Volume 31, Issue 3

T-type calcium channels are low voltage activated calcium channels that are widely expressed in various brain regions including stress-responsive regions. These channels regulate the diverse functions of the central nervous system, and modulation of these channels is shown to modulate the anxiety. Studies have described that modulation of T-type calcium channels may either aggravate or ameliorate anxiety-related behavior, suggesting the dual role of these channels. The studies employing animals with overexpression of T-type calcium channels reported their anxiety-inducing role. Therefore, the blockade of these channels using various pharmacological agents such as ethosuximide, plant extracts of linalool or rosemary, and corticotropin-releasing factor (CRF) is reported to ameliorate anxiety. On the contrary, knockout of the gene encoding these channels predisposes the rodents to anxiety-related disorders, suggesting the anxiety-attenuating role of these channels. It may be possible that these channels in normal or basal state attenuate anxiety, whereas activation of these channels in stressful condition may produce anxiety. The present review describes the dual role of T-type calcium channels in anxiety-related behavior in both preclinical and clinical studies.

Alzheimer’s disease (AD), which relates to nervous degeneration, is the most popular form of memory loss. The pathogenesis of AD is not fully understood, and there are no therapies for this disorder. Some drugs have been used in clinical applications for preventing and treating AD, but they have significant adverse reactions. Therefore, there is a need to develop treatment for AD. Traditional medicine has used many medicinal plants to alleviate the symptoms of AD. Medicinal plants may reduce neurodegenerative disorders with fewer side effects than chemical drugs, and they are promising drug candidates for AD therapy. This review is the summary of the pathogenesis and treatments of AD and includes information about the chemistry and bioactivities of some medicinal plants from the Huperzia species, such as Huperzia saururus , Huperzia selago , Huperzia phlegmaria , Huperzia fargesii , Huperzia serrata , Huperzia reflexa and Huperzia quadrifariata , that are used for the treatment of AD. We searched literature, including Medline, Embase, Google Scholar and PubMed database, and did a bibliographic review of relevant articles. Key words included Huperzia species, huperzine, huperin, Huperzia and Alzheimer’s disease. We found that the main bioactive compounds of the Huperzia species are alkaloids, which have shown significant effects on preventing the development of AD. They are new promising compounds against AD due to their antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities in the neural system. Our conclusion from this review is that the Huperzia species are potential source containing various pharmaceutical compounds for the treatment of AD.

Background The physiopathologies of many neurologic diseases are characterized by related biochemical dysfunctions that could be explored as drug targets. This study evaluated the effect of a methanol leaf extract of Antiaris africana (MEA) on critical bioindices of Parkinsonism and related neurologic dysfunctions in rats with rotenone-induced neurotoxicity. Methods Animals were administered 50 or 100 mg/kg MEA for 14 consecutive days. Rotenone (1.5 mg/kg) was administered three times per day on days 13 and 14. Coenzyme Q10 (5 mg/kg) was the reference drug. Complex I activity, dopamine level, activities of acetylcholinesterase, myeloperoxidase, Na + /K + ATPase and glutamine synthetase, as well as oxidative stress indices were evaluated at the end of the period of treatment. Results Rotenone-intoxicated group showed disruption of complex 1 activity, dopamine level, and glutamine synthetase activity with negative alterations to activities of acetylcholinesterase, myeloperoxidase, and Na + /K + ATPase as well as heightened cerebral oxidative stress. MEA restored brain mitochondria functionality, mitigated altered neurochemical integrity, and ameliorated cerebral oxidative stress occasioned by rotenone neurotoxicity. The activity of A. Africana was comparable with that of 5 mg/kg coenzyme Q10. Conclusions These results indicated that A. africana displayed therapeutic potential against Parkinsonism and related neurologic dysfunctions and support its ethnobotanical use for the treatment of neurologic disorders.

