Volume 30, Issue 4

Neurons have been considered the major functional entities of the nervous system that are responsible for most of the functions even though glial cells largely outnumber them. However, recent reports have proved that glial cells do not function just like glue in the nervous system but also substantially affect neuronal function and activities, and are significantly involved in the underlying pathobiology of various psychiatric disorders. Dysfunctional astrocytes and degeneration of glial cells are postulated to be critical factors contributing to the aggravation of depressive-like symptoms in humans, which was proved using animal models. Alteration in glial cell function predominantly targets three main brain regions – the prefrontal cortex, limbic areas including the hippocampus, and the amygdala, which have been extensively studied by various researchers across the globe. These studies have postulated that failure in adopting to the changing neurophysiology due to stress will lead to regressive plasticity in the hippocampus and prefrontal cortex, but to progressive plasticity in the amygdala. In this present review, an effort has been made to understand the different alterations in chronic stress models in correlation with clinical conditions, providing evidence on the defective maintenance of glial function and its potential role in the precipitation of neuropsychiatric disorders.

Background Natural medicinal plants have been the focus of current research for developing neuroprotective agents to be used in the diabetes-linked cognitive dysfunction. Trigonella foenum-graecum seeds (known as fenugreek, methi in Hindi), is a well-known traditional medicinal herb and possesses anti-diabetic, anti-oxidant, and anti-inflammatory properties. Purpose This study was undertaken to explore the ameliorative effects of T. foenum-graecum seed extract on diabetes-induced cognitive dysfunction. Methods Experimental diabetes was induced by administering a single dose of streptozotocin (60 mg/kg) through intraperitoneal dose. Cognitive function was assessed using a T-maze and the Morris water maze. Lipid peroxidation levels and oxidative stress in the hippocampus was measured. Quantification of hippocampal CA1 and CA3 regions was done using cresyl violet stain. Results Diabetic rats demonstrated learning and memory impairment, which was evident from poor performance in behavioral tasks, i.e. T-maze and Morris water maze tasks. Learning and memory impairment in diabetic animals is associated with increased blood glucose levels, increased oxidative stress in the hippocampus and decreased number of neurons in the CA1 and CA3 regions of the hippocampus. The diabetic rats administered with T. foenum-graecum showed improved performance in behavioral tasks, and these changes were associated with decreased blood glucose levels, decreased oxidative stress in the hippocampus, and decreased neuronal loss from the CA1 and CA3 regions of the hippocampus. Conclusion In conclusion, administration of T. foenum-graecum seed extract ameliorates diabetes-linked cognitive dysfunction in rats by decreasing blood glucose levels, reducing lipid peroxidation and oxidative stress in the hippocampus, and preventing neuronal loss from the hippocampus.

Background The objective of this investigation was to examine the impact of silymarin supplementation on locomotion, anxiety-related behavior, learning, and memory via several behavioral tests, such as open field, elevated plus maze, and Morris water maze tests in streptozotocin-induced diabetic rats. Methods The rats were divided into the control, diabetes, silymarin, and diabetes plus silymarin groups. On the 30th–35th days of the study, several behavioral tests were performed and blood and brain tissue samples were taken and brain-derived neurotrophic factor (BDNF) and histone deacetylase 3 (HDAC3) levels were analyzed. Results There was no significant difference in locomotor activity between the groups (p = 0.534). Spatial memory was lower (p = 0.000) but anxiety scores were higher (p = 0.005) in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups. Plasma (p = 0.000) and brain tissue (p = 0.007) BDNF levels were lower in the diabetes group than in the control, silymarin, and diabetes plus silymarin groups; however, plasma (p = 0.432) and brain tissue (p = 0.321) HDAC3 levels did not significantly differ between the groups. Conclusions The findings obtained from this study suggest that silymarin supplementation could improve anxiety-related behavior, and learning and memory in diabetic rats by increasing the BDNF levels.

