of the test materials followed the order: dichloromethane fraction (DCMF) > ethyl acetate fraction (EAF) > petroleum-ether fraction (PEF). The EAF yielded maximum amount of phenolic compounds (12.47 mg of GAE/g of sample). The DMF was most effective in terms of thrombolytic activity while the EAF protected the membrane integrity of erythrocyte by 63.47% inhibition of hemolysis induced by heat. Among all fractions, the PEF (400 mg/kg body weight) demonstrated highest analgesic activity in both tail immersion test (maximum elongations as 262.053%) and acetic acid-induced writhing method (66.02% writhing inhibition). During anti-diarrheal test, the plant samples significantly diminished the frequency of diarrheal episodes in mice. Similarly, the plant samples decreased the sleeping duration induced by thiopental sodium.ConclusionThe above outcome exposed that B. barbata possesses significant pharmacological potential, which validates its use in Bangladesh folk medicinal practices.

Analgesic and antiinflammatory activities of the capilliposide derived from Lysimachia capillipes Hemsl., a traditional Chinese medicinal herb

Pain and inflammation are associated with the pathophysiology of different clinical conditions. The Lysimachia capillipes Hemsl. capilliposide (LCc) is the main bioactive component of this Chinese medicinal herb, which is widely used as a remedy for the treatment of colds and arthritis. This study investigated the analgesic and antiinflammatory activities of LCc in an animal model. LCc had no significant influence on the spleen, lung, liver and stomach coefficients in mice. Pharmacological studies showed that LCc at all doses (40, 60 and 90 mg/kg) increased the latency period of paw licking induced by thermal stimulation, and at the dose of 40 mg/kg it significantly suppressed abdominal writhing episodes of mice induced by intraperitoneal (i.p.) injection of acetic acid. LCc also had antiinflammatory effect on inflammation models. Doses of 60 and 90 mg/kg suppressed paw edema induced by subcutaneous (s.c.) injection of carrageenan. Mechanistic studies revealed that the antiinflammatory effect of LCc was associated with inhibition of the production of malondialdehyde (MDA), prostaglandin E2 (PGE2), tumor necrosis factor (TNF-?), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in paw tissue of carrageenan-injected mice. These results show that LCc has analgesic and antiinflammatory effects in mice.

Antidiarrheal, Analgesic, and Anthelmintic Activities of Honeys in the Sundarbans Mangrove Forest, Bangladesh.

This study evaluated the antidiarrheal, analgesic, and anthelmintic activities of honey samples from the Sundarbans mangrove forest of Bangladesh. Composite raw honey (RH), and its diethyl ether (DEH), ethanol (ETH), methanol (MEH), and distilled water (DWH) fractions were investigated. RH and its fractions strongly inhibited castor oil-induced diarrheal episodes in mice at a concentration of 250 mg/kg body weight (b.w.) (P<0.05). At this concentration, RH, DEH, ETH, MEH, and DWH showed inhibitory activity on diarrheal episodes at 43.8, 47.4, 29.8, 12.3, and 38.5%, respectively, whereas for the inhibitory activity for the positive control (PC, 3 mg loperamide/kg b.w.) was 47.4%. Similarly, DEH (250 mg/kg b.w.) showed strongest inhibition (63.5%) of acetic acid-induced writhing in mice, followed by RH (55.7%), ETH (46.2%), MEH (37.6%), and DWH (32.9%). In a hot plate test, mice treated with DEH at a concentration 250 mg/kg b.w. showed the greatest increase in response time, followed by treatment with RH. RH was further used in an anthelmintic test, where it showed a strong dose-dependent reduction in both the paralysis time and the time until death of the parasite, Paramphistomum cervi. Honeys in the Sundarbans could therefore be of great use as nutraceuticals.

Exercise training prevents ventricular tachycardia in CPVT1 due to reduced CaMKII-dependent arrhythmogenic Ca2+ release.