Background Fixed-dose combinations (FDCs) are being widely prescribed for the treatment of various disorders in India. However, not all FDCs are rational. To know the awareness of physicians in prescribing rational FDCs was the need of the hour in order to assess the prescribing trends and rationality of FDCs. Eventually, this will help to formulate the guideline for rational use of FDCs. Methods This was a prospective observational study conducted in All India Institute of Medical Sciences Bhopal, MP, India. Prescriptions were collected over a period of 2 months by the convenience sampling method from hospital pharmacy. The data were subjected to descriptive analysis using Microsoft Excel and Graph Pad Prism. Results were expressed in mean ± standard deviation (SD), percentages and 95% confidence interval. Results A total of 2496 drugs were prescribed in 1008 prescriptions, of which 945 (37.82%) were FDCs with an average of 0.93 ± 0.94 (mean ± SD) per prescription. Of 945, 67 (7.09%) were included in National List of Essential Medicine 2015 considered as rational. The number of prescriptions containing one or more FDCs was 629 (62.40%). FDCs were more frequently prescribed to male patients (54.92%) and in the age group of 18–30 years (33.44%). FDCs containing a proton pump inhibitor were prescribed most frequently (16.29%) followed by nonsteroidal anti-inflammatory drugs (13.96%) and multivitamins (7.83%). Conclusions Prescribing irrational FDCs was very common, and hence there is an obvious need to update our prescribers about the irrationality of FDC and motivate them to develop a habit of rational prescribing.

Background The vascular changes due to cerebrovascular damage, especially on the capillaries, play a vital role in causing vascular dementia. Increasing oxidative stress can lead to tissue damage while reducing brain blood flow. The use of factors reducing the oxidative stress level can decrease the brain damages. Sulfur dioxide (SO 2 ) is one of the most important air pollutants that lead to the development of severe brain damage in large quantities. However, studies have recently confirmed the protective effect of SO 2 in cardiac ischemic injury, atherosclerosis and pulmonary infections. Methods The permanent bilateral common carotid artery occlusion (BCAO) method was used to induce chronic cerebral hypoperfusion (CCH). Two treatment groups of SO 2 were studied. The animal cognitive performance was evaluated using the Morris water maze. Hippocampal tissue damage was examined after 2 months of BCAO. In the biochemical analysis, the activity of catalase and lipid peroxidation of the hippocampus was studied. Results Neuronal damage in hippocampus, as well as cognitive impairment in ischemia groups treated with SO 2 showed a significant improvement. Catalase activity was also significantly increased in the hippocampus of treated groups. Conclusions According to the results, SO 2 is likely to be effective in reducing the CCH-caused damages by increasing the antioxidant capacity of the hippocampus.

Background An earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa . The aim of the study was to investigate the component responsible for these activities followed by an in vivo study. Methods In vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer’s disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4′-O-glucoside content using a validated thin layer chromatography densitometric method. Results STZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner. Conclusions Our results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer’s disease.

Background Parquetina nigrescens (Afzel) Bullock is a commonly used medicinal plant in African traditional medicine. The powdered roots and stems of the plant are taken with pap as a memory enhancer among the Yorubas of southwestern Nigeria. The mechanism by which scopolamine induces cognitive deficit mimics the pathogenesis of neurodegeneration in cognitive impairment. This study therefore, aimed at investigating the effect of the methanol stem extract of P . nigrescens on sub-chronically scopolamine-induced cognitive deficit in mice. Method Phytochemical screening was carried out on the extract using standard protocols. The oral median lethal dose (LD 50 ) was estimated according to the Organisation for Economic Cooperation and Development (OECD) 425 limit test guideline. Doses of 250, 500, and 1000 mg/kg of the extract were used for the study. The elevated plus maze (EPM) and novel object recognition tests (NORT) were used to assess cognitive function. The brain tissue was assayed for the level of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activity. Results The plant extract contains phenolics, carbohydrates, tannins, saponins, and unsaturated sterols.The extract decreased the transfer latencies on days 7 and 8 against the scopolamine group in EPM and increased the discrimination index decreased by scopolamine in NORT. The methanol stem extract of P. nigrescens significantly (p ≤ 0.01) reduced MDA level;  significantly  (p ≤ 0.01) increased SOD activity;  non-significantly increased GSH activity and the activity of AChE apeared not altered. Conclusion The methanol stem extract of P . nigrescens ameliorated sub-chronically scopolamine-induced cognitive deficit via antioxidant mechanism.

