Moringa seed-supplemented diets modulate ACE activity but not its gene expression in L-NAME-induced hypertensive rats.

INTRODUCTION: We investigated the effect of dietary inclusions of Moringa seed (5% and 10%) on blood pressure, angiotensin-1 converting enzyme (ACE) activity, and gene expression, as well as redox status in hypertensive rats. MATERIAL AND METHODS: Wistar strain albino rats were fed moringa seed-based diets for two weeks prior L-NAME (40 mg/kg/day, p.o.) administration for another ten days. Subsequently, the blood pressure was monitored. Furthermore, the kidney homogenates were assayed for ACE activity and gene expression, as well as oxidative stress markers. RESULTS: The increased (systolic = 297 ± 59.30 mmHg; diastolic= 242 ± 51.96 mmHg) blood pressure, arginase activity, and reduced nitric oxide level were significantly ameliorated in hypertensive rats treated with the seed. However, the elevated ACE activity was significantly reduced but not the upregulated ACE1 gene. Also, the reduced antioxidant enzyme activities were ameliorated with a significant downregulation in their regulator-Nrf2. Rutin (4.07 ± 0.02 mg/g) and quercitrin (4.06 ± 0.01 mg/g), among others, were found in the seed. DISCUSSION: This study suggests that moringa seed offers its antihypertensive properties by acting as an ACE inhibitor but not its gene modulator, and also modulates the antioxidant system through interaction with Nrf2. CONCLUSION: Moringa seed could act as an ACE inhibitor and not its gene modulator.

Neuroprotective properties of solanum leaves in transgenic Drosophila melanogaster model of Alzheimer's disease.

INTRODUCTION: We investigated the effect of African eggplant (AE) (Solanum macrocarpon L) and Black nightshade (BN) (Solanum nigrum L) leaves; two tropical vegetables consumed by humans on behavioural, biochemical and histological indices in Drosophila melanogaster model of Alzheimer's disease (AD). MATERIALS AND METHOD: Transgenic flies expressing human Amyloid Precursor Protein (hAPP) and ß-secretase (hBACE 1) were exposed to the pulverised leaf samples (0.1 and 1.0%) in their diets for fourteen days. Thereafter, the flies were assessed for their behavioural indices and routine histology of brain cells. Furthermore, fly head homogenates were assayed for ß-amyloid level, activities of acetylcholinesterase (AChE) and ß-secretase (BACE-1), as well as oxidative stress markers. RESULTS: Result showed that the significantly lower (p < 0.05) behavioural parameters (survival, locomotor performance and memory index), higher AChE and BACE-1 activities, ß-amyloid, ROS and lipid peroxidation levels, as well as reduced antioxidant indices observed in the AD flies, were significantly ameliorated (p < 0.05) in AD flies treated with the leaf samples. DISCUSSION: This study has showed that leaves of AE and BN ameliorated behavioural and biochemical indices in AD flies via neural enzyme modulatory, and antioxidant mechanisms. CONCLUSION: Hence, this study further justifies the neuroprotective properties of both AE and BN.

Effect of Solanum vegetables on memory index, redox status, and expressions of critical neural genes in Drosophila melanogaster model of memory impairment.