Background The 5HT4 receptor agonists are antidepressants with a unique mode of action. Many studies have been done on investigational drugs, and mosapride has been shown to have a 5HT3 antagonistic property. In this study, we assessed the potential anxiolytic and antidepressant effects of mosapride on Wistar albino rats. Methods The rats were randomly assigned to two models containing 4 groups of 6 animals each. In the anxiety model, four groups included 0.5 mL of 0.5% carboxymethyl cellulose (CMC), mosapride 1.5 mg/kg, mosapride 3 mg/kg and diazepam 2 mg/kg. They were dosed for 5 days. On the 3rd day, the elevated plus maze (EPM) was conducted, and on the 5th day, the open field (OF) tests were conducted. In the depression model, four groups included 0.5 mL of 0.5% CMC, mosapride 1.5 mg/kg, mosapride 3 mg/kg and imipramine 30 mg/kg. After 3 days of dosing, the forced swim test (FST) was conducted, followed by a washout period of 1 month. Then, the rats were subjected to chronic unpredictable stress with sucrose preference. Results Compared with the control, the mosapride-treated animals showed significant anxiolytic behavior at both high and low doses in the EPM and OF tests. In the FST, both high and low doses of mosapride reduced immobility. The climbing behavior was prominent at a high dose of mosapride, whereas swimming was prominent at a low dose. In the chronic stress model, both doses of mosapride preserved sucrose preference comparable to imipramine. Conclusion These findings suggest that mosapride has anxiolytic and antidepressant activities at clinically used doses.

Background We investigated the effects of a polyherbal formulation prepared from the extracts of Mondia whitei (Periplocaceae), Dracaena arborea (Dracaenaceae), and Bridelia ferruginea (Euphorbiaceae) (MDB) on the sexual behavior of normal rats (NR) and prediabetic rats (PR). Methods Male Wistar rats were administered with drinking fructose solution (21%) or tap water for 16 weeks. After induction of prediabetic status, NR (n = 30) and PR (n = 30) were randomly distributed into 10 groups of six animals each and orally treated with distilled water (10 mL/kg), sildenafil citrate (5 mg/kg), or MDB (50, 100, or 500 mg/kg) for 21 days. Sexual behavior parameters per series (S) of ejaculation were evaluated on days 1, 7, 14, and 21. Results Drinking fructose solution (21%) induced prediabetic status in rats, characterized by a significant (p < 0.01) increase in glycemia by 43.41% compared with the control group. MDB improved sexual performances of NR and PR by increasing the mount frequency (MF) and the intromission frequency (IF) as well as the number of rats capable of ejaculating. For instance, the MF and the IF were significantly increased in animals administered with MDB for 7 (50 mg/kg, S 1 and S 2 ), 14 (100 mg/kg, S 3 ), or 21 days (100 or 500 mg/kg, S 2 ). This increase was more pronounced on days 7 and 14 in NR and PR treated with sildenafil citrate or MDB extracts, respectively. Conclusions The mixture of MDB improved sexual activity in NR and PR. This result may further justify the traditional use of these plants as sexual performance enhancers.

Background Polycystic ovary syndrome (PCOS) is frequently associated with infertility, obesity, hypertension, and diabetes mellitus. Cardiac autonomic dysfunction is well documented in long-term patients of PCOS, with impairment being proportionate to disease duration. However, there is paucity of literature on cardiac autonomic tone in the “lean” phenotype of PCOS. We used exercise challenge to probe for autonomic dysfunction, as assessed by heart rate variability (HRV), an index of cardiac autonomic tone. Methods Our study population consisted of 27 newly diagnosed PCOS patients and 25 healthy females matched by age and body mass index. Short-term HRV was assessed using time and frequency domain indices. Moderate, isotonic exercise was used as an interventional tool. Indices of both groups were compared in three bins – at baseline, immediate, and late postexercise stages. Results The groups had comparable HRV indices at baseline. However, low-frequency (LF) power was significantly reduced in PCOS patients during immediate and late postexercise phases when compared with controls (p = 0.03 and 0.03, respectively). Time domain indices also exhibited a fall postexercise, although not statistically significant. Conclusions Although “lean” phenotype PCOS patients had comparable HRV parameters as controls at baseline, the administration of exercise challenge led to reduced sympathetic drive, evident by reduced LF power in patient group. This may be due to latent autonomic dysfunction in “lean” PCOS, which is unmasked on exposure to exercise challenge. We propose that the evaluation of HRV response to exercise may serve as a sensitive screening tool to detect early cardiovascular dysfunction in newly diagnosed lean PCOS patients.

