Neuroprotective activities of Boophone haemanthoides (amaryllidaceae) extract and its chemical constituents

Parkinson’s disease (PD) is a neurodegenerative condition that progresses as age increases, and some of its major symptoms include tremor and postural and movement-related difficulties. To date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed; hence, this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP+) and SH-SY5Y neuroblastoma cells

Design, synthesis, and evaluation of 3,7-substituted coumarin derivatives as multifunctional Alzheimer’s disease agents

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;mM. Significant neuroprotective effects towards MPPþ-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 mM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP+ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP+-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses

Extracts of Hunteria umbellata reverses the effect of streptozotocin‑induced pancreatic islet‑cell destruction

The use of extracts of plant parts in the treatment and/or management of diabetes mellitus has formed the basis of health care in most African countries. The aim of this study was to investigate the possible effect of oral administration of extracts Hunteria umbellata (HU) leaves and seeds on streptozotocin- induced pancreatic β-cell damage. Twenty four (24) adult wistar rats were selected into two control group (negative control group A and positive control group B) and two treatment groups (C & D) each containing six animals each (n= 6 per group). Rats in the positive control group (B) were giving intraperitoneal injection of with 50 mg/kg body weight of Streptozotocin (STZ) prepared with 0.05M Citrate buffer solution while the negative control group A rats were injected with a corresponding volume of Citrate buffer without STZ. Rats in the treatment groups were treated with 250 mg/kg body weight aqueous extract of seeds of Hunteria umbellata (group C) and 250 mg/kg body weight aqueous extract of leaves of Hunteria umbellata (group D) respectively. Blood samples were taken by repeated needle puncture of their tail tip vein every 72 hours at the end of a 12 hrs fasting. Fasting blood glucose was determined using a fine test glucometer and compatible glucose test strips. Rats were sacrificed by cervical dislocation on the 15th day and the pancreas was accessed and dissected out through a midline incision of the anterior abdominal wall of the rats. The pancreas was fixed in 10% buffered formal saline for routine histological examination. 5ml blood samples were collected in heparin coated tubes for serum anti-oxidant estimation. Results obtained showed that HU seeds and leaves extracts significantly (P < 0.05) increased Superoxide dismutase (SOD) and Catalase (CAT) activities and decrease in the activity of Thiobarbituric acid reactive species (TBARS) when compared streptozotocin injected rats. Histological sections showed marked distortion, vacoulation of the central part of the Islet. Treatment with Hunteria umbellata seed and leaf extracts reversed the cytoarchitectural distortion of pancreatic Islet cells caused by Streptozotocin. This suggests that extracts of HU seeds and leaves posses antidiabetic potential.Keywords: Hunteria umbellata, streptozotocin, pancreatic Islet, cytoarchitectural distortio

Neuroprotective Activities of Boophone haemanthoides (Amaryllidaceae) Extract and Its Chemical Constituents

Parkinson’s disease (PD) is a neurodegenerative condition that progresses as age increases, and some of its major symptoms include tremor and postural and movement-related difficulties. To date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed; hence, this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP+) and SH-SY5Y neuroblastoma cells. A total of seven compounds were isolated from BHE, viz distichamine (1), 1α,3α-diacetylnerbowdine (2), hippadine (3), stigmast-4-ene-3,6-dione (4), cholest-4-en-3-one (5), tyrosol (6), and 3-hydroxy-1-(4′-hydroxyphenyl)-1-propanone (7). Six compounds (1, 2, 4, 5, 6 and 7) were investigated, and five showed neuroprotection alongside the BHE. This study gives insight into the bioactivity of the non-alkaloidal constituents of Amaryllidaceae, since the isolated compounds and the BHE showed improved cell viability, increased ATP generation in the cells as well as inhibition of MPP+-induced apoptosis. Together, these findings support the claim that the Amaryllidaceae plant family could be a potential reserve of bioactive compounds for the discovery of neuroprotective agents

Characterization and Toxicity of Hypoxoside Capped Silver Nanoparticles

The reducing potential of plant extracts in the green synthesis of nanoparticles has been associated with their phytochemicals. Although pharmacologically inactive, a norlignan diglucoside “hypoxoside” (HP) occurs in large quantities in the extract of Hypoxis hemerocallidea (HE). In this work, HP was isolated from HE where both were used in the biosynthesis of the corresponding silver nanoparticles (HP-AgNPs and HE-AgNPs). The AgNPs were fully characterized using various physicochemical techniques and their antimicrobial and anticancer properties were evaluated. Transmission electron microscopy (TEM) revealed sizes of 24.3 ± 4 nm for the HE-AgNPs and 3.9 ± 1.6 nm for the HP-AgNPs. The HE-AgNPs demonstrated enhanced anti-bactericidal effects on Escherichia coli and Salmonella enterica with a minimum inhibitory concentration (MIC) value of 1.95 µg/mL, competing well with the standard drug. The cytotoxic activity showed that the HE-AgNPs reduced cell viability with an IC50 of 0.81 and 4.0 µg/mL, respectively, for the U87 and U251 cells, while the HP-AgNPs displayed 0.20 and 0.55 µg/mL for both cell lines, respectively. Furthermore, while the HE-AgNPs were selective to U87 alone, the HP-AgNPs were selective to both glioblastoma cells tested. The study demonstrated the ability of a single phytoconstituent (hypoxoside), not only as the chief bioreductant in the extract, but also as a standalone reducing and capping agent, producing ultra-small, spherical, and monodispersed AgNPs with enhanced biological properties

Neuroprotective Effects of <i>Glycyrrhiza glabra</i> Total Extract and Isolated Compounds

Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4′-O-glucoside (1), 3′,4′,7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3’[O], 4’-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4′-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4′-dihydroxy-2′-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18β-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra

Versatility of 7-substituted coumarin molecules as antimycobacterial agents, neuronal enzyme inhibitors and neuroprotective agents

Kapp, E., et al. 2017. Versatility of 7-substituted coumarin molecules as antimycobacterial agents, neuronal enzyme inhibitors and neuroprotective agents. Molecules, 22(10):1644, doi:10.3390/molecules22101644The original publication is available at http://www.mdpi.comENGLISH ABSTRACT: A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC99 values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents.http://www.mdpi.com/1420-3049/22/10/1644Publisher's versio