Ahsana Dar

The antinociceptive activity of Polygonatum verticillatum rhizomes in pain models

AIM OF THE STUDY The current study was designed to establish the pharmacological rationale for the traditional use of the rhizomes of Polygonatum verticillatum in the treatment of painful conditions and as a plant diuretic. MATERIALS AND METHODS The crude methanolic extract of the rhizomes of Polygonatumverticillatum (PR) was tested in various established pain models in rodents at 50, 100 and 200mg/kg i.p. while the diuretic activity was assessed at 300 and 600 mg/kg p.o. in rats. RESULTS PR demonstrated significant reduction (14-72%) in the number of writhes induced by acetic acid in a dose-dependent manner. When nociceptive threshold was measured in the formalin test, PR strongly attenuated the formalin-induced flinching behaviour in both phases (6-30% in first phase while 12-72% in second phase). Central involvement in the analgesic profile of PR was confirmed by the hot plate test, in which PR elicited a significant (P<0.01) analgesic activity by increasing latency time. However, an opioid receptor antagonist, naloxone (2mg/kg s.c.) strongly antagonized the antinociceptive activity of PR. As a plant diuretic, PR showed mild but statistically insignificant diuretic activity at 300 mg/kg. The crude extract and solvent fractions of the plant contained reasonable quantity of total saponin and alkaloid contents. CONCLUSIONS The mechanisms underlying the analgesic action of PR shows that the opioid dependant central mediation has synergistic effect by enforcing the peripheral analgesic effects. Interestingly, our findings not only substantiated the folk use of the plant as an analgesic but also reported for the first time in the whole genus.

Calcium antagonistic activity of Bacopa monniera on vascular and intestinal smooth muscles of rabbit and guinea-pig

The present study demonstrates the calcium antagonistic activity in ethanol extract of Bacopa monniera. The plant extract inhibited the spontaneous movements of both guinea-pig ileum (IC50 = 24+/-4 microg/ml) and rabbit jejunum (IC50 = 136+/-9 microg/ml). A marked reduction in acetylcholine- and histamine-induced responses (0.0001-10 microM) in the ileum was evident in the presence of extract (260 microg/ml). The acetylcholine (1 microM)-induced contraction in the ileum was also inhibited by the extract (100-700 microg/ml) in a concentration dependent way (IC50 = 285+/-56 microg/ml). All these results indicate a direct action of the extract on smooth muscles. Calcium chloride-induced responses in the rabbit blood vessels and jejunum were attenuated in the presence of plant extract (10-700 microg/ml) implying a direct interference of plant extract with influx of calcium ions in the cells. However, the lack of modification of either noradrenaline- or caffeine-induced contractions in the presence of extract suggests that extract has no detectable effect on mobilization of intracellular calcium. These results indicate that spasmolytic effect of the B. monniera extract in smooth muscles is predominantly due to inhibition of calcium influx via both voltage and receptor operated calcium channels of the cell membrane.

Behavioral and biochemical studies of dichloromethane fraction from the Areca catechu nut.

The dichloromethane fraction from Areca catechu was found to inhibit monoamine oxidase type A isolated from the rat brain with an IC50 of 665 +/- 65.1 microg/ml. Studies with pharmacological models of depression, i.e., forced swim and tail-suspension tests, indicated that it caused significant reduction in the immobility time similar to that of moclobemide (a selective inhibitor of MAO-A) without causing a significant change in motor performance. Alkaloids such as arecaidine, arecoline, and a few other constituents, reported to be present in Areca catechu were also tested, but none of them were found to inhibit MAO. Present study suggests that the dichloromethane fraction from A. catechu possesses antidepressant property via MAO-A inhibition.