Background Curcumin is extensively used as a therapeutic intervention for treating several ailments. The antioxidant curcumin has an anti-inflammatory and chelating property with arsenic to exhibit a strong therapeutic effect on reproductive organs. This study was undertaken to describe the protective effect of noninvasive administration of curcumin against sodium-arsenite-mediated uterine hazards in female Wistar rats. Methods Twenty-four female Wistar rats were randomly divided into four groups. The treatment was continued for 8 days and given orally sodium arsenite (10 mg/kg body weight) in combination with curcumin (20 mg/kg body weight). Results Our evaluation revealed that 8 days of sodium arsenite (10 mg/kg body weight) treatment reduced the activities of the uterine enzymatic antioxidants superoxide dismutase, catalase, and peroxidase. Blood levels of vitamin B 12 and folic acid decreased followed by an increased serum lactate dehydrogenase, homocysteine level, and hepatic metallothionein-1 in arsenic-treated rats. Necrosis of uterine tissue along with the disruption of ovarian steroidogenesis was marked in arsenic-treated rats with an upregulation of uterine NF-κB and IL-6 along with a raised level of serum TNF-α. Oral administration of curcumin (20 mg/kg body weight/day) in arsenic-treated rats significantly reinstated these alterations of the antioxidant system followed by an improvement of ovarian steroidogenesis and the circulating level of B 12 and folate along with the downregulation of serum homocysteine, metallothionein-1, and cytokines. Conclusions The findings of this study clearly and strongly elucidated that arsenic-induced oxidative stress in uterus is linked to an alteration of inflammation-signaling biomarkers and these have been protected through the co-administration of curcumin due to its anti-inflammatory, free radical scavenging, and antioxidant activity by the possible regulation of an S-adenosine methionine pool.

Background In this study, the hematological and antioxidant potential as well as the osmotic fragility effects of a Nigerian polyherbal formulation were evaluated. Materials and methods A total of 40 fats were divided into four groups of 10 rats each. Group 1 served as the control group, and the rest were assigned increasing daily oral administration of the extract for 28 days. At the end of treatment, blood was collected for hematological and osmotic fragility studies. The free radical scavenging effect of the extract was investigated via different in vitro models as well. Results Results showed that the nitric oxide scavenging and 2,2-diphenyl-1-picrylhydrazyl (DPPH) activities of the extract were significant (p < 0.05) and compared favorably with that of vitamin C. At 200 and 400 μg/mL, the nitric oxide scavenging activities for Ajumbise Polyherbal Extract (APE) were 60.71 ± 0.25% and 59.49 ± 0.98%, respectively, whereas for the same concentrations of vitamin C, 74.60 ± 0.25% and 85.24 ± 0.14 scavenging activities were obtained. The (DPPH) activity at 100 μg/mL was 81.24 ± 0.02% for the extract and 96.22 ± 0.18% for vitamin C. However, at all concentrations, the extract had significantly lower Ferric Reducing Antioxidant Power (FRAP) activity than vitamin C. Red blood cell counts (RBCC), hemoglobin and packed cell volume values (PCV) were significantly lowered only in groups treated with 400 and 800 mg/kg of the extract (p < 0.05), whereas other RBCC parameters and white blood cell counts (WBCC) were not significantly affected (p < 0.05). Platelet (PLT) count was also significantly lowered in all extract-treated groups. The extract also significantly reduced RBCC percentage hemolysis (p < 0.05). Conclusions Ajumbise polyherbal may be free of hematoxicity and may improve the integrity of the RBC membrane due to its appreciable antioxidant activity.

Background Doxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups. Methods Group 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20). Results The results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells. Conclusions This study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.

The present study investigated the phytochemicals and antidiabetic effect of the aqueous extract of the fruit of Punica granatum Linn. in streptozotocin (STZ)-induced diabetic mice. The fruit of P. granatum was extracted with water. The phytochemicals of the water extract were investigated by the liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. The water extract of P. granatum at doses of 150 and 300 mg/kg body weight (bw) was administered to mice for 21 days, and blood glucose level, triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme were estimated. Analyzed phytochemicals showed the fruit of P. granatum Linn has a high amount of phenolic and flavonoid compounds, which provide beneficial effect for this plant. The oral administration of the fruit extract of P. granatum at doses of 150 and 300 mg/kg bw for 21 days significantly reduced blood glucose level, triglycerides, serum cholesterol, LDL-cholesterol, AST and ALT enzyme. Our results suggested that the fruit extract of P. granatum has strong antidiabetic effect in STZ-induced diabetic mice. The fruit of this plant might be a potential source of drug for treatment of diabetes.

