Band 28, Heft 2

Background: Several preclinical studies have shown that serotonergic 5-HT 3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound “6n” (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT 3 receptor antagonist with an optimal log P (2.52) and pA 2 (7.6) value was screened for its neuro-pharmacological potential in chronic rodent models of depression and anxiety named traumatic brain injury (TBI). Methods: In this model, a 1 cm midline scalp incision was made, and the muscles were retracted to expose the skull. A stainless steel disc (10 mm in diameter and 3 mm in depth) was placed centrally between the lambda and bregma regions. The injury was induced using the impact acceleration model of TBI. Specifically, a 400 g metal weight was dropped from a height of 1 m guided by a straight pipe, onto the metal disc placed over the rat’s skull. Results: The behavioral anomalies of the TBI rats were attenuated by the chronic treatment of compound 6n (1 and 2 mg/kg, p.o.; 14 days) as observed by the modified open field test (ambulation, rearing, and fecal pellet), sucrose consumption test (% sucrose consumption), elevated plus maze [% open arm entries [OAE] and % time spent in open arm (TSOA)], and marble burying test (numbers). In addition, 6n also increased the levels of neurotransmitters (norepinephrine and serotonin) and brain derived neurotrophic factor (BDNF) in TBI rats. Conclusions: The result suggests that compound 6n exhibited antidepressant- and anxiolytic-like effects in rodent models of depression and anxiety.

Background: 5-HT 3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT 3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and p A 2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. Methods: LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. Results: The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS-induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. Conclusions: Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain.

Background: Diabetes mellitus (DM) of juvenile onset affects both the peripheral and central nervous systems (CNS). However, central effects are less documented and studied than peripheral deficits. Currently, the only feasible treatment available for type 1 DM (T1DM) is insulin which has its own limitations. Hence, an alternative therapy, especially a newer herbal formulation is very much the need of the time. The present study aimed to determine the effects of the alcoholic extracts of roots of the Salacia reticulata W. (SR) and Clitoria ternatea L. (CT) on cognitive and behavioral changes in juvenile diabetic rats. Methods: Diabetes was induced in 25-day-old Wistar rats by streptozotocin (50 mg/kg bw, IP). Animals were divided into seven groups (n=6). Rats were treated with root extracts of SR and CT (100 mg/kg BW each) for 30 days, from day 1 and day 20 of diabetes confirmation. Then, rats were tested in elevated plus maze (EPM) and Morris water maze (MWM). Results: A statistically significant (p<0.05) difference was observed between the SRCT group and diabetic groups of rats. Apart from decreasing FBS, the combined therapy also proved beneficial as nootropic agent in rats with early-onset diabetes. However, significant improvement is observed only in the learning and memory among preventive group, but not in the curative group. Conclusions: SRCT, a herbal formula, when used in combination, has a more potent effect in preventing the deleterious effects of juvenile diabetes on cognitive and behavioral changes.

Background: The superior genus Jacquemontia belongs to Convolvulaceae, with around 120 species, and is also considered taxonomically difficult. The aim of this experiment was to assess the sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f. Methods: The sedative and hypnotic activities were evaluated by hole-cross, open field, hole-board, elevated plus maze (EPM), and thiopental sodium-induced sleeping time determination tests in mice at doses of 200 and 400 mg/kg. Results: In this investigation, we found that methanol extract of Jacquemontia paniculata (MEJP) produced a significant dose-dependent inhibition of spontaneous activity of mice both in hole-cross and open field tests. In addition, it also decreased the number of head dips in hole-board test. In the case of EPM test, this crude extract induced an anxiogenic-like effect rather than anxiolytic effect in mice. Moreover, MEJP significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Conclusions: To conclude, these results suggest that the MEJP leaves possess potent sedative and hypnotic activities, which supported its therapeutic use for sleep disorders like insomnia.