African eggplant (Solanum macrocarpon L) (AE) and Black Nightshade (Solanum nigrum L) (BN) leaves are green leafy vegetables with nutritional and ethnobotanical values. We have previously characterized the vegetables via HPLC/LC-MS to reveal notable phenolic acids, flavonoids and alkaloids. In this present study, we addressed the efficacy of the two vegetables in mitigating mercuric chloride (HgCl2)-induced neurotoxicity and memory impairment in Drosophila melanogaster. Flies were exposed to HgCl2 (0.30 mg/g) alone or in combination with the vegetables (0.1 and 1.0%) of both samples in their diets for seven days. The results showed that HgCl2 (Hg)-exposed flies had significantly reduced survival rate and memory index, which were ameliorated in the Hg-exposed flies fed AE or BN. This was accompanied by increased reactive oxygen species (ROS) levels, reduced total thiol, as well as catalase, glutathione transferase (GST) and acetylcholine esterase (AChE) activities in Hg-exposed fly heads, but ameliorated in Hg-exposed flies fed dietary inclusions of the vegetables. In addition, the Hg-induced alterations in SOD, NF-ҝB/Relish, Dronc and Reaper mRNA levels were statistically indistinguishable from controls in Hg-treated flies fed diets containing AE or BN. Normalization of cnc/Nrf2 and FOXO were observed only in Hg-treated flies fed BN. These findings suggest that dietary AE or BN leaves offer protection against Hg-induced memory impairment and neurotoxicity in D. melanogaster, and further justify them as functional foods with neuroprotective properties.

Dietary inclusions of Solanum vegetables mitigate aluminum-induced redox and inflammation-related neurotoxicity in Drosophila melanogaster model.

BACKGROUND: This study investigated the modulatory capacity of two Solanum green leafy vegetables; S. macrocarpon L. (African eggplant AE) and S. nigrum L. (Black nightshade BN) on dysregulation of some antioxidant, pro-apoptotic, pro-inflammatory-like, acetylcholinesterase gene expression and redox status in the Drosophila melanogaster model of aluminum-induced neurotoxicity. METHODS: Flies were exposed to AlCl3 (6.7 mM) alone or in combination with the leaves (0.1 and 1.0%) from both samples in their diet for seven days. Thereafter, the fly heads were rapidly separated, homogenized, and used to assay for reactive oxygen species (ROS), total thiol content, catalase, glutathione-S-transferase (GST), acetylcholinesterase (AChE) activities, and the expression of antioxidant-mediators (Hsp70, catalase, cnc/Nrf2, Jafrac1 and FOXO), acetylcholinesterase (Ace1), pro-apoptotic caspase-like (Dronc) and its regulator (reaper), as well as inflammation-related (NF-kB/Relish) genes. RESULTS: Results showed that AlCl3-exposed flies had significantly reduced survival rate which were ameliorated by AlCl3 also elevated ROS, GST and reduced AChE activities in fly heads while dietary inclusions of AE and BN ameliorated survial rate and oxidative stress in AlCl3-exposed flies. In addition, Hsp70, Jafrac1, reaper and NF-kҝB/Relish were significantly upregulated in AlCl3-exposed fly heads, while cnc/Nrf2 and FOXO were significantly downregulated, but catalase, Dronc and Ace were, not significantly modulated. Nevertheless, these impairments in gene expression levels were ameliorated by dietary inclusions of AE and BN during AlCl3 exposure. CONCLUSION: These findings showed that dietary inclusions of AE and BN leaves offer protection against Al-induced neurotoxicity in D. melanogaster and thus, could serve as functional foods with neuroprotective properties.

Effect of citrus peels-supplemented diet on longevity, memory index, redox status, cholinergic and monoaminergic enzymes in Drosophila melanogaster model.

This study sought to determine the life span promoting effecof orange (Citrus sinensis), tangerine (Citrus maxima) and grapefruit (Citrus paradisi) peels in Drosophila melanogaster model. Flies (both gender, 3 to 5 days old) were divided into seven (7) groups (n = 5) containing 40 flies each; group I (control) flies were fed with basal diet, II-VII were flies were fed with basal diet containing 0.1 and 1.0% of tangerine peel (TP), orange peel (CP), and grapefruit peel (GP) respectively, for 14 days. Locomotor performance and memory index were assessed via negative geotaxis and aversive phototaxis suppression assays, respectively. Thereafter, the fly homogenates were assayed for activities of acetylcholinesterase (AChE), monoamine oxidase (MAO) and antioxidant enzymes as well as other indices of their redox. The results revealed that the citrus peels significantly improved longevity, locomotor performance, memory index, antioxidant status, and modulate cholinesterase and monoamine oxidase enzyme activities in treated flies when compared to the control. The results obtained suggest that the citrus peels offer potentials as dietary supplement with life span promoting properties in D. melanogaster model which could as well serve as a functional food additives. PRACTICAL APPLICATIONS: Citrus peels, although often considered agro-wastes, are used as food supplements and food ingredents especially in production of candies, jams and custards. This study suggests the use of orange (Citrus sinensis), tangerine (Citrus maxima), and grapefruit (Citrus paradisi) peels as dietary supplements which offers potential life span promoting properties.