Relaxant effect of ethanol extract of Bacopa monniera on trachea, pulmonary artery and aorta from rabbit and guinea-pig

The relaxant action of an ethanol extract of Bacopa monniera was examined on ring segments of pulmonary arteries (guinea‐pig and rabbit), aorta (rabbit) and tracheal preparations (guinea‐pig). The plant extract induced relaxation in all the tissues in a dose‐dependent manner. Guinea‐pig main pulmonary artery was found to be the most responsive to the plant extract, however, complete relaxation was obtained in the tracheal preparations. The relaxant response to the plant extract was unaffected by pretreatment of the blood vessels with either atropine or propranolol, whereas in the tracheal preparations propranolol partially blocked the response. Indomethacin reduced the plant extract‐induced relaxation in all the tissues. In blood vessels relaxation induced by the plant extract was not modified in the presence or absence of the endothelial layer. These results suggest that relaxation induced by Bacopa monniera possibly involves prostacyclin compounds (in all the tissues) and β‐adrenoceptors (in tracheal preparations). Furthermore, this relaxation is independent of endothelium and muscarinic receptors activation.

Broncho-vasodilatory activity of fractions and pure constituents isolated from Bacopa monniera

The present study demonstrates that various fractions and sub-fractions isolated from Bacopa monniera produced significant inhibition of carbachol-induced bronchoconstriction, hypotension and bradycardia in anaesthetized rats. All these showed more potency towards inhibition of tracheal pressure compared to either blood pressure or heart rate. The sub-sub fraction and compound 1 caused greater inhibition of tracheal pressure and heart rate compared to blood pressure. Thus, overall bioassay-directed fractionation of B. monniera improved the bronchodilatory activity in various fractions and compound 1 (2-219x) in anaesthetized rats. In vitro, the KCl-induced contraction was equally inhibited by crude extract, petroleum ether and methanol fractions on trachea suggesting bronchodilatory activity remained the same in fractions. On pulmonary artery petroleum ether, dichloromethane and methanol fractions produced 2-2.6 times more vasodilatation compared to crude extract of B. monniera. Subsequent sub-fractions failed to show the existence of broncho-vasodilatory activity, however, the CHCl(3)/MeOH sub-fraction significantly reduced the acetylcholine-induced contraction on ileum. Both the methanol fraction and CHCl(3)/MeOH sub-fraction caused marked reduction of barium chloride-, potassium chloride- and calcium chloride-induced contraction on guinea-pig ileum, indicating their interference with Ca(2+) ion movement. Thus, it may be concluded that various fractions derived from B. monniera possess broncho-vasodilatory activity, which is attributed mainly to inhibition of calcium ions.

A study on antioxidant, free radical scavenging, anti-inflammatory and hepatoprotective actions of Aegiceras corniculatum (stem) extracts

AIM OF THE STUDY The present study was conducted to evaluate the antioxidant, anti-inflammatory and hepatoprotective potential of Aegiceras corniculatum Linn. Blanco (Aegicerataceae). METHODS AND RESULTS The n-hexane, ethyl acetate and methanol extracts, derived from Aegiceras corniculatum stems, scavenged superoxide anions (O2*) and hydroxyl radicals (*OH) in nitro blue tetrazolium reduction and deoxyribose degradation assays, respectively. All the extracts inhibited the process of lipid peroxidation at its initiation step. Additionally, in rat liver microsomes n-hexane and ethyl acetate extracts also caused termination of radical chain reaction supporting their scavenging action towards lipid peroxy radicals (LOO*). Moreover, increased production of O2* in human neutrophils, stimulated by phorbol-12-myristate-13-acetate (PMA) and/or opsonized zymosan were also suppressed (IC50 approximately 3-20 microg/mL). Thereby, revealing the ability of plant extracts to antagonize the oxidative stress via interference with NADPH oxidase metabolic pathway. These in vitro results coincide with the reduction in the glucose oxidase-induced paw edema in mice in the presence of ethyl acetate and methanol extracts (10, 50, and 100mg/kg, i.p.). Plant extracts (250, 500 and 1000 mg/kg, p.o.) also significantly protected the carbon tetrachloride (CCl4)-induced oxidative tissue injury in rat liver. This was reflected by a approximately 60% decline in the levels of serum aminotransferase enzymes. CONCLUSION Aegiceras corniculatum extracts found to possess pronounced antioxidant effect that may be at least in part related to its anti-inflammatory and hepatoprotective activities. This study provides a scientific basis for the ethnomedical claims that Aegiceras corniculatum is effective against inflammation and liver injury.