Background The aim of this experiment was to evaluate the cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic activities of the methanolic extract of Ficus cunia leaves. Methods Primary phytochemical screening was accomplished by using established methods. Cytotoxicity was studied by brine shrimp lethality test, and the thrombolytic assay was conducted through clot lysis method with human blood. The in vivo action was done using mice of both sexes. The analgesic activity was evaluated by acetic acid-induced writhing test and formalin-induced paw licking test. Open field, hole cross and thiopental Na-induced sleeping time test were used to examine the sedative-hypnotic activity, and elevated plus maze (EPM) and hole board test were used to identify the anxiolytic activity. Results The results elicited that the extract contained several phytochemicals such as alkaloid, flavonoid, and tannin. The extract was found to have a median lethal concentration (LC 50 ) value of 55.48 μg/mL in the brine shrimp lethality bioassay. It was also assessed for antithrombotic activity when compared with streptokinase; it has significant (p < 0.001) thrombolytic effect (34.72 ± 1.74%) contrasted with standard streptokinase (67 ± 1.56%). The extract at doses of 200 and 400 mg/kg produced inhibition of 32.58% and 46.63% in acetic acid-induced pain and 45.88 and 61.18% in formalin-induced pain. The sedative and hypnotic activities on the central nervous system of the methanol extract of F. cunia (MEFC) leaves were evaluated. The extract delivered critical sedative impact at the doses of 200 and 400 mg/kg (by oral route) treated with reference to the substance diazepam, and the hypnotic impact was also observed in the case of mice. MEFC at its maximum dose (400 mg/kg) significantly (p < 0.01) increased the time spent in the open arms of the EPM. In the hole board test, there was a dose-dependent (at 200 and 400 mg/kg) and a significant (p < 0.05 and p < 0.01) increase in the number of head pokes in comparison to control. Conclusions The results of the present study gave a helpful baseline in progression for the possible use of MEFC as a cytotoxic, thrombolytic, analgesic, sedative-hypnotic and anxiolytic drug.

Background Recently, the incidences of hypertension and environmental pollution have increased significantly. This study investigates the antihypertensive effect of Annona muricata extract against K 2 Cr 2 O 7 -induced hypertension. Methods Fifty rats were used for this study, which were divided into five groups of 10 rats each. Rats in Group A received normal saline, and those in Groups B, C, D, and E were treated with A. muricata extract alone at 250 mg/kg, K 2 Cr 2 O 7 at 30 mg/kg, pretreated with the extract at 250 mg/kg, and pretreated with gallic acid at 60 mg/kg for 14 days, respectively, and thereafter administered with a single intraperitoneal injection of K 2 Cr 2 O 7 at 30 mg/kg. Results Administration of K 2 Cr 2 O 7 significantly increased systolic, diastolic, and mean arterial pressure and caused prolonged QT and QTc intervals. Further, pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg significantly reduced high blood pressure to near-normal values. K 2 Cr 2 O 7 intoxication led to significant increases in serum advanced oxidative protein products, myeloperoxidase, and xanthine oxidase, while serum nitric oxide (NO) also reduced significantly. Immunohistochemistry of the renal kidney injury molecule (Kim-1) and p38 MAPK showed increased expressions following the administration of K 2 Cr 2 O 7 together with the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg also increased the expressions of Nrf2 and downregulated Kim-1 and p38. Conclusion Together, we found that pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg normalized the blood pressure, reduced the markers of oxidative stress, and improved the antioxidant defense system and serum NO bioavailability.

Clomiphene citrate is a first-line drug for the induction of ovulation in infertility cases. Leukocytoclastic vasculitis (LCV) is an extremely rare serious adverse drug reaction to clomiphene. We report here the case of a 30-year-old Indian female patient who presented with generalized petechiae and palpable purpura without fever and sparing the mucosa, temporally related to clomiphene intake and consistent with LCV histologically. Clomiphene was stopped and the patient was treated symptomatically with prednisolone 40 mg/day, oral levocetirizine 5 mg twice daily, and emollients and calamine lotion topically. The patient improved over 3–4 weeks. The prednisolone dose was tapered weekly and withdrawn gradually. To date, drug-induced LCV has not been previously reported with clomiphene. Although rare, clomiphene could be considered a potential cause of drug-induced cutaneous LCV in the differential diagnosis of erythematosus rash with non-blanching petechiae and purpura.