Anticholinesterase activity and antioxidant properties of Heinsia crinita and Pterocarpus soyauxii in Drosophila melanogaster model.

BACKGROUND: Plant alkaloids have become important sources of nutraceuticals owing to their pharmacological importance especially in the management of neurodegenerative diseases such as Alzheimer's disease. In assessing the therapeutic potentials of plant phytochemicals, the fruit fly (Drosophila melanogaster) has emerged as a very veritable tool and has been largely accepted as an alternative model in biomedical research. OBJECTIVES: In this study, alkaloid extracts from bush apple (Heinsia crinita (Afzel.) G. Taylor and padauk (Pterocarpus soyauxii Taub.) leaves were assessed on D. melanogaster exposed to aluminum toxicity. MATERIALS AND METHODS: Alkaloid extracts were prepared by solvent extraction method. Thereafter, the extracts were evaluated for their in vitro antioxidant properties, Fe2+-chelating abilities and inhibitory effects on drosophila acetylcholinesterase (AChE) activity. The samples were also characterized for their constituent alkaloids via HPLC. Thereafter, effective safe dose of the extracts were determined in D. melanogaster (Harwich strain). Subsequently, flies assaulted with AlCl3 were co-treated with the extracts (8.3 and 16.6 µg/g) for seven days, during which their survival rate was monitored. This was followed by assaying for the activities of AChE, antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione-S-transferase (GST)]. Also, the flies were assayed for levels of thiobarbituric acid reaction substance (TBARS) and reactive oxygen species (ROS). RESULTS: The results revealed that both extracts showed in vitro antioxidant properties with Padauk showing significantly higher antioxidant properties in vitro. However, there was no significant difference in their in vitro AChE inhibition. In vivo, Al-induced toxicity reduced survival rate, elevated AChE, SOD and GST activities, as well as TBARS and ROS levels which were ameliorated by the extracts. It was also revealed that piperine was predominant in PA, while 1-cyclohexen-1-yl-pyrrolidine was predominant in BA. CONCLUSION: Our data suggest that the protective abilities of these extracts against Al-induced toxicity can be primarily associated with their anticholinesterase and metal chelating abilities. Thus, these vegetables can be potential sources of nutraceuticals against aluminum toxicity and associated diseases.

Solanum vegetable-based diets improve impairments in memory, redox imbalance, and altered critical enzyme activities in Drosophila melanogaster model of neurodegeneration.

The effects of two Solanum vegetables, S. macrocarpon L. (African eggplant), and S. nigrum L. (black nightshade) on aluminum model of neurodegeneration in Drosophila melanogaster was investigated. Flies were treated with AlCl3 alone or in combination with the leaves from both samples in their diets for 7 days. Thereafter, locomotor performance and aversive phototaxic suppression test for learning and memory were carried out. This was followed by assay for reactive oxygen species, antioxidant properties, and enzyme (monoamine oxidase and cholinesterase) activities. Also, the in vitro antioxidant properties and chromatographic phenolic and alkaloid characterization of the samples were determined. Results showed that impaired behavioral physiology, antioxidant status, and enzyme activities observed in Al-treated flies were ameliorated in flies treated with both samples. In addition, both samples exhibited in vitro antioxidant effects. The protective effects from these samples against Al-induced toxicity can be associated with their antioxidant, antimonoaminergic, and anticholinergic properties. PRACTICAL APPLICATIONS: In the quest for a holistic prevention/management approach to neurodegenerative diseases, functional foods are becoming prominent. The use of Drosophila melanogaster to study human diseases is gaining huge recognition due to the high homologue between disease-causing genes between the two organisms. Consequently, this study presents African eggplant and black nightshade leafy vegetables as sources of polyphenols and alkaloids which are able to ameliorate impaired learning and memory, redox status, and enzyme activities in Al-induced D. melanogaster model of neurodegeneration.