Background: The folkloric use of Bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders and as an anti-poison is a generally acceptable practice in the Niger Delta area of Nigeria. The testicular dysfunction induced by BLCO exposure is of public concern with a view to its folkloric usage. The present study investigated the effects of BLCO exposure and withdrawal on the levels of testicular stress proteins and apoptosis-related proteins in rats. Methods: Adult male Wistar rats were exposed to 800 mg/kg body weight of BLCO for 7 days. One-half of the rats in each group were sacrificed on day 8, while the remaining one-half stayed an additional 45 days without treatment. Results: Western blot analysis showed that administration of BLCO resulted in a significant increase in the levels of stress proteins and apoptosis-related proteins by 50% and above relative to control, except cytosolic nuclear factor-κB (NF-κB), which decreased significantly relative to control. This was followed by a concomitant increase in the expression of caspase-3, FasL, and NF-κB by immunofluorescence staining within the testicular germ cells. Apoptosis showed a significant increase in TUNEL-positive cells. Following withdrawal of treatment, BLCO-mediated alteration in stress proteins and induction of apoptosis persisted relative to control. Conclusions: Collectively, BLCO induced irreversible alteration in testicular stress proteins and apoptosis in rats within the time course of investigation. These findings highlight the potential long-term adverse effects of BLCO on individuals unduly exposed to BLCO.

Background: Literature has shown a significant association between asthma exacerbations and pollutant levels during that time. There is very limited evidence in India, especially Bangalore, for impacts of meteorological changes and pollution on asthma hospital admissions in adults. The objective was to study the impact of air pollution and meteorological parameters on asthma exacerbation in Bangalore. Methods: This study quantitatively analyzed the relation between acute exacerbations of asthma and related admissions to the hospital with the air pollution and the meteorological conditions during that time. Data regarding the daily hospital admissions in about 13 tertiary care centers in Bangalore, Karnataka and air pollutant levels and the meteorological conditions prevailing during each day over a year were collected from the Karnataka State pollution control board and meteorology departments, respectively. Results: An average daily asthma admission of 4.84±2.91, with clear seasonal variation and autocorrelations between meteorological parameters and pollutants was observed. Multiple linear regression analysis revealed that average temperature (p=0.005) and nitrogen dioxide (NO 2 ) (p=0.034) were the two factors that were affecting the number of admissions. Quasi-poisson regression analysis using multi-pollutants and meteorological variables showed that particulate matter and NO 2 had significant lag effect for up to 5 days (p<0.05) and rainfall for 1 day (p<0.001). Conclusions: In Bangalore city, levels of NO 2 and particulate matter, temperature, rainfall, and season increase asthma exacerbations.

Background: This study was conducted to determine the antioxidant and acetylcholinesterase inhibitory activities of the leaf extract and different fractions of Albizia adianthifolia (Schumach.) W. Wright, and also to identify and quantify some phenolic compounds in the extract. Methods: The antioxidant and acetylcholinesterase inhibitory activities of the methanol extract (CME), ethyl acetate (EAF), chloroform (CHF), and n -hexane (NHF) fractions of A. adianthifolia leaves were subjected to in vitro chemical analyses. Results: Phytochemical screening revealed important classes of secondary metabolites. All extracts showed good antioxidant and acetylcholinesterase inhibitory activities. The EAF and CHF gave the highest total phenolic contents of 18.02±0.14 and 18.43±0.95 mg gallic acid equivalent per gram of extract, respectively. The polar extracts gave the highest activity in both assays with lower IC 50 values. In the 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging activity assay, the IC 50 values of CME, EAF, CHF, and NHF were 77.74±0.84, 55.76±2.30, 58.47±0.72, and 232.24±2.70 µg/mL, respectively, while in the acetylcholinesterase inhibitory assay, the IC 50 values of CME, EAF, CHF, and NHF were 11.80±0.88, 10.04±1.67, 17.44±1.74, and 124.38±1.51 µg/mL, respectively. Conclusions: The results of this study suggest that the leaf of A. adianthifolia could serve as a potential candidate for future search of antioxidant and acetylcholinesterase inhibitors for the management of neurodegenerative disorders such as Alzheimer’s disease.