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is caused by mutations in the cardiac ryanodine receptor (RyR2) that lead to disrupted Ca(2+) handling in cardiomyocytes and ventricular tachycardia. The aim of this study was to test whether exercise training could reduce the propensity for arrhythmias in mice with the CPVT1-causative missense mutation Ryr2-R2474S by restoring normal Ca(2+) handling. Ryr2-R2474S mice (RyR-RS) performed a 2 week interval treadmill exercise training protocol. Each exercise session comprised five 8 min intervals at 80-90% of the running speed at maximal oxygen uptake (VO2max) and 2 min active rest periods at 60%. VO2max increased by 10 ± 2% in exercise trained RyR-RS (ET), while no changes were found in sedentary controls (SED). RyR-RS ET showed fewer episodes of ventricular tachycardia compared with RyR-RS SED, coinciding with fewer Ca(2+) sparks and waves, less diastolic Ca(2+) leak from the sarcoplasmic reticulum, and lower phosphorylation levels at RyR2 sites associated with Ca(2) (+)-calmodulin-dependent kinase type II (CaMKII) compared with RyR-RS SED. The CaMKII inhibitor autocamtide-2-related inhibitory peptide and also the antioxidant N-acetyl-l-cysteine reduced Ca(2+) wave frequency in RyR-RS equally to exercise training. Protein analysis as well as functional data indicated a mechanism depending on reduced levels of oxidized CaMKII after exercise training. Two weeks of detraining reversed the beneficial effects of the interval treadmill exercise training protocol in RyR-RS ET. Long-term effects of interval treadmill exercise training reduce ventricular tachycardia episodes in mice with a CPVT1-causative Ryr2 mutation through lower CaMKII-dependent phosphorylation of RyR2.

Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus.

Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck is the difficulty in modeling depressive episodes in animals. Here, we show that a transgenic mouse with chronic forebrain expression of a dominant negative mutant of Polg1, a mitochondrial DNA (mtDNA) polymerase, exhibits lethargic behavioral changes, which are associated with emotional, vegetative and psychomotor disturbances, and response to antidepression drug treatment. The results suggested a symptomatic similarity between the lethargic behavioral change that was recurrently and spontaneously experienced by the mutant mice and major depressive episode as defined by DSM-5. A comprehensive screen of mutant brain revealed a hotspot for mtDNA deletions and mitochondrial dysfunction in the paraventricular thalamic nucleus (PVT) with similar defects observed in postmortem brains of patients with mitochondrial disease with mood symptoms. Remarkably, the genetic inhibition of PVT synaptic output by Cre-loxP-dependent expression of tetanus toxin triggered de novo depression-like episodes. These findings identify a novel preclinical mouse model and brain area for major depressive episodes with mitochondrial dysfunction as its cellular mechanism.

Pharmacological investigation of selected medicinal plants of Bangladesh

Purpose: To pharmacologically investigate the methanol and petroleum ether extracts of the plant leaves of Manilkara zapota (MZME and MZPE, respectively), Abroma augusta (AAME and AAPE, respectively) and Vitex negundo (VNME and VNPE, respectively).Methods: Analgesic and anti-diarrheal activities were assessed by acetic acid-induced writhing and castor oil-induced diarrhea in mice, respectively, while CNS depressant activity was evaluated using hole-cross and open-field method by observing the decrease in exploratory behavior and spontaneous motor activity in mice, respectively.Results: All the extracts exhibited good analgesic activity at a dose of 200 mg/kg with the following rank order of activity: MZME &gt; MZPE &gt; VNME &gt; VNPE &gt; AAME &gt; AAPE. Analgesic activity was insignificant at 100 mg/kg dose except for VNPE (67.81 % inhibition). The extracts produced significant reduction in diarrheal episodes in mice at a dose of 400 mg/kg MZPE (highest protection: 80.3 %, p &lt; 0.05) and VNME (lowest protection: 38.6 %, p &lt; 0.001). The extracts demonstrated CNS depressant activity in a dose-dependent manner (p &lt; 0.05 compared to the standard except for AAME and AAPE which showed insignificant activity).Conclusion: The results indicate that the traditional use of the investigated plants appears to be justified; however, further studies are required to unravel the underlying mechanisms of action.Keywords: Manilkara zapota, Abroma augusta, Vitex negundo, Analgesic, Central nervous system depressant, Anti-diarrhoeal

Experimental evaluation of antipyretic and analgesic activity of aspartame.