Solanum leaves extracts exhibit antioxidant properties and inhibit monoamine oxidase and acetylcholinesterase activities (in vitro) in Drosophila melanogaster.

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.

Phenolic analysis and erectogenic function of African Walnut (Tetracarpidium conophorum) seeds: The impact of the seed shell on biological activity.

This study investigated the erectogenic potential of African walnut seed (AWS). The extract from AWS cooked with/without shell interacted with phosphodiesterase-5 (PDE-5), arginase, angiotensin-I converting enzymes (ACE), and acetylcholinesterase (AChE); enzymes associated with erectile dysfunction (ED) and Fe2+ -induced malonaldehyde (MDA) production in the isolated penile tissue. The results showed that the extracts inhibited the enzymes and MDA production, but Walnut cooked with shell had the highest effect. This agreed with increased phenolic acids and flavonoids, found in the AWS cooked with the shell, compared with that cooked without shell. The inhibition of enzymes and antioxidative potentials could be among the possible mechanisms of actions of AWS in the management/treatment of ED. However, cooking walnut seed with the shell seem to be a contributing factor, as this could prevent possible leaching out of the phytochemicals that could be responsible for these biological effects. PRACTICAL APPLICATIONS: Walnut seed possesses a high content of phenolic compounds and inhibit enzymes relevant to the management of erectile dysfunction. Traditionally, Walnut seed is being cooked with/without the shell and consumed for the purpose of alternative medicine in folklore. Our investigation revealed the possible mechanism underlying the therapeutic effect Walnut seed in the management of ED, but the impact of the shell during cooking contributes to this effect. This result will inform the consumers and food scientist on the importance of cooking Walnut seed with the shell in order to maximize its nutraceutical values.

Modulatory Effects of Alkaloid Extract from Gongronema latifolium (Utazi) and Lasianthera africana (Editan) on Activities of Enzymes Relevant to Neurodegeneration.

Most alkaloids are produced by plants as a defense mechanism against herbivores. Since alkaloids are known to possess pharmacological effects, this study sought to investigate the in vitro modulatory effect of alkaloid obtained from two commonly consumed vegetables in southern Nigeria, Lasianthera africana (editan) and Gongronema latifolium (utazi), on some enzyme activities relevant to neurodegeneration. Effects of the alkaloids on cholinesterases (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE]) and monoamine oxidase (MAO) activities were determined in vitro. In addition, Fe2+ chelating ability as well as radical-scavenging abilities were determined. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). The results revealed that the alkaloids inhibited AChE, BChE, and MAO activities in a concentration-dependent manner, such that the alkaloid from G. latifolium showed higher enzyme inhibition (AChE [IC50 = 87.39 µg/ml], BChE [IC50 = 118.65 µg/ml], and MAO [IC50 = 61.37 µg/ml]) than L. africana (AChE = 115.60 µg/ml; BChE = 169.48 µg/ml; MAO = 73.72 µg/ml). In addition, GC-FID analysis revealed abundance of choline in both extracts. Gongronema latifolium and Lasianthera africana alkaloid extracts inhibit enzymes (acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase) implicated in neurodegenerative diseases. Hence, these vegetables could offer dietary supplement in the management of neurodegenerative diseases.