Synthesis and Biological Screening of 2-Substituted 5,6-Dihydro-5-oxo- 4H-1,3,4-oxadiazine-4-propanenitriles and of Their Intermediates

To evaluate the effect of substituents on biological activities of electron-rich N-containing heterocycles, the variably 2-substituted 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles 26–33 were synthesized and evaluated for antibacterial, antifungal, and enzyme-inhibition activities. The target compounds were obtained from alkyl 4- or 3-hydroxy benzoates 1 and 2, respectively, and from methyl indoleacetate 3. The phenolic OH group of benzoates 1 and 2 were substituted with p-toluenesulfonyl (4 and 5), benzoyl (6 and 7), and benzyl groups (8 and 9) and then converted to 5,6-dihydro-5-oxo-4H-1,3,4-oxadiazine-4-propanenitriles. To establish structure-activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO-A inhibiting properties and intermediates 12, 24, 28, and 29 appreciable antifungal activities. Compound 7 inhibits α-chymotrypsin.

Antidepressant Effects of Ethanol Extract of Areca catechu in Rodents

We report on the antidepressant activity in the ethanol extract of Areca catechu. Antidepressant activity was evaluated in rodents using the forced swimming and tail suspension tests. The ethanol extract (4–80 mg/kg) caused a significant reduction in the immobility time without effecting the spontaneous motor activity. Our findings suggest that the ethanol extract possesses antidepressant activities.

In-vitro assessment of cytotoxicity of halloysite nanotubes against HepG2, HCT116 and human peripheral blood lymphocytes

Halloysite is a clay mineral with chemical similarity to kaolin, a pharmaceutical ingredient. It consists of mainly aluminosilicate nanotubular particles in the size range of ∼ 200-1000 nm. Many studies have tried to empirically explore this novel clay for its potential in drug delivery systems but no work has yet studied its cytotoxicity from the perspective of oral drug delivery system. In this study, the halloysite nanotubes (HNTs) were subjected to size distribution analyses, which reveal more than 50% of nanotubes in the size range of 500 nm and rest mainly in the sub micrometer range. HNTs were then evaluated for in-vitro cytotoxicity against HCT116 (colorectal carcinoma) and HepG2 (hepatocellular carcinoma) cells which represent the earliest entry point and the first accumulating organ, respectively, for nanoparticles en-route to systemic circulation after oral delivery. Moreover, HNTs were tested for their cytogenetic toxicity against human peripheral blood lymphocytes. Both these results collectively indicated that HNTs are generally safe at practical concentrations of excipients for oral dosage forms.

Potential antidepressant activity of Areca catechu nut via elevation of serotonin and noradrenaline in the hippocampus of rats.

The current study was aimed at investigating the potential antidepressant activity of Areca catechu nut ethanol extract and its various fractions using behavioral (acute and sub‐chronic forced swim tests) and biochemical (monoamines and their metabolite levels using high performance liquid chromatography) tests. The areca nut ethanol extract and its aqueous fraction exhibited antidepressant activity in both acute and sub‐chronic forced swim tests (IC50 ~ 50 and 20 mg/kg, respectively), which was further confirmed by unaltered locomotor (horizontal and vertical) activities of rats in the activity cage. Phytochemical analysis revealed that saponins of areca nut may be the active component in its antidepressant action. The rats treated sub‐chronically with areca nut extract displayed toxic effects, whereas its active aqueous fraction was non‐toxic, indicating the presence of different constituents for antidepressant and toxic effects. In the hippocampus of rats, the areca nut extract (50 mg/kg) and aqueous fraction (20 mg/kg) caused a significant elevation of serotonin (around 35%) and noradrenaline (around 30%) compared with the control (261 ± 25 and 512 ± 29 ng/g, respectively). In conclusion, the areca nut possesses potential antidepressant effect via the elevation of serotonin and noradrenaline. Copyright