Sir, It has been reported that aspartame is biologically active and appears to relieve pain and induce mild antithrombotic effects in humans, and decrease fever in animals.[1] There is, however, a paucity of data about the biological effects of aspartame, which prompted us to undertake the present study, with a view to investigate the possible antipyretic and analgesic effects of aspartame and its comparison with conventional drugs. Albino Wistar rats of either sex (age 3-4 months, weight 200 g) were used to study the antipyretic effect, while adult mice of either sex, weighing 20-30 g, were used to study the analgesic effect. The care and maintenance of animals were as per the approved guidelines and the study was approved by the Institutional Animal Ethics Committee. Aspartame was obtained from Zydus Cadila (Ahmedabad, India). The antipyretic effect was evaluated by a 2-hour test using TAB vaccine (0.3 mL, i.p.). Rectal temperature was recorded using a clinical thermometer for a period of 2 minutes, both in basal state and at 30 minutes interval for 2 hours after the administration of vaccine. The animals were divided into five groups of 10 animals each. Group I received 0.3 mL distilled water (control). Groups II, III and IV received aspartame in a dose of 2, 4 and 8 mg/kg, respectively. Group V was administrated paracetamol (220 mg/kg). The reduction in mean rise of temperature was noted. The analgesic effect was studied by acetic acid induced writhing method.[2] Mice were divided into five groups of 10 animals each. Group I received 0.3 mL distilled water (control). Groups II, III and IV received aspartame in doses of 2, 4 and 8 mg/kg, respectively. Group V was given diclofenac 1 mg/kg by intraperitoneal route, 15 minutes prior to acetic acid injection. After intraperitoneal injection of 3% aqueous acetic acid (300 mg/kg), the mice were observed under a bell jar for a period of 20 minutes and the number of writhing episodes was noted. An average value for each group was calculated and subsequently used for comparison. In addition, protection provided by the test drugs was also calculated using the formula % protection =100 –number of writhes in experimental group × 100 number of writhes in control group Table 1 shows the effect of aspartame on rectal temperature of rats following administration of TAB vaccine. Aspartame showed a statistically significant (P < 0.001) antipyretic effect at all the doses used and this was comparable with paracetamol. Table 2 shows the effect of aspartame and diclofenac on acetic acid induced writhing episodes in mice. Aspartame in doses of 4 and 8 mg/kg showed statistically significant (P < 0.01) protection against writhing. Diclofenac, a potent analgesic compound, produced highly significant (P < 0.001) effect on writhing in doses of 1 mg/kg, i.p. Table 1 Mean rise of rectal temperature (°F) in rats Table 2 Effect of aspartame and diclofenac on acetic acid induced writhing episodes in mice In our study, we found that aspartame has highly significant antipyretic effect in doses of 2, 4 and 8 mg/kg. To our knowledge, there are no published reports of experimental evaluation of antipyretic effect of aspartame in this model. We also found that in doses of 4 and 8 mg/kg, aspartame showed a significant analgesic activity. Another study has shown that oral administration of aspartame (2-16 mg/kg) significantly increased the pain threshold against acetic acid induced writhing in mice.[3] In yet another study, it has been shown that aspartame attenuates mechanical allodynia in high doses (50 mg/kg).[4] Since this study was conducted in carrageenan-induced monoarthritis model, it appears that differences in the experimental models of evaluation of analgesic activity may account for the variation in effective doses. Interference with rheumatoid factor activity has been proposed to alleviate the pain and immobility resulting from chronic inflammation of joint.[5] In the acetic acid induced writhing method, nociceptive response involves release of endogenous substrates like bradykinin and prostanoids.[6] It is speculated that the antagonism of these chemicals may underlie the pain-relieving mechanism of aspartame. However, the exact mechanism of analgesic action of aspartame can be investigated by further pharmacological studies to overcome the limitations of current work. To conclude, aspartame is an intense nutritive sweetener, which is widely used by diabetic patients and overweight persons. Our study has demonstrated an antipyretic effect of aspartame and confirmed its analgesic effect in an experimental model. Further studies on biological effects of aspartame are required to explore its therapeutic potential as an antipyretic and analgesic agent.