In vitro anticholinesterase, antimonoamine oxidase and antioxidant properties of alkaloid extracts from kola nuts (Cola acuminata and Cola nitida).

Background The development of cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for management of neurodegenerative diseases such as Alzheimer's disease (AD) has come with their undesirable side effects. Hence, research for potent but natural ChE and MAO inhibitors with little or no side effects is essential. This study investigated the potentials of alkaloid extracts from two Cola species as nutraceuticals for prevention and management of AD. Methods Alkaloid extracts were obtained from two Cola species (Cola nitida [KN] and Cola acuminata [KA]) by solvent extraction method. The extracts were characterized for their alkaloid contents using gas chromatography (GC). The effects of the extracts on ChE and MAO activities were investigated in vitro. Also, the extracts' ability to inhibit Fe2+-induced lipid peroxidation in rat brain homogenate, scavenge DPPH and OH radicals, as well as chelate Fe2+ were determined. Results GC characterization revealed the presence of augustamine and undulatine as the predominant alkaloids in the extracts. There was no significant (P > 0.05) difference in the inhibitory effects of the extracts on ChE activities. However, KA extract exhibited significantly higher (P < 0.05) MAO inhibitory effect than KN. Also, KA extract inhibited Fe2+- induced malondialdehyde (MDA) production in rat brain homogenate more significantly than KN, while there was no significant difference in DPPH and OH radicals scavenging, as well as Fe2+-chelating abilities of the extracts. Conclusions Our findings revealed that KN and KA alkaloid extracts exhibited significant effect in vitro on biological pathways that may contribute to neuroprotection for the management of neurodegenerative diseases.

Phenolic constituents and modulatory effects of Raffia palm leaf (Raphia hookeri) extract on carbohydrate hydrolyzing enzymes linked to type-2 diabetes.

This study sought to investigate the effects of Raffia palm (Raphia hookeri) leaf extract on enzymes linked to type-2 diabetes mellitus (T2DM) and pro-oxidant induced oxidative stress in rat pancreas. The extract was prepared and its α-amylase and α-glucosidase inhibitory effects were determined. Radical [2,2-diphenyl-1-picrylhydrazyl (DPPH)] scavenging and Fe2+-chelating abilities, and inhibition of Fe2+-induced lipid peroxidation in rat pancreas homogenate were assessed. Furthermore, total phenol and flavonoid contents, reducing property, and high performance liquid chromatography diode array detector (HPLC-DAD) fingerprint of the extract were also determined. Our results revealed that the extract inhibited α-amylase (IC50 = 110.4 µg/mL) and α-glucosidase (IC50 = 99.96 µg/mL) activities in concentration dependent manners which were lower to the effect of acarbose (amylase: IC50 = 18.30 µg/mL; glucosidase: IC50 = 20.31 µg/mL). The extract also scavenged DPPH radical, chelated Fe2+ and inhibited Fe2+-induced lipid peroxidation in rat pancreas all in concentration dependent manners with IC50 values of 402.9 µg/mL, 108.9 µg/mL and 367.0 µg/mL respectively. The total phenol and flavonoid contents were 39.73 mg GAE/g and 21.88 mg QAE/g respectively, while the reducing property was 25.62 mg AAE/g. The HPLC analysis revealed the presence of chlorogenic acid (4.17 mg/g) and rutin (5.11 mg/g) as the major phenolic compounds in the extract. Therefore, the ability of the extract to inhibit carbohydrate hydrolyzing enzymes and protect against pancreatic oxidative damage may be an important mechanisms supporting its antidiabetic properties and could make Raffia palm leaf useful in complementary/alternative therapy for management of T2DM. However, further studies such as in vivo should be carried out.

Quercetin and Its Role in Chronic Diseases.