Background Polyphenols are known because of their phytochemical constituents having antioxidative properties. In this regard, grape juice is highly enriched with polyphenolic constituents, and its supplementation has been known to improve many health and age-associated diseases and risk factors. Our study was entirely dedicated to evaluating the positive effects of grape juice on young and old rats’ erythrocytes and plasma. Methods Young (4 months) and old (24 months) male Wistar rats were given an oral dose of grape juice for 28 days. They were grouped into four categories (n = 6): Group I: young control rats; Group II: young grape juice treated rats; Group III: old control rats; Group IV: old treated rats. The treated groups were administered with 10 μL/g of grape juice according to body weight. The following biomarkers of antioxidant defense were measured: ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), plasma membrane redox system (PMRS), glutathione (GSH), osmotic fragility, and the decrease in lipid peroxidation measured in terms of malondialdehyde (MDA) levels. Results A significant increase (p<0.05) in antioxidant levels of FRAP, PMRS, and GSH and a significant decrease (p<0.05) in oxidized products such as ROS and MDA were seen in the treated rats in comparison to the controls. The decrease in ROS and rise in FRAP and PMRS levels suggest the ability of grape juice to combat oxidative stress effectively. Conclusion We propose the role of grape juice as a potent antioxidant because of its easy bioavailability and its role in combating stress. Our results also approve grape juice as a possible antiaging agent.

Background Oxidative stress plays a major role in the development of various human diseases. However, many antioxidant compounds can neutralize the excess of free radicals, protect the cells against their toxic effects and help prevent or treat a disease. This study investigated the cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on the tert-butyl hydroperoxide (TBHP)-induced damage on human fibroblast cells. Methods Human fibroblast cells were pretreated with different concentrations (1, 2, 4, 8 mg/mL) of Z. jujuba for 24 h and exposed to 75 μM TBHP for another 24 h. Cell viability was determined by the MTT assay. The antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods, and the intracellular antioxidant activity was evaluated with the Cellular antioxidant activity assay. Results Our data showed that treatment with TBHP reduced cell viability of human fibroblast cells, while pretreatment with Z. jujuba increased cell viability in a dose-dependent manner. This indicated the cytoprotective effects of Z. jujuba . Pretreatment with Z. jujuba increased the antioxidant capacity and scavenged the TBHP-produced peroxyl radicals in the human fibroblast cell medium. Moreover, Z. jujuba increased the intracellular antioxidant activity of human fibroblast cells. Conclusions These results demonstrated that the aqueous extract of the Z. jujuba fruit can prevent TBHP-induced cellular toxicity by enhancing the antioxidant activity in cells and their medium. So, Z. jujuba has a therapeutic potential to attenuate oxidative stress-induced diseases.

Background The physiological functions of the testis and spleen can be affected through several cellular and molecular mechanisms such as the generation of reactive oxygen species (ROS) that causes oxidative stress. This study aimed at investigating the protective effect of catechin, quercetin, and taxifolin in rotenone-induced testicular and splenetic toxicity. Methods Male Wistar rats were administered with 1.5 mg/kg rotenone (s.c.) for 10 days followed by post-treatment with catechin (5, 10, or 20 mg/kg), quercetin (5, 10, or 20 mg/kg), and taxifolin (0.25, 0.5, or 1.0 mg/kg) for 3 days (s.c.), followed by estimation of biochemical markers of oxidative stress, inflammatory activities, and tissue damage in testes and spleen. Results Exposure of rats to rotenone caused reduced body weight gain, increased organ weight, decreased glutathione level and activities of glutathione transferase and superoxide dismutase, enhanced lipid peroxidation, and increased activities of prooxidant/proinflammatory enzymes and lactate dehydrogenase, which were mitigated by post-treatment with flavonoids. In general, quercetin and taxifolin showed better activity than catechin. Conclusions Catechin, quercetin, and taxifolin ameliorated rotenone-induced weight disturbances and oxidative damage in rats, indicating their potential relevance in toxicant and pesticide-induced tissue injury.

