Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits.

Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Dioscorea nipponica Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that Dioscorea nipponica rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF.

Biological evidence of gintonin efficacy in memory disorders.

Gintonin is a novel glycolipoprotein, which has been abundantly found in the root of Korean ginseng. It holds lysophosphatidic acids (LPAs), primarily identified LPA C18:2, and is an exogenous agonist of LPA receptors (LPARs). Gintonin maintains blood-brain barrier integrity, and it has recently been studied in several models of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Gintonin demonstrated neuroprotective activity by providing action against neuroinflammation-, apoptosis- and oxidative stress-mediated neurodegeneration. Gintonin showed an emerging role as a modulator of synaptic transmission and neurogenesis and also potentially regulated autophagy in primary cortical astrocytes. It also ameliorated the toxic agent-induced and genetic models of cognitive deficits in experimental NDDs. As a novel agonist of LPARs, gintonin regulated several G protein-coupled receptors (GPCRs) including GPR40 and GPR55. However, further study needs to be investigated to understand the underlying mechanism of action of gintonin in memory disorders.

Pharmacological insights into Merremia vitifolia (Burm.f.) Hallier f. leaf for its antioxidant, thrombolytic, anti-arthritic and anti-nociceptive potential.

Merremia vitifolia (Burm.f.) Hallier f., an ethnomedicinally important plant, used in the tribal areas to treat various ailments including fever, headache, eye inflammation, rheumatism, dysentery, jaundice and urinary diseases. The present study explored the biological efficacy of the aqueous fraction of M. vitifolia leaves (AFMV) through in vitro and in vivo experimental models. The thrombolytic and anti-arthritic effects of AFMV were evaluated by using the clot lysis technique and inhibition of protein denaturation technique, respectively. The anti-nociceptive activity of AFMV was investigated in Swiss Albino mice by acetic acid-induced writhing test and formalin-induced paw licking test. The antioxidant activities of AFMV, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and total reducing power, were also tested. The qualitative phytochemical assays exhibited AFMV contains secondary metabolites such as alkaloid, carbohydrate, flavonoid, tannin, triterpenoids and phenols. In addition, AFMV showed strong antioxidant effects with the highest scavenging activity (IC50 146.61 µg/mL) and reducing power was increased with a dose-dependent manner. AFMV also revealed notable clot lysis effect and substantial anti-arthritic activity at higher doses (500 µg/mL) as compared with the control. The results demonstrated a promising reduction of the number of writhing and duration of paw licking in acetic acid-induced writhing test and formalin-induced paw licking test in a dose-dependent manner, respectively. In conclusion, AFMV provides the scientific basis of its folkloric usage, suggesting it as the vital source of dietary supplement.

Subacute oral toxicity of ayurvedic anti-diabetic preparation Jambadyarista in Sprague-Dawley rats.

BACKGROUND: Jambadyarista is an Ayurvedic polyherbal formulation widely prescribed by Ayurvedic practitioners for the management of diabetes and its associated complications. About 39 companies have marketed this formulation in Bangladesh with consent from the Directorate General of Drug Administration (DGDA). AIM: This study investigated the sub-acute oral toxicity of Jambadyarista in the Sprague-Dawley rat model. METHODS: The sub-acute toxicity studies were executed in Sprague-Dawley rats. Jambadyarista formulation was given for 28-days through oral gavage at 10 mL/kg and 20 mL/kg dose to two different groups comprising 6 rats of both sex/groups. Across the experimental period mortality, adverse reactions were closely monitored. After 28-day feeding hematological, biochemical, and relative organ weights were quantified. RESULTS: No mortality and/or signs of morbidity were observed for 28-day of repeated-dose sub-acute toxicity. Any pernicious change in body weight, biochemical, and hematological parameters along with relative organ weight were not observed for Jambadyarista. Correlation study among parameters of the renal profile, liver profile, lipid profile also metabolic hormones (T3 and TSH), and enzymes showed the non-toxic rather beneficial role (hypolipidemic) of Jambadyarista in Sprague-Dawley rats. CONCLUSION: Jambadyarista preparation did not cause any potential toxic effect in repeated dose subacute toxicity study over Sprague-Dawley rats orally. Therefore, low dose administration of Jambadyarista could have a beneficial effect on diabetes and can be considered safe before the chronic study.

Evaluation of carbon tetrachloride fraction of Actinodaphne angustifolia Nees (Lauraceae) leaf extract for antioxidant, cytotoxic, thrombolytic and antidiarrheal properties.