Quercetin, a member of the flavonoid class of polyphenol, is one of the most abundantly distributed flavonoids found in various food sources such as fruits, vegetables, nuts, wine and seeds. Quercetin and quercetin-rich foods have been reported to have wide range of health promoting effects, especially in the prevention and management of several diseases; however, the subject of its solubility and bioavailability has limited its use. This section will therefore, consider quercetin as a food-rich flavonoid, the various food sources, the limitations in its use and new approaches at improving its solubility and bioavailability. The therapeutic potentials of quercetin at the prevention/management of some degenerative diseases such as diabetes, hypertension and neurodegenerative diseases, as well as the underlying biochemical mechanisms such as free radical scavenging and enzyme inhibition will also be discussed.

Alkaloid extracts from Jimson weed (Datura stramonium L.) modulate purinergic enzymes in rat brain.

Although some findings have reported the medicinal properties of Jimson weed (Datura stramonium L.), there exist some serious neurological effects such as hallucination, loss of memory and anxiety, which has been reported in folklore. Consequently, the modulatory effect of alkaloid extracts from leaf and fruit of Jimson weed on critical enzymes of the purinergic [ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-NTDase), alkaline phosphatase (ALP) and Na+/K+ ATPase] system of neurotransmission was the focus of this study. Alkaloid extracts were prepared by solvent extraction method and their interaction with the activities of these enzymes were assessed (in vitro) in rat brain tissue homogenate and in vivo in rats administered 100 and 200mg/kg body weight (p.o) of the extracts for thirty days, while administration of single dose (1mg/kg body weight; i.p.) of scopolamine served as the positive control. The extracts were also investigated for their Fe2+ and Cu2+ chelating abilities and GC-MS characterization of the extracts was also carried out. The results revealed that the extracts inhibited activates of E-NTPDase, E-NTDase and ALP in a concentration dependent manner, while stimulating the activity of Na+/K+ ATPase (in vitro). Both extracts also exhibited Fe2+ and Cu2+ chelating abilities. Considering the EC50 values, the fruit extract had significantly higher (P<0.05) modulatory effect on the enzymes' activity as well as metal chelating abilities, compared to the leaf extract; however, there was no significant difference (P>0.05) in both extracts' inhibitory effects on E-NTDase. The in vivo study revealed reduction in the activities of ENTPDase, E-NTDase, and Na+/K+ ATPase in the extract-administered rat groups compared to the control group, while an elevation in ALP activity was observed in the extract-administered rat groups compared to the control group. GC-MS characterization revealed the presence of atropine, scopolamine, amphetamine, 3-methyoxyamphetamine, 3-ethoxyamhetamine cathine, spermine, phenlyephirine and 3-piperidinemethanol, among others in the extracts. Hence, alterations of activities of critical enzymes of purinergic signaling (in vitro and in vivo) by alkaloid extracts from leaf and fruit of Jimson weed suggest one of the mechanisms behind its neurological effects as reported in folklore.

Attenuation of gentamycin-induced nephrotoxicity in rats by dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes.

This study sought to investigate the modulatory effects of dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes on antioxidant status and renal damage induced by gentamycin in rats. Renal damage was induced in albino rats pretreated with dietary inclusion of ginger and turmeric (2% and 4%) by intraperitoneal (i.p.) administration of gentamycin (100 mg/kg body weight) for three days. Assays for renal damage biomarkers (plasma creatinine, plasma urea, blood urea nitrogen and plasma uric acid), malondialdehyde (MDA) content and reduced glutathione (GSH) content as well as renal antioxidant enzymes (catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were carried out. The study revealed significant (p < 0.05) increases in renal damage biomarkers following gentamycin administration with severe alteration in kidney antioxidant status. However, pretreatment with ginger and turmeric rhizome (2% and 4%) prior to gentamycin administration significantly (p < 0.05) protected the kidney and attenuated oxidative stress by modulating renal damage and antioxidant indices. This finding therefore suggests that dietary inclusion of ginger and turmeric rhizomes may protect against gentamycin-induced nephrotoxicity and oxidative stress.