Background In the present era, obesity is increasing rapidly, and high dietary intake of lipid could be a noteworthy risk factor for the occasion of obesity, as well as nonalcoholic fatty liver disease, which is the independent risk factor for type 2 diabetes and cardiovascular disease. For a long time, high-lipid diet (HLD) in “fast food” is turning into part of our everyday life. So, we were interested in fulfilling the paucity of studies by means of preliminary evaluation of these three alternative doses of HLD on a rat model and elucidating the possible mechanism of these effects and divulging the most alarming dose. Methods Thirty-two rats were taken, and of these, 24 were fed with HLD in three distinctive compositions of edible coconut oil and vanaspati ghee in a ratio of 2:3, 3:2 and 1:1 (n = 8), orally through gavage at a dose of 10 mL/kg body weight for a period of 28 days, whereas the other eight were selected to comprise the control group. Results After completion of the experiment, followed by analysis of data it was revealed that hyperlipidemia with increased liver and cardiac marker enzymes, are associated with hepatocellular injury and cardiac damage. The data also supported increased proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). As oxidative stress parameter increased in both liver and heart, there is also an increased in TNF-α due to an increased expression of inducible nitric oxide (NO) synthase, which led to a high production of NO. Moreover, HLD treatment explicitly weakens reasonability of hepatocytes and cardiomyocytes conceivably through G0/G1 or S stage capture or perhaps by means of enlistment of sub-G0/G1 DNA fragmentation and a sign of apoptosis. Conclusions Based on the outcomes, it tends to be inferred that consequences of the present examination uncovered HLD in combination of 2:3 applies most encouraging systemic damage by reactive oxygen species generation and hyperlipidemia and necroapoptosis of the liver and heart. Hence, outcome of this study may help to formulate health care strategy and warns about the food habit in universal population regarding the use of hydrogenated and saturated fats (vanaspati ghee) in diet.

Background This study sought to determine the in vitro antioxidant, anti-monoamine oxidase and anticholinesterase properties of extracts (aqueous and alkaloid) of two tropical vegetables from Solanum spp - African eggplant ( Solanum macrocarpon L) and black nightshade ( Solanum nigrum L) as indices of their neuroprotective properties. Methods Both aqueous and alkaloid extracts of African eggplant (AE) and black nightshade (BN) were prepared by solvent extraction according to standard methods. Thereafter, the inhibitory effects of the extracts on monoamine oxidase (MAO) and acetylcholinesterase (AChE) activities, as well as their free radical-scavenging and reducing abilities were assessed. Also, phytochemical analysis for phenols, flavonoids, and alkaloids were carried out. Results The results showed that the extracts inhibited MAO and AChE activities dose dependently, with aqueous extracts showing significantly higher MAO inhibition that the alkaloid extracts from both samples, but in all, BN showed higher MAO inhibitory effect compared to AE; the reverse was however, observed for AChE inhibition. Furthermore, the aqueous extracts showed significantly higher antioxidant properties than the alkaloid extracts, while BN had higher antioxidant properties compared to AN. The phytochemical analysis also showed that BN had significantly higher amount of phenols, flavonoids, and alkaloids than AE. Conclusions The anti-monoamine oxidase, anticholinesterase, and antioxidant properties exhibited by extracts from both samples could contribute to their neuroprotective abilities. Thus, these vegetables can be potential sources of functional foods and nutraceuticals in the management of neurodegenerative diseases, especially in the tropics.

Garcinia kola (GK) stem bark, Uvaria chamae (UC) root, and Olax subscorpioidea (OS) root are components of various indigenous/traditional anticancer regimens. It is, therefore, possible that they might combat oxidative stress and impair cellular proliferation linked to carcinogenesis. In this study, we investigated the antioxidative, mito-depressive, and DNA-damaging activities of the three plant extracts in order to provide further mechanistic insights into their potential anticancer roles in documented cancer remedies that include them. Antioxidative properties were investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays and an animal model of drug (cisplatin)-induced oxidative stress. The Allium cepa assay and the single cell gel electrophoresis (SCGE) assay were used to assess mito-depressive and DNA-damaging activities. GK and OS showed significantly higher antioxidant activities in the DPPH assay than ascorbic acid; OS had the lowest IC 50 of the three plants in the NO assay, comparable to that of ascorbic acid. Pretreatment with the extracts produced an ameliorative and protective effect against the cisplatin-induced oxidative stress as shown by inhibition of lipid peroxidation and improved or restored reduced glutathione and superoxide dismutase levels. In the Allium test, the three extracts produced significant decreases in root growth and also significant cytotoxicity as evidenced by decreased mitotic index. Each of the extracts also showed significantly increased tail DNA (%) in the SCGE assay, indicating the significant DNA-damaging effect. Taken together, this study demonstrates the possible chemopreventive and chemotherapeutic potentials of the three study extracts, which may explain the roles of their source plants in traditional remedies in the therapy of cancers.