Background: Dimethylnitrosamine (DMN) is a waste product of several industrial processes. α-Lipoic acid (ALA) is a vitamin-like chemical also called as an antioxidant. Therefore, the study was designed to investigate the potential benefits of ALA in reducing the nephropathy of DMN in male mice. Methods: Animals were divided into 6 groups (n=8) and received their treatment for 4 weeks as follows: groups 1–4 served as control, ALA-treatment (16.12 mg/kg), DMN low dose treatment and DMN high dose treatment, respectively. Groups 5 and 6 received ALA before DMN low dose and DMN high dose, respectively. Superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase, total antioxidant capacity, nitric oxide, lipid peroxidation as well as the levels of uric acid and creatinine were determined. The histological and ultrastructure changes of renal tissue were also evaluated. Results: Treatment of the DMN mice with ALA showed a reduction in the levels of kidney nitric oxide, lipid peroxidation, as well as creatinine and uric acid levels as compared with the DMN group. The results show that ALA plays an important role in quenching the free radicals resulting from the metabolism of DMN, thereby inhibiting lipid peroxidation and protecting membrane lipids from oxidative damage and, in turn, preventing oxidative stress and apoptosis. Histopathological and ultrastructure analysis of renal tissue confirmed the oxidative stress results occurred in DMN renal mice. Concomitant administration of ALA with DMN significantly decreased all the histopathological changes induced by DMN. Conclusions: The present study elucidated the therapeutic effects of ALA administered in combination with DMN to minimize its renal toxicity.

Background: Thyroid hormones are effective on oxidant-antioxidant balance by leading basal metabolic rate. In this study, the effects of altered thyroid states on low density lipoprotein (LDL) oxidation and oxidative stress parameters were investigated in an experimental animal model. Methods: Thirty female Wistar Albino rats were equally divided into 3 groups as follows: control group; hypothyroid group (methimazole (75 mg/100 g was added to diet); hyperthyroid group [ L -thyroxine (0.4 mg/100 g was added to diet)]. Oxidized LDL (ox-LDL) levels, thyroid, and lipid parameters were determined in serum. Also lipid peroxidation (LPO), sialic acid (SA) and glutathione levels (GSH), as well as superoxide dismutase (SOD) and catalase (CAT) activities were determined in tissue samples. Results: A significant increase in lipid parameters was observed in hypothyroid group, whereas these parameters were decreased in hyperthyroid group compared to control group. For ox-LDL levels, a significant increase was observed both in hypothyroid and hyperthyroid groups. In brain, liver and kidney tissues, LPO and SA levels were increased, whereas GSH levels were decreased both in hypothyroid and hyperthyroid groups. The SOD and CAT activities were significantly decreased in hypothyroid group, however, they were increased in hyperthyroid group compared to control group. Both hypothyroid and hyperthyroid conditions modify the oxidant-antioxidant state in serum and tissues. Conclusions: Increased SOD and CAT activities in hyperthyroid group suggest that elevated thyroid hormones can reduce oxidative stress by maintaining antioxidant defense and they might have a protective effect on some tissues against oxidants.

Background: Smoking has a thermogenic effect and is associated with low physical performance. Nevertheless, a direct, quantitative effect of acute smoking on exercise heat tolerance has not been reported. Methods: Sixteen healthy young male volunteers, eight cigarette smokers, and eight non-smokers participated in the study. All subjects performed a maximal oxygen consumption test (VO 2max ) and a standardized heat tolerance test (HTT) after at least 12 h without smoking under the following conditions: no nicotine exposure, 10 min after nicotine exposure (2 mg nicotine lozenge), and 10 min after smoking two cigarettes (0.8 mg nicotine in each cigarette, smokers only). Results: There was no significant effect of nicotine exposure on physiological performance and heat tolerance in the non-smokers group. In the smokers group, cigarette smoking, but not nicotine ingestion, resulted with higher heart rate (by 9±9 bpm) at the end of the HTT (p<0.05). Moreover, both smoking and nicotine ingestion increased smokers’ rectal temperature at the end of the HTT (by 0.24±0.16°C and 0.21±0.26°C, respectively, p<0.05) and were associated with higher sweat rate during the HTT (by 0.08±0.07 g/h and 0.06±0.08 g/h, respectively, p<0.05). Heart rate variability (HRV) analysis also revealed a higher LF/HF (low frequency/high frequency) ratio after exposure to nicotine and smoking in the smokers group compared with no exposure (2.13±2.57 and 2.48±2.76, respectively, p<0.05), indicating a higher sympathetic tone. Conclusions: According to this preliminary study, cigarette smoking and nicotine ingestion increase the physiological strain during a HTT in smokers. Acute smoking may, therefore, increase heat intolerance and the risk to heat injuries.