Anti-inflammatory and analgesic properties of Drynaria quercifolia (L.) J. Smith

Drynaria quercifolia (L.) J. Smith (Polypodiaceae), has been widely used by ethnic groups of India to treat inflammation, rheumatism, headache, bone fracture, jaundice, etc. To evaluate the anti-inflammatory and analgesic properties of the ethanolic extract of rhizome of Drynaria quercifolia (DQ) and its phytochemical profile. DQ was used to evaluate the anti-inflammatory and analgesic effects using carrageenan-induced paw oedema/cotton pellet-induced granuloma in Wistar rats and acetic acid-induced writhing/formalin-induced paw licking test in Swiss albino mice respectively. Oral administration of DQ produced significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. DQ significantly attenuated acute and delayed phases of formalin-induced pain and acetic acid-induced writhing episodes in mice. The analgesia was comparable to that produced by sodium salicylate and aspirin respectively. Phytochemical analysis gave positive tests for catechin, coumarins, flavonoids, phenolics, saponin, steroids, tannins, and triterpenes. The total phenolics in DQ was 244 mg/g and naringin content was 0.048%. The results suggest the presence of potent anti-inflammatory and analgesic principles in DQ that justifies its use for alleviating painful inflammatory conditions.

Repeated brief social defeat episodes in mice: Effects on cell proliferation in the dentate gyrus

Stressful experiences can affect hippocampal structure and function and can suppress new cell birth in the adult hippocampus in several species. Here we examine how repeated intermittent social defeat affects cell proliferation in the dentate gyrus (DG) in mice. Adult male CFW mice were subjected to 10 daily social defeat episodes, 3 defeat episodes within one day or a single defeat episode. Intruder mice were injected with 5-bromo-2′-deoxyuridine (BrdU, 200 mg/kg, i.p.) 1 h after the last fight, and incorporation of BrdU into proliferating cells in the DG was quantified. In a third experiment, aggressive resident mice were allowed to fight with an intruder mouse every day for 10 days, and these residents were injected with BrdU 1 h after the last aggressive encounter. There was a significant decrease in cell proliferation in mice that received 10 social defeats, confirming and extending earlier results. This decrease is correlated with the intensity of the defeat experiences, as quantified by frequency of attack bites. Cell proliferation was slightly inhibited after a single defeat, although this effect was not significant. Three defeats within a 5-h period had no effect on levels of proliferation. Offensive aggressive stress in the residents did not result in any changes in hippocampal cell proliferation. These data indicate that repeated intermittent social defeat experienced over multiple days suppresses proliferation in the DG, and this may have important implications for our understanding of hippocampal changes related to stress psychopathologies.

Hyperactive and anxious phenotype following brief ischemic episodes in mice

Post-stroke emotional and behavioural abnormalities include a wide range of emotional and cognitive disturbances and have significant impact on long-term outcome. In animals models of stroke however there is little evidence of possible behavioural correlates of such post-stroke neuropsychiatric conditions. Here, we tested whether mild focal brain ischemia induces long-term behavioural changes and neuropsychiatric outcome in mice. 129/SV wild-type mice were anesthetized with isofluorane and subjected to 30 min filamentous occlusion of the left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 10 animals per group). Eight weeks after MCAo, animals were consecutively subjected to three behavioural tests, i.e. (1) spontaneous locomotor activity testing (day 56), (2) the elevated plus-maze (day 63 and (3) the modified Porsolt forced swim test (on day 70). We present evidence that mild cerebral ischemia is associated with increased spontaneous locomotor activity (right MCAo > left MCAo > sham) and with post-stroke anxiety (left MCA > right MCAo > sham), but we obtained no evidence of a post-stroke depressive phenotype. Noradrenaline levels were significantly increased by 30 – 45% in the ischemic striatum and significantly correlated with locomotor activity (r = 0.48) while the levels of dopamine and homovanillinic acid were decreased compared to sham operated animals. The ischemic lesion was confined to the ipsilateral striatum and scattered neuronal death was observed in a number of remote brain regions. In conclusion, brief ischemic episodes induce an hyperactive, anxious but not depressive phenotype in mice, that may relate to left versus right hemispheric lesion location, specific alterations in brain monoamine levels and selective neurodegeneration.