Background The aim of this study was to evaluate the antioxidant activity and to determine the chemical compounds of organic extracts of fruits and leaves of Zizyphus lotus. The litholytic effect was determined on the basis of the in vitro effect of the aqueous extracts on the formation of crystals of stones. Finally, chemical compounds were investigated to identify their target using an in silico approach. Methods The antioxidant activity was determined with the diphenylpicrylhydrazyl radical trapping method. An aliquot of 2 mL of urine and 100 μL of an infusion of fruit and leaf aqueous extract of Z. lotus at different concentrations were used. The induction of calcium oxalate (CaOx) crystals was done by the addition of oxalic acid at 0.1 mol/L. The effect of aqueous extracts was compared with two inhibitors (citrate and magnesium) used as references. In silico modelization was carried out using SwissTargetPrediction. Results The antioxidant activity test showed that the methanol extract was active with an IC 50 of 5 mg/mL. The aqueous extracts of fruits and leaves inhibit the formation of crystals of CaOx. Then, the composition of the methanol extracts of the leaves and fruits in high-performance liquid chromatography showed majority compounds such as quercetin-3-galactoside and hyperin. In silico assays showed that the identified molecules exert their effect by targeting enzymes responsible for calcium regulation, urate regulation, and maintenance of acid-base balance, and that had anti-inflammatory properties. Conclusions The present study showed that Z. lotus may be considered as a functional or nutraceutical food. However, further studies should be carried out in order to extract and purify these compounds to test their effect on urinary lithiasis.

Background According to GLOBOCAN 2018, oral cancer was reported as the second highest cancer prevalent in India. Despite the several therapies available for oral cancer treatment, tumor recurrence and distant metastasis persist. This study investigates the anticancer potential of Persicaria odorata , commonly known as Vietnamese coriander, used widely in traditional systems of medicine for the treatment of inflammation, stomach ailments, tumors, etc. Methods The crude methanolic extract of P. odorata (MPo) was prepared. The anticancer properties of MPo on SAS cells and other human oral squamous cell carcinoma cell line were evaluated using in vitro experimental conditions. The phytochemical constituents present in the MPo were also determined. Results Persicaria odorata possesses antiproliferative, antisurvival, antimetastatic activities, and induced cell cycle arrest in the G2 phase. It inhibited Akt-mammalian target of rapamycin (mTOR) signaling pathway and also downregulated the expression of essential proteins that are involved in tumorigenesis such as cyclin D1, cyclooxygenase 2 (COX2), survivin, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor-A (VEGF-A). Moreover, the presence of flavonoids and quinones also revealed the anticancer activity of the plant. Conclusion Overall, our study concludes that P. odorata exhibits its anticancer properties through the downregulation of Akt/mTOR signaling pathway in a dose-dependent manner.

Background Clozapine is one of the most efficacious antipsychotic drug used for the treatment-resistant schizophrenia; it is sometimes associated with serious adverse reactions like agranulocytosis, myocarditis, cardiac rhythm disturbances, etc. Case presentation A 30-year-old patient with a primary diagnosis of paranoid schizophrenia (ICD code - F20.05) was on regular prescription for 6 years. Due to refractoriness, the patient was initiated on tablet clozapine. After 45 days of clozapine therapy, he presented with the complaints of worsening of positive symptoms and sudden falls associated with a brief period of unresponsiveness for which the patient was admitted for evaluation. After stabilization of the patient, it was concluded that he was suffering from ventricular ectopics based upon cardiac investigations like electrocardiogram (ECG) and Holter monitoring. Upon causality assessment between the adverse drug reaction (ADR) and the suspected drug using Naranjo Scale and WHO causality assessment scale, the ADR was found to be probable. Conclusions This case report will help to keep physicians vigilant about the rare cardiac side effects of clozapine and to do regular ECG monitoring of the patients who are on clozapine. Moreover, this case report generates the evidence of clozapine-induced arrhythmia, which is needed to be quantified with aggressive study design and there is a need to study the dose-dependent relationship of clozapine-induced arrhythmia.