Background: This study aims to evaluate the scientific basis of traditional application of Persicaria orientalis for reducing pain and inflammation. Methods: An in vitro method was performed to investigate the presence of the anti-inflammatory activity of methanolic crude extract of P. orientalis . In addition, an in vivo study was conducted in which the hot-plate and tail immersion methods were applied to explore the acute effect of P. orientalis on analgesia. The potency to inhibit chronic inflammation in mice was justified by the carrageenan-induced paw edema and formalin-induced edema methods. For all in vivo testing in animal models (albino mice and rats), plant extract was given via the oral route at doses of 250 mg/kg and 500 mg/kg. Results: The methanolic extract of P. orientalis produced a significant (p<0.001) inhibition of analgesia with a prolongation of pain response time by 61.80% at 500 mg/kg. The extract also exhibited a potential anti-inflammatory (56.99%) effect, which was also statistically significant (p<0.001). The present study suggests that the methanolic extract of P. orientalis has potential anti-inflammatory as well as analgesic activity and this extract is effective in the treatment of both acute and chronic pain. Conclusions: Our current study revealed pharmacological properties of the methanolic extract of P. orientalis and also gave a solid scientific platform against its traditional use. The protecting ability of P. orientalis against inflammatory stimuli may be due to phenolic or flavonoid compounds which we have found through phytochemical analysis.

Background: The root of Icacina senegalensis is used for the treatment of malaria and related conditions in southeastern Nigeria. Methods: To establish its efficacy, the ethanolic root bark extract was investigated as antiplasmodial agent against Plasmodium berghei in mice. A 4-day suppressive test and the curative effect against established infection models of antiplasmodial studies were used. Results: The root bark extract of I. senegalensis (50, 100, and 200 mg/kg) exhibited a significant (p<0.05) dose-dependent activity against the parasite based on suppressive and curative study. The antimalarial effect of I. senegalensis is compared with that of chloroquine (10 mg/kg), the standard drug. The ethanolic root bark extract also prolonged the survival time of infected mice. Conclusions: The results showed that the root bark extract possesses a potential antiplasmodial activity, which can be exploited for the possible development of new antimalarial agent.

Background: Synthetic drugs are going to be replaced by plant-derived traditional drugs due to their cost effectiveness, relatively less harmfulness, and efficacy against multidrug resistance organisms. Hygrophila spinosa (Acanthaceae) has been used in a wide range of ailments including flatulence, diarrhea, dysentery, gonorrhea, and menorrhagia. Therefore, we investigated the cytotoxic, antinociceptive, and antidiarrheal effects of H. spinosa ethanol extract (EExHs). Methods: Preliminary phytochemical screening was accomplished by established methods modified in experimental protocol. EExHs was undertaken for cytotoxic assay by Brine shrimp lethality bioassay, antinociceptive action by acetic acid induced writhing test, and antidiarrheal activity by castor oil induced antidiarrheal test. Data were analyzed by GraphPad Prism 6.0 software using Dunnett’s test for multiple comparisons. Results: Reducing sugar, steroid, glycoside, tannin, alkaloid, saponins, and flavonoids were found to be present in EExHs. Lethal concentration (LC 50 ) of EExHs for brine shrimps was 50.59 µg/mL which was relatively lower than that of the standard drug vincristine sulfate. In acetic acid induced writhing test, oral administration of EExHs at three different doses (125, 250, and 500 mg/kg) decreased writhing in dose-dependent manner while the highest dose (500 mg/kg) achieved the maximum percentages of pain inhibition (58.8%). Diclofenac sodium (25 mg/kg) was used as a reference antinociceptive drug. The antidiarrheal action of EExHs was not found to be very promising for further use; however, the pure compounds from EExHs could be analyzed to justify the effects. Conclusions: This research demonstrates that the secondary metabolites guided cytotoxic and analgesic effects could be extensively studied in multiple models to confirm the effects.