Actinodaphne angustifolia Nees (Family: Lauraceae) is commonly used in folk medicine against urinary disorder and diabetes. The objective of the present study was to evaluate the antioxidant, cytotoxic, thrombolytic, and antidiarrheal activities of carbon tetrachloride (CCl4) fraction of leaves of A. angustifolia (CTFAA) in different experimental models. Antioxidant activity was evaluated by using qualitative and quantitative assays, while antidiarrheal effects assessed with castor oil-induced diarrheal models in mice. The clot lysis and brine shrimp lethality bioassay were used to investigate the thrombolytic and cytotoxic activities, respectively. CTFAA showed antioxidant effects in all qualitative and quantitative procedures. The fraction produced dose-dependent and significant (P<0.05 and P<0.01) activities in castor oil-induced diarrheal models. Moreover, CTFAA significantly (P<0.05) demonstrated a 15.29% clot lysis effect in the thrombolytic test, and the brine shrimp lethality assay LC50 value was 424.16 µg/ml bioassay. In conclusion, the current study showed CTFAA has significant antidiarrheal effects along with modest antioxidant and thrombolytic effects, and these data warrant further experiment to justify and include CTFAA as a supplement to mitigate the onset of diarrheal and cardiovascular disease.

Biological efficacy of zinc oxide nanoparticles against diabetes: a preliminary study conducted in mice.

The antidiabetic, hypoglycemic and oral glucose tolerance test (OGTT) activities of zinc oxide nanoparticles (ZnONPs) were assessed in mice. ZnONPs were prepared by reacting Zn(NO3)2.6H2O and NaOH solution at 70°C with continuous stirring and then characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques. Diabetes was induced by the intraperitoneal injection of streptozotocin (STZ) in mice, and then the blood glucose levels were determined by the glucose oxidase method. The experimental results revealed that ZnONPs suggestively (p<0.001) declined the blood glucose levels (39.79%), while these reductions were 38.78% for the cotreatment of ZnONPs and insulin, and 48.60% for insulin, respectively. In the hypoglycemic study, ZnONPs (8 and 14 mg/kg b.w) reduced approximately 25.13 and 29.15% of blood glucose levels, respectively. A similar reduction was found in the OGTT test, which is also a dose- and time-dependent manner. Overall, ZnONPs possess a potential antidiabetic activity, which could be validated by further mechanistic studies.

Nootropic and Anti-Alzheimer's Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer's Neuropathology.

Medicinal plants are the backbone of modern medicine. In recent times, there is a great urge to discover nootropic medicinal plants to reverse cognitive dysfunction owing to their less adverse effects. Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the inevitable loss of cognitive function, memory and language impairment, and behavioral disturbances, which turn into gradually more severe. Alzheimer's has no current cure, but symptomatic treatments are available and research continues. The number of patients suffering from AD continues to rise and today, there is a worldwide effort under study to find better ways to alleviate Alzheimer's pathogenesis. In this review, the nootropic and anti-Alzheimer's potentials of 6 medicinal plants (i.e., Centella asiatica, Clitoria ternatea, Crocus sativus, Terminalia chebula, Withania somnifera, and Asparagus racemosus) were explored through literature review. This appraisal focused on available information about neuroprotective and anti-Alzheimer's use of these plants and their respective bioactive compounds/metabolites and associated effects in animal models and consequences of its use in human as well as proposed molecular mechanisms. This review progresses our existing knowledge to reveal the promising linkage of traditional medicine to halt AD pathogenesis. This analysis also avowed a new insight to search the promising anti-Alzheimer's drugs.

Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study.

Cognitive impairment is a state that affects thinking, communication, understanding, and memory, and is very common in various neurological disorders. Among many factors, age-related cognitive decline is an important area in mental health research. Research to find therapeutic medications or supplements to treat cognitive deficits and maintain cognitive health has been ongoing. Ginseng and its active components may have played a role in treating chronic disorders. Numerous preclinical studies have confirmed that ginseng and its active components such as ginsenosides, gintonin, and compound K are pharmacologically efficacious in different models of and are linked to cognitive impairment. Among their several roles, they act as an anti-neuroinflammatory and help fight against oxidative stress and modulate the cholinergic signal. These roles may be involved in enhancing cognition and attenuating impairment. There have been some clinical studies on the activity of ginseng in cognitive impairment, but many ginseng species and active compounds remain to be investigated. In addition, new formulations of active ginseng components such as nanoparticles and liposomes could be used for preclinical and clinical models of cognitive impairment. Here, we discuss the therapeutic potential of active ginseng components in cognitive impairment and their chemistry and pharmacokinetics and consider prospects for their delivery and clinical study with respect to cognitive impairment.

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders.

Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa and has various pharmacological activities, such as protection against oxidative stress, inflammation, and infections. In addition, it might be a potential neuropharmacological agent because it exhibits versatile potential for attenuating neurological impairments. It features greater beneficial effects in toxin-induced neuroinflammation and neurotoxicity. In various models of neurological disorders, it demonstrates emergent functions, including safeguarding various neurodegenerative diseases and other neurological diseases, such as stroke, schizophrenia, and epilepsy. TQ also has potential effects in trauma mediating and chemical-, radiation-, and drug-induced central nervous system injuries. Considering the pharmacokinetic limitations, research has concentrated on different TQ novel formulations and delivery systems. Here, we visualize the neuropharmacological potential, challenges, and delivery prospects of TQ, specifically focusing on neurological disorders along with its chemistry, pharmacokinetics, and toxicity.

In vivo sedative and hypnotic activities of methanol extract from the leaves of Jacquemontia paniculata (Burm.f.) Hallier f. in Swiss Albino mice.

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.