Anxious and Hyperactive Phenotype Following Brief Ischemic Episodes in Mice

Poststroke emotional and behavioral abnormalities have an impact on outcome but have scarcely been characterized in animal models. We tested whether brief ischemic episodes induce behavioral changes in mice. 129/Sv mice were subjected to 30-min occlusion of left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 9 or 10 per group). Eight to ten weeks later, mice were tested for spontaneous locomotor activity, anxiety in the elevated plus maze, and depressive behavior in the modified Porsolt forced swim test. Outcome was correlated to monoamine and amino acid levels and compared with histologic damage at 10 weeks. Ischemia was associated with increased activity (right MCAo) and anxiety (left MCAo), but not poststroke depression. Noradrenaline increased by 30%-45% in the ischemic striatum and correlated with locomotor activity (r = .48); dopamine and homovanillinic acid were decreased compared with sham. The lesion was confined to the striatum, and scattered neuronal death was observed in a number of remote brain regions. Brief ischemic episodes in the mouse induce an anxious, hyperactive but not depressive phenotype that may relate to left versus right hemispheric lesion location, alterations in brain monoamine levels, and selective neurodegeneration.

Preliminary pharmacological studies on Piper chaba stem bark

Piper chaba Hunter (Piperaceae) is a common pepper in the southern part of Bangladesh. Various parts of this plant have been extensively used in different traditional formulations including ayurveda. In order to rationalize the ethnomedical uses of this plant in a number of ailments, the methanol extract of the stem bark was subjected to preliminary evaluation for analgesic, anti-inflammatory, diuretic, anti-diarrhoeal, effect on gastrointestinal motility and CNS depressant activity in mice and rat at 125, 250 and 500 mg/kg body weight doses. The extract at given doses significantly and dose dependently reduced the frequency of acetic acid induced writhing in mice, prolonged the tail flicking latency in mice, reduced Carrageenan-induced paw edema volume in rat, delayed the onset as well as reduced the frequency of castor oil induced diarrhoeal episodes in mice, decreased gastrointestinal motility as assessed by the charcoal motility test in mice and prolonged pentobarbitone induced sleeping time in mice. However at the same doses, the extract exhibited moderate diuretic activity only at the highest dose.

Altered distribution and toxicity of digitoxigenin in fasted mice

Intravenous administration of digitoxigenin (DTXGN) evokes seizure episodes in mice which may be dependent on brain biogenic amines such as serotonin (5-HT). Fasting is known to have effects on both drug toxicity and brain 5-HT synthesis. The purpose of this study was to assess the effects of overnight fasting on DTXGN toxicity. The i.v. LD-50 of DTXGN was increased by 61% in fasted mice. Adjustment of DTXGN dose for the decrease in body weight of fasted mice did not alter the fasting induced protection. A loading dose of 1-tryptophan (25 mg/kg, i.p.) did not alter mortality rates in either fed or fasted mice. Cortical levels of 3H-DTXGN were decreased significantly by 25% in fasted mice. Liver and blood levels were elevated significantly. These data suggest that decreased DTXGN toxicity is associated with a decrease in its distribution to the cerebral cortex and emphasize the importance of acute dietary status in the expression of drug toxicity.

Genetically determined spontaneous and pentylenetetrazol-induced brief spindle episodes in mice

Regular 7 s , 1- to 5-s bursts of high-amplitude spindles were observed in the cortical electroencephalogram of DBA mice. We named these bursts “brief spindle episodes” (BSE). The BSEs were bilaterally symmetrical and could be seen to occur earlier in more frontal derivations. BSEs appeared to actively suppress overt body movement, though some facial twitching could be observed. Two convulsant agents, pentylenetetrazol (PTZ) and picrotoxin, provoked BSE activity; a third, nicotine, suppressed BSE activity at both sub- and supraconvulsant doses. Three other inbred mouse strains were also tested for BSE occurrence. Two, C57BL 6 and BALB c mice, failed to show BSE activity either spontaneously or after PTZ. The third strain, C3H, showed lower-amplitude, shorter-duration, and less well-organized BSE activity spontaneously and after PTZ. Juvenile DBA mice (21 to 25 days) showed slower, lower-amplitude, shorter-duration BSEs than did adults. Older mice (31 to 36 days) showed more adult BSEs. The possibility that BSEs are an epileptic phenomenon is discussed. It is clear that they are a genetically determined electroencephalographic characteristic that may provide a useful tool for studying genetic determination of nervous system functioning as well as mechanisms of cortical hypersynchrony.